Foc

Neurosurgical Infectious Disease
Surgical and Nonsurgical Management

Neurosurgical Infectious Disease
Surgical and Nonsurgical Management
Walter A. Hall, MD, MBA

Professor of Neurosurgery
Department of Neurological Surgery
SUNY Upstate Medical University
Syracuse, New York
Peter D. Kim, MD, PhD

Neurosurgeon
Department of Neurosurgery
Gillette Children’s Specialty Healthcare
St. Paul, Minnesota
Thieme
New York · Stuttgart
Thieme Medical Publishers, Inc.
333 Seventh Ave.
New York, NY 10001
Executive Editor: Kay Conerly

Managing Editor: Judith Tomat
Editorial Assistant: Lorina Lana
Senior Vice President, Editorial and Electronic Product Development: Cornelia Schulze
Production Editor: Kenneth L. Chumbley
International Production Director: Andreas Schabert
Vice President, Finance and Accounts: Sarah Vanderbilt
President: Brian D. Scanlan
Compositor: Prairie Papers Inc.
Printer: Everbest Printing Co.
Library of Congress Cataloging-in-Publication Data
Neurosurgical infectious disease : surgical and nonsurgical management / [edited by] Walter A. Hall,
Peter D. Kim.
p. ; cm.
Includes bibliographical references.
ISBN 978-1-60406-805-4 (alk. paper)—ISBN 978-1-60406-821-4 (eISBN)
I. Hall, Walter A., 1957- II. Kim, Peter D.
[DNLM: 1. Central Nervous System Infections—therapy. 2. Anti-Infective Agents—therapeutic use.
3. Central Nervous System Infections—diagnosis. 4. Communicable Diseases—therapy. WL 301]
RC386.5
616.8′3—dc23
2013003829
Copyright © 2014 by Thieme Medical Publishers, Inc. This book, including all parts thereof, is legally
protected by copyright. Any use, exploitation, or commercialization outside the narrow limits set by
copyright legislation without the publisher’s consent is illegal and liable to prosecution. This applies in
particular to photostat reproduction, copying, mimeographing or duplication of any kind, translating,
preparation of microfilms, and electronic data processing and storage.
Important note: Medical knowledge is ever-changing. As new research and clinical experience broaden
our knowledge, changes in treatment and drug therapy may be required. The authors and editors of the
material herein have consulted sources believed to be reliable in their efforts to provide information that
is complete and in accord with the standards accepted at the time of publication. However, in view of the
possibility of human error by the authors, editors, or publisher of the work herein or changes in medical
knowledge, neither the authors, editors, nor publisher, nor any other party who has been involved in the
preparation of this work, warrants that the information contained herein is in every respect accurate
or complete, and they are not responsible for any errors or omissions or for the results obtained from
use of such information. Readers are encouraged to confirm the information contained herein with other
sources. For example, readers are advised to check the product information sheet included in the package
of each drug they plan to administer to be certain that the information contained in this publication is
accurate and that changes have not been made in the recommended dose or in the contraindications for
administration. This recommendation is of particular importance in connection with new or infrequently
used drugs.
Some of the product names, patents, and registered designs referred to in this book are in fact registered
trademarks or proprietary names even though specific reference to this fact is not always made in the
text. Therefore, the appearance of a name without designation as proprietary is not to be construed as a
representation by the publisher that it is in the public domain.
Printed in China
54321
ISBN 978-1-60406-805-4
Also available as an e-book:

eISBN 978-1-60404-821-4
This book is dedicated to Madeleine and Stanley Smalley for their unwavering support,
encouragement, and love over three decades.
Walter A. Hall
This book is dedicated, with love and gratitude, to my parents, Kenneth and Susan Kim.
Peter D. Kim
Contents
Foreword................................................................................................................................................ ix
Patricia Ferrieri, MD
Preface ................................................................................................................................................................xi
Contributors........................................................................................................................................xiii
I Background Information
1 Immunology of the Central Nervous System............................................................................3
Pragati Nigam and Maciej S. Lesniak
2 Microbiological Diagnosis of Central Nervous System Infections................................... 16
Yuriko Fukuta and Karin Byers
3 Antibiotics and the Development of Resistance.................................................................... 30
Peter D. Kim and Walter A. Hall
4 Radiology of Central Nervous System Infections ................................................................. 35
Kunal M. Patel and Charles L. Truwit
II Etiologic Agents

5 Viral Infections of the Central Nervous System..................................................................... 51
Joseph B. Domachowske, Manika Suryadevara, and Walter A. Hall
6 Fungal Infections of the Central Nervous System................................................................. 68
Walter A. Hall and Peter D. Kim
7 Parasitic Infections of the Central Nervous System.............................................................. 81
Ali Akhaddar and Mohamed Boucetta
8 Bacterial Brain Abscess.................................................................................................................. 95
III CNS Locations for Infection
9 Meningeal Infections....................................................................................................................107
Manika Suryadevara and Joseph B. Domachowske
10 Epidural and Subdural Infections.............................................................................................125
Sandi Lam and Peter C. Warnke
11 Infectious Intracranial Aneurysms..........................................................................................133
Hoon Choi, Walter A. Hall, and Eric M. Deshaies
12 Vertebral Column Infections......................................................................................................147
Kyle I. Swanson and Daniel K. Resnick
13 Spinal Canal Infections................................................................................................................163
Ian E. McCutcheon
IV Neurosurgical Issues

14 Neurosurgical Antibiotic Prophylaxis.....................................................................................185
Daraspreet Singh Kainth, Dino Terzic, and Stephen J. Haines
15 Postoperative Intracranial Infections......................................................................................196
Arya Nabavi, Frederike Knerlich-Lukoschus, and Andreas M. Stark
16 Implanted Devices and Central Nervous System Infection..............................................208
Ramesh Grandhi, Gillian Harrison, and Elizabeth Tyler-Kabara
V Special Populations
17 Pediatric Central Nervous System Infections.......................................................................233
Contents
Ian Mutchnick and Thomas M. Moriarty

18 Central Nervous System Infections in Immunocompromised Hosts............................247
Ouzi Nissim, Gahl Greenberg, Zvi R. Cohen, and Roberto Spiegelmann
19 Systemic Infections in the Neurologic Intensive Care Unit..............................................269
Michael F. Regner, Christopher D. Baggott, Barry C. Fox, and Joshua E. Medow
Index ............................................................................................................................................................285
viii
Foreword
This book of nineteen chapters, edited by with its discussion and management of ce-
Drs. Walter A. Hall and Peter D. Kim, is a rebrospinal fluid ventricular shunt infec-
comprehensive exposition of the major as- tions. The imaging scans presented are of
pects of common and rare central nervous excellent resolution both here and in other
system (CNS) infections in neurosurgical chapters, for example, Chapter 8 on brain
patients, their diagnosis, and surgical and abscesses. The details on complications,
nonsurgical management. sequelae, and prognosis are very complete.
It is characterized by a finely tuned In summary, this book should be of inter-
balance between basic information and est to many different professionals: medi-
scholarly documentation of the entities de- cal students, graduate health professional
scribed. Chapters 1 and 2, on the Immunolo- students, medical and surgical residents,
gy of the CNS and Microbiological Diagnosis neurosurgical residents, pediatricians, in-
of CNS Infections, are of special interest. ternists, neurosurgeons, and consultants
These are unique examples because of the in adult/pediatric neurology and infectious
fine details that are provided and their ap- diseases.
plications to patient management. The bib-
liography in each chapter is up to date and Patricia Ferrieri, MD
documents the newest developments in the Professor
diagnosis of common and more unusual in- Chairman’s Fund Endowed Chair in
fectious agents and the complication(s) that Laboratory Medicine and Pathology
may occur. Professor
Chapter 9, on meningeal infections, Department of Pediatrics,
presents the most common pathogens for Division of Infectious Diseases
acute bacterial meningitis by age group, University of Minnesota Medical School
the recommended empirical therapy, and Minneapolis, Minnesota
provides helpful epidemiological informa- Director, Clinical Microbiology Laboratory
tion on these infections. A chapter focus- University of Minnesota Medical Center,
ing on the pediatric patient population and Fairview
infections of the CNS is especially welcome, Fairview, Minnesota
Preface
Infections involving the central nervous such as immunology of the CNS, microbio-
system (CNS) can cause significant neurological diagnosis of CNS infection, antibiotic
logical morbidity and mortality. Evolving resistance, and imaging of CNS infections.
threats such as insect-borne encephalitides The second section identifies specific
make news headlines, while familiar diseas- etiological agents that result in infection,
es such as bacterial meningitis and postop- including viruses, fungi, parasites, and
erative infection continue to burden society bacteria. The various anatomical locations
with significant morbidity. The clinical out- (meninges, epidural and subdural spaces,
come in these patients with CNS infection intracranial vasculature, vertebral column,
is often related to the speed with which the and the spinal canal) where CNS infections
diagnosis is made and appropriate surgi- are manifest are addressed in the third sec-
cal and medical management is initiated. tion. Distinctly neurosurgical issues, such
Expeditious identification of an infectious as antibiotic prophylaxis, postoperative
process is now possible through enhanced intracranial infection, and the infection of
radiological screening through magnetic implanted devices, constitute the fourth
resonance imaging, while advanced mi- section. Unique patient populations are
crobiological techniques, such as the poly- discussed in the fifth and last section and
merase chain reaction, allow for earlier include pediatric patients, immunocom-
identification of the responsible infectious promised hosts, and those that experience
agents. All the while, an ever expanding systemic infection while in the neurocriti-
arsenal of antimicrobial agents exists in cal care unit.
tenuous balance with the rapid spread of Having been involved in the formulation
resistant bacterial strains. All of these ad- of two previous texts on this extremely im-
vancements are discussed in this compila- portant topic, the senior author (WAH) felt
tion, making it an appropriate resource for compelled to update the current level of
medical students, residents, internists, mi- knowledge of the surgical and nonsurgical
crobiologists, neurologists, neurosurgeons, management of these disease entities by
and infectious disease specialists. recruiting an array of expects with a global
In order to inform the medical commu- depth to share their cumulative experience
nity of the advances in the treatment of and insight with the reading audience.
these once dreaded infections, this work
was conceived due to the last in-depth cov- Walter A. Hall
erage of this topic being introduced more Syracuse, New York
than a decade ago. The format of the mate-
rial presented is categorized into five sec- Peter D. Kim
tions that include background information, St. Paul, Minnesota
Contributors
Ali Akhaddar, MD Zvi R. Cohen, MD

Full Professor of Neurosurgery Staff Neurosurgeon
Department of Neurosurgery Chaim Sheba Medical Center
Mohammed V Military Teaching Hospital Tel Hashomer, Israel
Mohammed V Souissi University–Hay Riyad Lecturer
Rabat, Morocco The Sackler School of Medicine
Tel Aviv, Israel
Christopher D. Baggott, MD
Resident Eric M. Deshaies, MD
Department of Neurological Surgery Director
University of Wisconsin School of SUNY Upstate Neurovascular Center
Medicine and Public Health Assistant Professor of Neurosurgery
Madison, Wisconsin Assistant Professor of Neuroscience and
Physiology
Mohamed Boucetta, MD Department of Neurosurgery
Full Professor of Neurosurgery SUNY Upstate Medical University
Department of Neurosurgery Syracuse, New York
Mohammed V Military Teaching Hospital
Mohammed V Souissi University–Hay Riyad Joseph B. Domachowske, MD
Rabat, Morocco Professor of Pediatrics, Microbiology, and
Immunology
Karin Byers, MD, MS Department of Pediatrics
Clinical Director SUNY Upstate Medical University
Division of Infectious Diseases Syracuse, New York
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania Barry C. Fox, MD
Clinical Professor of Medicine
Hoon Choi, MD Division of Infectious Diseases
Resident University of Wisconsin Hospital and
Department of Neurosurgery Clinics
SUNY Upstate Medical University Madison, Wisconsin
Syracuse, New York
Yuriko Fukuta, MD
Infectious Diseases and Internal Medicine
Wheeling Clinic
Wheeling, West Virginia
Ramesh Grandhi, MD Sandi Lam, MD, MBA
Resident Assistant Professor
Department of Neurological Surgery Section of Neurosurgery
University of Pittsburgh School of Medicine Department of Surgery
Pittsburgh, Pennsylvania University of Chicago
Chicago, Illinois
Gahl Greenberg, MD
Staff Neurosurgeon Maciej S. Lesniak, MD, MHCM, FACS
Department of Neurosurgery Professor of Neurosurgery, Neurology, and
Chaim Sheba Medical Center Cancer Biology
Tel Hashomer, Israel Director
Neurosurgical Oncology and the
Stephen J. Haines, MD Neuro-Oncology Research Laboratories
Lyle A. French Chair University of Chicago
Professor and Head Chicago, Illinois
University of Minnesota Ian E. McCutcheon, MD
Minneapolis, Minnesota Professor
Walter A. Hall, MD, MBA The University of Texas M. D. Anderson
Professor of Neurosurgery Cancer Center
Department of Neurological Surgery Houston, Texas
SUNY Upstate Medical University
Syracuse, New York Joshua E. Medow, MD, MS, FAANS
Endovascular Neurosurgeon and
Gillian Harrison, BS Neurointensivist
Director of Neurocritical Care
Contributors
Medical Student
University of Pittsburgh School of Medicine Assistant Professor of Neurosurgery and
Pittsburgh, Pennsylvania Biomedical Engineering
University of Wisconsin School of
Daraspreet Singh Kainth, MD Medicine and Public Health
Resident Madison, Wisconsin
University of Minnesota Thomas M. Moriarty, MD, PhD
Minneapolis, Minnesota Chief
Department of Pediatric Neurosurgery
Peter D. Kim, MD, PhD Kosair Children’s Hospital
Neurosurgeon Norton Neuroscience Institute
Department of Neurosurgery Louisville, Kentucky
Gillette Children’s Specialty Healthcare
St. Paul, Minnesota Ian Mutchnick, MD, MS
Attending Physician
Frederike Knerlich-Lukoschus, MD Department of Pediatric Neurosurgery
Clinic of Neurosurgery Kosair Children’s Hospital
University Medical Center Norton Neuroscience Institute
Schleswig-Holstein–Kiel Louisville, Kentucky
Kiel, Germany
xiv
Arya Nabavi, MD, PhD, MaHM Andreas M. Stark, MD, PhD
Professor of Neurosurgery Professor of Neurosurgery
Vice Chairman Department of Neurosurgery
Department of Neurosurgery University Medical Center
University Medical Center Schleswig-Holstein–Kiel
Schleswig-Holstein–Kiel Kiel, Germany
Kiel, Germany
Manika Suryadevara, MD
Pragati Nigam, PhD Assistant Professor of Pediatrics
Postdoctoral Fellow Department of Pediatrics
The Brain Tumor Center SUNY Upstate Medical University
University of Chicago Syracuse, New York
Chicago, Illinois
Kyle I. Swanson, MD
Ouzi Nissim, MD Resident
Staff Neurosurgeon Department of Neurosurgery
Department of Neurosurgery University of Wisconsin School of
Chaim Sheba Medical Center Medicine and Public Health
Tel Hashomer, Israel Madison, Wisconsin
Kunal M. Patel, MD Dino Terzic, MD

Neuroradiology Fellow Resident
Department of Radiology Department of Neurosurgery
University of California–San Diego University of Minnesota
San Diego, California Minneapolis, Minnesota
Contributors
Michael F. Regner, BA Charles L. Truwit, MD
Medical Student Professor and Chief of Radiology
Department of Neurosurgery Hennepin County Medical Center
University of Wisconsin School of Minneapolis, Minnesota
Medicine and Public Health
Madison, Wisconsin Elizabeth Tyler-Kabara, MD, PhD
Assistant Professor
Daniel K. Resnick, MD, MS Department of Neurological Surgery and
Professor and Vice Chairman Bioengineering
Department of Neurosurgery Director
University of Wisconsin School of Department of Pediatric Epilepsy Surgery
Medicine and Public Health University of Pittsburgh Medical Center
Madison, Wisconsin Pittsburgh, Pennsylvania
Roberto Spiegelmann, MD Peter C. Warnke, MD

Head, Stereotactic Radiosurgery Unit and Associate Professor of Surgery
Functional Neurosurgery Service Director
Department of Neurosurgery Department of Stereotactic and Functional
Chaim Sheba Medical Center Neurosurgery
Senior Lecturer University of Chicago
The Sackler School of Medicine Chicago, Illinois
Tel Aviv, Israel
xv
I
Background Information
1
Immunology of the Central
Nervous System
Pragati Nigam and Maciej S. Lesniak
The brain is an organ with unique charac- that the brain and eyes harbor specialized
teristics that function to restrain immu- microvasculature where events such as
nologic responses that could potentially lymphocyte adhesion to the endothelium
damage tissue. In this chapter, we describe and the free exchange of solutes are highly
how the immune responses in the central regulated.3–5 Furthermore, the CNS lacks
nervous system (CNS) are modulated and classic antigen-presenting cells (APCs), as
regulated. We also discuss the resident im- well as constitutive expression of major
mune cells in the CNS, the trafficking of histocompatibility complex I and II (MHC
lymphocytes across the blood–brain bar- I, II). Similarly, the CNS is devoid of lym-
rier (BBB), and the chemokines that func- phatic vessels.
tion to recruit lymphocytes in the CNS Currently, it is recognized that the CNS
microvasculature. immune privilege phenomenon is not
complete, and that foreign materials im-
planted within the CNS can elicit an im-
■■ Immunosurveillance of the mune response, although it is delayed and
tightly controlled.6 It has also been ob-
Central Nervous System served that tissue grafts implanted within
Certain organs, such as the brain, eyes, and the CNS are eventually rejected, and de-
testicles, are particularly sensitive to dam- layed-type hypersensitivity reactions can
age due to inflammation. Thus, these tis- occur. Pathogenic autoimmune diseases of
sues have developed singular properties the CNS exist as well, as demonstrated by
that limit the immunologic responses to experimental autoimmune encephalomy-
antigenic challenge—a phenomenon that elitis (EAE). Thus, the CNS is more appro-
has been termed immunologic privilege.1 priately described as an immunologically
In agreement with this hypothesis, Sir Pe- specialized organ than as an immunologi-
ter Medawar observed that the brain does cally privileged one.
not reject foreign tissue grafts.2 The ratio-
nale for the existence of the phenomenon
of immunologic privilege is that activation ■■ Vascular Anatomy
of the immune system in these organs can
be extremely deleterious to the organ- The CNS microvessels are designed to per-
ism. The brain is susceptible to increases form two major tasks: (1) prevent ions and
in tissue volume because of limitations in other solutes in the blood from entering
space imposed by the dura mater and the the parenchyma and (2) enhance regional
cranium. Once neurons are damaged, they blood flow wherever needed. The anatom-
cannot be replaced. It is well established ic structures consist of a series of barri-
ers; these include the blood–cerebrospinal ■■ Immune Cells in the
fluid (CSF) barrier, which prevents the free
Central Nervous System
exchange of solutes between the blood and
the CSF, and the BBB, which is the most Environment
prominent interface between the immune
Even under normal physiologic conditions,
and nervous systems. The blood–CSF bar-
the CNS is not an environment that lacks
rier results from the presence of the cho-
cells of hematopoietic origin. Various cells
roid plexus epithelium, in which the cells
reside in the CNS that constitute a resident,
are connected by tight junctions and are
quiescent immune system. The distribution
responsible for secreting CSF into the brain
of hematopoietic cells resident in the CNS
ventricles. The BBB consists of endothe-
is compartmentalized, indicative of specific
lial cells of the cerebral microvasculature,
functions attributed to cells present in dis-
pericytes, and astrocytes, which have been
tinct microenvironments. The major cells
well characterized in terms of their mor-
of hematopoietic origin present in the CNS
phology and biochemistry. The transcel-
are microglia and APCs. Microglia are local-
lular passage of molecules across the BBB
ized predominantly in the parenchyma of
is inhibited as a result of low pinocytotic
the CNS (although also present in the peri-
activity. The elaborate network of tight
vascular area) and function in the mainte-
junctions between the endothelial cells of
nance of neuronal homeostasis as well as
BBB7 limits the paracellular diffusion of hy-
tissue surveillance, whereas APCs reside
drophilic molecules. It is also known that
predominantly in the interface between
blood molecules are prevented from enter-

the CNS and the blood–CSF space.12–17
ing the parenchyma by several permanent-
ly active transportation mechanisms.8
The first evidence that T cells can mi- Antigen-Presenting Cells
grate across the healthy BBB into the CNS
Perivascular Antigen-Presenting Cells
came from animal models of neurodegen-
erative diseases, including multiple scle- Perivascular APCs consist of a heteroge-
rosis and EAE. Here, it was demonstrated neous population that includes perivascu-
that autoreactive CD4+ T cells recently ac- lar macrophages, perivascular microglia,
tivated in vitro could migrate into the CNS and dendritic cells (DCs).18,19 It is thought
and initiate a series of events culminating that perivascular APCs act as sentinels at
in inflammation, loss of barrier restriction, the BBB, their endocytic and phagocytic
edema formation, and demyelination.9 T activity scanning for both the presence of
cells were found to reside in the CNS peri- pathogens and neuronal damage.20 These
vascular spaces, allowing encounter with cells localize to the perivascular spaces
antigen presented by MHC class II–positive around cerebral vessels of small to medium
perivascular macrophages.10 T cells in the size.21 Perivascular cells are continuously
resting state were unable to migrate across replenished from the bone marrow, and
the BBB and could not transfer the disease. it is estimated that one-third of these cells
This indicated an active role for the BBB in are replaced during a trimester period in
regulating the entry of lymphocytes into rats, indicating that precursor cells of peri-
the CNS by restricting migration to activat- vascular APCs (most likely monocytes) can
ed T cells. It is interesting to observe that cross the intact BBB.22
CD3+ T cells can also be found in postmor- Perivascular macrophages have a role in
tem samples of choroid plexus in individu- the recruitment of lymphocytes across the
als with no known neurologic disorders, BBB and can also promote the invasion of
indicating that some lymphocytes may en- activated T cells into the parenchyma of the
ter the CNS during steady state.11 CNS.23,24 In addition, it has been shown that
4
these cells have an essential role in the ac- to have a key function during the develop-
tivation of recently immigrated pathogenic ment and maintenance of the CNS.37 During
CD4+ T cells.18,25 Macrophages and DCs embryogenesis, massive developmental
are enriched in the meninges and choroid apoptosis occurs in the nervous system;
plexus, probably because of proximity to twice the number of neurons are gener-
the CSF space.26 It has been hypothesized ated than is present in the adult organism.
that perivascular macrophages sample the Microglial functions have been implicated
CSF for the presence of pathogens, tissue in the phagocytosis of apoptotic cells. They
debris, tumor cells, and red blood cells. also promote the death of developing neu-
rons36,38 and are active at synaptic stripping
during pathologic processes39 and in syn-
Microglia
aptic remodeling.29
Microglia are the predominant cell type of Another key difference between the
1 Immunology of the Central Nervous System

the innate immune system within the CNS function of microglia and that of other
parenchyma. The distribution of microg- APCs is the interaction between microg-
lial cells varies in the different areas of the lia and neurons that leads to the inhibi-
CNS, ranging from approximately 5% in the tion of microglial cell activation. Microglia
cortex and corpus callosum to 12% in the are the only mononuclear phagocytes that
substantia nigra of the murine brain,27 and express neurotransmitter receptors, and
from 0.5% in the gray matter of the cerebel- they are rich in purinoceptors (e.g., dopa-
lum and cerebral cortex to greater than 16% mine receptors and adrenoreceptors). In the
in the pons and medulla in a noninflamed normal, healthy CNS, experiments using
human brain.28,29 Microglia belong to the cell two-photon imaging have shown that mi-
class of hematopoietic mononuclear phago- croglia inspect neuronal synapses in vivo in
cytic lineage; however, they are less efficient the adult cerebral cortex.35 Neuron–microg-
at antigen presentation than DCs. Microglia lial cell inhibitory signaling can be mediated
share many features with other myeloid via several mechanisms; these include con-
cells, as they express Fc and complement tact-dependent inhibitory influences, such
receptors CD11b and F4/80.30,31 However, as CD172A-CD47,40 CD200-CD200R,41,42
some of the molecular differences between CD22-CD45,42,43 and ICAM5-LFA1,44 as well
microglia and other dedicated phagocytic as soluble inhibitory cytokines, such as
APCs include secretion of significantly low- CX3CL1-CX3CR1 interactions.45 Microglia
er levels of superoxide dismutase (SOD) in sense damage once neuronal inhibition is
comparison with macrophages from the removed or silenced (Fig. 1.1).
spleen or bone marrow.32 Additionally, In their homeostatic resting state, mi-
much of the interaction between microglia croglia express very low levels of MHC
and T cells in the parenchyma occurs at a class II molecules46 and CD45.47 In the pres-
distance and is mediated via cytokine secre- ence of inflammation or pathologic events,
tion, not antigen specificity. microglia become activated and undergo
Microglia appear to survey the mi- morphological and immunophenotypic
croenvironment with highly motile fine alterations, including the upregulation
protrusions.33 It has been suggested that of MHC class II molecules.48 Under these
microglial protrusions survey the environ- conditions, microglia secrete a diversity
ment for inflammatory molecules, thus of chemokines, such as CCL1, CCL2, CCL5,
having an immunologic function. Recent and CXCL10, that function in the recruit-
studies, however, have shown that microg- ment of lymphocytes and other APCs, such
lia play a role in synaptogenesis,34 and in as macrophages and DCs. Evidence for the
the monitoring and maintenance of syn- role of chemokines secreted by microglia in
aptic functions35 as well as the apoptosis T-cell migration into the CNS parenchyma
of Purkinje cells.36 Thus, microglia appear was provided by a study involving macro-
5
Fig. 1.1 Neuron–microglia
interactions lead to the inhi-
bition of microglial activity
via cell contact–dependent
mechanisms or soluble in-
hibitory molecules.
phage colony–stimulating factor (M-CSF). mately twice per day; this provides a con-
Microglial activation is impaired in M-CSF– tinuous influx of lymphocytes that have
deficient mice, which significantly reduced different T-cell-receptor (TCR) specificities,

T-cell migration but did not affect axonal which allows a rapid reaction to antigens
repair.49 Corroborating evidence for the im- that are present within the subarachnoid
portance of microglia-derived chemokines space.51–53
in T-cell migration was also provided by a In various different neuropathologic
study conducted by Heppner et al, which conditions, T cells cross the BBB and par-
revealed that microglial paralysis inhibits ticipate in inflammatory reactions that are
the development and maintenance of in- deleterious to the individual. One example
flammatory CNS lesions in the EAE mouse is multiple sclerosis (MS), in which the
model.50 presence of CD4+ T cells that display a pro-
inflammatory Th1 or Th17 profile (along
with other inflammatory factors) results
T Cells
in an autoimmune disease characterized
Under normal physiologic conditions, the by recurrent episodes of demyelination
CNS tightly regulates cell entry into the and axonal lesions. The cytokines secret-
parenchyma and localizes immunosurveil- ed by Th1 (interferon-γ [INF-γ]) and Th17
lance to the perivascular and subarach- (interleukin-17 [IL-17]) result in the dif-
noid spaces. The CSF of normal healthy ferent clinical forms of MS.54,55 In the EAE
individuals contains approximately 0.15 × model, although Th1- and Th17-mediated
106 T cells, of which greater than 80% are lesions differ in their composition, there is
central memory CD4+ T cells (which ex- no difference in the localization of lesions
press CD45RO+/CD27+/CCR7+/CXCR3+ and within the CNS. The Th17 cells present in
L-selectin).51 It has been suggested that lesions can convert to IFN-γ–producing
the central memory CD4+ T cells present Th1-like cells. There is also a difference
in the CSF are responsible for the routine between the lytic potential of Th1 and
immunosurveillance of the CNS, by search- Th17 cells present at EAE lesions; the Th1
ing for recall antigens presented by mac- cells lysed astrocytes and fibroblasts that
rophages.26 It has been estimated that the presented autoantigen, whereas the Th17
T cells present in the CSF are replaced by cells acquired cytotoxic potential only af-
newly immigrating lymphocytes approxi- ter conversion to the IFN-γ-producing Th1
6
phenotype.56 The presence of Th17 cell in- proliferation, or secreting regulatory cy-
filtrates in the brain has also been shown tokines, although it seems likely that NK
in the experimental mouse model of ma- cells differentially regulate inflammatory
lignant glioma and in human gliomas.57 responses at various anatomic sites.
CD4+ regulatory T cells have also been
shown to cross over the BBB and infiltrate
the CNS in human glioblastoma multi- ■■ T
-Cell Recruitment into the
forme,58 other astrocytomas,59 and viral in- Central Nervous System
fections such as West Nile virus infection,60
and their presence has been reported in the T cells can enter the CNS via several routes,
CSF of patients with MS.61 The presence of including migration from the blood to the
regulatory T cells in the peripheral tissues CSF across the choroid plexus or meningeal
can serve to generate tolerance against vessels into the subarachnoid space, mi-

self-antigens and thus control autoim- gration from the blood to the parenchymal
mune reactions. The presence of high lev- perivascular spaces of the brain, and mi-
els of CD4+ Tregs within the CNS in mouse gration from the blood to the parenchymal
models of glioma is indicative of poor sur- perivascular space of the spinal cord. These
vival, as shown by the increase in life span different migration routes involve the
after the depletion of Tregs in this model.62 transport of the T cells across various bar-
This finding remains to be corroborated for riers: the blood–CSF barrier, the BBB, and
gliomas in humans. the blood–spinal cord barrier.51–53 Under
Cytotoxic T lymphocytes (CTLs) facili- inflammatory conditions, the expression of
tate the killing of specific target cells via adhesion molecules and chemokines is in-
the formation of the immunologic syn- duced on the endothelium at the BBB. This
apse, in which after antigen recognition, provides trafficking signals for circulating
CD3/TCR complex is recruited to the area leukocytes to enter the CNS. When the en-
of contact between the CTL and the target dothelial BBB allows transendothelial mi-
cell and forms a central cluster. The T-cell gration, T-cell recruitment into the CNS is
cytoskeleton and the TCR-rich area under- still highly regulated because the lympho-
go a series of alterations that result in the cytes found in the perivascular spaces have
directed secretion of cytotoxic granules. A a homogeneous effector memory pheno-
recent study demonstrates that infiltrating type that distinguishes them from lympho-
CTLs in glioblastoma can generate immu- cytes found in other inflamed tissues.51,65,66
nologic synapses with tumor cells.63 CD8+ T-cell migration into the CNS involves a
T cells that establish immunologic synaps- three-step interaction between the leuko-
es with glioma cells and express polarized cytes and the endothelium: (1) tethering
granzyme B as an effector molecule may be and rolling of leukocytes on the BBB, (2)
critical for antitumor-mediated immuno- activation and firm adhesion, and (3) dia-
logic responses within the CNS in human pedesis (transendothelial migration). Each
glioblastoma. of these steps is described in detail below.
Natural Killer (NK) Cells Tethering and Rolling of Leukocytes on

Endothelium
Natural killer (NK) cells are recruited to the
CNS in response to tissue injury. NK-cell The contact between vascular endothelium
depletion induces severe EAE.64 Impaired and circulating lymphocytes is the result of
recruitment of NK cells is associated with fluid dynamics within the blood vessel. The
increased mortality related to EAE, as well term leukocyte margination describes the
as spastic paraplegia and inflammatory le- phenomenon in which cells flowing within
sions with hemorrhage. Some studies indi- the blood vessel are positioned closer to the
cate that NK cells may limit autoimmune vascular wall than to the center of the ves-
responses by killing DCs, regulating T-cell sel.67 Here, lymphocytes make a transient
7
and reversible contact with the vascular During inflammatory diseases such as EAE,
endothelium. This contact is mediated by tethering and rolling of leukocytes can be
adhesion molecules of the selectin family observed in superficial brain and menin-
and their carbohydrate ligands, initiating geal microvessels by performing intravital
the rolling of leukocytes on the endothe- microscopy.69 In inflamed murine vessels,
lial surface. This interaction, although not CD8+ T cells have been shown to roll by
strong enough to anchor cells against the adhering to the endothelium via P-selectin
force of blood flow, allows cells to roll along glycoprotein ligand-1 (PSGL-1), whereas
the endothelium, continually making and CD4+ T cells roll via α4-integrin.70 P- and
breaking contact (Fig. 1.2). E-selectin can also mediate lymphocyte
The microvessels of a healthy brain and rolling in inflamed brain vessels.71,72 During
spinal cord of SJL/N mice constitutively EAE, there is upregulation of both VCAM-1
express vascular cell adhesion molecule-1 and ICAM-1 on the CNS endothelium, but
(VCAM-1), platelet endothelial cell adhe- not of P- or E-selectin.73 It has been sug-
sion molecule-1 (PECAM-1), and intercel- gested that the α4-integrin/VCAM-1 inter-
lular adhesion molecule-2 (ICAM-2). (The actions mediate the steps of adhesion of
latter two molecules are also expressed on lymphocytes to the BBB because antibod-
vascular endothelial cells at other sites.68) ies that block α4-integrins or endothelial
a b
Fig. 1.2 Structure of the blood–brain barrier (BBB) and T-cell recruitment into the central nervous system
(CNS). (a) BBB: 1, neuron; 2, astrocyte; 3, pericyte; 4, endothelial capillary cell; 5, tight junction. (b) Structure of
normal, noninflamed BBB: lymphocytes and red blood cells flow through the blood vessel. (c) Recruitment of T
cells across the inflamed BBB. Figure depicts the multistep process leading to the transendothelial migration of
8 T cells into the CNS parenchyma.
VCAM-1 significantly reduce the adhesion vitro studies confirm that diapedesis across
of lymphocytes to the brain vascular endo- the BBB is a process that involves LFA-1 and
thelium; however, they have little effect on ICAM-1.85 Blocking LFA-1 on autoreactive
transendothelial migration of autoreactive T cells resulted in a significantly reduced
lymphocytes.74 number of T cells migrating across the vas-
cular endothelium into the spinal cord pa-
Activation and Firm Adhesion renchyma, demonstrating that LFA-1 is used
for transendothelial migration, but not for
For leukocytes to adhere to the endothe- capture and adhesion in microvessels. Fur-
lium, it is essential for integrin activation thermore, other studies show that endothe-
to occur. This is mediated via G-protein– lioma cells that lack both ligands for LFA-1
coupled receptors (GPCRs). Intravital mi- (ICAM-1 and ICAM-2) can mediate adhesion
croscopy studies of T-cell interactions with of T cells to activated endothelium, but no
microvasculature in the brain and spinal

longer mediate transendothelial migration86
cord have shown that GPCR signaling is es- (see Fig. 1.2).
sential for the firm adhesion of autoreac-
tive T cells on endothelium of CNS.72,75 Prior
rolling of lymphocytes along the endo-
thelium allows sampling of the surface of ■■ E
xpression and Function
endothelial cells, resulting in activation of of Chemokines and Their
integrins on lymphocytes and subsequent Receptors at the Blood–Brain
adhesion and firm arrest.76–78 Chemokines Barrier
secreted by the inflamed BBB bind their
receptors, resulting in increased affinity of The CNS endothelium secretes a diversity
integrin binding and clustering at the cell of chemokines, each with distinct effects
surface; this in turn leads to the enhanced on circulating lymphocytes. The expression
avidity of the adhesion molecules for their and regulation of inflammatory chemokines
ligands.79,80 The inflamed BBB endothelium in the CNS microvasculature have been
in EAE secretes the homeostatic chemo- less studied than in the peripheral lym-
kines CCL19 and CCL21,81,82 which allows phoid tissues or other organs. As a result,
the binding of B cells, T cells, and mature the number of studies that have character-
DCs that express the CCR7 (see Fig. 1.2). ized the in vivo expression of inflammatory
The upregulation of ICAM-1 and VCAM-1 cytokines in the brain is limited. However,
on endothelial cells of the CNS microvas- several studies have characterized inflam-
culature during EAE allows the binding matory chemokines in in vitro preparations
of inflammatory cells expressing the re- of brain microvasculature endothelium.
spective ligands lymphocyte function–as- This section focuses on homeostatic che-
sociated antigen-1 (LFA-1, also known as mokines that have a role during the occur-
α1β2-integrin) and α4β1-integrin, but rence of inflammation within the CNS.
not L-selectin or α4β7-integrin.73,83 The G-
protein–dependent activation of LFA-1 on CCL19 and CCL21
lymphocytes allows the firm adhesion on
endothelial ICAM-1 and arrests the roll- The chemokines CCL19, also known as
ing of lymphocytes along the endothelium. macrophage inflammatory protein-3β
Only activated integrins can mediate the (MIP-3β), and CCL21, also known as sec-
firm adhesion of leukocytes to the vascular ondary lymphoid tissue chemokine (SLC),
endothelium. function under physiologic conditions to
recruit naïve T cells and B cells and mature
Diapedesis (Transendothelial Migration) DCs, which bind to the chemokine via its
receptor CCR7 into lymphoid tissues.87–90
During diapedesis, leukocytes migrate The expression of these cytokines has been
across an inflamed BBB through endothe- studied in the CNS microvasculature under
lial cells, leaving tight junctions intact.84 In normal physiologic conditions, as well as 9
in neuroinflammatory conditions such as by endothelial cells).97 The CXCL12-CXCR4
MS and its mouse model, EAE. Messenger signaling pathway has been shown to be in-
RNA (mRNA) transcripts of CCL19 are con- volved in the development and modulation
stitutively expressed in both normal and of synapse formation within the CNS. There
inflamed endothelium of postcapillary ve- is widespread expression of CXCL12 and
nules; however, mRNA transcripts of CCL21 CXCR4 within the CNS, including the endo-
are induced during the course of EAE. thelium of the BBB, hippocampus, cortex,
One study demonstrated that the ex- olfactory bulb, meninges, and cerebellum.98
pression of CCL21 but not CCL19 by oligo- Similarly, the expression of CXCR4 is readily
dendrocytes in transgenic mice leads to detectable on many cells in the CNS, includ-
inflammation within the CNS. The mice ing microglia, endothelial cells of the BBB,
expressing CCL19 displayed normal devel- astrocytes, oligodendrocytes, and neurons.99
opment, whereas the mice that expressed In MS lesions, the expression of CXCL12
CCL21 in oligodendrocytes did not survive along the blood vessels of the BBB and in
past 4 weeks post partum91 because of de- astrocytes is increased. In studies conduct-
ficiency in motor function. The inflamma- ed in the EAE mouse model, the levels of
tion of the CNS was caused predominantly CXCL12 were significantly increased at the
by neutrophil and eosinophil infiltration peak of the disease, and the expression of
and by reactive microglia and astrocytes; this chemokine was localized to the mi-
however, the expression of CCL21 alone crovessels along the parenchymal surface
did not lead to lymphocytic infiltration. of endothelial cells, as opposed to the ab-
Another study examined the expression luminal surface in the noninflamed endo-
of these chemokines and the receptor in thelium. Similarly, CXCL12 was expressed
brain and CSF samples from patients with predominantly along the parenchymal sur-
MS.92 The authors found a large number of face of BBB endothelium in the arterioles
CCR7+ cells and the expression of MHC II and venules of the CNS in normal individu-
and CD86 (markers of antigen presentation als and in the noninflamed areas of the MS
by DCs) within MS lesions. It is interesting brain, whereas the expression of this che-
to note that T cells localized to the lesions mokine in venules shifted to the luminal
did not express CCR7; however, T cells and side of the endothelial surface in patients
DCs in the CSF expressed CCR7. The au- with MS.100,101
thors proposed that activated microglia
and macrophages express signals associat- CCL2
ed with maturing DCs, including CCR7, that
are capable of stimulating central memory Studies in CCL2 knockout mice demonstrate
T cells locally. that this chemokine has a nonredundant
role in regulating monocyte infiltration of
the CNS during inflammatory processes.
CXCL12
Similarly, mice deficient in CCR2 (recep-
The chemokine CXCL12 (also known as tor for CCL2) have impaired recruitment
stromal cell–derived factor-1) functions as of monocytes to tissues.102 Patients with
a potent chemoattractant for lymphocytes MS have lower levels of CCL2 in the CSF in
and monocytes.93 In addition, CXCL12 aids comparison with patients who have other
in angiogenesis by recruiting endothelial noninflammatory neurologic diseases. Lev-
precursor cells from the bone marrow.94 els of CCL2 decrease in the CSF during the
CXCL12 is implicated in carcinogenesis be- active phase of MS.53,103 The lower levels of
cause of its role in the neovascularization CCL2 in the CSF of these patients have been
of tumors.95 It has also been shown to have attributed to the consumption of CCL2 by
a role in tumor metastasis.96 CCR2+ monocytes and T cells. It is also
In the CNS, CXCL12 is expressed as three possible that CCR2 is downregulated in
different isoforms: CXCL12α (expressed by migrating cells.104,105 Transgenic mice that
neurons), CXCL12β, and CXCL12γ (expressed constitutively express low levels of CCL2 in
10
the CNS have a reduced severity of EAE in ■■ Conclusion
comparison with littermate controls, pos-
sibly because of the effects of CCL2 on cir- As depicted in this chapter, the brain is
culating lymphocytes.106 an immunologically specialized organ in
which surveillance is tightly regulated. Un-
CXCL9 and CXCL10 der normal physiologic conditions, the pas-
sage of molecules across the BBB is limited
It has been suggested that CXCR3 (recep- by the presence of tight junctions between
tor for CXCL9, CXCL10, and CXCL11) has its endothelial cells. The main immune cells
a role in the trafficking of leukocytes into present in the CNS under normal condi-
the CNS during neuroinflammatory patho- tions are perivascular APCs and microglia.
logic conditions. CXCR3 is expressed on B The latter have immunologic functions as
cells, NK cells, activated T cells, and some well as a role in the monitoring and main-
monocytes.107 The chemokines CXCL9 and

tenance of synaptic functions. However, in
CXCL10 are readily detected in the brain various inflammatory and neurodegenera-
during EAE.53 The presence of neutralizing tive diseases, other immune cells, such as
antibodies specific for CXCL10 leads to a CD4+ T cells, NK cells, and CTLs, cross the
reduced severity of EAE and lower levels of BBB and infiltrate the CNS parenchyma,
inflammatory T cells in the CNS.108 Thus, it with deleterious results to the individual.
is surprising to observe that mice deficient These cells infiltrate the CNS because of the
in CXCL10 are more susceptible to EAE. It is chemoattractant properties of molecules
possible that the absence of CXCL10 is asso- secreted by the brain endothelium. The
ciated with the upregulation of CXCL11 in chemokines displayed on the endothelium
the CNS and the downregulation of CXCL9 bind to the receptors on circulating leuko-
in lymph nodes. Although CXCR3 is impor- cytes and initiate reactions that result in
tant for T-cell trafficking into the CNS, its integrin activation, arrest, firm adhesion,
role is not pivotal for the transendothelial and finally extravasation to within the CNS.
migration of memory CD4+ T cells into the The degree to which these processes occur
BBB.109 This is further demonstrated by the ultimately determines the degree of the
fact that CXCR3 knockout mice have an immune response.
enhanced severity of EAE, which may be
due to the lack of CXCR3-mediated INF-γ References
secretion.110
1. Barker CF, Billingham RE. Immunologically privi-
leged sites. Adv Immunol 1977;25:1–54 PubMed
CX3CL1 2. Medawar PB. Immunity to homologous grafted
skin; the fate of skin homografts transplanted
CX3CL1 is a type 1 transmembrane glyco- to the brain, to subcutaneous tissue, and to the
protein chemokine that is present at high anterior chamber of the eye. Br J Exp Pathol
levels in the neurons of the normal CNS,111 1948;29(1):58–69 PubMed
3. Pachter JS, de Vries HE, Fabry Z. The blood-brain
but not on blood vessels.112,113 It functions barrier and its role in immune privilege in the
as an adhesion molecule or as a chemoat- central nervous system. J Neuropathol Exp Neu-
tractant once proteolytically cleaved. Its rol 2003;62(6):593–604 PubMed
receptor CX3CR1 is expressed by NK cells, 4. Rubin LL, Staddon JM. The cell biology of
the blood-brain barrier. Annu Rev Neurosci
lymphocytes, and monocytes, and in the 1999;22:11–28 PubMed
CNS it is also expressed by microglia.33,114 5. Schlosshauer B. The blood-brain barrier: mor-
The absolute number of NK cells is sig- phology, molecules, and neurothelin. Bioessays
1993;15(5):341–346 PubMed
nificantly reduced in the inflamed CNS of 6. Ransohoff RM, Kivisäkk P, Kidd G. Three or
mice with EAE that are CX3CR1-deficient more routes for leukocyte migration into the
in comparison with wild-type mice. This central nervous system. Nat Rev Immunol
impaired recruitment of NK cells into the 2003;3(7):569–581 PubMed
7. Reese TS, Karnovsky MJ. Fine structural localiza-
CNS is associated with increased severity tion of a blood-brain barrier to exogenous per-
of disease and decreased survival.64 oxidase. J Cell Biol 1967;34(1):207–217 PubMed
11
8. Z lokovic BV. The blood-brain barrier in health in experimental autoimmune encephalomyelitis. J
and chronic neurodegenerative disorders. Neu- Exp Med 2006;203(4):1007–1019 PubMed
ron 2008;57(2):178–201 PubMed 25. M cMahon EJ, Bailey SL, Castenada CV, Waldner H,
9. Hickey WF, Hsu BL, Kimura H. T-lymphocyte en- Miller SD. Epitope spreading initiates in the CNS
try into the central nervous system. J Neurosci in two mouse models of multiple sclerosis. Nat
Res 1991;28(2):254–260 PubMed Med 2005;11(3):335–339 PubMed
10. Cross AH, Cannella B, Brosnan CF, Raine CS. Hom- 26. M cMenamin PG. Distribution and phenotype
ing to central nervous system vasculature by of dendritic cells and resident tissue macro-
antigen-specific lymphocytes. I. Localization of phages in the dura mater, leptomeninges, and
14
C-labeled cells during acute, chronic, and re- choroid plexus of the rat brain as demonstrated
lapsing experimental allergic encephalomyelitis. in wholemount preparations. J Comp Neurol
Lab Invest 1990;63(2):162–170 PubMed 1999;405(4):553–562 PubMed
11. Kivisäkk P, Mahad DJ, Callahan MK, et al. Human 27. L awson LJ, Perry VH, Dri P, Gordon S. Hetero-
cerebrospinal fluid central memory CD4+ T cells: geneity in the distribution and morphology of
evidence for trafficking through choroid plexus microglia in the normal adult mouse brain. Neu-
and meninges via P-selectin. Proc Natl Acad Sci roscience 1990;39(1):151–170 PubMed
USA 2003;100(14):8389–8394 PubMed 28. M ittelbronn M, Dietz K, Schluesener HJ, Meyer-
12. Aloisi F. Immune function of microglia. Glia mann R. Local distribution of microglia in the
2001;36(2):165–179 PubMed normal adult human central nervous system dif-
13. Kreutzberg GW. Microglia: a sensor for patho- fers by up to one order of magnitude. Acta Neuro-
logical events in the CNS. Trends Neurosci pathol 2001;101(3):249–255 PubMed
1996;19(8):312–318 PubMed 29. K ofler J, Wiley CA. Microglia: key innate immune
14. Matyszak MK, Perry VH. The potential role of cells of the brain. Toxicol Pathol 2011;39(1):
dendritic cells in immune-mediated inflamma- 103–114 PubMed
tory diseases in the central nervous system. Neu- 30. P erry VH, Hume DA, Gordon S. Immunohisto-
roscience 1996;74(2):599–608 PubMed chemical localization of macrophages and mi-
15. Karman J, Ling C, Sandor M, Fabry Z. Initiation of croglia in the adult and developing mouse brain.
immune responses in brain is promoted by local Neuroscience 1985;15(2):313–326 PubMed

dendritic cells. J Immunol 2004;173(4):2353– 31. H anisch UK. Microglia as a source and target of
2361 PubMed cytokines. Glia 2002;40(2):140–155 PubMed
16. Fischer HG, Reichmann G. Brain dendritic cells 32. E nose Y, Destache CJ, Mack AL, et al. Proteomic
and macrophages/microglia in central ner- fingerprints distinguish microglia, bone mar-
vous system inflammation. J Immunol 2001; row, and spleen macrophage populations. Glia
166(4):2717–2726 PubMed 2005;51(3):161–172 PubMed
17. Streit WJ. Microglia as neuroprotective, immu- 33. N immerjahn A, Kirchhoff F, Helmchen F. Rest-
nocompetent cells of the CNS. Glia 2002;40(2): ing microglial cells are highly dynamic sur-
133–139 PubMed veillants of brain parenchyma in vivo. Science
18. Greter M, Heppner FL, Lemos MP, et al. Dendritic 2005;308(5726):1314–1318 PubMed
cells permit immune invasion of the CNS in an 34. R oumier A, Béchade C, Poncer JC, et al. Impaired
animal model of multiple sclerosis. Nat Med synaptic function in the microglial KARAP/
2005;11(3):328–334 PubMed DAP12-deficient mouse. J Neurosci 2004;24(50):
19. Mrass P, Weninger W. Immune cell migration as a 11421–11428 PubMed
means to control immune privilege: lessons from 35. W ake H, Moorhouse AJ, Jinno S, Kohsaka S, Na-
the CNS and tumors. Immunol Rev 2006;213: bekura J. Resting microglia directly monitor the
195–212 PubMed functional state of synapses in vivo and deter-
20. Williams K, Alvarez X, Lackner AA. Central nervous mine the fate of ischemic terminals. J Neurosci
system perivascular cells are immunoregulatory 2009;29(13):3974–3980 PubMed
cells that connect the CNS with the peripheral im- 36. M arín-Teva JL, Dusart I, Colin C, Gervais A, van
mune system. Glia 2001;36(2):156–164 PubMed Rooijen N, Mallat M. Microglia promote the
21. Bechmann I, Priller J, Kovac A, et al. Immune death of developing Purkinje cells. Neuron
surveillance of mouse brain perivascular spaces 2004;41(4):535–547 PubMed
by blood-borne macrophages. Eur J Neurosci 37. P rinz M, Mildner A. Microglia in the CNS: im-
2001;14(10):1651–1658 PubMed migrants from another world. Glia 2011;59(2):
22. Hickey WF, Vass K, Lassmann H. Bone marrow- 177–187 PubMed
derived elements in the central nervous system: 38. B essis A, Béchade C, Bernard D, Roumier A. Mi-
an immunohistochemical and ultrastructural croglial control of neuronal death and synaptic
survey of rat chimeras. J Neuropathol Exp Neurol properties. Glia 2007;55(3):233–238 PubMed
1992;51(3):246–256 PubMed 39. Trapp BD, Wujek JR, Criste GA, et al. Evidence
23. T ran EH, Hoekstra K, van Rooijen N, Dijkstra CD, for synaptic stripping by cortical microglia. Glia
Owens T. Immune invasion of the central nervous 2007;55(4):360–368 PubMed
system parenchyma and experimental allergic en- 40. J unker A, Krumbholz M, Eisele S, et al. MicroRNA
cephalomyelitis, but not leukocyte extravasation profiling of multiple sclerosis lesions identifies
from blood, are prevented in macrophage-depleted modulators of the regulatory protein CD47. Brain
mice. J Immunol 1998;161(7):3767–3775 PubMed 2009;132(Pt 12):3342–3352 PubMed
24. A grawal S, Anderson P, Durbeej M, et al. Dystrogly- 41. H
oek RM, Ruuls SR, Murphy CA, et al. Down-
can is selectively cleaved at the parenchymal base- regulation of the macrophage lineage through
12 ment membrane at sites of leukocyte extravasation
interaction with OX2 (CD200). Science 2000; tal autoimmune encephalomyelitis. PLoS ONE
290(5497):1768–1771 PubMed 2010;5(11):e15531 PubMed
42. Barclay AN, Wright GJ, Brooke G, Brown MH. 57. Wainwright DA, Sengupta S, Han Y, Ulasov IV, Lesn-
CD200 and membrane protein interactions in iak MS. The presence of IL-17A and T helper 17 cells
the control of myeloid cells. Trends Immunol in experimental mouse brain tumors and human
2002;23(6):285–290 PubMed glioma. PLoS ONE 2010;5(10):e15390 PubMed
43. Ransohoff RM, Cardona AE. The myeloid cells of 58. El Andaloussi A, Lesniak MS. An increase in

the central nervous system parenchyma. Nature CD4+CD25+FOXP3+ regulatory T cells in tumor-in-
2010;468(7321):253–262 PubMed filtrating lymphocytes of human glioblastoma mul-
44. Gahmberg CG, Tian L, Ning L, Nyman-Huttunen tiforme. Neuro Oncol 2006;8(3):234–243 PubMed
H. ICAM-5—a novel two-facetted adhesion mol- 59. E
l Andaloussi A, Lesniak MS. CD4+ CD25+ FoxP3+
ecule in the mammalian brain. Immunol Lett T-cell infiltration and heme oxygenase-1 expres-
2008;117(2):131–135 PubMed sion correlate with tumor grade in human glio-
45. Hundhausen C, Misztela D, Berkhout TA, et al. The mas. J Neurooncol 2007;83(2):145–152 PubMed
disintegrin-like metalloproteinase ADAM10 is 60. S
tewart BS, Demarest VL, Wong SJ, Green S, Ber-
involved in constitutive cleavage of CX3CL1 (frac- nard KA. Persistence of virus-specific immune
talkine) and regulates CX3CL1-mediated cell-cell responses in the central nervous system of mice

adhesion. Blood 2003;102(4):1186–1195 PubMed after West Nile virus infection. BMC Immunol
46. de Haas AH, Boddeke HW, Biber K. Region-spe- 2011;12:6 PubMed
cific expression of immunoregulatory proteins 61. F
ritzsching B, Haas J, König F, et al. Intracerebral
on microglia in the healthy CNS. Glia 2008;56(8): human regulatory T cells: analysis of CD4+ CD25+
888–894 PubMed FOXP3+ T cells in brain lesions and cerebrospinal
47. Ford AL, Goodsall AL, Hickey WF, Sedgwick JD. Nor- fluid of multiple sclerosis patients. PLoS ONE
mal adult ramified microglia separated from other 2011;6(3):e17988 PubMed
central nervous system macrophages by flow cyto- 62. El Andaloussi A, Han Y, Lesniak MS. Prolongation
metric sorting. Phenotypic differences defined and of survival following depletion of CD4+CD25+ reg-
direct ex vivo antigen presentation to myelin basic ulatory T cells in mice with experimental brain tu-
protein-reactive CD4+ T cells compared. J Immunol mors. J Neurosurg 2006;105(3):430–437 PubMed
1995;154(9):4309–4321 PubMed 63. B
arcia C Jr, Gómez A, Gallego-Sanchez JM, et al.
48. Perry VH. A revised view of the central nervous Infiltrating CTLs in human glioblastoma establish
system microenvironment and major histocom- immunological synapses with tumorigenic cells.
patibility complex class II antigen presentation. J Am J Pathol 2009;175(2):786–798 PubMed
Neuroimmunol 1998;90(2):113–121 PubMed 64. H
uang D, Shi FD, Jung S, et al. The neuronal che-
49. K
alla R, Liu Z, Xu S, et al. Microglia and the early mokine CX3CL1/fractalkine selectively recruits
phase of immune surveillance in the axotomized NK cells that modify experimental autoimmune
facial motor nucleus: impaired microglial activa- encephalomyelitis within the central nervous
tion and lymphocyte recruitment but no effect on system. FASEB J 2006;20(7):896–905 PubMed
neuronal survival or axonal regeneration in mac- 65. Z
eine R, Owens T. Direct demonstration of the
rophage-colony stimulating factor-deficient mice. infiltration of murine central nervous system by
J Comp Neurol 2001;436(2):182–201 PubMed Pgp-1/CD44high CD45RB(low) CD4+ T cells that
50. Heppner FL, Greter M, Marino D, et al. Experimen- induce experimental allergic encephalomyelitis.
tal autoimmune encephalomyelitis repressed J Neuroimmunol 1992;40(1):57–69 PubMed
by microglial paralysis. Nat Med 2005;11(2): 66. E
ngelhardt B, Martin-Simonet MT, Rott LS, Butch-
146–152 PubMed er EC, Michie SA. Adhesion molecule phenotype
51. Engelhardt B, Ransohoff RM. The ins and outs of of T lymphocytes in inflamed CNS. J Neuroimmu-
T-lymphocyte trafficking to the CNS: anatomical nol 1998;84(1):92–104 PubMed
sites and molecular mechanisms. Trends Immu- 67. G
oldsmith HL, Spain S. Margination of leukocytes
nol 2005;26(9):485–495 PubMed in blood flow through small tubes. Microvasc Res
52. Ubogu EE, Cossoy MB, Ransohoff RM. The ex- 1984;27(2):204–222 PubMed
pression and function of chemokines involved 68. E
ngelhardt B. Molecular mechanisms involved in
in CNS inflammation. Trends Pharmacol Sci T cell migration across the blood-brain barrier. J
2006;27(1):48–55 PubMed Neural Transm 2006;113(4):477–485 PubMed
53. R
ebenko-Moll NM, Liu L, Cardona A, Ransohoff 69. K
erfoot SM, Kubes P. Overlapping roles of P-se-
RM. Chemokines, mononuclear cells and the ner- lectin and alpha 4 integrin to recruit leukocytes
vous system: heaven (or hell) is in the details. Curr to the central nervous system in experimen-
Opin Immunol 2006;18(6):683–689 PubMed tal autoimmune encephalomyelitis. J Immunol
54. El-behi M, Rostami A, Ciric B. Current views on 2002;169(2):1000–1006 PubMed
the roles of Th1 and Th17 cells in experimental 70. Battistini L, Piccio L, Rossi B, et al. CD8+ T cells from
autoimmune encephalomyelitis. J Neuroimmune patients with acute multiple sclerosis display se-
Pharmacol 2010;5(2):189–197 PubMed lective increase of adhesiveness in brain venules:
55. Brucklacher-Waldert V, Stuerner K, Kolster M,
a critical role for P-selectin glycoprotein ligand-1.
Wolthausen J, Tolosa E. Phenotypical and functional Blood 2003;101(12):4775–4782 PubMed
characterization of T helper 17 cells in multiple scle- 71. C
arvalho-Tavares J, Hickey MJ, Hutchison J, Mi-
rosis. Brain 2009;132(Pt 12):3329–3341 PubMed chaud J, Sutcliffe IT, Kubes P. A role for platelets
56. Domingues HS, Mues M, Lassmann H, Wekerle and endothelial selectins in tumor necrosis fac-
H, Krishnamoorthy G. Functional and pathogenic tor-alpha-induced leukocyte recruitment in the
differences of Th1 and Th17 cells in experimen- 13
brain microvasculature. Circ Res 2000;87(12): 85. C arman CV, Springer TA. A transmigratory cup
1141–1148 PubMed in leukocyte diapedesis both through individual
72. Piccio L, Rossi B, Scarpini E, et al. Molecular vascular endothelial cells and between them. J
mechanisms involved in lymphocyte recruit- Cell Biol 2004;167(2):377–388 PubMed
ment in inflamed brain microvessels: critical 86. L yck R, Reiss Y, Gerwin N, Greenwood J, Adamson
roles for P-selectin glycoprotein ligand-1 and P, Engelhardt B. T-cell interaction with ICAM-1/
heterotrimeric G(i)-linked receptors. J Immunol ICAM-2 double-deficient brain endothelium in
2002;168(4):1940–1949 PubMed vitro: the cytoplasmic tail of endothelial ICAM-1
73. Steffen BJ, Butcher EC, Engelhardt B. Evidence for is necessary for transendothelial migration of T
involvement of ICAM-1 and VCAM-1 in lympho- cells. Blood 2003;102(10):3675–3683 PubMed
cyte interaction with endothelium in experimen- 87. R obbiani DF, Finch RA, Jäger D, Muller WA, Sar-
tal autoimmune encephalomyelitis in the central torelli AC, Randolph GJ. The leukotriene C(4)
nervous system in the SJL/J mouse. Am J Pathol transporter MRP1 regulates CCL19 (MIP-3beta,
1994;145(1):189–201 PubMed ELC)-dependent mobilization of dendritic cells to
74. Laschinger M, Vajkoczy P, Engelhardt B. Encepha- lymph nodes. Cell 2000;103(5):757–768 PubMed
litogenic T cells use LFA-1 for transendothelial 88. Reif K, Ekland EH, Ohl L, et al. Balanced re-
migration but not during capture and initial ad- sponsiveness to chemoattractants from adja-
hesion strengthening in healthy spinal cord mi- cent zones determines B-cell position. Nature
crovessels in vivo. Eur J Immunol 2002;32(12): 2002;416(6876):94–99 PubMed
3598–3606 PubMed 89. B romley SK, Thomas SY, Luster AD. Chemokine
75. Vajkoczy P, Laschinger M, Engelhardt B. Alpha4- receptor CCR7 guides T cell exit from peripheral
integrin-VCAM-1 binding mediates G protein- tissues and entry into afferent lymphatics. Nat
independent capture of encephalitogenic T cell Immunol 2005;6(9):895–901 PubMed
blasts to CNS white matter microvessels. J Clin 90. Y oshida R, Nagira M, Kitaura M, Imagawa N, Imai
Invest 2001;108(4):557–565 PubMed T, Yoshie O. Secondary lymphoid-tissue chemo-
76. Ley K. Molecular mechanisms of leukocyte re- kine is a functional ligand for the CC chemo-
cruitment in the inflammatory process. Cardio- kine receptor CCR7. J Biol Chem 1998;273(12):
vasc Res 1996;32(4):733–742 PubMed 7118–7122 PubMed

77. Johnston B, Butcher EC. Chemokines in rapid leu- 91. C hen SC, Leach MW, Chen Y, et al. Central ner-
kocyte adhesion triggering and migration. Semin vous system inflammation and neurological
Immunol 2002;14(2):83–92 PubMed disease in transgenic mice expressing the CC che-
78. Ley K, Laudanna C, Cybulsky MI, Nourshargh S. mokine CCL21 in oligodendrocytes. J Immunol
Getting to the site of inflammation: the leuko- 2002;168(3):1009–1017 PubMed
cyte adhesion cascade updated. Nat Rev Immunol 92. K ivisäkk P, Mahad DJ, Callahan MK, et al. Ex-
2007;7(9):678–689 PubMed pression of CCR7 in multiple sclerosis: implica-
79. Adamson P, Wilbourn B, Etienne-Manneville S, tions for CNS immunity. Ann Neurol 2004;55(5):
et al. Lymphocyte trafficking through the blood- 627–638 PubMed
brain barrier is dependent on endothelial cell 93. B leul CC, Fuhlbrigge RC, Casasnovas JM, Aiuti A,
heterotrimeric G-protein signaling. FASEB J 2002; Springer TA. A highly efficacious lymphocyte che-
16(10):1185–1194 PubMed moattractant, stromal cell-derived factor 1 (SDF-
80. Alon R, Feigelson S. From rolling to arrest on blood 1). J Exp Med 1996;184(3):1101–1109 PubMed
vessels: leukocyte tap dancing on endothelial integ- 94. Z heng H, Fu G, Dai T, Huang H. Migration of en-
rin ligands and chemokines at sub-second contacts. dothelial progenitor cells mediated by stromal
Semin Immunol 2002;14(2):93–104 PubMed cell-derived factor-1alpha/CXCR4 via PI3K/Akt/
81. Columba-Cabezas S, Serafini B, Ambrosini E, Al- eNOS signal transduction pathway. J Cardiovasc
oisi F. Lymphoid chemokines CCL19 and CCL21 Pharmacol 2007;50(3):274–280 PubMed
are expressed in the central nervous system dur- 95. K
ryczek I, Wei S, Keller E, Liu R, Zou W. Stroma-
ing experimental autoimmune encephalomyeli- derived factor (SDF-1/CXCL12) and human tu-
tis: implications for the maintenance of chronic mor pathogenesis. Am J Physiol Cell Physiol
neuroinflammation. Brain Pathol 2003;13(1): 2007;292(3):C987–C995 PubMed
38–51 PubMed 96. M
üller A, Homey B, Soto H, et al. Involvement of
82. Alt C, Laschinger M, Engelhardt B. Functional ex- chemokine receptors in breast cancer metastasis.
pression of the lymphoid chemokines CCL19 (ELC) Nature 2001;410(6824):50–56 PubMed
and CCL 21 (SLC) at the blood-brain barrier sug- 97. S
tumm RK, Rummel J, Junker V, et al. A dual role
gests their involvement in G-protein-dependent for the SDF-1/CXCR4 chemokine receptor sys-
lymphocyte recruitment into the central ner- tem in adult brain: isoform-selective regulation
vous system during experimental autoimmune of SDF-1 expression modulates CXCR4-depen-
encephalomyelitis. Eur J Immunol 2002;32(8): dent neuronal plasticity and cerebral leukocyte
2133–2144 PubMed recruitment after focal ischemia. J Neurosci
83. B
aron JL, Madri JA, Ruddle NH, Hashim G, Janeway 2002;22(14):5865–5878 PubMed
CA Jr. Surface expression of alpha 4 integrin by 98. v
an der Meer P, Ulrich AM, Gonźalez-Scarano F,
CD4 T cells is required for their entry into brain pa- Lavi E. Immunohistochemical analysis of CCR2,
renchyma. J Exp Med 1993;177(1):57–68 PubMed CCR3, CCR5, and CXCR4 in the human brain: po-
84. Engelhardt B, Wolburg H. Mini-review: Transen- tential mechanisms for HIV dementia. Exp Mol
dothelial migration of leukocytes: through the Pathol 2000;69(3):192–201 PubMed
front door or around the side of the house? Eur J 99. K
rumbholz M, Theil D, Cepok S, et al. Chemo-
14 Immunol 2004;34(11):2955–2963 PubMed kines in multiple sclerosis: CXCL12 and CXCL13
up-regulation is differentially linked to CNS im- 108. Sorensen TL. Targeting the chemokine recep-
mune cell recruitment. Brain 2006;129(Pt 1): tor CXCR3 and its ligand CXCL10 in the central
200–211 PubMed nervous system: potential therapy for inflamma-
100. McCandless EE, Piccio L, Woerner BM, et al. Path- tory demyelinating disease? Curr Neurovasc Res
ological expression of CXCL12 at the blood-brain 2004;1(2):183–190 PubMed
barrier correlates with severity of multiple scle- 109. Callahan MK, Williams KA, Kivisäkk P, Pearce
rosis. Am J Pathol 2008;172(3):799–808 PubMed D, Stins MF, Ransohoff RM. CXCR3 marks CD4+
101. Holman DW, Klein RS, Ransohoff RM. The memory T lymphocytes that are competent to
blood-brain barrier, chemokines and multiple migrate across a human brain microvascular en-
sclerosis. Biochim Biophys Acta 2011;1812(2): dothelial cell layer. J Neuroimmunol 2004;153(1-
220–230 PubMed 2):150–157 PubMed
102. Charo IF, Ransohoff RM. The many roles of che- 110. Liu L, Huang D, Matsui M, et al. Severe disease,
mokines and chemokine receptors in inflamma- unaltered leukocyte migration, and reduced
tion. N Engl J Med 2006;354(6):610–621 PubMed IFN-gamma production in CXCR3-/- mice with
103. Sørensen TL, Ransohoff RM, Strieter RM, Selleb- experimental autoimmune encephalomyelitis. J
jerg F. Chemokine CCL2 and chemokine receptor Immunol 2006;176(7):4399–4409 PubMed
CCR2 in early active multiple sclerosis. Eur J Neu- 111. Bazan JF, Bacon KB, Hardiman G, et al. A new class

rol 2004;11(7):445–449 PubMed of membrane-bound chemokine with a CX3C
104. Kivisäkk P, Trebst C, Liu Z, et al. T-cells in the cere- motif. Nature 1997;385(6617):640–644 PubMed
brospinal fluid express a similar repertoire of in- 112. Sunnemark D, Eltayeb S, Nilsson M, et al. CX3CL1
flammatory chemokine receptors in the absence (fractalkine) and CX3CR1 expression in myelin
or presence of CNS inflammation: implications for oligodendrocyte glycoprotein-induced experi-
CNS trafficking. Clin Exp Immunol 2002;129(3): mental autoimmune encephalomyelitis: kinetics
510–518 PubMed and cellular origin. J Neuroinflammation 2005;
105. Mahad D, Callahan MK, Williams KA, et al. Modu- 2:17 PubMed
lating CCR2 and CCL2 at the blood-brain barrier: 113. Harrison JK, Jiang Y, Chen S, et al. Role for
relevance for multiple sclerosis pathogenesis. neuronally derived fractalkine in mediating
Brain 2006;129(Pt 1):212–223 PubMed interactions between neurons and CX3CR1-
106. Elhofy A, Wang J, Tani M, et al. Transgenic expres- expressing microglia. Proc Natl Acad Sci USA
sion of CCL2 in the central nervous system prevents 1998;95(18):10896–10901 PubMed
experimental autoimmune encephalomyelitis. J 114. Nishiyori A, Minami M, Ohtani Y, et al. Localiza-
Leukoc Biol 2005;77(2):229–237 PubMed tion of fractalkine and CX3CR1 mRNAs in rat
107. Liu L, Callahan MK, Huang D, Ransohoff RM. Che- brain: does fractalkine play a role in signaling
mokine receptor CXCR3: an unexpected enigma. from neuron to microglia? FEBS Lett 1998;429(2):
Curr Top Dev Biol 2005;68:149–181 PubMed 167–172 PubMed
15
2
Microbiological Diagnosis of
Central Nervous System Infections
Yuriko Fukuta and Karin Byers
The central nervous system (CNS) may Cerebrospinal Fluid

be infected by various organisms, includ-
Lumbar puncture with cerebrospinal fluid
ing bacteria, viruses, fungi, and parasites.
(CSF) analysis is usually essential to diag-
Numerous noninfectious etiologies may
nose CNS infections. Typical CSF findings in
mimic CNS infections. The causative or-
meningitis are shown in Table 2.1.
ganisms in postoperative infections are
quite different from those of nonsurgical
infections. The patient’s endogenous skin Opening Pressure and Appearance
flora, primarily gram-positive bacteria, are The CSF opening pressure is measured with
a frequent cause of postoperative infec- an air–water manometer. In adults, the
tion. Hospital-acquired pathogens, includ- normal CSF opening pressure ranges from
ing Staphylococcus aureus, gram-negative 50 to 190 mm H2O. Variation of pressure
bacilli, and fungi, are the other group of with deep respiration provides assurance
pathogens commonly encountered; the that fluid flow into the manometer is un-
latter group are often resistant to multiple obstructed. Opening pressure in bacterial
antimicrobial agents. CNS infections often meningitis ranges from 200 to 500 mm H2O.
necessitate emergent interventions be- The CSF is normally clear and color-
cause of high mortality and complications. less but may appear cloudy or turbid in
This chapter reviews the microbiological patients with increased concentrations of
diagnosis of CNS infections. white blood cells (> 200/mm3), red blood
cells (> 400/mm3), bacteria (> 105 colony-
forming units /mL), or protein. In patients
with a traumatic tap, an initially bloody CSF
■■ S
pecimen Selection and should clear as the flow of CSF continues.
Collection
Selection of the appropriate specimens and Cell Count
tests for the detection of causative organ- The normal CSF white blood cell (WBC)
isms is crucial in treating infectious dis- count in children and adults is 0 to 5/mm3.
eases. Whenever possible, antimicrobial The CSF WBCs may be slightly higher in neo-
therapy should be held until appropriate tates. In a study of uninfected neonates aged
specimens are collected unless delay in 0–28 days, the median count was 3 WBCs/
treatment poses an unacceptable risk to the mm3, but it was up to 19/mm3 (95th percen-
patient. tile). It decreased to a median of 2 WBCs/
Table 2.1 Typical cerebrospinal fluid findings in patients with selected infectious causes of meningitis
WBC count Primary Glucose Protein

(cells/mm3) cell type (mg/dL) (mg/dL)
Normal range 0–5a 0.6b < 50
2 Microbiological Diagnosis of Central Nervous System Infections

Acute viral meningitis 50–1,000 Mononuclear > 45 < 200
Acute bacterial meningitis 1,000–5,000 Neutrophilic < 40 100–500
Neurosyphilis >10 Mononuclear Decreased Elevated
Lyme meningitis < 500 Mononuclear Normal < 620
Primary amebic meningoencephalitisc Elevated Neutrophilic Decreased Elevated
Angiostrongylus cantonensis meningitis Elevated Eosinophilic Normal Elevated

(16–72%)
Tuberculous meningitis 50–300 Mononuclear < 45 50–300
Cryptococcal meningitis 20–500 Mononuclear < 40 > 45
Coccidioidal meningitis < 700 Mononuclear or Decreased Elevated

eosinophilic
Abbreviations: CSF, cerebrospinal fluid; RBC, red blood cell; WBC, white blood cell
a
May be up to 10/mm3 in neonates.
b
Ratio of CSF glucose to blood glucose. A value of less than 0.5 should be considered abnormal.
c
A high RBC count in CSF is commonly seen.
mm3. The 95th percentile was 9 WBCs/ concentrations greater than 50 mg/dL and
mm3.1 The CSF WBC count may be increased ventricular CSF concentrations greater
after neurosurgical procedures. Elevations of than 15 mg/dL are considered abnormal.
CSF WBC counts can occur in patients with A CSF glucose concentration of less than
traumatic lumbar puncture or in patients 34 mg/dL, a ratio of CSF glucose to blood
with intracerebral or subarachnoid hemor- glucose of less than 0.23, a CSF protein con-
rhage. In these situations, the following for- centration greater than 220 mg/dL, a CSF
mula should be used as a correction factor leukocyte count of more than 2,000/mm3,
for the true WBC count in the presence of or a CSF neutrophil count of more than
CSF red blood cells (RBCs): 1,180/mm3 is highly predictive of bacterial
meningitis.2
Corrected WBC in CSF =
Total WBC in CSF – (WBC in Blood ×
CSF Culture
RBC in CSF/RBC in Blood)
From 1 to 2 mL of CSF specimen should be
Glucose and Protein sent for bacterial culture, and optimally
from 5 to 10 mL for mycobacterial and fun-
The actual CSF glucose concentration may gal culture.
be falsely low in the presence of hypogly-
cemia; therefore, the CSF glucose should
Other Diagnostic Methods
always be compared with a simultaneous
serum glucose; the normal ratio of CSF Many immunologic tests and nucleic acid
glucose to serum glucose is approximately amplification tests are useful for the evalu-
0.6, and ratios of less than 0.5 should be ation of CNS infections. Please refer to each
considered abnormal. Lumbar CSF protein section for details.
17
■■ Acute Meningitis/Ventriculitis a facial nerve palsy. Clinical neurosyphilis
is divided into four distinct syndromes:
Microbiology syphilitic meningitis and meningovascu-
lar syphilis usually occur within 5 years of
Common organisms and useful diagnostic
infection, whereas parenchymatous neuro-
tests are shown in Table 2.2.
syphilis and gummatous neurosyphilis oc-
cur 10 to 20 years after infection.
Viral Meningitis Borrelia burgdorferi usually disseminates
Enteroviruses (primarily echoviruses and to the CNS early in infection. From 10 to 15%
coxsackieviruses) are the most common of patients with Lyme disease have nervous
cause of viral meningitis. HSV can also cause system involvement, including lympho-
a viral meningitis. HSV-2 meningitis is gen- cytic meningitis, in the third stage, several
erally seen with a primary genital outbreak. months to years after initial infection.6
HSV-1 may also cause viral meningitis. When
this is recurrent it is thought to be a cause Amebic Meningitis
of Mollaret’s meningitis, which is defined
Naegleria fowleri and Acanthamoeba spe-
as a benign, recurrent lymphocytic menin-
cies are the common organisms. N. fowleri
gitis. Other herpesviruses, including HSV-1,
usually lives in freshwater. It causes a rap-
varicella-zoster virus (VZV), cytomegalovirus
idly fatal meningoencephalitis in healthy
(CMV), Epstein-Barr virus (EBV), and human
persons with recreational freshwater ex-
herpesviruses types 6, 7, and 8 (HHV-6, -7,
posure. Granulomatous amebic encepha-
-8), cause aseptic meningitis and encephali-

litis with Acanthamoeba species occurs in
tis. Aseptic meningitis and encephalitis due
immunocompromised patients subacutely.
to mumps are commonly seen in unimmu-
nized patients. From 5 to 10% of patients in-
Helminthic Meningitis
fected with human immunodeficiency virus
(HIV) develop acute viral meningitis either Angiostrongylus cantonensis and Gnathos-
when the virus is acquired or during the toma spingerum are the most common or-
seroconversion phase.4 Arthropod-borne vi- ganisms of eosinophilic meningitis outside
ruses, such as West Nile virus, cause menin- Europe and North America.7 They are ac-
goencephalitis in areas of endemicity. quired by eating infected hosts (i.e., snails
or freshwater prawns for A. cantonensis,
Bacterial Meningitis undercooked freshwater fish or chicken for
G. spingerum).
Streptococcus pneumoniae is the most com-
mon organism. S. pneumoniae, Neisseria
meningitidis, S. aureus, other streptococci, Diagnosis
Listeria monocytogenes, and Haemophilus Tests that should be sent routinely when
species account for most of the community- acute meningitis is suspected are sum-
acquired meningeal pathogens.5 Hospital- marized in Table 2.3. Additional tests
acquired meningitis typically occurs after should be considered based on suspected
neurosurgical procedures. Postoperative CSF organisms.
leak and traumatic CSF leak are known risk
factors for meningitis. About half of cases are Viral Meningitis
caused by gram-negative bacilli (primarily
Pseudomonas aeruginosa, Klebsiella species, Cerebrospinal Fluid
and Escherichia coli). S. aureus and coagulase-
negative staphylococci are also common. Viral meningitis usually causes a lym-
phocytic pleocytosis with mildly elevated
protein and decreased glucose concentra-
Spirochetal Meningitis
tions; however, one study reported that
Treponema pallidum invades the CNS dur- about half of patients with viral meningi-
18 ing early infection. Early infections may re- tis had a neutrophil predominance in the
sult in cranial nerve palsies and particularly CSF for more than 24 hours after the onset
Table 2.2 Common organisms of acute meningitis and useful diagnostic tests
Tests
Risk factors/
Organisms areas of endemicity CSF Blood
Viruses

Nonpolio enteroviruses PCR
HSV-1, HSV-2, VZV PCR
CMV Immunocompromised PCR
Epstein-Barr virus Immunocompromised PCR
Mumps virus Unimmunized Complement fixation,

hemagglutination
inhibition
West Nile virus United States WNV-specific IgM

by ELISA, PCR
St. Louis encephalitis virus United States Anti-St. Louis Anti-St. Louis
encephalitis virus encephalitis virus
IgM antibodies IgM antibodies
HIV Sexual contact, HIV ELISA (negative

intravenous drug use in acute phase), PCR
Bacteria
Streptococcus pneumoniae Bacterial culture Blood culture
Neisseria meningitidis Bacterial culture Blood culture
Streptococcus agalactiae Bacterial culture
Haemophilus influenzae Bacterial culture
Listeria monocytogenes Bacterial culture Blood culture
Staphylococcus aureus Surgical procedures Bacterial culture
Coagulase-negative Surgical procedures Bacterial culture

staphylococci
Gram-negative rods Surgical procedures Bacterial culture
Propionibacterium acnes Surgical procedures Bacterial culture
Mycobacterium tuberculosis Prior residence or travel AFB culture

in a country with a high
prevalence of TB, known
contact, IVDA
Spirochetes
Treponema pallidum Sexual contact VDRL
Borrelia burgdorferi Tick bite Western blot ELISA (screening)
Amebae, helminths
Naegleria fowleri Swimming in freshwater CSF wet mount, PCR
Angiostrongylus cantonensis Travel history to the South Microscopic exam

Pacific and Southeast Asia
Abbreviations: AFB, acid-fast bacillus; CMV, cytomegalovirus; CSF, cerebrospinal fluid; ELISA, enzyme-linked immunosorbent
assay; HIV, human immunodeficiency virus; HSV, herpes simplex virus; IgM, immunoglobulin M; PCR, polymerase chain 19
reaction; VDRL, Venereal Disease Research Laboratory; VZV, varicella-zoster virus; WNV, West Nile virus
Table 2.3 Routine tests for cerebrospinal fluid in with meningococcal or L. monocytogenes
patients with suspected acute meningitis meningitis. Also, neutrophils usually pre-
White blood cell count with differential dominate, although approximately 10% of
patients present with a predominance of
Red blood cell count
lymphocytes in the CSF. This is more com-
Glucose concentration mon in neonatal gram-negative bacillary
Protein concentration
meningitis and meningitis caused by L.
monocytogenes.11 Patients with very low
Gram stain CSF WBC counts (0–20/mm3) despite high
Bacterial culture CSF bacterial concentrations tend to have a
poor prognosis.12
Elevated CSF protein and decreased CSF
glucose concentrations are seen in bacterial
of symptoms.8 A CSF neutrophil predomi-
meningitis; however, normal CSF WBC and
nance is not useful as a sole criterion in dis-
protein concentrations may be seen in pa-
tinguishing between aseptic and bacterial
tients with neonatal meningitis and severely
meningitis. Viral culture is not clinically
immunocompromised patients and in speci-
useful because it takes too long for identifi-
mens obtained at the onset of symptoms.
cation and the sensitivity is low.9
Immunology Cerebrospinal Fluid Culture

Gram stain of the CSF shows bacteria in
Paired serology is diagnostic for herpes

90% of S. pneumoniae and Haemophilus in-
simplex encephalitis and enterovirus infec-
fluenzae cases, 75% of N. meningitidis cases,
tions but is not useful clinically as serocon-
50% of gram-negative bacilli cases, and 24
version typically takes weeks, emphasizing
to 50% of L. monocytogenes cases.13,14 Prior
the importance of polymerase chain reac-
antimicrobial therapy decreases the prob-
tion (PCR) in the detection of viruses in
ability of identifying organisms by 50%.
CSF specimens. Complement fixation and
CSF culture is considered a gold stan-
hemagglutination inhibition in serum
dard. The probability of identifying the
specimens are the most reliable for mumps
organism may be decreased to less than
meningitis because the viral culture is not
50% in patients with prior antimicrobial
practically useful. Testing of paired acute
therapy. Fungal culture and acid-fast bacil-
and convalescent sera, collected 2–3 weeks
lus (AFB) culture need to be considered in
apart, should demonstrate a diagnostic
immunocompromised patients or patients
fourfold rise in mumps antibody titer.
with subacute or chronic symptoms.
Nucleic Acid Amplification Tests
Blood Culture
PCR is the standard test for the detection of
Blood culture is also crucial to diagnose
enteroviruses and HSV, VZV, EBV, CMV, or
bacterial meningitis. The causative organ-
HHV-6 meningoencephalitis. The sensitiv-
ism was recovered from 86% of pediatric
ity of PCR for HSV encephalitis were 98%
patients.15 Blood samples should be drawn
and the specificity were 94%.10 PCR may
at first, even if antimicrobial therapy needs
become positive only a few days after the
to be started before lumbar puncture be-
onset of symptoms.
cause of clinical deterioration.
Bacterial Meningitis
Markers of Inflammation
Cerebrospinal Fluid
C-reactive protein (CRP) and serum pro-
The CSF WBC count is usually elevated calcitonin (PCT) levels were significantly
to 1,000 to 5,000/mm3; however, it can higher in acute bacterial meningitis than in
be normal in neonates and in patients acute viral meningitis.16,17 The high nega-
20
tive predictive value may be used to rule Amebic Meningitis
out bacterial meningitis when CSF analysis
Primary amebic meningoencephalitis usu-
is inconclusive and Gram stain is negative.
ally reveals a neutrophilic pleocytosis with
a low glucose level, high protein level, and
Nucleic Acid Amplification Tests
red blood cells.

The use of broad-based bacterial PCR in CSF The Gram stain is not useful. The CSF
for community-acquired bacterial menin- specimen should be stained with Giemsa
gitis has been studied. One study showed or Wright stain to identify trophozoites.
59% sensitivity and 97% specificity.19 This The value of serologic testing is variable.
test may be useful for excluding bacterial
meningitis or when patients have received Helminthic Meningitis
prior antimicrobial therapy.
Fifty percent of cases of A. cantonensis
meningitis show an eosinophilic pleocy-
Spirochetal Meningitis
tosis with a high protein level. Larvae may
Treponema pallidum sometimes be found on microscopy of the
CSF in A. cantonensis meningitis. The sen-
CSF abnormalities are common in syphi- sitivity and specificity of serologic studies
litic meningitis. are variable.7
The sensitivity of CSF Venereal Disease
Research Laboratory (VDRL) testing is 30 to
70%, but it is very specific. A reactive CSF
VDRL test is sufficient to diagnose neuro- ■■ Shunt Infections
syphilis, but a nonreactive result does not
Microbiology
exclude the diagnosis.20 Serum RPR for VDRL
should be monitored for a fourfold decrease Coagulase-negative staphylococci are the
in titers over 6–12 months. CSF WBCs and most common organisms.22 S. aureus;
VDRL should also improve and eventually gram-negative bacteria, including Aci-
return to normal after treatment. netobacter, E. coli, Klebsiella pneumoniae,
and Pseudomonas aeruginosa; diphthe-
Borrelia burgdorferi roids, such as Propionibacterium acnes;
and anaerobes are also seen.23 Gram-neg-
Lyme meningitis typically causes lympho-
ative organisms are commonly found in
cytic pleocytosis with elevated protein
specimens from patients with shunts ter-
concentration. Enzyme-linked immuno-
minating in the peritoneal cavity.24 Shunt
sorbent assay (ELISA) with B. burgdorferi
infections due to Candida species may be
antigen is recommended for the initial
seen in immunocompromised patients,
screening test. If it is positive, the diagno-
patients receiving broad-spectrum anti-
sis should be confirmed with Western blot
microbial therapy, and those with indwell-
of the CSF specimen because of the high
ing bladder or intravenous catheters.25
number of false-positive reactions.21 If the
suspicion is high and Western blot is nega-
tive, this should be repeated in 2 weeks. If Diagnosis
the Western blot confirms the diagnosis Cerebrospinal Fluid
of Lyme disease and there is concern for
Lyme meningitis, then a lumbar puncture Leukocytosis is seen in 80% of shunt infec-
should be performed. This usually causes tions.26 Leukocyte counts in CSF obtained
a lymphocytic pleocytosis. CSF should be by lumbar puncture or valve puncture tend
evaluated for intrathecal antibodies against to be higher than those in ventricular CSF.
Borrelia burgdorferi. CSF PCR could also Progressively decreasing CSF glucose and
support this diagnosis. increasing CSF protein accompanied by ad-
21
vancing CSF pleocytosis suggest infection ■■ Chronic Meningitis/
even if all cultures are negative.
Ventriculitis
Cultures Microbiology
Cerebrospinal Fluid Culture Common organisms and diagnostic tests for
Microorganisms are recovered more often chronic meningitis are shown in Table 2.4.
from valve puncture CSF specimens and
ventricular CSF specimens than from lum- Bacterial Meningitis
bar CSF specimens. The diagnosis may be Tuberculous meningitis is the most com-
more difficult when the distal portion of mon form of chronic meningitis. It is dif-
the shunt is infected. ficult to diagnose, sometimes requiring
empiric treatment.
Blood Culture
Blood cultures should be obtained in pa- Fungal Meningitis
tients with ventriculoatrial shunts because Cryptococcal meningitis is the most com-
blood cultures are positive in more than mon fungal meningitis. Coccidioidal menin-
90% of cases.27 gitis is endemic in the American Southwest.
Brief exposure of visitors from outside the
Nucleic Acid Amplification Tests area of endemicity can result in the acquisi-
Banks et al reported that CSF PCR was positive tion of meningeal disease. The Midwest and
and cultures were negative in 49% of cases. Southeast in the United States are the ma-
Most of these cases had received prolonged jor areas where histoplasmosis is endemic.
intravenous antibiotics previously.28 There Other forms of fungal meningitis are usually
was no positive culture result with negative seen in immunocompromised patients.
CSF PCR. The PCR method has not yet been
standardized; however, it can be considered Amebic Meningitis
when all cultures are negative despite sug- Granulomatous meningitis due to Acan-
gestive symptoms and CSF cell analysis. thamoeba species may cause symptoms
over a period of weeks to months. It is
usually seen in those who are immuno-
■■ Hardware Infection compromised due to other diseases, such
as diabetes, alcoholism, cirrhosis, HIV, che-
Many types of hardware are placed in motherapy, or transplantation.
neurosurgical procedures, including deep
brain stimulation surgery, as well as in Diagnosis
bone flaps and shunts.
Bacterial Meningitis
Microbiology
Cerebrospinal Fluid
S. aureus is the most common organism.29
P. acnes and gram-negative rods, including The CSF in tuberculous meningitis usu-
Acinetobacter baumannii and P. aeruginosa, ally shows lymphocytic pleocytosis with
are also reported. a low glucose level. Adenosine deaminase
(ADA) may be elevated, but it is not use-
ful to distinguish tuberculous meningitis
Diagnosis
from bacterial meningitis.30 The most com-
The most useful cultures are intraoperative mon strains use the acid-fast properties
specimens. Superficial cultures may be dif- of mycobacteria. These include the Ziehl-
ficult to interpret because the most com- Neelson stain and the Kinyoun stain. The
mon pathogens are also skin flora. sensitivity of these stains is 25%. The sensi-
22
Table 2.4 Common organisms of chronic meningitis and the diagnostic tests
Tests
Risk factors/
Organisms areas of endemicity CSF Others
Bacteria

Coagulase-negative Neurosurgery Culture
staphylococci
Mycobacterium Microbacterial culture (5–10 mL), AFB culture (5–10 mL) PPD, interferon
tuberculosis TB PCRb gamma release
assays
Actinomyces Immunocompromise, Anaerobic culture Pathology

dental infection
Nocardiaa Immunocompromise Culture
Fungi
Cryptococcus neoformans HIV Antigen, india ink, Antigen

culture
Coccidioides immitis Arizona, California Complement

fixation test, culture
Histoplasma capsulatum Midwest, Southeast Anti-Histoplasma Urine antigen,

antibodies, culture serum antigen
Candida species Immunocompromise Culture
Sporothrix schenckii Immunocompromise, Culture Skin biopsy

skin injury
Blastomyces dermatitidis Southeastern and central Antigen, culture

states
Virus
Echovirus X-linked agammaglobulinemia Viral culture
Parasites
Angiostrongylus Travel history Microscopic exam

cantonensis
Abbreviations: AFB, acid-fast bacillus; CSF, cerebrospinal fluid; HIV, human immunodeficiency virus; PPD, purified protein
derivative
a
Usually occurs with brain abscesses. The microbiology laboratory should be informed when nocardial infection is suspected
because the use of selective media is preferable and requires prolonged incubation.
b
If a larger sample can be obtained and centrifuged, the pellet may have a higher yield.
tivity of culture for these organisms ranges Tuberculin Skin Test and Interferon Gamma
from 18–83%.31 Many studies of the use of Release Assay
PCR have been carried out; however, the
method and the interpretation have not yet These tests are appropriate to diagnose la-
been standardized. tent tuberculosis; however, neither can be
Organisms are not frequently recovered used to support or exclude the diagnosis of
from lumbar CSF in patients with postop- meningitis because of insufficient sensitiv-
erative chronic meningitis; however, they ity and specificity.32
may be found on implanted material when
it is removed. 23
Fungal Meningitis The common causes of infectious encepha-
litis are described in Table 2.5.
Generally, a large amount of CSF is required
The CSF opening pressure, cell count
to increase the sensitivity of fungal CSF cul-
with differential, and protein and glucose
ture. Immunologic tests should be also con-
concentrations should be measured, and
sidered based on the potential organisms.
Gram stain, bacterial cultures, and PCR
In cryptococcal meningitis, the open-
studies for HSV and VZV should be per-
ing pressure is often elevated. If the open-
formed in immunocompetent patients.
ing pressure is ≥ 25 cm H2O and there are
Lymphocytic pleocytosis with a normal
symptoms of elevated intracranial pres-
glucose level and an elevated protein level
sure, it may require serial drainage or
are generally seen in the CSF of patients
even placement of a lumbar drain. Cryp-
with viral encephalitis.
tococcal polysaccharide antigen testing
In immunocompromised patients, CSF
in serum and CSF is widely used because
PCR for CMV and HHV-6 should be per-
of high accuracy.33 The CSF is more often
formed. PCR for JC virus, HIV, and EBV
positive than the serum for antigen. India
should also be considered. The specificity
ink smears of CSF are positive in 50% of pa-
of viral CSF cultures is very high, although
tients without acquired immunodeficien-
the sensitivity is quite low.
cy syndrome (AIDS) and more than 80% of
patients with AIDS. Cryptococcus neofor-
mans is generally recovered from CSF cul- ■■ Brain Abscess
tures in 3 to 7 days in untreated patients.
In coccidioidal meningitis, the comple- Microbiology

ment fixation test in CSF is very sensitive
and specific. CSF culture and smear are not The causative organisms frequently depend
commonly positive. on the predisposing conditions (Table 2.6).
In Histoplasma meningitis, anti-Histo- Brain abscess can occur after cranial opera-
plasma antibodies in the CSF are found in tions, including craniotomy and brain bi-
80% of cases. At least 10 mL of CSF should opsy.35 The incidence of brain abscess after
be sent for culture to recover Histoplasma. intracranial procedures ranges from 0.2%
The serum or urine Histoplasma antigen to 0.6%.35,36
test is useful if patients have disseminated Streptococci are the organisms most
histoplasmosis.34 If the result is positive, it commonly cultured from patients with
would support this diagnosis. brain abscess.37 They are frequently isolat-
ed in mixed infections. S. aureus, P. acnes,
Amebic Meningitis Enterobacteriaceae (e.g., Proteus species,
E. coli, Klebsiella species, and Pseudomonas
If there is a space-occupying lesion and species), and Clostridium species are also
evidence of intracranial pressure, a lumbar commonly found in patients after neu-
puncture should not be performed. If it can be rosurgery.35,38 Infection due to anaerobes
done safely, then a wet mount should be per- and polymicrobial infection are commonly
formed. A Giemsa stain may reveal Acantham- seen in brain abscess related to dental in-
oeba. If available, PCR may make the diagnosis fection or otogenic infection.
of Balamuthia. However, if these are negative, Nocardial brain abscess may occur as an
a brain biopsy has the highest diagnostic yield. isolated CNS lesion or as part of disseminat-
ed infection in association with a pulmonary
or cutaneous lesion. Mycobacterium tuber-
■■ Encephalitis culosis, nontuberculous mycobacteria, and
Toxoplasma gondii have been observed in
Distinguishing among encephalitis, en- HIV patients and non-HIV patients. Candida
cephalopathy, and postinfectious immune- species have emerged as the most prevalent
mediated processes is challenging because fungal agents.39 Most cases of aspergillosis
24 of the nonspecific clinical presentations. and mucormycosis occur in severely immu-
Table 2.5 Common Organisms of Encephalitis and the Diagnostic Tests
Tests
Risk Factors/
Organisms Areas of Endemicity CSF Others
Viruses

HSV-1, VZV PCR
HHV-6 Immunocompromised PCR
Nonpolio enteroviruses Neonates, PCR

hypogammaglobulinemia,
summer
CMV Immunocompromised PCR
WNV United States WNV-specific IgM by

ELISA
JC virus HIV PCR
EBV Immunocompromised PCR
St. Louis encephalitis virus North and South America Anti-St. Louis Anti-St. Louis
encephalitis virus encephalitis virus
IgM antibodies IgM antibodies,
viral culture of brain
tissue, 4-fold rise in
serum antibodies
EEE virus North and South America Anti-EEE virus IgM IgM antibodies,
antibodies 4-fold rise in serum
antibodies
California encephalitis North America Anti-California IgM antibodies,

group of viruses encephalitis group of 4-fold rise in serum
viruses IgM antibodies antibodies
Bacteria
Mycoplasma pneumoniae PCR
Mycobacterium tuberculosis a
PCR, AFB culture
Abbreviations: AFB, acid-fast bacillus; CMV, cytomegalovirus; CSF, cerebrospinal fluid; EBV, Epstein-Barr virus; EEE, Eastern
equine encephalitis; ELISA, enzyme-linked immunosorbent assay; HHV, human herpesvirus; HIV, human immunodeficiency
virus; HSV, herpes simplex virus; IgM, immunoglobulin M; PCR, polymerase chain reaction; VZV, varicella-zoster virus; WNV,
West Nile virus
a
Usually presents as meningoencephalitis.
nocompromised patients. Several protozoa At the time of aspiration, specimens

and helminths, such Trypanosoma cruzi40 should be sent for Gram stain, routine
and Entamoeba histolytica,41 have been re- aerobic and anaerobic cultures, and fungal
ported to produce brain abscess. culture. If a fungal infection is strongly sus-
pected, special stains (e.g., mucicarmine,
Diagnosis Grocott-Gomori methenamine-silver ni-
trate) should be performed. Acid-fast
Cultures
stains with cultures for mycobacteria and
Stereotactic computed tomography (CT)– Nocardia should be sent to the lab if these
guided aspiration facilitates the microbio- organisms are suspected. The microbiol-
logical diagnosis and guides antimicrobial ogy laboratory should always be informed
therapy. when nocardiosis is suspected because 25
Table 2.6 Predisposing conditions and common organisms of brain abscess
Predisposing conditions Common organisms
Neurosurgery or trauma Staphylococcus aureus, streptococci, Propionibacterium acnes,

Enterobacteriaceae, Clostridium species
Otogenic infection or sinusitis Streptococci, Enterobacteriaceae, Haemophilus species,

Bacteroides species, Prevotella species
Dental infection Streptococci, Fusobacterium species, Prevotella species,

Actinomyces species, Bacteroides species
Lung abscess or empyema Streptococci, Nocardia species, Fusobacterium species, Bacteroides

species, Prevotella species
Bacterial endocarditis Streptococci, Staphylococcus aureus
Human immunodeficiency virus Toxoplasma gondii, Cryptococcus neoformans, Mycobacterium

infection species
Immunosuppressant use Aspergillus species, Candida species, Scedosporium species,

gram-negative rods, Nocardia species
the diagnosis may be missed using routine ■■ Subdural Empyema/

laboratory methods. Fungi can often be
Cranial Epidural Abscess/
identified by the appearance in tissue even
if the cultures are negative. Ideally, both Suppurative Intracranial
culture and histologic examination should Thrombophlebitis
be done together.
Multiple sequenced 16S ribosomal DNA Microbiology
PCR amplification revealed more types of Subdural Empyema
bacteria than routine cultures in one study.42
The detection of fastidious organisms, such The most common conditions predisposing
as Mycoplasma hominis and Fusobacterium to cranial subdural empyema are otorhino-
necrophorum, was more rapid with mo- logic infections.43 Subdural empyema also
lecular detection. Molecular techniques can occurs after head trauma or neurosurgery.
be used for patients with negative cultures Common organisms include streptococ-
likely due to prior antibiotic use. ci, staphylococci, aerobic gram-negative
bacilli, and anaerobes.44 Polymicrobial in-
Immunology fections are common. Postoperative and
posttraumatic infections are more com-
Elevated anti-Toxoplasma immunoglobu- monly caused by staphylococci and aero-
lin G antibody aids the diagnosis in an im- bic gram-negative bacilli.45 Also, P. acnes
munosuppressed host (mainly with AIDS) is isolated after trauma and neurosurgical
who has characteristic neuroradiographic procedures.
abnormalities.
26
Cranial Epidural Abscess/Suppurative lococci and gram-negative rods, including
Intracranial Thrombophlebitis E. coli and P. aeruginosa, are sometimes re-
covered from patients with prolonged bac-
Cranial epidural abscess is often accompa- teremia.48,49 Isolation of coagulase-negative
nied by cranial subdural empyema because staphylococci, P. acnes, gram-negative rods,
cranial epidural abscess can cross the cranial and Candida species is frequently associ-

dura along emissary veins. Suppurative in- ated with spinal surgeries. Anaerobes and
tracranial thrombophlebitis frequently oc- gram-negative rods are recovered when in-
curs in association with subdural empyema, fections are adjacent to soft tissue, such as
epidural abscess, or bacterial meningitis. in a sacral decubitus ulcer. The possibility
Therefore, the causative organisms of cranial of tuberculous spondylitis (Pott disease),
epidural abscess and suppurative intracra- usually a result of past hematogenous foci,
nial thrombophlebitis are usually similar to should be considered, especially in areas of
those of cranial subdural empyema. Cranial endemicity.
epidural abscess may also occur after fetal Spinal subdural empyema is very un-
scalp monitoring and halo pin penetration.46 common. It occurs hematogenously or con-
tiguously.50 The most frequent microbial
Diagnosis isolate is S. aureus.
Cultures
Diagnosis
Cranial subdural empyema and epidural
abscesses usually require neurosurgical Cultures
exploration in addition to antimicrobial Blood Culture
agents. Aerobic and anaerobic cultures of
purulent material are needed to direct the Blood cultures are crucial when vertebral
specific antimicrobial therapy. osteomyelitis is suspected. Positive blood
cultures occur in 30 to 78% of cases.51
Cerebrospinal Fluid
Tissue Culture
A lumbar puncture with CSF analysis is
contraindicated in patients with subdural A biopsy is warranted if blood cultures are
empyema because it may precipitate ce- negative or when polymicrobial osteomy-
rebral herniation.47 Also, CSF cultures are elitis is suspected. Biopsy specimens should
negative unless subdural empyema is com- be cultured for aerobic and anaerobic bac-
plicated by bacterial meningitis. teria and for fungi. Cultures for mycobacte-
ria or Brucella should be performed if the
patient has risk factors. For mycobacteria
this would include immunosuppression or
■■ Vertebral Osteomyelitis/ a mycobacterial infection at another site.
Spondylodiskitis/ For Brucella, this would include exposure
Spinal Epidural Abscess/ to domestic farm animals or consumption
Spinal Subdural Empyema of raw meat or unpasteurized milk prod-
ucts. Open biopsy has a sensitivity ranging
Microbiology from 75% to 93%.52,53 On the other hand, the
sensitivity of CT-guided percutaneous bi-
Vertebral osteomyelitis and spondylodiski-
opsy is 50%.
tis, infection of the intervertebral disk, can
be hematogenous or continuous to a soft
Markers of Inflammation
tissue infection. Spinal epidural abscess
usually occurs hematogenously or by local The erythrocyte sedimentation rate and C-
extension from vertebral osteomyelitis. It reactive protein level are increased in 98 and
can also occur postoperatively. 100% of cases, respectively.52,54 Therefore, a
S. aureus is overall the most common mi- negative value is helpful to rule out vertebral
croorganism.48 Coagulase-negative staphy- osteomyelitis when cultures are negative. 27
References 17. A lkholi UM, Abd Al-Monem N, Abd El-Azim AA,
Sultan MH. Serum procalcitonin in viral and
1. Kestenbaum LA, Ebberson J, Zorc JJ, Hodinka RL, bacterial meningitis. J Glob Infect Dis 2011;3(1):
Shah SS. Defining cerebrospinal fluid white blood 14–18 PubMed
cell count reference values in neonates and young 18. S aha SK, Darmstadt GL, Yamanaka NP, et al. Rapid
infants. Pediatrics 2010;125(2):257–264 PubMed diagnosis of pneumococcal meningitis: impli-
2. Spanos A, Harrell FE Jr, Durack DT. Differential cations for treatment and measuring disease
diagnosis of acute meningitis. An analysis of the burden. Pediatr Infect Dis J 2005;24(12):1093–
predictive value of initial observations. JAMA 1098 PubMed
1989;262(19):2700–2707 PubMed 19. W elinder-Olsson C, Dotevall L, Hogevik H, et al.
3. Kupila L, Vuorinen T, Vainionpää R, Hukkanen V, Comparison of broad-range bacterial PCR and
Marttila RJ, Kotilainen P. Etiology of aseptic men- culture of cerebrospinal fluid for diagnosis of
ingitis and encephalitis in an adult population. community-acquired bacterial meningitis. Clin
Neurology 2006;66(1):75–80 PubMed Microbiol Infect 2007;13(9):879–886 PubMed
4. de Almeida SM, Letendre S, Ellis R. Human immu- 20. Hook EW III, Marra CM. Acquired syphilis in adults.
nodeficiency virus and the central nervous sys- N Engl J Med 1992;326(16):1060–1069 PubMed
tem. Braz J Infect Dis 2006;10(1):41–50 PubMed 21. W ormser GP, Dattwyler RJ, Shapiro ED, et al. The
5. McMillan DA, Lin CY, Aronin SI, Quagliarello VJ. clinical assessment, treatment, and prevention of
Community-acquired bacterial meningitis in Lyme disease, human granulocytic anaplasmosis,
adults: categorization of causes and timing of and babesiosis: clinical practice guidelines by the
death. Clin Infect Dis 2001;33(7):969–975 PubMed Infectious Diseases Society of America. Clin Infect
6. Halperin JJ. Neurologic manifestations of Lyme Dis 2006;43:1086–1134
disease. Curr Infect Dis Rep 2011;13(4):360–366 22. N aradzay JF, Browne BJ, Rolnick MA, Doherty
[epub ahead of print] PubMed RJ. Cerebral ventricular shunts. J Emerg Med
7. Ramirez-Avila L, Slome S, Schuster FL, et al. Eo- 1999;17(2):311–322 PubMed
sinophilic meningitis due to Angiostrongylus 23. S acar S, Turgut H, Toprak S, et al. A retrospective
and Gnathostoma species. Clin Infect Dis 2009; study of central nervous system shunt infections
48(3):322–327 PubMed diagnosed in a university hospital during a 4-year

8. Negrini B, Kelleher KJ, Wald ER. Cerebrospinal flu- period. BMC Infect Dis 2006;6:43 PubMed
id findings in aseptic versus bacterial meningitis. 24. S hapiro S, Boaz J, Kleiman M, Kalsbeck J, Mealey J.
Pediatrics 2000;105(2):316–319 PubMed Origin of organisms infecting ventricular shunts.
9. Polage CR, Petti CA. Assessment of the utility of Neurosurgery 1988;22(5):868–872 PubMed
viral culture of cerebrospinal fluid. Clin Infect Dis 25. Montero A, Romero J, Vargas JA, et al. Candida
2006;43(12):1578–1579 PubMed infection of cerebrospinal fluid shunt devices: re-
10. Lakeman FD, Whitley RJ; National Institute of Al- port of two cases and review of the literature. Acta
lergy and Infectious Diseases Collaborative Anti- Neurochir (Wien) 2000;142(1):67–74 PubMed
viral Study Group. Diagnosis of herpes simplex 26. Conen A, Walti LN, Merlo A, Fluckiger U, Battegay M,
encephalitis: application of polymerase chain re- Trampuz A. Characteristics and treatment outcome
action to cerebrospinal fluid from brain-biopsied of cerebrospinal fluid shunt-associated infections in
patients and correlation with disease. J Infect Dis adults: a retrospective analysis over an 11-year pe-
1995;171(4):857–863 PubMed riod. Clin Infect Dis 2008;47(1):73–82 PubMed
11. Mylonakis E, Hohmann EL, Calderwood SB. Central 27. K aufman BA. Infections of cerebrospinal fluid
nervous system infection with Listeria monocyto- shunts. In: Scheld WM, Whitley RJ, Durack DT,
genes. 33 years’ experience at a general hospital and eds. Infections of the Central Nervous System.
review of 776 episodes from the literature. Medi- 2nd ed. Philadelphia, PA: Lippincott–Raven Pub-
cine (Baltimore) 1998;77(5):313–336 PubMed lishers; 1997:555–577
12. Pagliano P, Fusco U, Attanasio V, et al. Pneumo- 28. B anks JT, Bharara S, Tubbs RS, et al. Polymerase
coccal meningitis in childhood: a longitudinal chain reaction for the rapid detection of cerebro-
prospective study. FEMS Immunol Med Microbiol spinal fluid shunt or ventriculostomy infections.
2007;51(3):488–495 PubMed Neurosurgery 2005;57(6):1237–1243, discus-
13. Gray LD, Fedorko DP. Laboratory diagnosis sion 1237–1243 PubMed
of bacterial meningitis. Clin Microbiol Rev 29. Boviatsis EJ, Stavrinou LC, Themistocleous M,
1992;5(2):130–145 PubMed Kouyialis AT, Sakas DE. Surgical and hardware com-
14. Brouwer MC, van de Beek D, Heckenberg SG, plications of deep brain stimulation. A seven-year
Spanjaard L, de Gans J. Community-acquired Lis- experience and review of the literature. Acta Neu-
teria monocytogenes meningitis in adults. Clin rochir (Wien) 2010;152(12):2053–2062 PubMed
Infect Dis 2006;43(10):1233–1238 PubMed 30. T uon FF, Higashino HR, Lopes MI, et al. Adenosine
15. Coant PN, Kornberg AE, Duffy LC, Dryja DM, Has- deaminase and tuberculous meningitis—a sys-
san SM. Blood culture results as determinants in tematic review with meta-analysis. Scand J Infect
the organism identification of bacterial meningitis. Dis 2010;42(3):198–207 PubMed
Pediatr Emerg Care 1992;8(4):200–205 PubMed 31. van Well GT, Paes BF, Terwee CB, et al. Twenty
16. Ibrahim KA, Abdel-Wahab AA, Ibrahim AS. Diag- years of pediatric tuberculous meningitis: a retro-
nostic value of serum procalcitonin levels in chil- spective cohort study in the western cape of South
dren with meningitis: a comparison with blood Africa. Pediatrics 2009;123(1):e1–e8 PubMed
leukocyte count and C-reactive protein. J Pak 32. P ark SY, Jeon K, Um SW, Kwon OJ, Kang ES, Koh
Med Assoc 2011;61(4):346–351 PubMed WJ. Clinical utility of the QuantiFERON-TB Gold
28
In-Tube test for the diagnosis of active pulmo- 43. S ilverberg AL, DiNubile MJ. Subdural empyema
nary tuberculosis. Scand J Infect Dis 2009;41(11- and cranial epidural abscess. Med Clin North Am
12):818–822 PubMed 1985;69(2):361–374 PubMed
33. Goodman JS, Kaufman L, Koenig MG. Diagnosis of 44. D ill SR, Cobbs CG, McDonald CK. Subdural empy-
cryptococcal meningitis. Value of immunologic ema: analysis of 32 cases and review. Clin Infect
detection of cryptococcal antigen. N Engl J Med Dis 1995;20(2):372–386 PubMed
1971;285(8):434–436 PubMed 45. D ashti SR, Baharvahdat H, Spetzler RF, et al. Oper-

34. Wheat LJ, Musial CE, Jenny-Avital E. Diagno- ative intracranial infection following craniotomy.
sis and management of central nervous sys- Neurosurg Focus 2008;24(6):E10 PubMed
tem histoplasmosis. Clin Infect Dis 2005;40(6): 46. Papagelopoulos PJ, Sapkas GS, Kateros KT, Pa-
844–852 PubMed padakis SA, Vlamis JA, Falagas ME. Halo pin in-
35. McClelland S III, Hall WA. Postoperative central tracranial penetration and epidural abscess in a
nervous system infection: incidence and associ- patient with a previous cranioplasty: case report
ated factors in 2111 neurosurgical procedures. and review of the literature. Spine (Phila Pa 1976)
Clin Infect Dis 2007;45(1):55–59 PubMed 2001;26(19):E463–E467 PubMed
36. Korinek AM; Service Epidémiologie Hygiène et
47. N athoo N, Nadvi SS, van Dellen JR, Gouws E.
Prévention. Risk factors for neurosurgical site infec- Intracranial subdural empyemas in the era of
tions after craniotomy: a prospective multicenter computed tomography: a review of 699 cases.
study of 2944 patients. The French Study Group of Neurosurgery 1999;44(3):529–535, discussion
Neurosurgical Infections, the SEHP, and the C-CLIN 535–536 PubMed
Paris-Nord. Neurosurgery 1997;41(5):1073–1079, 48. Z immerli W. Clinical practice. Vertebral osteo-
discussion 1079–1081 PubMed myelitis. N Engl J Med 2010;362(11):1022–
37. Prasad KN, Mishra AM, Gupta D, Husain N, Hu- 1029 PubMed
sain M, Gupta RK. Analysis of microbial etiology 49. Bhavan KP, Marschall J, Olsen MA, Fraser VJ,
and mortality in patients with brain abscess. J In- Wright NM, Warren DK. The epidemiology of
fect 2006;53(4):221–227 PubMed hematogenous vertebral osteomyelitis: a cohort
38. Lu CH, Chang WN, Lin YC, et al. Bacterial brain study in a tertiary care hospital. BMC Infect Dis
abscess: microbiological features, epidemio- 2010;10:158 PubMed
logical trends and therapeutic outcomes. QJM 50. D e Bonis P, Anile C, Pompucci A, Labonia M, Lu-
2002;95(8):501–509 PubMed cantoni C, Mangiola A. Cranial and spinal sub-
39. Cortez KJ, Walsh TJ. Space-occupying fungal le- dural empyema. Br J Neurosurg 2009;23(3):
sions. In: Scheld WM, Whitley RJ, Marra CM, eds. 335–340 PubMed
Infections of the Central Nervous System. 3rd ed. 51. M ylona E, Samarkos M, Kakalou E, Fanourgiakis
Philadelphia, PA: Lippincott Williams & Wilkins; P, Skoutelis A. Pyogenic vertebral osteomyelitis:
2004:713–734 a systematic review of clinical characteristics. Se-
40. Yoo TW, Mlikotic A, Cornford ME, Beck CK. Con- min Arthritis Rheum 2009;39(1):10–17 PubMed
current cerebral American trypanosomiasis and 52. Jensen AG, Espersen F, Skinhøj P, Frimodt-Møller
toxoplasmosis in a patient with AIDS. Clin Infect N. Bacteremic Staphylococcus aureus spondylitis.
Dis 2004;39(4):e30–e34 PubMed Arch Intern Med 1998;158(5):509–517 PubMed
41. Morishita A, Yamamoto H, Aihara H. A case of ame- 53. N olla JM, Ariza J, Gómez-Vaquero C, et al. Spon-
bic brain abscess. No Shinkei Geka 2007;35(9): taneous pyogenic vertebral osteomyelitis in
919–925 PubMed nondrug users. Semin Arthritis Rheum 2002;
42. Al Masalma M, Armougom F, Scheld WM, et al. 31(4):271–278 PubMed
The expansion of the microbiological spectrum 54. K han MH, Smith PN, Rao N, Donaldson WF. Se-
of brain abscesses with use of multiple 16S ri- rum C-reactive protein levels correlate with clini-
bosomal DNA sequencing. Clin Infect Dis 2009; cal response in patients treated with antibiotics
48(9):1169–1178 PubMed for wound infections after spinal surgery. Spine J
2006;6(3):311–315 PubMed
29
3
Antibiotics and the
Development of Resistance
Since their introduction into medical prac- icillin-sensitive Staphylococcus aureus than
tice, antibiotics have played an enormous either cephazolin or oxacillin.
role in decreasing morbidity from bac- A second key principle for therapeutic
terial infection and have therefore been success is that, although the excessive use
invaluable in neurosurgical practice. Enti- of antibiotics should be avoided, complete
ties such as meningitis and brain abscess, eradication of an infection is necessary for a
which were associated with high mortal- successful clinical outcome. Therefore, sur-
ity rates before antibiotic therapy, are now gical treatment is necessary if hardware is
frequently cured with appropriate combi- involved (that may be removed), such as a
nations of surgery and antibiotic therapy. cerebrospinal fluid (CSF) shunt or an intra-
Because of the immune-privileged nature thecal catheter. Similarly, if a suppurative
of the central nervous system (CNS), the collection exists, such as a bacterial brain
common use of implanted devices, and abscess, subdural empyema, or cranial
the frequent use of steroids, infection is epidural abscess that is too large for anti-
of great concern in neurosurgical prac- biotic penetration, surgical evacuation is
tice; therefore, the rational, effective use necessary. Attempting to treat an infection
of antibiotics is of great importance. An through medical management only, such as
understanding of antibiotic mechanisms in the case of a partially drained abscess1 or
of action and the mechanisms with which an infected CSF shunt that is not removed,2
microbes develop resistance is essential for can often result in a recurrent infection.
the neurosurgeon. In the practice of surgery, antibiot-
The intelligent use of antibiotics is crucial ics have played an enormous role in pre-
for the successful prevention and manage- venting surgical site infections and in the
ment of infections. The principle of using provision of effective surgical treatment.
the agent with the narrowest spectrum Antibiotic prophylaxis, which is discussed
for the least amount of time to eradicate a in Chapter 14, is standard practice in neu-
particular infection is well recognized, but rosurgery. Postoperative infections, when
not universally practiced. The lack of a de- they do occur, are treatable with antibiot-
finitive culture is often an impediment to ics, although reoperation is often essential.
successful treatment. Additionally, the in- Of course, antibiotic prophylaxis will not
correct assumption that antibiotics with compensate for poor sterile technique, and
broad coverage are more effective than an in the case of contamination from a breach
appropriate narrow-spectrum antibiotic or from penetrating cerebral trauma, infec-
against a particular microbial species can tions are likely to occur. Failure of wound
lead to antibiotic misuse. Vancomycin, for healing due to lapses in surgical technique,
example, is no more effective against meth- poor nutritional status, or CSF fistula offers
a portal for bacterial invasion that will oc- 1975 to 1991, the rate of MRSA infections
cur despite antibiotic prophylaxis. In these in the hospital setting rose from 2.4 to 29%.6
circumstances, the identification of the in- Additionally, the incidence of community-
fectious agent and its sensitivities is critical associated MRSA infections has been on
for the successful eradication of the infec- the rise.7 By the following decade, MRSA
tion, as is the removal of any modifiable risk infections were estimated to account for
factors for the development of infection. approximately 2% of all hospital admis-
In treating infections of the CNS, the sions.8 Vancomycin was developed with the
concept of the blood–brain barrier (BBB) intention that it would be highly resistant
plays an important role. Antibiotic pen- to the development of bacterial resistance,
etration into the central nervous system and its name is based on the fact that its
(CNS) is variable, which can influence an- developers thought that the resistant bac-
3 Antibiotics and the Development of Resistance

tibiotic selection, although the BBB may teria might be vanquished. Despite these
be compromised during infection, allow- high hopes, strains of vancomycin-resis-
ing hydrophilic antibiotics to enter the tant enterococci (VRE) and some strains of
CSF. Vancomycin and the fluoroquinolones, S. aureus that are vancomycin intermediate
which are lipophilic molecules, cross the (VISA) or vancomycin resistant (VRSA) have
BBB particularly well. Aminoglycosides and been isolated. The newer drug linezolid is
β-lactam antibiotics are hydrophilic and the first line in the treatment of infections
therefore do not penetrate the BBB very resistant to vancomycin; however, the in-
easily. Intraventricular or intrathecal ad- creased use of linezolid will no doubt ulti-
ministration of antibiotics can provide di- mately lead to the development of strains
rect entry into the CSF space; however, the resistant to this antibiotic.
presence of external ventricular drainage or Antibiotics are categorized into classes
a lumbar drain is required for drug instilla- based on their structure and mechanisms
tion. Intraventricular antibiotics have been of action. Antibiotics can further be classi-
suggested both as treatment for ventriculi- fied as bacteriocidal or bacteriostatic. Bac-
tis3 and for prophylaxis at the time of sur- teriostatic agents depend on the functional
gery to prevent shunt infection.4 β-Lactam immune system to destroy the bacteria but
antibiotics can be epileptogenic and are may be as effective as bacteriocidal drugs
therefore generally not administered via in the right setting. The mechanisms and
an intraventricular route despite their rela- spectra of commonly used antibiotics are
tively poor penetration of the BBB.5 listed in Table 3.1.
Allergies may also play a role in the Antibiotic resistance occurs via multiple
choice of which antibiotic to use. Patients mechanisms (see Table 3.1). Resistance to
with chronic diseases may have had expo- β-lactam antibiotics occurs when bacteria
sure to multiple antibiotics, with the op- express β-lactamase, an enzyme that simply
portunity to develop multiple sensitivities breaks down the drug. Bacterial circumven-
to the drugs. The specifics of a patient’s re- tion of the toxicity of several antibiotics occurs
action to a particular allergy are important when the bacteria synthesize altered proteins
to note because some reactions may not be that do not bind the drugs. This phenomenon
true allergies, and others, such as “red man occurs in resistance to aminoglycoside and
syndrome” from vancomycin, may not pre- macrolide antibiotics. A third mechanism of
clude the use of the agent if it is given in resistance involves the use of efflux pumps,
concert with diphenhydramine. such as in tetracycline resistance.
Antibiotic resistance has been exten- Genes for antibiotic resistance are often
sively discussed both in the scientific lit- encoded on plasmids, which are extra-
erature and the popular media, and its chromosomal elements that replicate sta-
importance cannot be overstated. The rise bly in bacterial hosts.9 Many plasmids are
in the prevalence of methicillin-resistant capable of conjugation, a process in which
Staphylococcus aureus (MRSA) has been rapid transfer of the plasmid occurs be-
well documented. In the United States from tween bacteria. Conjugation can occur
31
Table 3.1 Antibiotics commonly used in central nervous system infections
Mechanism of Mechanism of
Class Examples Spectrum action resistance
Aminoglycosides Gentamycin, Gram-negative Protein synthesis Altered protein

tobramycin
Macrolides Azithromycin Gram-positive Protein synthesis Altered protein

(including
intracellular)
Fluoroquinolones Levofloxacin, Broad DNA replication Altered protein

gatifloxacin,
ciprofloxacin
β-Lactams Penicillins, Gram- Cell wall formation β-Lactamase

cephalosporins, positive→broad
meropenem
Glycopeptide Vancomycin Gram-positive Cell wall formation Altered peptide

(including MRSA)
Oxazoladinones Linezolid Gram-positive Protein synthesis Altered rRNA,

(including VRE) efflux pump
Nitroamidazole Metronidazole Anaerobic DNA breakdown Decreased activation
Abbreviations: MRSA, methicillin-resistant Staphylococcus aureus; rRNA, ribosomal RNA; VRE, vancomycin-resistant
enterococci
across a wide array of species and can even is probably a better choice for preoperative
occur from gram-negative to gram-positive prophylaxis than is cefazolin.12
bacteria and vice versa. The timing of antibiotic administration
Because of the ease with which an- is another important consideration. In gen-
tibiotic resistance can spread from site eral, antibiotic administration should be
to site within the body and between pa- delayed until a culture of the suspected site
tients, the control of reservoirs of antibi- of infection has been obtained. The rate at
otic resistance can be helpful in reducing which antibiotic administration decreases
hospital-acquired infections and those at culture sensitivity is not known for most
the surgical site. Of utmost importance is situations; however, unless the patient is
rigorous adherence to protocols aimed at critically ill and culture cannot be obtained
reducing the spread of antibiotic-resistant in a timely fashion, it is reasonable in most
bacteria from patient to patient. Hand situations to wait for the culture results. A
washing and gel-based decontamination, frustrating situation arises when a known
when practiced, reduce the prevalence infection is being treated but positive cul-
of MRSA and other antibiotic-resistant tures are not available from which to tailor
bacterial strains within the hospital set- antibiotic treatment. The length of treat-
ting.10 Intranasal mupirocin administered ment with antibiotics is also important
preoperatively for decolonization of MRSA because the premature cessation of treat-
has been demonstrated in the orthope- ment will often lead to the recurrence of
dic literature to reduce the rate of surgi- infection and may place the patient at risk
cal site infections11 and may be useful in for antibiotic resistance. The timing of an-
neurosurgical procedures. In settings with tibiotic administration in presurgical pro-
a high risk for MRSA infection, vancomycin phylaxis has been intensively scrutinized,
32
and many institutions have protocols in References
place to maximize the effectiveness of pre- 1. Kondziolka D, Duma CM, Lunsford LD. Factors
surgical antibiotics. that enhance the likelihood of successful stereo-
Antibiotic-impregnated materials have tactic treatment of brain abscesses. Acta Neuro-
chir (Wien) 1994;127(1-2):85–90 PubMed
also been used in an attempt to prevent col- 2. Simon TD, Hall M, Dean JM, Kestle JR, Riva-
onization and the subsequent infection of Cambrin J. Reinfection following initial cerebro-
hardware. Shunt tubing impregnated with spinal fluid shunt infection. J Neurosurg Pediatr
rifampin and clindamycin (Bactiseal; Cod- 2010;6(3):277–285 PubMed
3. Tängdén T, Enblad P, Ullberg M, Sjölin J. Neuro-
man, Raynham, Massachusetts) has been surgical gram-negative bacillary ventriculitis and
used with reports of success in lowering meningitis: a retrospective study evaluating the
the rate of device-associated infection.13–16 efficacy of intraventricular gentamicin therapy in
31 consecutive cases. Clin Infect Dis 2011;52(11):
Increased antibiotic resistance in isolates
1310–1316 PubMed
3 Antibiotics and the Development of Resistance

from infections that do occur have not been 4. Gruber TJ, Riemer S, Rozzelle CJ. Pediatric neu-
reported, but that possibility is at least a rosurgical practice patterns designed to prevent
theoretical consideration. Data regarding cerebrospinal fluid shunt infection. Pediatr Neu-
rosurg 2009;45(6):456–460 PubMed
similar antibiotic-impregnated external 5. Nau R, Sörgel F, Eiffert H. Penetration of drugs
ventricular drains are less clear in revealing through the blood-cerebrospinal fluid/blood-
a therapeutic benefit.17 Antibiotic-coated brain barrier for treatment of central nervous
sutures (Vicryl Plus; Ethicon, San Angelo, system infections. Clin Microbiol Rev 2010;
23(4):858–883 PubMed
Texas ) are also available, and they may de- 6. Panlilio AL, Culver DH, Gaynes RP, et al. Methicillin-
crease the rate of postoperative infection.18 resistant Staphylococcus aureus in U.S. hospitals,
1975-1991. Infect Control Hosp Epidemiol 1992;
13(10):582–586 PubMed
7. David MZ, Daum RS. Community-associated
■■ Conclusion methicillin-resistant Staphylococcus aureus: epi-
demiology and clinical consequences of an emerg-
ing epidemic. Clin Microbiol Rev 2010;23(3):
The prevention and treatment of infec-
616–687 Review PubMed
tions are an important part of neurosurgi- 8. David MZ, Medvedev S, Hohmann SF, Ewigman B,
cal practice. The optimal use of antibiotics Daum RS. Increasing burden of methicillin-resis-
is important in managing patients and in tant Staphylococcus aureus hospitalizations at US
academic medical centers, 2003-2008. Infect Con-
preventing the development and spread trol Hosp Epidemiol 2012;33(8):782–789 PubMed
of antibiotic-resistant strains. Despite the 9. Firshein W, Kim P. Plasmid replication and parti-
availability of multiple classes of antimi- tion in Escherichia coli: is the cell membrane the
crobial agents with diverse mechanisms key? Mol Microbiol 1997;23(1):1–10 PubMed
10. Sakamoto F, Yamada H, Suzuki C, Sugiura H,
of action, resistance will invariably devel- Tokuda Y. Increased use of alcohol-based hand
op with extensive antibiotic use and can sanitizers and successful eradication of meth-
spread rapidly within the hospital envi- icillin-resistant Staphylococcus aureus from a
neonatal intensive care unit: a multivariate time
ronment. Strict attention to hygiene, with series analysis. Am J Infect Control 2010;38(7):
pre- and postoperative protocols, can re- 529–534 PubMed
duce surgical site infections. Appropriate 11. R ao N, Cannella BA, Crossett LS, Yates AJ Jr, Mc-
treatment when infections do occur lowers Gough RL III, Hamilton CW. Preoperative screen-
ing/decolonization for Staphylococcus aureus to
the risk for recurrence and the spread of prevent orthopedic surgical site infection: pro-
antibiotic-resistant pathogens. spective cohort study with 2-year follow-up. J
Obviously, the neurosurgeon will not Arthroplasty 2011;26(8):1501–1507 PubMed
12. Tacconelli E, Cataldo MA, Albanese A, et al. Vanco-
have the background of the microbiolo-
mycin versus cefazolin prophylaxis for cerebrospinal
gist or pharmacologist when choosing an shunt placement in a hospital with a high prevalence
antibiotic regimen. For that reason, it is of meticillin [sic]-resistant Staphylococcus aureus. J
important for the neurosurgeon to work in Hosp Infect 2008;69(4):337–344 PubMed
13. E ymann R, Chehab S, Strowitzki M, Steudel WI,
concert with the infectious disease special- Kiefer M. Clinical and economic consequences of
ists and the pharmacist when necessary antibiotic-impregnated cerebrospinal fluid shunt
to devise treatment regimens for patients catheters. J Neurosurg Pediatr 2008;1(6):444–
with infections of the CNS. 450 PubMed
33
14. Hayhurst C, Cooke R, Williams D, Kandasamy J, treatment of hydrocephalus. J Neurosurg 2005;
O’Brien DF, Mallucci CL. The impact of antibiotic- 103(2, Suppl)131–136 PubMed
impregnated catheters on shunt infection in chil- 17. S
onabend AM, Korenfeld Y, Crisman C, Badjatia N,
dren and neonates. Childs Nerv Syst 2008;24(5): Mayer SA, Connolly ES Jr. Prevention of ventric-
557–562 PubMed ulostomy-related infections with prophylactic
15. Parker SL, Attenello FJ, Sciubba DM, et al. Com- antibiotics and antibiotic-coated external ven-
parison of shunt infection incidence in high-risk tricular drains: a systematic review. Neurosur-
subgroups receiving antibiotic-impregnated ver- gery 2011;68(4):996–1005 PubMed
sus standard shunts. Childs Nerv Syst 2009;25(1): 18. R
ozzelle CJ, Leonardo J, Li V. Antimicrobial su-
77–83, discussion 85 PubMed ture wound closure for cerebrospinal fluid shunt
16. Sciubba DM, Stuart RM, McGirt MJ, et al. Effect surgery: a prospective, double-blinded, random-
of antibiotic-impregnated shunt catheters in de- ized controlled trial. J Neurosurg Pediatr 2008;
creasing the incidence of shunt infection in the 2(2):111–117 PubMed
34
4
Radiology of Central Nervous
System Infections
Kunal M. Patel and Charles L. Truwit
Imaging plays a central role in the evalua- puncture (LP) are often diagnostic, but neu-
tion of patients with central nervous sys- roimaging is useful to exclude other pathol-
tem (CNS) infections. This is particularly ogies, identify complications, and confirm
true in the neurosurgical patient, in whom the diagnosis in an equivocal setting.
postoperative infections, although rare, CT is usually pursued in the evaluation
can be fatal if not promptly identified and of an acutely comatose patient, but scans
treated.1 Computed tomography (CT) often are often normal in the setting of acute
serves as a key first test in the critically ill bacterial meningitis. Specific signs of men-
patient. Magnetic resonance (MR) imaging ingitis include high density in the sub-
is the modality of choice in the evaluation arachnoid space (similar to hemorrhage)
of suspected CNS infection because of its and effacement of the basilar cisterns.3 On
superior contrast resolution and increased contrast-enhanced CT scans, leptomenin-
sensitivity in detecting meningeal disease, geal enhancement may be seen.3 In addi-
infarction, and posterior fossa pathology. tion to enhancement of the basal cisterns,
Ultrasound (US) has a very limited role and occasionally enhancement of the subarach-
is applicable only in infants with an open noid space between the horizontal folia of
anterior fontanelle; however, it can provide the vermis may lead one to the diagnosis.
valuable information in the right setting CT can also be diagnostic of the complica-
without the ionizing radiation of CT or se- tions of meningitis, such as hydrocephalus,
dation requirement of MR.2 subdural effusions (often seen in infants)
and empyema, infarction (venous or arte-
rial), and abscess formation.3 Before LP, CT
should be performed to identify the cause
■■ D
iffuse Central Nervous of increased intracranial pressure, such as
System Infections diffuse cerebral edema, hydrocephalus,
and cerebral herniation.
Meningitis
MR imaging is far superior to CT in vi-
Acute bacterial meningitis is inflamma- sualizing the abnormalities of bacterial
tion of the meninges caused by bacterial meningitis. The inflammatory exudate of
microorganisms that seed the leptomen- meningitis is often isointense on T1-
inges through hematogenous spread (most weighted images and hyperintense on T2-
common mechanism), local spread from an weighted images compared with adjacent
adjacent nidus of infection, retrograde peri- parenchyma. Unenhanced fluid-attenuated
neural spread, or direct introduction from a inversion recovery (FLAIR) images may be
recent procedure, surgery, or trauma. Cere- abnormal, reflecting altered protein con-
brospinal fluid (CSF) studies from a lumbar tent of the CSF and/or inflammation of the
leptomeninges; however, they are unfor- finding has been reported in 1% of all pa-
tunately often normal. Contrast-enhanced tients after uncomplicated LP procedures.5
FLAIR images are extremely sensitive, Diffusion-weighted imaging (DWI) is ex-
and likely more so than conventional T1- tremely sensitive in the early detection of
weighted post-contrast images, in detect- arterial infarction from meningitis-induced
ing early leptomeningeal inflammation. vasospasm, or subdural empyema (Fig. 4.1),
Contrast-enhanced T1-weighted images and venous infarction secondary to venous
are, however, more specific in detecting as- or dural sinus thrombosis. The area of in-
sociated parenchymal abnormalities and farction develops increased signal on FLAIR
should be retained in MR protocols focused and T2-weighted images 12 to 24 hours
on CNS infection.4 Diffuse pachymeningeal later. In the acute stage, subcortical T2-
enhancement should be interpreted with hyperintensity is the key finding in men-
caution in the post-LP setting because this ingitis-induced cortical venous infarction.
a b c
Fig. 4.1a–c Subdural empyema with venous infarction. Diffusion-weighted images (a) show foci of restricted
diffusion that reflect bacterial meningitis, subdural empyema, and venous infarction related to cortical venous
thrombosis. Axial fluid-attenuated inversion recovery (FLAIR) and contrast-enhanced T1-weighted (b) magnetic
resonance images show multiloculate rim-enhancing subdural fluid collections with extension to interhemi-
spheric fissure. Sagittal T1-weighted images pre- and post-contrast (c) show isointense thrombus, as well as
filling defect within contrast enhancement of the anterior aspect of the superior sagittal sinus. (Images courtesy
of C. Truwit, MD.)
36
MR angiography and MR venography may TB meningitis and its predilection for in-
be considered when arterial or venous infants and children make early diagnosis and
farction is suggested on standard MR pulse treatment imperative. CT has a limited role
sequences. Spread of subdural empyema in detecting TB meningitis.
into the interhemispheric fissure presages The classic MR finding of TB meningi-
a potentially ominous course of the disease. tis (Fig. 4.3) is marked nodular thickening
Viral or “aseptic” meningitis is typically and enhancement of the meninges at the
caused by enteroviruses, and neurologic base of the brain (in distinction to bacterial
deficits are uncommon. Because imag- meningitis, which involves the convexi-
ing studies are usually normal, they are ties to a greater extent). This MR finding is
not part of routine work-up. Occasionally, often difficult to distinguish from the MR
subtle meningeal enhancement can be de- appearance of neurosarcoidosis, carcino-
4 Radiology of Central Nervous System Infections

tected on post-contrast turboFLAIR MR im- matous meningitis, and fungal meningitis.
ages (Fig. 4.2). Associated tuberculomas are often seen
Tuberculous (TB) meningitis is in- and are characterized by single or multiple
creasing in incidence in the United States intraparenchymal masses with variable
because of immigration from areas of en- enhancement. Nodular meningeal thicken-
demicity, acquired immunodeficiency syn- ing in addition to tuberculomas is highly
drome (AIDS), and multidrug resistance. suggestive of CNS TB. Vasculitis and subse-
This infection is typically a secondary in- quent infarction can result from infiltration
fection from a primary pulmonary source of the exudate into the perivascular spaces.
and is the most common form of CNS TB. DWI is invaluable in the early detection of
High rates of morbidity and mortality from this complication.3
a b c
Fig. 4.2a–c Meningitis. Pre-contrast (a) and post-contrast (b) fluid-attenuated inversion recovery (FLAIR) im-
ages show subtle leptomeningeal enhancement (arrows). Subsequent lumbar puncture (LP) revealed aseptic
meningitis. Low-lying cerebellar tonsils were incidentally noted on sagittal T1-weighted image (c), indicating
a Chiari I malformation. Patient did not have an adverse outcome after LP. (Images courtesy of C. Truwit, MD.)
37
Fig. 4.3 Tuberculous meningitis. Diffusion-weighted image (far left) shows mildly restricted diffusion in the left
cerebellopontine angle cistern. Coronal and axial contrast-enhanced T1-weighted images reveal marked nodular
enhancement of the meninges in the basilar cisterns with extension into the left middle cerebellar peduncle. No
discrete tuberculoma was present in this patient, who had recently emigrated from Mexico. (Images courtesy of
C. Truwit, MD.)
Fungal meningitis, like TB meningitis, acute or subacute stage, CT may show low
must be considered in immunocompro- attenuation in the temporal lobes and insu-
mised patients. Numerous organisms are la. Hemorrhage on CT is often a late finding
included under this umbrella term, and and is associated with a poor prognosis.
imaging findings are often nonspecific. In The best imaging clue on MR is in-
cryptococcal meningitis, dilated perivas- creased signal on T2 and FLAIR images in
cular spaces in the deep gray nuclei maybe the limbic system cortical and subcortical
seen on MR. With time, these may evolve areas (particularly medial temporal and in-
into gelatinous pseudocysts. Absence of ferior frontal), with relative sparing of the
enhancement is typical in an AIDS patient. white matter and basal ganglia (Fig. 4.4).
As the patient’s immune status improves Limbic encephalitis can have a similar MR
after initiation of antiretroviral therapy, en- appearance, although a history of primary
hancement may appear in the areas of sig- malignancy (often lung) and subacute on-
nal abnormality. In the angioinvasive form set of symptoms distinguish it from herpes
of zygomycosis (mucormycosis), a stroke encephalitis. Additionally, the constella-
protocol MR with MR angiography may be tion of DWI restriction, cingulate gyrus
useful in evaluating complications such as involvement, and contralateral temporal
arteritis, arterial occlusion with or without lobe involvement is highly suggestive of
infarction, and mycotic aneurysms.6 CT has herpes encephalitis.7 Although bilateral
no established diagnostic role in the spe- signal abnormalities are present in 60% of
cific diagnosis of fungal meningitis. cases in the acute stage, findings are often
more prominent on one side.6 In the set-
ting of hemorrhage, susceptibility-weight-
Encephalitis
ed sequences (such as T2* images) show
Encephalitis is most commonly caused by “blooming” of decreased signal in the areas
viruses. The location of parenchymal abnor- of edematous brain.7 Atrophy is a typical
mality depends on the specific pathogen. finding in the chronic or treated stage of
Herpes encephalitis results from reacti- herpes encephalitis.
vation of the herpes simplex virus in immu- Human immunodeficiency virus (HIV)
nocompetent patients, has a predilection for encephalitis and progressive multifocal
the limbic system, and carries a high mortal- leukoencephalopathy (PML) are discussed
ity rate (50–70%). CT is often normal, espe- in the section of this chapter on immuno-
cially early in the disease course. In the late compromised patients.
38
a b c
Fig. 4.4a–c Herpes encephalitis. Axial diffusion-weighted image, apparent diffusion coefficient (ADC) map (a),
and T2-weighted and fluid-attenuated inversion recovery (FLAIR) (b) images show asymmetric restricted diffu-
sion and altered signal in the medial left temporal lobe and hippocampus. No significant enhancement is seen on
post-contrast axial and coronal T1-weighted images (c). Cerebrospinal fluid analysis confirmed herpes simplex
virus. (Images courtesy of C. Truwit, MD.)
Prion Diseases idence that vCJD is linked to the consump-

tion of meat produced from BSE-infected
Creutzfeldt-Jacob disease (CJD) is a rare, cattle. In contrast to the classic form of CJD,
transmissible spongiform encephalopathy vCJD affects younger patients (mean age,
that is invariably fatal. On MR, symmetric 28 years) and is characterized by promi-
FLAIR hyperintensity in the caudate and pu- nent psychiatric and sensory symptoms.8
tamen with relative sparing of the pre- and Two classic findings are often present on
postcentral gyri is typical in this condition. the MR images of patients with vCJD (Fig.
Thalamic involvement is less common in CJD 4.5). The “pulvinar sign” arises from a rela-
than in variant CJD (vCJD), also known as bo- tive T2 hyperintensity in the pulvinar of
vine spongiform encephalopathy (BSE). the thalamus compared with the anterior
BSE, also known as mad cow disease, is putamen, whereas the “hockey stick sign”
a chronic neurodegenerative disease that is the result of symmetric pulvinar and dor-
affects the CNS of cattle. There is strong ev- somedial thalamic nuclear hyperintensity.
39
a b
c d
Fig. 4.5a–d Variant Creutzfeldt-Jakob disease (vCJD). “Hockey” sign is characterized by symmetric pulvinar and
dorsomedial thalamic restricted diffusion (a,b) and fluid-attenuated inversion recovery (FLAIR) hyperintensity (c).
Note absence of contrast enhancement (d). This is highly suggestive of vCJD. (Images courtesy of C. Truwit, MD.)
■■ F ocal Central Nervous acterized pathologically by tissue

edema, vascular congestion, mi-
System Infections
croscopic hemorrhage, and early
Cerebritis/Abscess necrosis without tissue destruc-
tion.9 MR imaging typically shows
The progression of focal unencapsulated focal but ill-defined and poorly
cerebritis to a discrete abscess has been marginated areas of edema (T1-
established in animal models.6 Four typical hypointense and T2-hyperintense
stages (early and late cerebritis, early and signal abnormality) with mild or
late capsule) are recognized, although it is no contrast enhancement. If mi-
rare to see all four stages clinically. The im- crohemorrhages are present, areas
aging findings of each stage are unique and of “blooming” may be seen on sus-
outlined below. ceptibility-weighted images. CT is
often normal or may show areas of
■■ Early cerebritis. This stage clas- low attenuation and local mass ef-
sically presents 3 to 5 days after fect evidenced by sulcal effacement
the onset of infection and is char- or ventricular compression.
40
■■ Late cerebritis. This stage classically smaller adjacent daughter abscesses
presents 4 to 14 days after onset may also be seen.
and is characterized pathologically ■■ Late capsule. This stage classically
by necrosis with tissue destruction, presents more than a month after the
inflammatory cells, and granulation onset of infection and is character-
tissue.9 Compared with the findings ized pathologically by three capsule
in early cerebritis, the area involved layers: an inner layer of gelatinous
now has a necrotic core on CT and material, a middle layer of collagen,
MR, with an irregular and a thin en- and an outer layer of gliosis.9 On CT
hancing rim and perilesional vaso- and MR, the capsule appears thicker,
genic edema. but the central core is much smaller,
■■ Early capsule. This stage classically with significant regression in adja-

presents 2 to 4 weeks after the on- cent mass effect and edema.
set of infection and is characterized
pathologically by increased colla- In the equivocal setting, DWI is often
gen deposition along the liquefied used to help distinguish between abscess
necrotic margin.9 On CT and MR, a and intracranial neoplasm (Fig. 4.6). The
thick-walled rim is seen, as is nearly central core of most bacterial abscesses
homogeneous enhancement. There demonstrates restricted diffusivity attrib-
is greater vasogenic edema and mass uted to the highly cellular macromolecular
effect from the larger necrotic core; contents within the cavity. MR spectrosco-
a b
c d
Fig. 4.6a–d Brain abscess. Axial diffusion weighted image (a) and apparent diffusion coefficient (ADC) map (b)
reveal restricted diffusion in right frontal mass. TurboFLAIR (c) and contrast-enhanced T1-weighted (d) images
show altered intralesional signal and rim enhancement, all of which are typical of bacterial abscess, as was con-
firmed at surgery. (Images courtesy of C. Truwit, MD.) 41
py can also be helpful because the central Cerebral aspergillosis is a serious infec-
necrotic area of an abscess may show the tious process that has an associated mor-
presence of amino acids, such as succinate tality rate approaching nearly 100% in
and acetate, that are not typically present immunocompromised patients. On MR, as-
in neoplasms.4 pergillosis is characterized by multifocal le-
sions demonstrating a random distribution
that relates to the angioinvasive character
■■ S
pecial Conditions and of the disease.11 Intralesional hemorrhage
Populations (Fig. 4.9) is a key imaging finding in a sig-
nificant percentage of cases. Although of-
Immunocompromised Patients ten evident on T2-weighted and gradient
echo images, susceptibility-weighted im-
HIV encephalitis is the most common CNS aging appears to be the most reliable test
complication in HIV patients and is present for elucidating such hemorrhage.
in 30% of them. Diffuse, centrally located,
nonenhancing periventricular white mat- Developing Nations and Immigrants
ter lesions are present. Detection of these
white matter lesions and cortical atrophy Neurocysticercosis is a CNS infection caused
on MR is highly suggestive of HIV en- by the larval form of the pork tapeworm
cephalitis despite the absence of enhance- Taenia solium. Although this organism is
ment. MR spectroscopy can be helpful in endemic in Latin America, Asia, Africa, and
Eastern Europe, its incidence in the United
the equivocal setting. Interrogation of the

white matter abnormalities often reveals States is increasing as a consequence of im-
decreased N-acetyl-aspartate (NAA) levels migration and travel. This infection is char-
as measured by reduced NAA-to-choline acterized by four pathologic stages.
and NAA-to-creatine ratios; this is attrib-
uted to neuronal loss.6 CT is often normal, ■■ Vesicular. The viable larva forms a
although it may show volume loss and single cyst or a cluster of cysts with-
should be considered only to exclude other in the ventricles or subarachnoid
pathologies in an HIV patient. space of the brain and spinal cord
PML is an opportunistic infection by the (Fig. 4.10). When the larva is in the
papovavirus (JC virus) that is seen almost ex- subarachnoid space (subarachnoid
clusively in immunocompromised patients. neurocysticercosis), viable cysts are
MR findings include patchy, nonenhancing seen. MR typically shows fluid col-
white matter lesions that can mimic the lections with CSF-like intensity that
findings of HIV encephalitis. However, the may or may not reveal the scolex.
abnormalities in PML (Fig. 4.7) are asym- When such lesions are no longer vi-
metric and peripheral, as opposed to the able, grapelike clusters (racemose
bilateral and central abnormalities seen in neurocysticercosis) can be seen.
HIV encephalitis. Foci of subjacent leptomeningeal
Toxoplasmosis results from reactivation enhancement may be seen, but in-
of the soil protozoan Toxoplasma gondii in tracystic scolices are not. Typical
the CNS of an immunocompromised host. locations for racemose neurocysti-
On MR, it is characterized by a T2 centrally cercosis are the sylvian fissures and
hypointense lesion with a nodular enhanc- perimesencephalic and suprasellar
ing rim and significant adjacent edema cisterns.
(Fig. 4.8). The presence of an enhancing ■■ Colloidal. In this stage, the larva be-
nodule within the enhancing rim (target gins to degenerate, with increased
sign) is highly suggestive of toxoplasmo- surrounding edema and inflamma-
sis.10 MR spectroscopy can show a promi- tion. T1 shortening (hyperintensity)
nent lipid peak, but this test is not typically is noted within the scolex on MR
necessary. (Figs. 4.11, 4.12). Heterogeneous sig-
42 nal within the cyst may be present,
a b c
d e f
Fig. 4.7a–f Progessive multifocal leukoencephalopathy (PML). Axial unenhanced computed tomography (a)
and fluid-attenuated inversion recovery (FLAIR) magnetic resonance (b–e) images show typical features of
multifocal, asymmetric, predominantly white matter lesions of the cerebrum and cerebellum. Subtle gray mat-
ter hyperintensity is somewhat atypical. Contrast enhancement (f) is exceptional in PML. (Images courtesy of
C. Truwit, MD.)
most likely reflecting increased tur- MR. Adjacent daughter cysts are
bidity within the cystic cavity. Many common as well.
complications, such as the develop- ■■ Nodular calcified. The lesion is com-
ment of acute hydrocephalus and pletely mineralized in this stage. Ap-
associated infarctions, occur during pearance is best seen on CT: small
this stage (Fig. 4.11). Intraventricu- calcified nodule with little or no sur-
lar cysts may be mobile, potentially rounding edema.
complicating surgical interventions.
In such cases, intraoperative CT or Two other patterns are worth noting.
MR imaging in the surgical position Occasional overwhelming infection is
is recommended. seen, typically described as encephalitic
■■ Granular nodular. This is the heal- neurocysticercosis. Lesions are seen at the
ing stage, in which the cyst begins gray–white junction of the brain and are
to collapse, with regression of sur- typically “too numerous to count.” Finally,
rounding edema and inflammation. patients with neurocysticercosis may have
Intense enhancement of the cyst concomitant TB. In such cases, a calcified,
wall and occasional mass effect due granulomatous reaction of the basal me-
to perilesional edema are seen on ninges may be seen. 43
a
Fig. 4.8a,b Toxoplasmosis. Axial diffusion-weighted, T2, and fluid-attenuated inversion recovery (FLAIR) imag-
es (a) show left caudate head and lentiform nucleus lesions with perilesional vasogenic edema. Note absence of
restricted diffusion. Contrast-enhanced axial and coronal T1-weighted images (b) show moderate rim enhance-
ment. These features are highly suggestive of toxoplasmosis in this patient with human immunodeficiency virus
(HIV) infection and acquired immunodeficiency syndrome (AIDS), although lymphoma could be considered on
the basis of the location and imaging characteristics. (Images courtesy of C. Truwit, MD.)
Pediatric Patients patients. MR offers superior images but

typically requires sedation in infants and
Today’s multidetector CT scanners allow young children. US is a unique modality in
the rapid and efficient imaging of pediatric the evaluation of CNS infection in infants
patients, often without the need for seda- that is not applicable in adults.
tion. However, one must consider the po- As in adults, the most common infec-
tentially harmful long-term side effects of tion in pediatric patients is meningitis.
ionizing radiation that CT delivers to young Although the spectrum of pathogens var-
44
a b
c d
Fig. 4.9a–d Aspergillosis. Axial fluid-attenuated inversion recovery (FLAIR) (a) and T2-weighted (b) images
show abnormal focus of hyperintensity within right posterior temporal lobe. Subtle hypointensity (arrow) is seen
on susceptibility-weighted images (c), reflecting intralesional hemorrhage, typical of aspergilloma. Contrast-
enhanced T1-weighted images (d) show moderate enhancement. (Images courtesy of C. Truwit, MD.)
ies based on the age group, the CT and more common in infants than in older chil-
MR findings are usually similar to those dren and adults. Additionally, TB meningi-
in adult patients. US can be used to iden- tis has a strong predilection for pediatric
tify and follow ventriculomegaly in infants patients, but the imaging findings are simi-
with hydrocephalus resulting from menin- lar for both age groups.
gitis. Echogenic sulci, abnormal parenchy- Because sinusitis is a very common con-
mal echogenicity, meningeal thickening, dition in pediatric patients, intracranial
and hyperemia have also been reported in complications from this ailment deserve
infants with bacterial meningitis.2 In com- special attention. These occur in 3.7 to 11%
plicated meningitis, subdural effusions are of pediatric patients hospitalized for sinus-
45
a b c
Fig. 4.10a–c Racemose neurocysticercosis. Axial computed tomography (a) and fluid-attenuated inversion re-
covery (FLAIR) (b) images show abnormal cerebrospinal fluid–like collections around the brainstem, as well as
hydrocephalus. Note dilated third ventricle (arrow). Coronal contrast-enhanced T1-weighted (c) image shows
focal enhancement (arrow) of the leptomeningeal process along left margin of the midbrain. (Images courtesy
of C. Truwit, MD.)
itis and include meningitis, epidural or sub- initial test of choice in suspected osteo-
dural empyema, cerebritis/abscess, mycotic myelitis and shows the lytic and sclerotic
aneurysm, and infarction.12 The neuroim- changes of the involved bone as well as fo-
aging appearance of these abnormalities is cal osseous defects, calvarial thickening,
typically similar in pediatric and adult pa- and new bone formation. MR is also helpful
tients. Additionally, orbital involvement by in diagnosing osteomyelitis, with accuracy
sinusitis can lead to cavernous sinus throm- rates reported as high as 94%. MR findings
bosis, in which CT and MR imaging show an of osteomyelitis include an intradiploic
engorged ipsilateral superior ophthalmic mass and heterogeneous T1 and T2 signal
vein, prominent extraocular muscles, and of the involved bone. Fat suppression is key
loss of the flow void in the cavernous sinus in evaluating post-contrast images, which
on T2-weighted images.13 typically show strong but inhomogeneous
enhancement of osteomyelitis. Focal ab-
Neurosurgical Patients sence of enhancement in the center of an
avidly enhancing calvaria often suggests
After Craniotomy/Craniectomy necrotic bone or developing abscess, which
may prompt percutaneous or surgical
Surgical site infections lead to increased management.15
morbidity and mortality and to prolonged
hospitalization of the postoperative pa-
Implanted Devices
tient. Although uncomplicated cellulitis at
the surgical site typically does not require Foreign devices implanted into the CNS may
imaging work-up, superficial surgical site also serve as nidi for infection. Because for-
infections may be complicated by osteo- eign material is known to reduce the host’s
myelitis of the bone flap. Deeper extension capacity to resist pathogens, CNS infections
of the infection may result in meningitis, in the setting of implanted devices can be
cerebritis, and abscess.14 CT is often the rapidly fatal.16 Permanent indwelling cath-
46
a b c
Fig. 4.11a-c Colloidal phase, intraventicular neurocysticercosis. Axial unenhanced computed tomography (a)
scans show subtle lesion at the foramen of Monro (arrow), calcification of the left frontal lobe, and hydrocepha-
lus. Axial diffusion-weighted (b) images show abnormal foci of hyperintensity within the splenium, reflecting
ischemia secondary to stretching of the corpus callosum in acute hydrocephalus. Focal hyperintensity of the
scolex in the third ventircular lesion is seen as well. Axial fluid-attenuated inversion recovery (FLAIR) (c) images
show interstitial edema secondary to hydrocephalus and hyperintensity of the neurocysticercosis cyst of the
third ventricle. Hyperintensity of the scolex is seen only in colloidal phase. (Images courtesy of C. Truwit, MD.)
eters such as ventriculoperitoneal shunts CT is usually insensitive for evaluation, and

can serve as a route for the spread of peri- MR is the test of choice. MR shows intra-
toneal space infection (e.g., from colonic ventricular debris or pus (often with fluid–
perforation) into the cranial vault and re- fluid levels), abnormal periventricular and
sultant cerebritis or abscess.17 Ventriculitis subependymal signal intensity, and en-
and other related conditions (ependymitis, hancement of the ventricular lining. FLAIR
intraventricular abscess, ventricular empy- imaging and DWI have been suggested as
ema, or pyocephalus) are uncommon but the most effective MR sequences to detect
can be seen in patients with CSF shunts.18 intraventricular debris.19
47
a b
Fig. 4.12a,b Colloidal phase, intraventicular neurocysticercosis. Sagittal T1-weighted (a) image shows the hy-
perintense scolex within the encysted fourth ventricle. Contrast-enhanced fluid-attenuated inversion recovery
(FLAIR) (b) image reveals the remainder of the lesion. As in the previous case, hyperintensity of the scolex is seen
only in the colloidal phase. (Images courtesy of C. Truwit, MD.)
References
1. cClelland S III, Hall WA. Postoperative central
M 10. P rovenzale J. Toxoplasmosis. Salt Lake City, Utah:
nervous system infection: incidence and associ- STATdx; 2011, 07 15
ated factors in 2111 neurosurgical procedures. 11. Tempkin AD, Sobonya RE, Seeger JF, Oh ES. Cerebral
Clin Infect Dis 2007;45(1):55–59 PubMed aspergillosis: radiologic and pathologic findings.
2. Yikilmaz A, Taylor GA. Sonographic findings in Radiographics 2006;26(4):1239–1242 PubMed
bacterial meningitis in neonates and young in- 12. Zeifer B. Pediatric sinonasal imaging: normal
fants. Pediatr Radiol 2008;38(2):129–137 PubMed anatomy and inflammatory disease. Neuroimag-
3. Olsen WL. Central nervous system infections. In: ing Clin N Am 2000;10(1):137–159, ix PubMed
Brant WE, Helms CA, eds. Fundamentals of Di- 13. Reid JR. Complications of pediatric paranasal sinus-
agnostic Radiology. Philadelphia, PA: Lippincott itis. Pediatr Radiol 2004;34(12):933–942 PubMed
Williams & Wilkins; 2007:156–181 14. H osein IK, Hill DW, Hatfield RH. Controversies in
4. Karagulle-Kendi AT, Truwit C. Neuroimaging of the prevention of neurosurgical infection. J Hosp
central nervous system infections. In: Roos KL, Infect 1999;43(1):5–11 PubMed
Tunkel AR, eds. Handbook of Clinical Neurology: 15. K lisch JS, Spreer J, Bötefür I, et al. Calvarial scle-
Bacterial Infections of the Central Nervous Sys- rosing osteomyelitis. Pediatr Neurosurg 2002;
tem. New York, NY: Elsevier; 2010:239–255 36(3):128–132 PubMed
5. Bakshi R, Mechtler LL, Kamran S, et al. MRI findings 16. Nohra GK, Parks PJ. Reduction of surgical-site in-
in lumbar puncture headache syndrome: abnormal fections in neurosurgery–the advantage of anti-
dural-meningeal and dural venous sinus enhance- septics combined with a sterile surface. Eur Neurol
ment. Clin Imaging 1999;23(2):73–76 PubMed Rev 2009;4(2):116–119
6. Hudgins P. Imaging of intracranial infections. In: 17. Vougioukas VI, Feuerhake F, Hubbe U, Reinacher
Chung EM, Galvin JR, Glassman LM, et al, eds. Ra- P, Van Velthoven V. Latent abscess formation adja-
diologic Pathology. 2011:451–459 cent to a non-functioning intraventricular cathe-
7. Salzman KL. Herpes encephalitis. Salt Lake City, ter. Childs Nerv Syst 2003;19(2):119–121 PubMed
Utah: STATdx; 2011, 07 14 18. C inalli GS, Spennato P, Ruggiero C, et al. Compli-
8. U.S. Department of Agriculture. Bovine spongi- cations following endoscopic intracranial proce-
form encephalopathy–mad cow disease. 2005. dures in children. Childs Nerv Syst 2007;23(6):
http://www.fsis.usda.gov/factsheets/bovine_ 633–644 PubMed
spongiform_encephalopathy_mad_cow_disease/ 19. Fujikawa AT, Tsuchiya K, Honya K, Nitatori T. Com-
index.asp. Accessed July 20, 2011 parison of MRI sequences to detect ventriculitis. AJR
9. Osborne A. Diagnostic Radiology. St. Louis, MO: Am J Roentgenol 2006;187(4):1048–1053 PubMed
Mosby; 1994
48
II
Etiologic Agents
5
Viral Infections of the Central
Nervous System
Joseph B. Domachowske, Manika Suryadevara, and Walter A. Hall
Viral infections of the central nervous sys- reflecting the transmission of arboviruses
tem (CNS) can be divided into aseptic men- during peak mosquito breeding periods.
ingitis, encephalitis, meningoencephalitis, Encephalitis outbreaks due to arboviruses
and infection-associated myelitis and my- can be geographically localized or epi-
elopathies of the spinal cord. Substantial demic, depending on the range of the mos-
overlap exists among the agents that can quito vector(s) and the presence of natural
cause each of these presentations, but animal reservoirs. Worldwide, arboviruses
some viral infections are predictably more are the most important and most com-
severe than others. Aseptic viral meningitis mon causes of severe encephalitis. Since its
is relatively common and usually self-limit- emergence in the late 1800s, Japanese en-
ed, although exceptions are well described. cephalitis virus, a mosquito-borne flavivi-
Encephalitis and meningoencephalitis are rus, has spread throughout Asia to become
less common, but because of parenchymal the most common single agent of epidemic
involvement, the illness is more severe and encephalitis, with up to 50,000 cases and
often life-threatening. Acute transverse 10,000 deaths annually.1
myelitis, manifesting as progressive bilat- Before 1999, La Crosse virus was the
eral sensory, motor, or autonomic dysfunc- most commonly identified arbovirus in the
tion of the spinal cord, has been associated United States. Since 1999, this distinction
with certain viral infections but carries a has gone to West Nile virus (WNV). Soon
broader differential diagnosis that includes after its emergence in 1999 in New York
noninfectious causes. City, WNV spread rapidly across the coun-
try and into Mexico and Canada.2 Between
1999 and 2005, more than 18,000 cases
were documented, including approximate-
■■ Incidence and Demographics ly 700 deaths. Although it is estimated that
of Viral Meningitis and fewer than 1% of WNV infections are severe,
Meningoencephalitis up to 20% of pediatric patients with this in-
fection may present with encephalitis.3
In temperate climates, most cases of asep- During the prevaccination era, mumps
tic meningitis occur during the summer virus was the leading cause of meningoen-
months, reflecting the epidemiology and cephalitis in the United States. Presently,
transmission of enteroviruses, the group mumps infection (caused by a member of
of agents responsible for the vast majority the Paramyxoviridae family) is uncommon
of these cases. Similarly, most episodes of in developed countries where mumps vac-
encephalitis occur during summer and fall, cine coverage rates are high, although a
large U.S. outbreak occurred in 2006, most- Pathogenesis of Viral Meningitis and
ly in college students. During that outbreak, Meningoencephalitis
more than 6,000 cases of mumps were
documented, and among those, at least Most cases of viral meningitis and menin-
13 patients developed encephalitis (none goencephalitis are secondary to a primary
died).4 Historically, encephalitis compli- infection at a different anatomic site. Gen-
cated mumps in 0.75 per 1,000 cases, with erally, after the virus is inhaled, ingested, or
a 14% case-fatality rate.5 Of interest, other inoculated by an arthropod vector, it enters
members of the Paramyxoviridae family, the lymphatic system, where it replicates,
which have emerged globally, are also now then seeds the bloodstream and solid or-
known to cause outbreaks of encephali- gans. In most cases, virus is amplified at
tis. One of these, Nipah virus, is a wide- these sites, causing a secondary viremia. It
scale epizootic viral agent of encephalitis is during this viremic phase that the CNS
identified in 1999 among Malaysian pig becomes infected. Infection of the brain
farmers, who were infected directly from can also occur when viruses infect periph-
animals. Subsequent outbreaks in humans eral or cranial nerves. This retrograde path
have occurred in Singapore, Bangladesh, of infection is important in the pathogen-
and India.6 Human rabies encephalitis is esis of encephalitis caused by rabies virus
very uncommon in developed countries and HSV.
but remains a major problem in resource- As a syndrome, acute transverse myelitis
poor areas of the world, causing more than (ATM) is defined as progressive spinal cord
55,000 deaths worldwide annually, almost dysfunction manifesting with sensory, mo-
always after the victim has been exposed tor, and/or autonomic signs and symptoms.
to a rabid dog.7 The infection is usually This collection of findings can be caused
by a heterogeneous group of infectious
II Etiologic Agents
fatal, but recent advances and aggressive

supportive care have led to a handful of in- and noninfectious disorders. Although the
dividuals who survived infection. broad diagnostic possibilities are beyond
In the United States, where arbovirus the scope of this chapter, it is included here
encephalitis is uncommon, mumps in- because several viral infections can cause
fection is largely controlled through vac- ATM, including herpes group viruses (HSV-
cination programs, and rabies is rare, the 1, HSV-2, EBV, cytomegalovirus [CMV],
herpesviruses remain the most frequently varicella-zoster virus [VZV], enteroviruses,
identified agents of encephalitis. Herpes WNV, human immunodeficiency virus
simplex virus (HSV) encephalitis is the type 1 or 2 [HIV-1 or -2], and human T-
most common cause of acute sporadic fa- lymphotropic virus type 1 or 2 [HTLV-1 or
tal encephalitis in the United States, with -2]). These viruses can also cause menin-
approximately 50% of cases occurring in goencephalitis, but the two conditions are
adults older than 50 years of age and 30% only rarely seen in the same patient at the
of all cases occurring in persons in the first same time. The reasons why some patients
two decades of life.8 Epstein-Barr virus develop ATM and others develop aseptic
(EBV)–associated meningoencephalitis is meningitis or encephalitis from the same
seen in approximately 1% of primary EBV viral etiology are unknown.
infections, usually in older children, ado-
lescents, and young adults. Although this Etiology of Viral Meningitis and
is an uncommon manifestation of EBV Meningoencephalitis
infection, the ubiquitous nature of infec-
Herpesviruses
tious mononucleosis means that most
primary care physicians who care for ado- Most infections caused by the human her-
lescents will encounter this complication pesviruses HSV-1 and -2, EBV, CMV, and
in practice. VZV are self-limited. Unfortunately, how-
52
ever, because of the neurotropism of her- lesions are noticed. Unlike in HSV encepha-
pesviruses, severe infections of the CNS are litis, recovery is almost always complete,
not uncommon, particularly in immuno- even without antiviral therapy, although
compromised patients. acyclovir is recommended to accelerate re-
Herpes simplex virus. HSV accounts for covery. Therefore, HSV meningitis mimics
2 to 5% of encephalitis cases in the United other causes of viral “aseptic” meningitis
States.9 The case-fatality rate associated and carries the same excellent prognosis.
with untreated disease is as high as 70%, HSV encephalitis, on the other hand, is a
and survivors are almost always neuro- highly lethal infection caused by HSV-1 in
logically impaired. Both HSV-1 and HSV-2 more than 90% of cases.10 Infection can be
cause encephalitis, but beyond the newborn either a result of primary HSV infection or
period, most cases are caused by HSV-1. associated with HSV reactivation.11 Unlike
5 Viral Infections of the Central Nervous System

Although HSV is known to replicate in all ar- most of the other, more common causes of
eas of the brain, the infection has a predilec- viral meningoencephalitis, such as entero-
tion for the temporal lobes and the orbital virus and arbovirus infection, HSV disease is
regions of the frontal lobes (Fig. 5.1). HSV not seasonal. From a diagnostic standpoint,
encephalitis must be differentiated from the cerebrospinal (CSF) reveals pleocytosis
HSV meningitis, which is usually caused with a mononuclear cell predominance. The
by HSV-2 and is a complication of primary majority of cases are associated with hem-
genital herpes infection. In HSV meningitis, orrhagic necrosis, so erythrocytes are found
headache, photophobia, and meningismus on CSF examination. As many as 25% of pa-
appear before or shortly after the genital tients will have hypoglycorrhachia with an
elevated CSF protein concentration (mean
levels of approximately 80 mg/dL are seen
in nearly all patients).12 HSV is only rarely
cultured from CSF, so historically, brain bi-
opsy was required to confirm a suspected
diagnosis. With the development of sensi-
tive and specific DNA amplification assays
over the past 15 years, the gold standard for
diagnosis from CSF is now polymerase chain
reaction (PCR).13 Among available neurodi-
agnostic tests, only electroencephalography
has proved somewhat useful. A typical pat-
tern of uni- or bilateral periodic focal spikes
against a background of slow activity, re-
ferred to as paroxysmal lateral epileptiform
discharges (PLEDs), is suggestive of HSV en-
cephalitis. For neuroimaging, magnetic res-
onance (MR) imaging is generally preferred
over computed tomography (CT) during
the initial evaluation because MR imaging
findings are more likely to be abnormal.14
Imaging studies performed later during the
Fig. 5.1 Axial magnetic resonance diffusion-weight-
illness may reveal low-density, contrast-en-
ed imaging showing an area of increased signal in the hancing lesions, particularly in the temporal
right medial temporal lobe that was confirmed to be lobe. Patients with abnormalities like these,
herpes simplex encephalitis by polymerase chain reac- or who have already developed edema and/
tion analysis of the cerebrospinal fluid. or hemorrhage, have a poor prognosis.15
53
Epstein-Barr virus. Acute neurologic dermatologic findings consistent with var-
symptoms complicate between 1 and 5% icella or zoster and who experience CNS
of infectious mononucleosis cases. EBV en- symptoms should be evaluated and treated
cephalitis may present in the absence of for the possibility that the infection has in-
infectious mononucleosis syndrome and volved the CNS.
should be considered as a cause of acute Herpes B virus. Herpes B virus, a patho-
neurologic symptoms, particularly in teen- gen indigenous in macaques, is a nonhuman
agers. Typical CSF findings in cases of EBV herpesvirus that can cause encephalitis
encephalitis include a mild to moderate in humans. Transmission occurs by direct
pleocytosis with mononuclear cells pre- contact with the virus, usually from a mon-
dominating, a slight elevation in CSF pro- key bite. The high prevalence of excretion of
tein, and a normal glucose.16 Serologic proof herpes B virus in the saliva of macaques has
of acute EBV infection is strongly diagnostic, important implications for zoo handlers,
whereas CSF PCR specific for EBV provides a veterinarians, and laboratory researchers.
definitive diagnosis. The prognosis is gen- A vesicular rash may occur at the inocula-
erally favorable, but long-term sequelae are tion site, signaling a herpes-type infection.
well described. EBV-associated cerebellitis The virus has robust neurovirulence, caus-
is a rare occurrence that develops primarily ing rapidly progressive, often fatal hem-
in children.17 Full recovery is expected but orrhagic encephalitis. Guidelines for the
may require several weeks. Cranial nerve prevention of herpes B viral infection em-
palsies, single or in combination, have also phasize proper and expert animal handling
been described. Other manifestations of and assume that all macaques are shedding
cranial nerve involvement with EBV infec- herpes B virus unless proven otherwise. For
tion include optic neuritis, deafness, and cases of macaque bites, post-exposure rec-
II Etiologic Agents
ophthalmoplegia. Some cases of brainstem ommendations are available from the U.S.
encephalitis have also been reported.18 Centers for Disease Control and Prevention
Cytomegalovirus. CNS involvement is (Viral Exanthems and Herpesvirus Branch,
common in infants with symptomatic Division of Viral Diseases [1-404-639-3595
congenital CMV infection, but in postna- or 1-888-232-6348]), including the use of
tal life, CMV meningoencephalitis is quite acyclovir pending culture results.23
rare.19 When it does occur, it may appear
as a complication of CMV mononucleosis,
Enteroviruses and Parechoviruses
as an isolated manifestation of primary
CMV infection, or more likely as a primary Enteroviruses and parechoviruses com-
or recurrent (reactivation) infection in an prise two genera of the family Picornaviri-
immunocompromised host.20 Patients with dae and include more than 100 distinct
solid-organ transplants may develop CMV human viruses. These small RNA viruses
encephalitis as a complication of their im- are responsible for frequent and often sig-
munosuppression, and the recognition that nificant infections, including neurologic ill-
patients with acquired immunodeficiency ness. By far, the most common neurologic
syndrome (AIDS) develop meningoenceph- manifestation of enterovirus infection is
alitis secondary to CMV infection is well aseptic meningitis, which can occur either
established.21 sporadically or in epidemics. In general,
Varicella-zoster virus. CNS complications infection is more common in children, but
of varicella, which may precede or follow during large outbreaks, substantial num-
the chickenpox, include transient cerebel- bers of adults develop aseptic meningitis
lar ataxia, encephalitis, aseptic meningitis, as well. Virtually all patients have fever and
and transverse myelitis.22 Encephalopathy pharyngitis. Adolescents and adults often
as a sequela of Reye syndrome has become experience retrobulbar pain and photo-
a rare complication because of the nearly phobia, whereas young infants present
complete elimination of aspirin use in pe- with fever and irritability. Examination of
diatric patients. Patients who present with the CSF will reveal a pleocytosis. Depend-
54
ing on the timing of the lumbar puncture, fests in one of three ways: systemic febrile
a neutrophil predominance may be ob- illness, hemorrhagic fever, or neuroinvasive
served, but neutrophils rarely account for disease. When neuroinvasion occurs, it may
more than 60% of the total number of cells manifest as aseptic meningitis, encephali-
(as is seen in bacterial meningitis). CSF tis, or acute flaccid paralysis. Following a
protein levels are usually normal or slightly prodrome of fever, the neurologic symp-
elevated, and CSF glucose concentrations, toms begin, sometimes progressing rap-
characteristically normal, may be slightly idly. The severity and long-term outcome
depressed. CSF PCR specific for enterovirus depend on the etiologic agent and several
is available and should be used to confirm host factors, such as age, immune function,
the etiology. The duration of illness is typi- and underlying medical conditions.
cally less than a week, although headaches In the United States, eight specific arbo-

may persist longer. The prognosis for en- viruses that cause encephalitis have been
terovirus aseptic meningitis is excellent. isolated: the eastern equine encephalitis
Enteroviruses can also cause encephalitis, (EEE), western equine encephalitis (WEE),
with echovirus 9 the most frequent cause Venezuelan equine encephalitis (VEE), St.
of this more serious CNS infection. In gen- Louis encephalitis, Powassan, West Nile,
eral, patients with enteroviral encephalitis California encephalitis, and Colorado tick
have a good prognosis, although fatalities fever viruses. EEE occurs throughout the
do occur. Enterovirus 71 tends to infect the eastern part of the United States. Most
brainstem and since the 1980s has caused cases are sporadic and occur in the sum-
severe outbreaks in Asia. During some of mer or fall in Florida and Georgia, although
those epidemics, mortality from entero- swampy areas as far north as New York
virus 71 encephalitis was as high as 30%.24 State also harbor the virus, leading to rare
Enteroviruses may also cause acute flaccid human infections. The mosquito vector
paralysis. The tropism of enteroviruses for thrives only in swampy environments,
the anterior horn cells is well appreciated limiting the spread of the infection much
in paralytic polio, but it should be men- beyond these specific environs. Subclinical
tioned that other enteroviuses, includ- cases of EEE in humans are not common.
ing coxsackievirus A7 and enteroviruses Illness is abrupt, with high fever, headache,
70 and 71, have been linked to polio-like vomiting, seizures, and coma. The case-
outbreaks.25,26 fatality rate is approximately 30%. WEE in
Adenovirus. Adenoviruses only rarely the United States is slightly more common
cause meningitis and meningoencephali- than EEE but geographically shifted west
tis, but when they do, the illness is gener- of the Mississippi River. Colorado leads the
ally more severe than infection caused by United States in the number of reported
enteroviruses.27 cases. The case-fatality rate is approxi-
mately 25%.28 The VEE virus, named such
because it was isolated first in that coun-
Arboviruses
try, causes encephalitis, although infection
Arboviruses are RNA viruses that are trans- is typically less severe, and with support-
mitted to humans through the bite of in- ive care, fatalities are rare. Adults typi-
fected arthropods, such as mosquitoes, cally develop only an influenza-like illness,
ticks, sand flies, and midges. Among the while encephalitis is confined to children.
more than 400 distinct arthopod-borne Outbreaks of VEE with epizootic spread
viruses, at least 150 are known to cause to humans can be extensive. One such
human disease. The medically important outbreak in 1971, extending from Central
viruses that cause human CNS infections America into Texas, killed 200,000 horses
are listed in Table 5.1, along with their ar- and infected thousands of people.29 St. Lou-
thropod vectors and geographic distribu- is encephalitis virus is the most important
tion. Although most arbovirus infections mosquito-borne viral cause of epidemic
are subclinical, symptomatic illness mani- encephalitis in the United States. The last
55
Table 5.1 Medically significant arthropod-borne viruses causing human central nervous system infections
Primary arthropod Endemicity in the

Genus Virus vector(s) United States Global distribution
Flavivirus West Nile Culex mosquitoes Widespread Canada, Europe,

Africa, Asia
Flavivirus St. Louis encephalitis Culex mosquitoes Widespread Entire western

hemisphere
Flavivirus Powassan Ixodes ticks Northeastern and Canada, Russia

north central states
Flavivirus Tickborne encephalitis Ixodes ticks Imported only Europe,

northern Asia
Flavivirus Japanese encephalitis Culex mosquitoes Imported only Asia
Alphavirus Eastern equine Aedes and Culiseta Eastern and Gulf Canada, Central and
mosquitoes states South America
Alphavirus Western equine Culex and Culiseta Central and west- Mexico,
mosquitoes ern states South America
Alphavirus Venezuelan equine Aedes and Culex Imported only Mexico, Central and
mosquitoes South America
Bunyavirus La Crosse (the most Aedes mosquitoes Widespread in Canada

II Etiologic Agents
prevalent and patho- the Midwest and

genic of the California southeastern states
serogroup viruses) (not California)
Coltivirus Colorado tick fever Dermacentor ticks Western states, Canada

especially Colorado
major outbreak occurred in the late 1970s, first detected in the western hemisphere
when thousands of individuals in the Mid- in 1999, it has become the leading cause
west were infected. Cases are concentrated of neuroinvasive arboviral illness in the
in the states of Indiana, Illinois, Ohio, Mis- United States. Among 629 cases reported in
sissippi, Florida, and Texas, but nearly all 2010, half of the patients had encephalitis,
states in the United States have reported 38% had meningitis, and 8% had acute flac-
some disease activity over the past 50 cid paralysis. Mortality was 9%. California
years. On average, approximately 200 cases serogroup viruses that cause encephalitis
are reported in a given year, with the vast in the United States include the endemic La
majority occurring in the elderly popula- Crosse virus and the less commonly appre-
tion; however, only 10 cases were reported ciated California encephalitis and James-
in 2010.30 The overall case-fatality rate is town Canyon viruses. Most infections with
between 5 and 15%. Powassan virus is a La Crosse virus are subclinical. Typically,
rare cause of meningoencephalitis in the when clinical disease is seen, it occurs in
northeastern United States and Canada young children. Infection can progress to
that, unlike the other arthropod-borne in- fulminant encephalitis, but La Crosse virus
fectious agents found in the United States, encephalitis is only rarely fatal. Colorado
is transmitted by ticks, not by mosquitoes. tick fever virus is prevalent in the western
There were no fatalities among the eight mountainous region of the United States,
cases reported in 2010. Since WNV was where the tick vector resides. The typical
56
infection caused by this virus is an influen- common presentation is referred to as furi-
za-like illness with fever, myalgia, and mal- ous rabies. Such patients exhibit extreme
aise. Neuroinvasive disease, although rare, agitation, hyperactivity, fluctuating levels
can occur in young children. Like other vi- of consciousness, hypersalivation, and hy-
ral infections of the CNS, illness can be self- drophobia. Paralytic rabies is not associat-
limited to meningeal irritation or progress ed with hydrophobia; instead, the patient
to encephalitis with coma. Fatalities from develops acute flaccid paralysis, usually
CNS complications are reported.31 beginning in the limb that was bitten. The
cranial nerves are involved, and rather than
expressing agitation and fright, the patient
Rabies Virus
appears expressionless. Paralytic rabies
Rabies is an acute, progressive, and al- can be confused with Guillain-Barré syn-

most uniformly lethal viral infection of the drome. Distinguishing features supporting
CNS that is transmitted to humans from a diagnosis of rabies include fever, intact
animals. Rabies is transmitted from an in- sensation, and urinary incontinence.33 The
fected animal to a human through a bite, majority of patients with rabies will have
scratch, or aerosol. Domestic animals, es- meningismus, with the CSF findings ab-
pecially dogs, account for nearly all rabies normal in a minority. When abnormal, the
cases outside developed countries. In the CSF shows a mild mononuclear cell pleocy-
United States and Canada, the raccoon has tosis. Rabies-specific diagnostic testing in-
replaced the skunk as the most important cludes direct fluorescent antibody staining
potential source of rabies exposure. Hu- of corneal epithelial cells, which are easily
mans who are scratched or bitten by wild obtained from corneal impressions on a
mammals should be evaluated for post- glass slide, and of skin from a punch biopsy
exposure prophylaxis, which, when carried at the nape of the neck. These results are
out properly, prevents rabies very effec- positive early because the virus migrates
tively. Unlike bites from potentially rabid from the brain along the richly innervated
raccoons, skunks, foxes, and other medi- cornea and hair follicles.34 Additional test-
um-size wild mammals, the bite from a bat, ing to consider as the diagnosis is being
especially during sleep, can go completely established or confirmed includes CSF and
unnoticed. For this reason, bat bites can go saliva for rabies PCR and culture. The di-
unrecognized, resulting in a patient who agnosis can be confirmed post mortem by
does not seek post-exposure prophylaxis. identifying the pathognomonic Negri bod-
Perhaps this explains why nearly all nonim- ies (cytoplasmic inclusions) in brain tissue.
ported human cases of rabies in developed The acute neurologic phase of infection
countries are caused by bat strain viruses. continues for approximately a week until the
The incubation period between the patient develops coma. Before death, some
bite and the onset of symptoms is usually patients are described as having acute, brief
20 to 90 days; however, well-documented periods of lucidity fluctuating with periods
cases have occurred 6 years following ex- of agitation and hopelessness. During the
posure.32 Occasionally, symptoms occur comatose period, complications to be ex-
sooner, with the shortest incubation peri- pected include cerebral edema, syndrome
ods being 7 to 10 days, usually when the of inappropriate antidiuretic hormone se-
animal has bitten or scratched the victim’s cretion, diabetes insipidus, and other mani-
face. The earliest symptoms are rather festations of hypothalamic dysfunction.
vague and insidious, but the most striking Cardiac arrhythmias are common. Survival
clinical clue may be pain, itching, burning, after rabies infection has been documented
or tingling at the inoculation site. Together in a very small number of patients, most of
with fever and nausea, this prodrome lasts whom were previously vaccinated.35 The
several days, after which time the more first unvaccinated patient to survive rabies
obvious neurologic symptoms result. Two was a 15-year-old girl, who was treated
broad presentations are seen. The more with coma induction, midazolam, ribavi-
57
rin, ketamine, and amantadine.36 Multiple pairment in immunocompromised patients,
subsequent attempts at using this original without systemic symptoms such as fever.
Milwaukee protocol for rabies treatment PML occurs when the host immune system
have been discouraging, and two children fails to keep JC virus latent, and as it repli-
who survived the initial phase died of com- cates in oligodendroglia, the cerebral white
plications during rehabilitation.37 Details re- matter is destroyed in a multifocal pattern.
garding the outcomes of 43 patients treated Up to 25% of adults patients with AIDS will
with evolving versions of the Milwaukee develop PML.39 Other immunosuppressed
protocol can be found at http://www.mcw patients are also at risk for PML, particularly
.edu/Pediatrics/InfectiousDiseases/Patient those with primary T-cell deficiencies and
Care/Rabies.htm. Detailed metabolomics those who have undergone a solid-organ or
performed serially on CSF obtained from hematopoietic stem cell transplant. The clin-
patients with rabies will likely allow further ical manifestations of PML vary and depend
advances in treatment protocols. All human on the distribution of the patchy, multifo-
rabies cases should be managed with assis- cal areas of injury. Patients develop behav-
tance from the U.S. Centers for Disease Con- ioral changes and cranial nerve dysfunction,
trol and Prevention so that the most current which can lead to blindness, deafness, and/
protocols can be implemented. or lack of coordination.40 The neurologic
symptoms progress over a period of weeks
to months. CSF analysis is usually normal.
Lymphocytic Choriomeningitis Virus
Viral culture and serology are not reliable for
Lymphocytic choriomeningitis virus (LCMV) detecting the JC virus; however, the isolation
is an arenavirus that only rarely causes human of viral DNA from CSF with PCR is the diag-
infection. Illness usually follows exposure to nostic test of choice.41 In adult patients with
II Etiologic Agents
rodents or rodent urine, as mice are the natu- AIDS and neurologic symptoms, the detec-
ral reservoir. Most infections are mild and self- tion of JC virus DNA in CSF has a predictive
limiting, but more serious infections can lead value of 99%, whereas the results from tissue
to meningitis and meningoencephalitis. The obtained by brain biopsy are slightly lower.42
meningeal form of infection begins with an in- Neuroimaging demonstrates patchy demy-
fluenza-like systemic illness, followed by signs elination. Gray matter findings are subtle, if
and symptoms of aseptic meningitis. Progres- present at all. Histologic examination of the
sion to meningoencephalitis leads to a more brain reveals foci of demyelination, enlarged
serious, life-threatening infection. CSF findings oligodendrocytes, and giant astrocytes in a
show a mild to moderate mononuclear cell background of florid neutrophil infiltration.43
pleocytosis with normal or slightly elevated
protein and normal glucose levels. CSF PCR
Human T-Cell Lymphotropic Virus
with LCMV-specific primers may yield the di-
agnosis. Serologic testing requires demonstrat- HTLV-1 is a human retrovirus that is known
ing a fourfold change in antibody titers when to be associated with myelopathy. HTLV-1–
the acute and convalescent sera are compared. associated myelopathy (HAM) is identical
Other CNS manifestations that have been asso- to the clinical syndrome of tropical spastic
ciated with LCMV infection include transverse paraparesis (TSP), which was described in
myelitis, a Guillian-Barré–like syndrome, and tropical areas of the world for many de-
transient or permanent hydrocephalus.38 cades. HAM/TSP is now the accepted acro-
nym to describe this disorder.44 The disease
occurs most commonly in areas of the
JC Virus
world where HTLV-1 is endemic, including
The human JC polyomavirus causes most the Caribbean, southern Japan, equatorial
cases of progressive multifocal leukoenceph- and southern Africa, and Central and South
alopathy (PML). This clinical syndrome is America. In HTLV-1–seropositive persons,
characterized by progressive neurologic im- the incidence of HAM/TSP is estimated to
58
be 3 to 22 per 100,000 HTLV-1–infected mans can transmit spongiform encepha-
people per year.45 The onset of symptoms lopathy to primates. The emergence of
usually occurs in the fourth decade of life. bovine spongiform encephalopathy (BSE)
Clinical features include progressive spas- in the United Kingdom during the mid
tic paraparesis and lower-extremity weak- 1980s received global attention. In the
ness, resulting in a fairly characteristic gait United Kingdom alone, more than 100 hu-
disturbance. Neurologic examination re- man cases of BSE were described, nearly
veals hyperreflexia, clonus, extensor plan- a quarter of a million cattle died, and an
tar reflexes, proximal muscle wasting, and additional 4.5 million were destroyed pre-
spastic paresis with a slow, deliberate, scis- sumptively.49 The natural history of TSE
soring gait. Although disease progression is disease is best described for CJD. Three
variable, slow deterioration results in the models of disease acquisition have been

inability to walk over a 10-year period in described: (1) sporadic, (2) genetic (inher-
almost half of affected individuals. Treat- ited mutations in the PrPc gene), and (3)
ments with systemic and/or intrathecal acquired disease following exposure to the
corticosteroids provide a transient benefit protein. Sporadic CJD is the most common
to some patients, and the combination of form,50 occurring in approximately 1 per
zidovudine with interferon-α has shown million population. Most patients present
some promise in delaying disease progres- between 55 and 65 years of age, although
sion.46 Evidence suggests that the related several older teenagers have also been re-
retrovirus, HTLV-2, may also be associated ported. In the late 1980s, CJD was reported
with neurologic disorders ranging from in several children and young adults who
spastic paraparesis that is indistinguish- had received human growth hormone pre-
able from HAM/TSP to more widespread pared from human cadavers. Since then,
involvement of the CNS.47 more than 100 individuals have been given
a diagnosis of CJD transmitted from growth
hormone preparations predating the use of
Transmissible Spongiform
recombinant hormone.51 Other sources of
Encephalopathies
iatrogenic TSE reported have involved the
The neurodegenerative diseases of this use of dural grafts, corneal transplants,
group are referred to as prion disease. They contaminated stereotactic neurosurgical
are not caused by viruses, but rather by the equipment, and even blood transfusions.
accumulation of insoluble proteinaceous Transmission of BSE from cows to humans
material in the CNS, leading to progressive in the United Kingdom is now the known
cortical dysfunction. The abnormal depo- cause of vCJD, and although the origin of
sition of an isoform of a cellular protein the problem remains somewhat contro-
termed PrPc is thought to result in the char- versial, most investigations have concluded
acteristic neurologic dysfunction. Kuru was that changes in the process used to render
the first among the human transmissible fat from cows and sheep for use in ani-
spongiform encephalopathies (TSEs) to be mal feeds contributed to the problem. The
described. The observation that kuru was finding of BSE in U.S. cows has led to their
seen only in members of the Fore tribe in exportation being banned in several im-
Papua New Guinea, who practiced ritual- portant economic markets.52
istic cannibalism, including the consump- Clinical signs and symptoms of spo-
tion of human brain,48 provided the clue radic CJD during the early stages are sub-
that neurologic tissue was the source. Early tle, usually including motor and sensory
studies of kuru and subsequent studies of disturbances. Headache and dizziness are
the related TSEs known as Creutzfeldt-Ja- common, and as the disease progresses, in-
kob disease (CJD), Gerstmann-Sträussler- tellectual dysfunction with memory loss,
Scheinker disease, fatal familial insomnia, speech disturbance, and anxiety have been
and variant CJD (vCJD) have demonstrated described.53 Neurologic abnormalities may
that brain homogenates from infected hu- include hyperreflexia and spasticity, indicat-
59
ing corticospinal tract dysfunction. Visual ■■ S
pecific Risk Factors for the
disturbances are common. Patients dete-
Development of Central
riorate into a persistent vegetative state and
usually die within a year of symptom onset. Nervous System Viral Infection
The symptoms of vCJD differ in comparison.
Hypogammaglobulinemia. Patients with
Psychiatric and sensory symptoms prevail.
X-linked agammaglobulinemia (Bruton
These patients are generally younger than
disease) and those with hyperimmuno-
those with sporadic CJD and more typically
globulin M syndrome secondary to CD40
describe anxiety, depression, social with-
ligand deficiency are susceptible to re-
drawal, and other nonspecific complaints.
current and severe enterovirus infection,
As the disease progresses, pyramidal tract
including chronic meningoencephalitis.57
dysfunction, rigidity, myoclonus, and cer- Enterovirus-directed therapies are not
ebellar symptoms become apparent. The available, and despite aggressive support-
duration of illness is usually longer than a ive care and high-dose enterovirus-specific
year before the patient succumbs to a com- immunoglobulin therapy, the most com-
plication of the vegetative state. mon cause of death in patients with Bruton
The diagnosis of TSE requires a high de- disease is chronic enterovirus infection.58
gree of clinical suspicion. A detailed history Toll-like receptor signaling defects. Toll-
may reveal risk factors associated with beef like receptors (TLRs) are responsible for a
consumption during the peak of BSE in the myriad of innate immune responses that
United Kingdom, and any potential trans- ultimately lead to recruitment and acti-
mission from an iatrogenic source should vation of antigen-specific B and T cells to
be immediately recognized from the pa- sites of infection. Emerging evidence links
tient’s history. Routine laboratory tests, in- defects in three different TLR signaling pro-
II Etiologic Agents
cluding a CSF examination, are nonspecific. teins with a predisposition to severe HSV
CT findings on neuroimaging are not suf- encephalitis. Mutations in TLR-3, in UNC-
ficiently specific to be helpful. On the other 93B1, a protein essential for signaling via
hand, MR imaging findings of increased T2 TLR-3, -7, -8, and -9, and in TRAF3, a pro-
signals from the striatum and thalamus can tein that functions downstream of UNC-
offer a high index of suspicion for prion dis- 93B1, have been described in children with
ease.54 Definitive diagnosis requires brain recurrent and/or severe HSV encephalitis.59
biopsy. Histopathologic diagnosis should
include immunocytochemical staining
and Western blotting to detect the abnor- ■■ Clinical Presentation
mal PrPc protein.55 Instruments used dur-
ing neurosurgical procedures in patients The patient’s age, viral etiology, and the
with suspected CJD or other TSE require immune competence of the patient all in-
strict decontamination protocols to elimi- fluence the clinical manifestations of viral
nate the potential for transmission of the meningitis. Patients with enteroviral men-
TSE agent during subsequent procedures ingitis typically present with a prodrome
on other individuals. Detailed procedures of fever, malaise, and headache. The classic
have been developed by the World Health findings of meningismus and photophobia
Organization and are endorsed by the U.S. are seen in about half of adult patients with
Centers for Disease Control and Prevention. meningitis, but infants and young children
This 35-page document addresses infec- only infrequently have nuchal rigidity. The
tion control procedures for surgical instru- index of suspicion for meningitis needs to
ments, occupational exposure, handling be high for the very young, the very old,
of human tissue, and handling of bodies and those with compromised immune
post mortem in the hospital and funeral systems because these patients often pres-
home.56 There are no known treatments for ent in an atypical manner. Patients with
patients with any of the TSEs. encephalitis will develop clinical evidence
60
of parenchymal disease. Some viruses, like studies (Table 5.2). Attention to the possi-
rabies virus and herpes B virus, produce bility that a bacterial agent is causing the
encephalitis without significant menin- problem is crucial because early empiric
geal involvement. Most other viral agents antibiotic therapy can be lifesaving. Sei-
of encephalitis cause enough inflammation zures can be secondary to neuroinvasion
of the meninges that the clinical descrip- by the virus, inflammatory vasculitis, and/
tion for these infections is more accurately or electrolyte disturbances. Patients with
referred to as meningoencephalitis. Early cerebral edema may require ICP monitor-
in infection, during the primary viremia, ing, osmotic therapy, and CSF removal in
the patient will exhibit symptoms of leth- attempts to maintain an acceptable intra-
argy, fever, anorexia, and nausea. As the cerebral pressure.62
neurologic infection becomes established, HSV encephalitis can initially show

headache, altered levels of consciousness, low-density areas in the temporal lobes
irritability, and seizures develop. Coma with mass effect on CT. These hypodense
may ensue. Some patients exhibit bizarre areas in the temporal lobes can become
behavior or describe vivid hallucinations. hemorrhagic with progression of the dis-
The Alice in Wonderland syndrome, de- ease. On MR imaging, HSV encephalitis
scribed clearly by some patients with will involve the medial temporal lobe and
EBV-associated meningoencephalitis, rep- will appear as an area of increased signal
resents visual hallucinations of geometric on diffusion-weighted imaging (Fig. 5.1)
shapes changing in size and color.60 Clini- and fluid-attenuated inversion recovery
cal manifestations also predictably reflect (FLAIR) imaging (Fig. 5.2). Within days, the
the anatomic location(s) of the virus rep- disease process can extend from the tem-
lication, which can be focal or diffuse. For
example, HSV-1 encephalitis tends to in-
volve the inferotemporal frontal area of the
cortex, resulting in focal seizures, person-
ality changes, and aphasia, which reflect
involvement of the internal capsule, limbic
system, and Broca area.61 Similarly, early
on, rabies infects the limbic system, pro-
ducing personality changes, while sparing
the cortical regions. The result is a patient
who has periods of complete lucidity, dur-
ing which he or she describes the fear of
impending death.
The clinical approach to a patient with
presumed CNS viral infection depends on
the severity of the illness and the extent
of the neurologic findings. Invasive moni-
toring of the intracranial pressure (ICP) is
helpful in patients with encephalitis who
have signs of increased ICP. Once the car-
diorespiratory status of the patient is sta-
bilized, efforts to establish the etiologic Fig. 5.2 Axial fluid-attenuated inversion recov-
diagnosis should be pursued. Infections for ery (FLAIR) magnetic resonance image showing the
which specific antiviral therapy is available same area of increased signal that was visible on the
should be considered and empiric therapy diffusion-weighted image in the right medial temporal
initiated pending the results of diagnostic lobe, representing herpes simplex encephalitis.
61
Table 5.2 Preventive measures, diagnostic testing, and treatment for viral infections of the central nervous system
Virus Preventive measures Diagnostic testing Treatment
Herpes simplex None CSF PCR Acyclovir

type 1 or 2 virus Mucous membrane cultures and/or PCR
Epstein-Barr None Epstein-Barr virus serology Supportive

virus CSF PCR
Cytomegalovirus None CSF PCR Ganciclovir
Varicella-zoster Active immunization CSF PCR Acyclovir

virus (Varivax; Merck, White- Skin vesicle PCR and/or culture
house Station, NJ)
Passive protection (varicella
immune globulin)
Herpes B virus Monkey bite avoidance Contact CDC Acyclovir

Post-exposure prophylaxis CSF and mucous membrane samples
with acyclovir for PCR and culture
http://www.cdc.gov/herpesbvirus/
index.html
Enterovirus Polio vaccine CSF PCR Supportive

No vaccine for other Stool cultures for virus
enteroviruses
Adenovirus None CSF PCR Supportive

II Etiologic Agents
Respiratory virus culture and/or PCR
Arboviruses Mosquito deterrent Virus-specific PCR testing of CSF Supportive

Vaccine for Japanese Serologic testing of paired sera
encephalitis virus obtained during acute infection and
convalescence
Serum West Nile IgM more sensitive
than CSF PCR during acute infection
with WNV
Rabies virus Post-exposure prophylaxis Corneal impressions for DFA testing Largely sup-
with rabies vaccine and Skin biopsy of nape of neck for DFA portive; see
rabies immune globulin and/or PCR text for current
Pre-exposure for high-risk Saliva for PCR and/or culture protocols
occupations Serology
CSF PCR
Brain biopsy for PCR and detection of
pathognomonic Negri bodies
Lymphocytic Rodent avoidance CSF PCR Supportive

choriomeningitis Paired serology
virus
JC virus None CSF PCR (blood PCR not helpful) Supportive
HTLV-1 None Serology Zidovu-

dine with
interferon-α
Prion disease None Brain biopsy to detect abnormal Supportive

protein by immunocytochemistry
and/or Western blotting
62 Abbreviations: CDC, Centers for Disease Control and Prevention; CSF, cerebrospinal fluid; DFA, direct fluorescent antibody;
HTLV-1, human T-lymphotropic virus type 1; IgM, immunoglobulin M; PCR, polymerase chain reaction; WNV, West Nile virus
poral lobe into the insula and subfrontal prophylaxis is the mainstay of treatment
regions (Figs. 5.3 and 5.4). Because of the for most cases of potential rabies exposure
wide variety of diseases that can mimic through the use of both rabies immune
HSV encephalitis, a brain biopsy should be globulin and rabies vaccine.
considered for those patients in whom PCR Routine childhood immunizations
of the CSF is negative for HSV DNA. It has have led to nearly complete elimination
been estimated that 45% of those who have of mumps and measles as causes of me-
a brain biopsy for a focal encephalopathic ningoencephalitis in regions of the world
process will have HSV encephalitis.10 where vaccine programs are robust. Vac-
cination has also dramatically changed
the global challenge of poliomyelitis, with
■■ Treatment and Prevention elimination of the infection in the western

hemisphere63 and dramatic reductions in
Prevention of infection by viruses that polio infection in the rest of the world. Such
cause CNS infection is best accomplished progress offers hope for global eradication
through avoidance of exposure. Arbovirus of polio in the coming decade. To date, the
infections, for example, are best prevented only enterovirus infection that is controlled
through the use of chemical and physical through immunization programs is polio,
mosquito deterrents and for some viruses which explains why enteroviral meningi-
through public health–initiated mosquito tis remains so common. Vaccines have also
abatement programs. Specific treatment is been developed for some arbovirus infec-
available for only a limited number of caus- tions (Table 5.2). Vaccine programs for the
ative agents (Table 5.2), and post-exposure prevention of Japanese encephalitis virus
Fig. 5.3 With continued progression of herpes sim- Fig. 5.4 Axial fluid-attenuated inversion recovery
plex encephalitis, the insula is now involved, as dem- (FLAIR) magnetic resonance image showing exten-
onstrated by the fluid-attenuated inversion recovery sion of herpes simplex encephalitis into the subfrontal
(FLAIR) signal in that location on this axial magnetic region from the site of origin in the medial temporal
resonance image. lobe.
63
infection have reduced the disease burden ■■ C
omplications, Sequelae, and
in Asia, but problems still exist in China, Prognosis
with more than 10,000 cases of Japanese
encephalitis virus infection annually.64 To Encephalitis, unlike meningitis, has a high
date, safe and effective HSV vaccines have morbidity and mortality rate. Case-fatal-
remained elusive. ity rates differ based on the cause of the
The treatment of CNS viral infections infection and the condition of the host.
starts with identifying those agents for Among the arbovirus infections, St. Louis
which specific antiviral therapy is available. encephalitis carries a mortality rate of ap-
Empiric therapy with acyclovir should be proximately 2% in children and 20% in the
used in all cases of suspected HSV meningo- elderly,66 while other viruses, such as WEE
encephalitis until that virus is excluded or virus and EEE virus, produce higher mor-
the responsible, alternative virus is found. bidity and mortality in children than in
Complications should be anticipated for adults. Rabies is almost always fatal, but
every patient with viral meningitis or me- progress in understanding the metabolic
ningoencephalitis, and supportive therapy disturbances that occur during infection
for those complications should be initiated have provided some insights. Seizures are
early and aggressively. Dehydration and common during acute viral encephalitis.
fever are easily treated. Patients may also Among the sporadic viral encephalitides,
require treatment of seizures, syndrome of HSV encephalitis is most frequently asso-
inappropriate antidiuretic hormone secre- ciated with epilepsy, which may often be
tion, hydrocephalus, and raised ICP. severe. Seizures may be the presenting fea-
Traditionally, neurosurgical interven- ture in 50% of patients with HSV encephali-
tion in patients suspected to have viral en- tis because of the involvement of the highly
II Etiologic Agents
cephalitis due primarily to HSV has usually epileptogenic frontotemporal cortex. The
included either brain biopsy for diagnosis occurrence of seizures in HSV encephalitis
or the placement of an ICP monitor in the is associated with a poor prognosis. Among
face of suspected elevated ICP. However, the arboviral encephalitides, Japanese en-
there is a role for emergency surgical de- cephalitis is most commonly associated
compression in the presence of uncal her- with seizures, especially in children. Other
niation.65 Surgical decompression can be viruses, like measles virus, varicella virus,
necessary more that 10 days after the on- mumps virus, influenza virus, and entero-
set of the clinical course because the esti- viruses, may cause seizures, depending on
mated peak in ICP does not occur until the the area of brain involved.67 Details on the
12th day of the illness.65 risk for epilepsy following recovery from
Infections for which specific antiviral each specific type of viral encephalitis have
therapy is available include those caused not been published. Prognosis once a di-
by HSV-1 and -2, VZV, CMV, and herpes B agnosis of viral encephalitis is confirmed
virus. With the use of acyclovir, the mor- depends on the infecting agent and on the
bidity and mortality from neonatal HSV extent of parenchymal involvement. The
encephalitis has declined from 70 to 40%. risk for death from rabies, PML, and EEE is
Varicella immune globulin and acyclovir extremely high, whereas mortality from
have reduced the complications of prima- EBV and La Crosse virus encephalitis is un-
ry VZV infection in immunocompromised common. The TSEs are uniformly fatal.
patients, and although randomized trials Polio. The most feared complication of in-
have not evaluated the efficacy of acyclo- fection with poliovirus is paralytic disease.
vir for VZV encephalitis, the medication The onset of paralysis may be abrupt, with
is routinely used to treat this complica- complete loss of motor strength in one or
tion. Ganciclovir and foscarnet are antivi- more extremities. Bladder paralysis occurs
ral medications that are used to treat CMV in approximately 20% of patients. Bulbos-
encephalitis, although their efficacy in this pinal poliomyelitis is an unusual complica-
context is unknown. tion. Involvement of cranial nerves VII and
64
X can manifest as facial, pharyngeal, and vances in molecular viral diagnostic testing
vocal cord paralysis. Hypoxia and hyper- have facilitated the identification of infecting
capnia requiring mechanical ventilation agents and enabled further understanding
can occur secondary to pharyngeal paraly- of the pathogenesis and spectrum of dis-
sis, cervical cord involvement with respi- ease. Treatment is largely supportive; how-
ratory muscle weakness or paralysis, or ever, some viral infections of the CNS require
rarely parenchymal involvement with true the prompt initiation of antiviral agents, and
polio encephalitis. The initial presentation other infections may benefit from emerging
of paralytic polio infection can mimic Guil- therapies whose benefit is yet to be proven.
lain-Barré syndrome.68
Subacute sclerosing panencephalitis (SSPE). References
SSPE is an uncommon, slowly progressive 1. Tsai TF. New initiatives for the control of Japanese

disease of the CNS that is almost universally encephalitis by vaccination: minutes of a WHO/
fatal. The most consistent risk factor for the CVI meeting, Bangkok, Thailand, 13-15 October
1998. Vaccine 2000;18(Suppl 2):1–25 PubMed
development of SSPE is natural measles in-
2. Centers for Disease Control and Prevention. West
fection before the age of 2 years.69 The de- Nile virus activity—United States Jan 1-Dec 2005.
crease in cases of SSPE after the introduction Morb Mortal Wkly Rep 2005;54:1253–1256
of measles vaccination programs helped to 3. Hayes EB, O’Leary DR. West Nile virus infec-
tion: a pediatric perspective. Pediatrics 2004;
establish the measles virus as the causative 113(5):1375–1381 PubMed
agent. Available data suggest that the patho- 4. Dayan GH, Quinlisk MP, Parker AA, et al. Recent
genesis of SSPE as a persistent infection of the resurgence of mumps in the United States. N Engl
CNS with measles virus is secondary to an J Med 2008;358(15):1580–1589 PubMed
5. Centers for Disease Control. Encephalitis surveil-
abnormal host response to the initial measles lance: annual summary 1977. Issued December
infection and the generation of viral mutants 1979
during the acute infection that can establish 6. Bellini WJ, Harcourt BH, Bowden N, Rota PA.
Nipah virus: an emergent paramyxovirus caus-
persistence. The mean age at presentation ing severe encephalitis in humans. J Neurovirol
with symptoms was around 6 years before 2005;11(5):481–487 PubMed
vaccination programs. The child presents 7. World Health Organization. WHO expert consul-
with psycho-intellectual disturbances (emo- tation on rabies. WHO Technical Report Series
2005;931:1–121
tional lability, a decrease in school perfor- 8. Whitley RJ, Kimberlin DW. Herpes simplex en-
mance, and hyperactivity). Within 6 months, cephalitis: children and adolescents. Semin Pedi-
a variety of motor or convulsive findings atr Infect Dis 2005;16(1):17–23 PubMed
9. Rantala H, Uhari M. Occurrence of childhood en-
become manifest, sometimes with severe
cephalitis: a population-based study. Pediatr In-
myoclonic jerks. Spasticity may evolve dur- fect Dis J 1989;8(7):426–430 PubMed
ing this stage.70 The illness progresses to fre- 10. W hitley RJ. Herpes simplex encephalitis: ado-
quent and severe myoclonic jerks, rigidity, lescents and adults. Antiviral Res 2006;71(2-3):
141–148 PubMed
and decerebrate or decorticate posturing. 11. Nahmias AJ, Whitley RJ, Visintine AN, Takei Y,
Hypothalamic dysfunction is expected, with Alford CA Jr. Herpes simplex virus encephalitis:
spells of diaphoresis, hyerpyrexia, and flush- laboratory evaluations and their diagnostic signif-
ing. Death is usually secondary to a compli- icance. J Infect Dis 1982;145(6):829–836 PubMed
12. Koskiniemi M, Vaheri A, Taskinen E. Cerebrospinal
cation of living in a vegetative state. fluid alterations in herpes simplex virus encepha-
litis. Rev Infect Dis 1984;6(5):608–618 PubMed
13. L akeman FD, Whitley RJ; National Institute of Al-
lergy and Infectious Diseases Collaborative Anti-
■■ Conclusion viral Study Group. Diagnosis of herpes simplex
encephalitis: application of polymerase chain re-
CNS viral infections have a broad spectrum action to cerebrospinal fluid from brain-biopsied
patients and correlation with disease. J Infect Dis
of severity, depending on the nature of the
1995;171(4):857–863 PubMed
infecting virus and on host factors such as 14. S chroth G, Gawehn J, Thron A, Vallbracht A, Voigt
age and immune status. A clinical diagnosis K. Early diagnosis of herpes simplex encephalitis
of CNS viral infection requires a detailed his- by MRI. Neurology 1987;37(2):179–183 PubMed
15. M orawetz RB, Whitley RJ, Murphy DM. Experi-
tory and physical examination to uncover ence with brain biopsy for suspected herpes en-
clues to the most likely etiologic agent. Ad- 65
cephalitis: a review of forty consecutive cases. ogy of human paralytic rabies. J Neurovirol 2005;
Neurosurgery 1983;12(6):654–657 PubMed 11(1):93–100 PubMed
16. Domachowske JB, Cunningham CK, Cummings 34. K och FJ, Sagartz JW, Davidson DE, Lawhaswasdi
DL, Crosley CJ, Hannan WP, Weiner LB. Acute K. Diagnosis of human rabies by the cornea test.
manifestations and neurologic sequelae of Ep- Am J Clin Pathol 1975;63(4):509–515 PubMed
stein-Barr virus encephalitis in children. Pediatr 35. P orras C, Barboza JJ, Fuenzalida E, Adaros HL,
Infect Dis J 1996;15(10):871–875 PubMed Oviedo AM, Furst J. Recovery from rabies in man.
17. Connelly KP, DeWitt LD. Neurologic complica- Ann Intern Med 1976;85(1):44–48 PubMed
tions of infectious mononucleosis. Pediatr Neurol 36. Willoughby RE Jr, Tieves KS, Hoffman GM, et al.
1994;10(3):181–184 PubMed Survival after treatment of rabies with induc-
18. North K, de Silva L, Procopis P. Brain-stem en- tion of coma. N Engl J Med 2005;352(24):2508–
cephalitis caused by Epstein-Barr virus. J Child 2514 PubMed
Neurol 1993;8(1):40–42 PubMed 37. Jackson AC. Therapy of human rabies. Adv Virus
19. Bale JF Jr. Human cytomegalovirus infection and Res 2011;79:365–375 PubMed
disorders of the nervous system. Arch Neurol 38. B arton LL, Hyndman NJ. Lymphocytic choriomen-
1984;41(3):310–320 PubMed ingitis virus: reemerging central nervous system
20. Rafailidis PI, Mourtzoukou EG, Varbobitis IC, pathogen. Pediatrics 2000;105(3):E35 PubMed
Falagas ME. Severe cytomegalovirus infection in 39. B erger JR, Levy RM. The neurologic complications
apparently immunocompetent patients: a sys- of human immunodeficiency virus infection.
tematic review. Virol J 2008;5:47–51 PubMed Med Clin North Am 1993;77(1):1–23 PubMed
21. Nielsen SL, Petito CK, Urmacher CD, Posner JB. 40. B erger JR, Pall L, Lanska D, Whiteman M. Pro-
Subacute encephalitis in acquired immune defi- gressive multifocal leukoencephalopathy in pa-
ciency syndrome: a postmortem study. Am J Clin tients with HIV infection. J Neurovirol 1998;4(1):
Pathol 1984;82(6):678–682 PubMed 59–68 PubMed
22. Johnson R, Milbourn PE. Central nervous system 41. T elenti A, Aksamit AJJ Jr, Proper J, Smith TF. De-
manifestations of chickenpox. Can Med Assoc J tection of JC virus DNA by polymerase chain
1970;102(8):831–834 PubMed reaction in patients with progressive multifocal
23. Cohen JI, Davenport DS, Stewart JA, Deitchman S, leukoencephalopathy. J Infect Dis 1990;162(4):
Hilliard JK, Chapman LE; B Virus Working Group. 858–861 PubMed
Recommendations for prevention of and therapy for 42. d e Luca A, Cingolani A, Linzalone A, et al. Im-
exposure to B virus (cercopithecine herpesvirus 1). proved detection of JC virus DNA in cerebrospinal
II Etiologic Agents
Clin Infect Dis 2002;35(10):1191–1203 PubMed fluid for diagnosis of AIDS-related progressive
24. Wang SM, Liu CC, Tseng HW, et al. Clinical spec- multifocal leukoencephalopathy. J Clin Microbiol
trum of enterovirus 71 infection in children in 1996;34(5):1343–1346 PubMed
southern Taiwan, with an emphasis on neuro- 43. Vazeux R, Cumont M, Girard PM, et al. Severe en-
logical complications. Clin Infect Dis 1999;29(1): cephalitis resulting from coinfections with HIV and
184–190 PubMed JC virus. Neurology 1990;40(6):944–948 PubMed
25. Hayward JC, Gillespie SM, Kaplan KM, et al. Out- 44. W orld Health Organization. Report of the Scien-
break of poliomyelitis-like paralysis associated tific Group on HTLV-1 and Associated Diseases,
with enterovirus 71. Pediatr Infect Dis J 1989; Kogoshima, Japan, December 1988: Viral Diseas-
8(9):611–616 PubMed es. Wkly Epidemiol Rec 1989;49:382–383
26. Grist NR, Bell EJ. Enteroviral etiology of the 45. M aloney EM, Cleghorn FR, Morgan OS, et al. Inci-
paralytic poliomyelitis syndrome. Arch Environ dence of HTLV-I-associated myelopathy/tropical
Health 1970;21(3):382–387 PubMed spastic paraparesis (HAM/TSP) in Jamaica and
27. Kelsey DS. Adenovirus meningoencephalitis. Pe- Trinidad. J Acquir Immune Defic Syndr Hum Ret-
diatrics 1978;61(2):291–293 PubMed rovirol 1998;17(2):167–170 PubMed
28. Reeves WC. The discovery decade of arbovirus re- 46. Gout O, Gessain A, Iba-Zizen M, et al. The effect of
search in western North America, 1940-1949. Am J zidovudine on chronic myelopathy associated with
Trop Med Hyg 1987;37(3, Suppl):94S–100S PubMed HTLV-1. J Neurol 1991;238(2):108–109 PubMed
29. Weaver SC, Salas R, Rico-Hesse R, et al; VEE Study 47. Murphy EL, Engstrom JW, Miller K, Sacher RA,

Group. Re-emergence of epidemic Venezuelan Busch MP, Hollingsworth CG; REDS Investigators.
equine encephalomyelitis in South America. Lan- HTLV-II associated myelopathy in 43-year-old
cet 1996;348(9025):436–440 PubMed woman. Lancet 1993;341(8847):757–758 PubMed
30. Centers for Disease Control and Prevention. West 48. H
adlow WJ. Scrapie and kuru. Lancet 1959;2:
Nile virus disease and other arboviral diseases— 289–290
United States 2010. Morb Mortal Wkly Rep 2011; 49. B
rown P, Will RG, Bradley R, Asher DM, Detwiler
60:1009–1013 L. Bovine spongiform encephalopathy and variant
31. Spruance SL, Bailey A. Colorado tick fever. A re- Creutzfeldt-Jakob disease: background, evolution,
view of 115 laboratory confirmed cases. Arch In- and current concerns. Emerg Infect Dis 2001;
tern Med 1973;131:288–293 7(1):6–16 PubMed
32. Warrell DA. The clinical picture of rabies in man. 50. B
rown P, Cathala F, Raubertas RF, Gajdusek DC,
Trans R Soc Trop Med Hyg 1976;70(3):188– Castaigne P. The epidemiology of Creutzfeldt-
195 PubMed Jakob disease: conclusion of a 15-year investiga-
33. Hemachudha T, Wacharapluesadee S, Mitrabhakdi tion in France and review of the world literature.
E, Wilde H, Morimoto K, Lewis RA. Pathophysiol- Neurology 1987;37(6):895–904 PubMed
66
51. Brown P, Preece M, Brandel JP, et al. Iatrogenic 60. C inbis M, Aysun S. Alice in Wonderland syndrome as
Creutzfeldt-Jakob disease at the millennium. an initial manifestation of Epstein-Barr virus infec-
Neurology 2000;55(8):1075–1081 PubMed tion. Br J Ophthalmol 1992;76(5):316–318 PubMed
52. Richt JA, Kunkle RA, Alt D, et al. Identification and 61. C assady KA, Whitley RJ. Pathogenesis and patho-
characterization of two bovine spongiform en- physiology of viral central nervous system infec-
cephalopathy cases diagnosed in the United States. tions. In: Scheld WM, Whitley RJ, Durack DT, eds.
J Vet Diagn Invest 2007;19(2):142–154 PubMed Infections of the Central Nervous System. 2nd ed.
53. Brown P, Cathala F, Castaigne P, Gajdusek DC. Philadelphia, PA: Lippincott–Raven Publishers;
Creutzfeldt-Jakob disease: clinical analysis of a con- 1997:7–22
secutive series of 230 neuropathologically verified 62. B ale JF Jr. Viral encephalitis. Med Clin North Am
cases. Ann Neurol 1986;20(5):597–602 PubMed 1993;77(1):25–42 PubMed
54. Finkenstaedt M, Szudra A, Zerr I, et al. MR im- 63. C enters for Disease Control and Prevention. Ex-
aging of Creutzfeldt-Jakob disease. Radiology panded program on immunization: certification
1996;199(3):793–798 PubMed of poliomyelitis eradication—the Americas. Morb
55. Budka H, Aguzzi A, Brown P, et al. Neuropathologi- Mortal Wkly Rep 1994;43:720–722
cal diagnostic criteria for Creutzfeldt-Jakob disease 64. R osen L. The natural history of Japanese encepha-

(CJD) and other human spongiform encephalitis virus. Annu Rev Microbiol 1986;40:395–414
lopathies (prion diseases). Brain Pathol 1995; 65. Yan HJ. Herpes simplex encephalitis: the role
5(4):459–466 PubMed of surgical decompression. Surg Neurol 2002;
56. WHO infection control guidelines for transmis- 57(1):20–24 PubMed
sible spongiform encephalopathies. Report of a 66. H o DD, Hirsch MS. Acute viral encephalitis. Med
WHO consultation, Geneva, Switzerland, 23–26 Clin North Am 1985;69(2):415–429 PubMed
March, 1999 67. Misra UK, Tan CT, Kalita J. Viral encephalitis and ep-
57. Cunningham CK, Bonville CA, Ochs HD, et al. ilepsy. Epilepsia 2008;49(Suppl 6):13–18 PubMed
Enteroviral meningoencephalitis as a complica- 68. Y ohannan MD, Ramia S, al Frayh ARS. Acute para-
tion of X-linked hyper IgM syndrome. J Pediatr lytic poliomyelitis presenting as Guillain-Barré
1999;134(5):584–588 PubMed syndrome. J Infect 1991;22(2):129–133 PubMed
58. Winkelstein JA, Marino MC, Lederman HM, et 69. Detels R, Brody JA, McNew J, Edgar AH. Further ep-
al. X-linked agammaglobulinemia: report on a idemiological studies of subacute sclerosing pan-
United States registry of 201 patients. Medicine encephalitis. Lancet 1973;2(7819):11–14 PubMed
(Baltimore) 2006;85(4):193–202 PubMed 70. R isk WS, Haddad FS. The variable natural history
59. Dropulic LK, Cohen JI. Severe viral infections of subacute sclerosing panencephalitis: a study
and primary immunodeficiencies. Clin Infect Dis of 118 cases from the Middle East. Arch Neurol
2011;53(9):897–909 PubMed 1979;36(10):610–614 PubMed
67
6
Fungal Infections of the
Walter A. Hall and Peter D. Kim
Fungal infections that affect the central C. gattii is endemic in Australia and can be
nervous system (CNS) usually cause chron- isolated from eucalyptus trees.
ic meningitis or brain abscess. Most clini- The incidence of fungal brain abscess has
cally significant fungal infections involve increased because of the administration
patients with altered immune function, al- of corticosteroids, immunosuppressive
though immunocompetent hosts can also agents, and broad-spectrum antibiotics.3
become infected. Fungal infections are of- Many cases of fungal brain abscess remain
ten overlooked as a cause of CNS disease, undiagnosed until autopsy. Fungal brain
and delays in diagnosis from 2 months to abscess is due to Aspergillus species in 18
11 years have been reported.1 No consis- to 28% of patients.4 Aspergillus meningitis
tent guidelines regarding the neurosurgical rarely occurs because of the large size of
management of these infections have been the hyphae (Fig. 6.1) at body temperature,
established because of their infrequent which are unable to infiltrate the microvas-
occurrence. This chapter focuses on the culature of the meninges.4
medical and surgical management of these Some fungal infections are associated
uncommon entities. with specific geographic locations. Coc-
cidioidomycosis is found in the southwest-
ern United States, particularly in Arizona
■■ Incidence and Demographics and California’s San Joaquin Valley. Histo-
plasmosis is found throughout the United
The incidence of fungal infections involv-
ing the CNS has increased in recent years
because of the growing number of patients
with compromised immune systems. This
is in large part due to the increased use
of immunosuppressive agents, which are
commonly given to treat inflammatory
conditions, malignancies, and acquired im-
munodeficiency syndrome (AIDS). They
are also given to transplant recipients.
The most common causes of fungal
meningitis are Cryptococcus neoformans
and Cryptococcus gattii. C. neoformans is
found throughout the world in soil con- Fig. 6.1 Gomori methenamine silver stain showing
taminated by bird feces and in fruits, veg- the large fugal hyphae of Aspergillus species (magni-
etables, and dairy products.2 In contrast, fication x 64).
States except for the Rocky Mountain states diabetes mellitus, chronic granulomatous
and the Pacific Northwest and is endemic disease, or thermal injuries. Also at risk are
in the valleys of the Ohio, Mississippi, St. patients who have a central venous cath-
Lawrence, and Rio Grande Rivers. Histo- eter or who have received chemotherapy,
plasma capsulatum is the most common antimicrobial therapy, corticosteroids, or
fungus causing pulmonary infections.4 immunosuppressive therapy following a
Blastomyces dermatitidis is found through- bone marrow or solid-organ transplant.3,4
out the southern and central United States, The fungal species C. neoformans forms
and young men are most often infected be- the only known encapsulated yeast that
cause of greater environmental exposure is pathogenic to humans.4–6 The polysac-
to the fungus.5 charide capsule is responsible for the viru-
lence of the organism because it inhibits
6 Fungal Infections of the Central Nervous System

phagocytosis and antigen presentation.4,5
■■ Etiology and Pathogenesis This organism reproduces by budding. The
primary site of entry of C. neoformans into
Candida species are normal flora for the the host is through the lungs by the inhala-
mucosa of the genital and gastrointestinal tion of infected soil or dust. Hematogenous
tracts.5 Common clinical manifestations dissemination of the organism to the CNS
of infection due to Candida species are occurs most often in immunocompromised
thrush and vulvovaginitis. Of all the Can- patients or in the face of overwhelming ex-
dida species identified, only 10 have been posure in immunocompetent individuals.
found to cause human disease, with Can- CNS involvement is in the form of menin-
dida albicans, Candida krusei, and Torulop- goencephalitis (Fig. 6.2) in 90% of patients
sis glabrata the most frequently identified with disseminated disease.4 Defective T-
agents.4 These thin-walled oval organisms lymphocyte function is the primary pre-
reproduce in the yeast form, and true hy-
phae are usually found only in active infec-
tion.4 Systemic candidiasis results when
organisms enter the bloodstream after
penetrating the mucosal surface following
surgery, with intravenous drug use, or in
the presence of an indwelling intravenous
catheter. Nearly half of patients with sys-
temic disease develop CNS involvement,
although the incidence reaches nearly 80%
in the presence of endocarditis.4 CNS infec-
tion with Candida species is nosocomial in
95% of patients, but infection after neuro-
surgery is rare.1
The most common etiologic agents for
fungal brain abscess at autopsy are Candida
species, which can cause microabscesses,
macroabscesses, noncaseating granulomas,
and glial nodules located at the gray–white
junction.3 Other infectious CNS manifes-
tations associated with Candida species
are mycotic aneurysms, vasculitis leading
to vessel thrombosis and infarction, and
intraventricular fungal balls.1 Patients at
risk for Candida species brain abscess are Fig. 6.2 Coronal T1-weighted contrast-enhanced
premature infants with a low birth weight magnetic resonance image demonstrating cryptococ-
and those who have cancer, neutropenia, cal meningoencephalitis of the cerebellum.
69
disposing factor for cryptococcosis and is taminated dust and is usually limited to
associated with AIDS, hematologic malig- the lungs. Acute disease manifests as fever,
nancies, collagen vascular diseases, immu- hypoxia, and pulmonary infiltrates, with
nosuppression following organ transplant, severity dependent on the size of the in-
and corticosteroid use.4,5 Early in the AIDS fectious inoculum. The normal immune re-
epidemic, 6 to 8% of patients developed sponse in an immunocompetent individual
cryptococcal meningoencephalitis.7 Be- is the formation of caseating granulomas,
cause of the presence of global immune which calcify and restrict disease to the
dysfunction, AIDS patients do not devel- lungs. Disseminated disease is uncommon
op a significant inflammatory response, in immunocompetent individuals and is
necrotizing granulomas do not form, and usually associated with immunosuppres-
lymphocyte-mediated activation of macro- sion following organ transplant or AIDS.
phages is impaired.8 The widespread CNS Systemic disease is characterized by ane-
involvement that is seen in AIDS patients mia, splenomegaly, leukopenia, cachexia,
with cryptococcal meningoencephalitis is and fever.5 Involvement of the CNS occurs
due to the inability of the microglia and in 10 to 20% of disseminated cases through
astrocytes within the brain to contain the hematogenous spread.4 The two primary
infection. C. neoformans can replicate and modes of CNS involvement are (1) basilar
survive within human microglia.1 leptomeningitis with multiple cranial neu-
Coccidioides immitis forms nonseptate ropathies, hydrocephalus, and seizures and
hyphae that become airborne and are in- (2) intraparenchymal mass lesions ranging
haled as arthroconidia in infected dust. Dis- from multiple miliary granulomas to large
ease due to C. immitis is usually restricted histoplasmomas, with symptomatology re-
to the lungs and causes flulike symptoms, ferable to their location in the brain. Spinal
II Etiologic Agents
although dissemination can occur through histoplasmomas can cause myelopathy but
lymphatic and hematogenous routes, lead- the infection is usually clinically silent.1
ing to caseous granulomas. One-third to B. dermatitidis is found in soil and de-
one-half of patients with disseminated caying wood in its hyphal form; however,
coccidioidomycosis develop CNS involve- in infected tissue it forms spherical yeasts.4
ment, usually 4 to 12 weeks after the pul- Conidia are initially inhaled in the lungs
monary infection.4 Basilar leptomeningitis in most cases of blastomycosis, although
with cerebrospinal fluid (CSF) obstruction the disease can be contracted via exposed
leading to hydrocephalus is the most com- areas of the skin that will develop subcu-
mon form of CNS involvement in coccidioi- taneous nodules and can ulcerate.5 The
domycosis. Other CNS infectious processes genitourinary tract and the skull can be-
due to C. immitis are encephalitis, multiple come infected with B. dermatitidis. The
miliary granulomas, and solitary brain CNS is infected in fewer than 5% of cases
abscess. Vasculitis of the small and medi- of disseminated disease by hematog-
um-size arteries due to C. immitis can re- enous spread or through direct extension
sult in cerebral ischemia and infarction of of cranial or vertebral osteomyelitis.4,6 In-
the deep white matter and basal ganglia tracerebral blastomycomas and chronic
or the formation of mycotic aneurysms. meningitis are the most common forms of
The spinal meninges can also be involved, CNS involvement.
resulting in paraplegia from occlusion of Fungal infection can involve the brain
the anterior spinal artery or necrotizing in 10 to 50% of patients with invasive as-
meningomyelitis.4 pergillosis. The primary site of infection is
H. capsulatum is found in soil contami- usually the lungs.4 In immunocompetent
nated by bird feces. This fungus is pres- individuals, a local immediate hypersen-
ent in the mycelial form in the wild but sitivity reaction in the lungs leads to the
converts to a budding yeast form at hu- formation of granulomas that contain the
man body temperature.4 Infection with H. organism.4 Dissemination to the brain is
capsulatum is contracted by inhaling con- either through the bloodstream or by di-
70
rect extension from the paranasal sinuses.1
Risk factors for Aspergillus species infec-
tion of the brain include neutropenia from
a hematologic malignancy, hepatic disease,
Cushing syndrome, AIDS, diabetes melli-
tus, chronic granulomatous disease, intra-
venous drug use, organ transplant, bone
marrow and stem cell transplant, chronic
corticosteroid use, malnutrition, chronic
pulmonary disease, and prior cranioto-
my.3,4,9 Of the 350 different Aspergillus spe-
cies, Aspergillus fumigatus and Aspergillus

flavus, acting as opportunistic pathogens, Fig. 6.3 Gomori methenamine silver stain revealing
Aspergillus fumigatus hyphae in the wall of a fungal my-
cause most infections in humans.4
cotic aneurysm (magnification unknown). This fungus
Aspergillus species have a predilection has a propensity to invade blood vessel walls, leading
for invading blood vessel walls (Fig. 6.3) in to thrombosis, occlusion, and infarction.
medium-size to large arteries, where they
destroy the internal elastic layer, causing
thrombosis, vascular occlusion, and sub-
sequent cerebral infarction in the distribu-
tion of the artery. The resulting necrotic
brain parenchyma serves as an ideal envi-
ronment for fungal proliferation, leading to
the formation of a brain abscess that can
reach several centimeters in diameter. In
addition to causing brain abscesses, Asper-
gillus species can cause mycotic aneurysms
(Fig. 6.4) to form through their effect on
the wall of the blood vessel, which is usu-
ally an anterior or middle cerebral artery.
Rupture of these intracranial aneurysms
can result in intracerebral hematomas (Fig.
6.5) or subarachnoid hemorrhage.4 Direct
extension of Aspergillus species from the
paranasal sinuses (Fig. 6.6) or orbits can
lead to a solitary frontal lobe brain abscess
Fig. 6.4 This posterior circulation cerebral angio-
adjacent to the site of intracranial entry. gram shows a large Aspergillus species fungal mycotic
Organisms of the genera Rhizopus, Ab- aneurysm arising from the trunk of the basilar artery.
sidia, and Mucor (family Mucoraceae) cause
mucormycosis. The Mucor mold is found
worldwide in rotting organic matter. The
nonseptate hyphae branch at right angles. Mucormycosis is an aggressive fun-
The fungal spores become airborne as in- gal infection that can involve the brain
fected dust and can be cultured from the through hematogenous spread or after
nose and throat of healthy individuals. This head trauma, but it typically results from
fungal infection enters the skin after trauma direct extension of an infection involving
or a burn.4 Like Aspergillus species, this fun- the face or nasopharynx (Fig. 6.7). Predis-
gus frequently involves medium-size and posing conditions for mucormycosis are
large blood vessels, resulting in thrombosis the following: diabetes mellitus (70% of
and widespread necrosis of the mucosa and patients, usually with ketoacidosis); aci-
skull base, which creates an ideal environ- demia from sepsis, dehydration, diarrhea,
ment for growth and dissemination. or renal failure; intravenous drug abuse;
71
Fig. 6.5 Computed tomographic scan of the brain
showing a large intracerebral hematoma in a patient
known to have a systemic Aspergillus species infection Fig. 6.6 Axial T1-weighted contrast-enhanced magnet-
that was presumed to be due to the rupture of a fungal ic resonance image of the brain demonstrates an Asper-
mycotic aneurysm.
II Etiologic Agents
gillus species infection in the left maxillary sinus. A frontal

brain abscess eventually developed through direct exten-
sion in this patient with a bone marrow transplant.
gus from contaminated needles. Normal

hosts account for fewer than 5% of cases
of CNS mucormycosis. Rhizopus arrhizus is
one of the most common of the Mucor spe-
cies causing brain abscess and belongs to
the order Mucorales. R. arrhizus and Rhizo-
pus oryzae are responsible for 95% of infec-
tions in humans.5
Scedosporium apiospermum is the asex-
ual form of Pseudallescheria boydii. It can
enter the CNS by direct extension from
trauma or infected sinuses, by hematog-
Fig. 6.7 Intraoperative photograph shows a bifron- enous dissemination from a pulmonary fo-
tal Mucor species brain abscess that invaded the brain cus, or by an intravenous catheter. Normal
from the paranasal sinuses by direct extension. The pa- hosts or immunocompromised individuals
tient had poorly controlled juvenile diabetes mellitus. with neutropenia or cellular immunode-
ficiency can develop CNS infection from
Scedosporium species.11 Brain abscess is the
hematologic malignancy; renal transplant; most common CNS manifestation of Scedo-
and the use of deferoxamine for iron over- sporium species infection, although men-
load.3,10 Intravenous drug abusers are at ingitis and ventriculitis can occur.
risk for cerebral mucormycosis via direct Other fungi that have been reported
inoculation of the blood stream with fun- to cause brain abscess include Cladophia-
72
lophora bantiana, Bipolaris hawaiiensis, longed periods required indwelling intra-
Bipolaris spicifera, Exophiala (Wangiella) venous catheters through which the fungus
dermatitidis, Ochroconis gallopava (Dacty- has access to the bloodstream. Congenital
laria constricta var. gallopava), Ramichlo- malformations of the intestine or urinary
ridium mackenziei, Curvularia pallescens, tract that have required surgical repair can
and Acrophialophora fusispora.3 also act as a portal for Candida entry into
the blood. Hydrocephalus can already be
present when Candida meningitis is di-
agnosed, and CSF shunts that become in-
■■ Presentation fected with Candida are at risk for partial
or complete obstruction, usually requiring
Clinical Features
multiple surgical revisions. One retrospec-

Chronic meningitis usually presents with tive review of pediatric shunt infections
the onset of indolent symptoms of at least found that 17% were Candida-related.15 The
4 weeks’ duration.12 It is necessary to dis- etiology of shunt infection due to Candida
tinguish this entity from recurrent aseptic species was either contamination at the
meningitis and persistent encephalitis. De- time of placement or hematogenous dis-
termining the date of the onset of symptoms semination from a remote source.4
and the timing of symptom development Patients with cryptococcal meningoen-
can be important in confirming the diagno- cephalitis often have an insidious clinical
sis of chronic meningitis. Symptoms associ- presentation, leading to a delay in diagnosis.
ated with chronic meningitis can wax and Underlying disease entities that predispose
wane for weeks to months. Early symptoms to cryptococcal meningitis are corticoste-
may include headache, nausea, decreased roid therapy and AIDS. Symptoms associat-
memory and comprehension, decreased ed with raised intracranial pressure due to
vision, double vision, vomiting, confusion, hydrocephalus, such as headaches, nausea,
unsteady gait, and cranial nerve palsies. A and vomiting, may be the only complaints.4
dementia-like picture can be present in the Psychosis and confusion can be presenting
face of hydrocephalus. With worsening ce- symptoms. Visual symptoms such as de-
rebral edema, papilledema and brainstem creased acuity due to papilledema or rapid
compression with upper motor neuron visual deterioration from neuritis of the op-
signs, increased deep tendon reflexes, and tic nerves or chiasm can occur.1
Cheyne-Stokes respiration can develop. Exposure to Coccidioides species is nec-
A normal neurologic examination and essary for infection, which usually begins
an absence of fever may be seen in pa- as a pulmonary process 2 to 4 weeks after
tients with chronic meningitis. Skin lesions exposure. In immunosuppressed patients,
may require a biopsy for the diagnosis of coccidioidal meningitis presents as a sys-
cryptococcosis, coccidioidomycosis, blas- temic illness with fever, malaise, headache,
tomycosis, or sporotrichosis. Skin lesions cranial nerve findings, and skin lesions.
will precede meningeal symptoms in 10% Histoplasma meningitis can occur in im-
of patients with cryptococcosis.13 Lymph- munosuppressed patients who have AIDS,
adenopathy may be present with histo- are organ transplant recipients, or are
plasmosis. Retinal lesions are sometimes taking corticosteroids or tumor necrosis
present in patients with cryptococcosis or factor-α inhibitors.16
coccidioidomycosis. Fungal abscesses can develop in any
Candida meningitis is rare except in pa- part of the brain, and the clinical presenta-
tients who are immunosuppressed, have tion depends on their location. Headache,
had prior neurosurgery, or have a hema- seizures, altered level of consciousness,
tologic malignancy, and in very low birth encephalopathy, focal neurologic defi-
weight newborns.14 Newborns with Can- cits, meningismus, personality changes,
dida meningitis have typically had long and aphasia can be seen with fungal brain
intensive care unit stays and have for pro- abscess. Nearly a third of bone marrow
73
transplant recipients who have Candida
species brain abscesses may have no clini-
cal findings.3 Blastomycomas will be either
asymptomatic or cause symptoms related
to their location in the brain. Chronic men-
ingitis can also result from B. dermatitidis
infection, which presents similarly to tu-
berculous meningitis and often results in
the development of hydrocephalus. The
presentation of cranial and spinal epidural
blastomycoccal abscesses can be due to
the underlying mass effect on the brain
or spinal cord. Histoplasmomas can occur
throughout the brain and cause symptoms
that reflect their location.
Aspergillus species brain abscess can
present with a strokelike syndrome due ei-
ther to vascular occlusion or to hemorrhage Fig. 6.8 Axial T1-weighted contrast-enhanced mag-
netic resonance image of the brain shows the bifrontal
that is referable to the area of the brain that
Mucor species brain abscess that is visible in the intra-
is involved. Severely immunocompromised operative photograph of Fig. 6.7.
patients can present with relatively non-
specific clinical findings, such as altered
consciousness or seizure activity, whereas
immunocompetent individuals may have immunocompromised patients or in im-
II Etiologic Agents
headache or focal neurologic findings.3 munocompetent patients 15 to 30 days af-

Rhinocerebral mucormycosis will usually ter near-drowning.3
present with findings referable to the eyes
or the sinuses, such as headache, facial pain
Microbiology
or edema, nasal congestion, and epistax-
is.10 Fever and abnormalities involving cra- The CSF will show signs of inflammation
nial nerves II through VII are common, and in chronic meningitis.12 To recover fungi
blindness, diplopia, chemosis, proptosis, from the CSF, it is important to obtain an
and ophthalmoplegia can also result from adequate CSF volume of 3 to 5 mL for cul-
invasion of the orbit, cavernous sinus, and ture.13 In the presence of Candida species
ophthalmic artery. Invasion of the carotid meningitis, microscopic analysis of the
artery with thrombosis and hemiparesis CSF will often reveal the organism, which
is possible because of the potential for this can be cultured, and a polymorphonuclear
mold to invade blood vessels. As the infec- pleocytosis.6 In patients with AIDS, CSF
tion spreads to adjacent structures, necrot- cultures for cryptococcal meningitis can
ic lesions can involve the nares, turbinates, become positive within a few days; howev-
hard palate, sphenoid sinus, sella turcica, er, a longer incubation period is necessary
and cribriform plate. Findings in advanced in immunocompetent patients. In immu-
mucormycosis include blindness, diabetes nocompromised individuals, C. neoformans
insipidus, carotid artery occlusion, cavern- can occasionally be isolated from the blood
ous sinus thrombosis, and bifrontal brain or urine.4,18 An India ink preparation can
abscess (Fig. 6.8).4,17 Hematogenous dis- occasionally demonstrate the organism in
semination of Mucor species to the basal the CSF.5 CNS blastomycosis can be diffi-
ganglia in intravenous drug abusers can cult to diagnose in the absence of chronic
lead to brain abscess that presents with pulmonary blastomycosis; however, with
fever, headache, and a neurologic defi- chronic meningeal involvement, the organ-
cit such as a hemiparesis.3 Scedosporium isms can occasionally be identified micro-
apiospermum can cause brain abscess in scopically or by culture.
74
■■ Diagnosis Imaging
Candida species can cause multiple brain
Laboratory
abscesses in patients with disseminated
When the CSF is sampled, the opening disease. These microabscesses are often less
pressure is usually elevated and the glu- than 1 mm in size, can be difficult to detect on
cose concentration is below 40 mg/dL in imaging, and may or may not enhance with
fungal meningitis.13 A Candida-specific contrast.4 Foci of high signal on T2-weight-
mannan antigen titer and a polymerase ed and proton density–weighted magnetic
chain reaction (PCR)–based test for the de- resonance (MR) imaging can be indicative of
tection of C. albicans in the CSF are avail- Candida species infection in the CNS.1 In the
able.4 There is no reliable serologic test for early stages of CNS cryptococcal infection,

CNS candidiasis.1,6 the perivascular subarachnoid spaces can
Other tests that may identify fungal appear dilated with hypodense lesions on
infection in the CSF are cryptococcal anti- computed tomographic (CT) scans because
gen, complement fixation antibody to Coc- of the formation of gelatinous pseudocysts.4
cidioides species, Histoplasma antigen, and These lesions are usually hyperintense on
Aspergillus galactomannan.13 Rapid latex T2-weighted imaging and hypointense on
agglutination and enzyme immunoassays T1-weighted imaging, and they do not en-
can detect the cryptococcal capsular poly- hance with contrast administration on either
saccharide antigen in the blood and CSF.1 CT scans or MR images. In contrast to these
Serum serology can be useful in diagnos- pseudocysts, cryptococcomas enhance after
ing coccidioidomycosis. Serum antigen contrast administration on CT scans or MR
tests for Cryptococcus species and serum images and display varying degrees of vaso-
or urine antigen tests for Histoplasma can genic edema. A contrast-enhanced MR image
be useful for establishing a diagnosis, par- can demonstrate hydrocephalus or intracra-
ticularly in the presence of disseminated nial mass lesions such as granulomas due to
disease. Eosinophilia in the blood or CSF cryptococcosis or histoplasmosis. Increased
can be a sign of coccidioidal meningitis, al- intracranial pressure may be inferred if there
though the single best test for diagnosis is is flattening of the cerebral gyri over the con-
a positive complement fixation test of CSF. vexities of the hemispheres.
This test is sensitive and specific, unlike an Blastomycosis can result in chronic men-
immunodiffusion test, which is less spe- ingitis or brain abscess formation. Blasto-
cific, or enzyme-linked immunosorbent mycomas enhance homogeneously or in a
assays (ELISAs), which lack both sensitivity ringlike manner on CT scans and MR images
and specificity.13 with contrast administration when sur-
In a patient with a ring-enhancing in- rounded by vasogenic edema.4 Histoplas-
tracranial mass consistent with a brain momas can be ring-enhancing on contrast
abscess surrounded by cerebral edema, a CT and MR imaging and demonstrate vary-
lumbar puncture is usually contraindicated ing degrees of surrounding cerebral edema.
because of the risk for cerebral herniation. Aspergillus species brain abscesses typi-
Furthermore, when CSF is obtained from cally are ring-enhancing lesions with sur-
a patient with an Aspergillus species brain rounding edema on contrast CT or MR
abscess, the findings are usually nonspe- imaging (Fig. 6.9). However, there may be
cific and nondiagnostic. There is no reliable little (Fig. 6.10) or no enhancement on MR
serologic test for aspergillosis, but diag- imaging in immunosuppressed patients
nostic tests such as PCR and Western blot with CNS aspergillosis.19 An MR image of
analysis are under development.1 Diagnos- the paranasal sinuses can demonstrate an
ing cerebral mucormycosis can be difficult infection due to mold. Radiographic find-
because the CSF findings are nonspecific ings of rhinocerebral mucormycosis can
and the serologic testing is unreliable.4 include sinus opacification, bone erosion,
75
Fig. 6.9 Aspergillus species brain abscess of the left Fig. 6.10 Weak, patchy enhancement can be seen
temporal lobe as seen on a contrast-enhanced T1- in the anterior and posterior right frontal regions on
weighted axial magnetic resonance image in a patient a contrast-enhanced T1-weighted axial magnetic reso-
II Etiologic Agents
with a history of chronic pulmonary disease. nance image in this recipient of a hepatic transplant.
frontal lobe infiltration, and cavernous

sinus involvement. CT may demonstrate
bony destruction of the facial bones and
skull base with air–fluid levels in the pa-
ranasal sinuses.4 The infected mucosa of
the paranasal sinuses and nasopharynx
demonstrates a low signal intensity on T1-
weighted, T2-weighted, and proton densi-
ty–weighted MR images.1 This appearance
on MR imaging is thought to be due to the
paramagnetic metals associated with the
fungal infection and can help distinguish
infection from benign mucosal swelling.1
Mucor species brain abscess can demon-
strate ring enhancement on CT and MR
imaging and hemorrhage within the in-
fectious collection. Contrast enhancement
of the infected mucosa (Fig. 6.11), orbital
structures, and dura mater can be seen
on MR imaging. Absence of contrast en-
Fig. 6.11 T1-weighted axial magnetic resonance
hancement in mucormycosis carries a poor
image of the brain in a patient with diabetes mellitus
prognosis because it suggests that the host shows contrast enhancement of infected mucosa in
defenses can no longer encapsulate the or- the sphenoid sinus that is due to Mucor species.
76
ganism.3 Vascular imaging is useful for de- looked. The propensity of Mucor species
tecting thrombosis of the internal carotid to invade blood vessels, leading to cerebral
arteries or cavernous sinus. infarction, can result in the decreased de-
livery of antifungal agents to the location
of the infection. Radical surgical removal
■■ Histology of necrotic, infected tissue is often the
only effective way to reduce the number
On histologic examination of tissue speci- of invading fungal elements and to prevent
mens, Aspergillus species have septate them from spreading locally within the in-
hyphae with acute-angle, dichotomous tracranial compartment. Once intracranial
branching at regular intervals. Irregular extension is established, surgical resection
hyphae with right-angle branching and of the abscess capsule is required for pro-

absence of septa are seen with mucormy- longed survival.16 As with other CNS fungal
cosis. The diagnosis of mucormycosis will infections, surgical drainage is the corner-
often require the histopathologic examina- stone of effective treatment for Scedospo-
tion of biopsied or debrided necrotic tissue rium brain abscess.20
to show these findings. Scedosporium ap- C. albicans shunt infections should be
iospermum, Scedosporium prolificans, and treated with removal of the entire shunt
Fusarium hyphae cannot be distinguished system and placement of an external ven-
histologically from Aspergillus species.20 tricular drain, in combination with the ad-
ministration of intravenous amphotericin B.
The Candida-specific mannan antigen lev-
■■ Treatment els can be followed during treatment with
amphotericin B and should be normal for
Surgical Approaches 1 week before replacement of a previously
Candida-infected shunt.22 CNS cryptococco-
The initial evaluation of the patient sus- mas rarely need to be surgically removed,
pected to have a brain abscess should in- but months of antimicrobial treatment may
clude contrast-enhanced CT or MR imaging be required before they decrease in size
of the brain. If one or more ring-enhancing on CT scans or MR images.23 In the pres-
brain lesions measuring greater than 2.5 cm ence of symptomatic hydrocephalus and
in diameter are found, the patient should the absence of an intracranial mass lesion,
be taken to the operating room for either external CSF drainage via repeat lumbar
surgical excision or aspiration. The surgi- punctures or placement of an external
cal specimens should be sent for pathologic ventricular or lumbar drain is indicated.
examination and culture and sensitivity. If Persistent hydrocephalus may require
the lesions are smaller than 2.5 cm or in the permanent CSF diversion by placement of
cerebritis stage, the largest lesion should a shunt, which can be performed success-
be biopsied or aspirated for diagnosis and fully in an ongoing infection as long as the
identification of the organism.3 An open or foreign body is placed after the initiation
stereotactic biopsy is often the only way to of antifungal therapy for cryptococcosis.23
confirm the presence of a histoplasmoma Permanent CSF diversion can be necessary
or blastomycoma. Excisional surgery or to treat hydrocephalus resulting from basi-
drainage is a key factor for success in treat- lar meningitis due to H. capsulatum.
ing CNS aspergillosis.21 Repeat surgical
debridement of the Aspergillus species ab-
scess or a hemorrhagic infarct may be nec- Medical Approaches
essary, even at multiple intracranial sites, in Antimicrobial Agents
the face of progressive disease despite ap-
propriate antimicrobial therapy. Once the offending organism has been iden-
The role of surgery in the treatment of tified, antimicrobial agents can be adjusted
cerebral mucormycosis cannot be over- for optimal treatment. In immunocompro-
77
mised patients, the mortality rate remains blastomycosis should be treated with am-
high, even with appropriate treatment. photericin B because azole agents poorly
However, these infections can be effectively cross the blood–brain barrier. However, in
treated if the white blood cell counts return the absence of CNS involvement, systemic
to normal or the immunosuppressive drug blastomycosis has been successfully treated
dose is lowered or discontinued. with itraconazole or ketoconazole.1
Amphotericin B is the primary treat- Previously, the treatment for Aspergillus
ment for cryptococcal meningitis at a dose brain abscess was amphotericin B deoxy-
of 0.7 mg/kg per day for 6 weeks. Liposo- cholate (0.8 to 1.25 mg/kg per day up to 1.5
mal amphotericin B and the lipid com- mg/kg per day depending on the therapeu-
plex at doses of 3 to 6 mg/kg per day have tic response); however, few instances of
provided successful treatment for cryp- survival have been reported.25 Eradication
tococcal meningitis with reduced renal of CNS Aspergillus has required more than a
toxicity.23 Because of the development of total of 3 g of amphotericin B. Even though
resistance, flucytosine cannot be used as a high-dose itraconazole has resulted in the
single agent against Cryptococcus species successful eradication of CNS Aspergil-
and is generally combined with amphoter- lus in a few case reports, because of lim-
icin B at a dose of 100 mg/kg per day.23 Flu- ited experience and unreliable absorption,
conazole and itraconazole have been used this agent and posaconazole are better for
successfully to treat cryptococcal meningi- salvage therapy than as a primary treat-
tis. Maintenance therapy with fluconazole ment.3 Amphotericin B has been placed in
appears to be more effective than itracon- an Aspergillus abscess cavity even though
azole, but the latter agent should be used it is neurotoxic to the brain.26 Voriconazole
when the former is not tolerated.1 Criteria is now considered the drug of choice for
II Etiologic Agents
for the discontinuation of antifungal ther- treating CNS aspergillosis.21 The response
apy are not well defined but have included rate to voriconazole in patients with inva-
the resolution of symptoms, two negative sive aspergillosis in studies has been ap-
CSF cultures, and a normal CSF glucose proximately 35%.21 The total duration of
level.23 The return of new clinical signs or treatment with antifungal agents remains
symptoms and repeat positive CSF cultures unclear, although patients receiving cu-
are the two clearest signs of relapse neces- mulative doses of intravenous amphoteri-
sitating a change in treatment.23 cin B of 9.5 g and 11.45 g followed by 3 to
For candidal meningitis and brain ab- 6 months of high-dose oral itraconazole
scess, the treatment of choice is amphoteri- have responded to treatment.1
cin B deoxycholate, liposomal amphotericin Mucormycosis should be treated with
B, or amphotericin B lipid complex with amphotericin B deoxycholate, liposomal
5-flucytosine. Fluconazole is a second-line amphotericin B, or amphotericin B lipid
agent that has not been formally evaluated. complex; aggressive surgical debride-
The dosages for C. albicans brain abscess are ment; and the correction of any underlying
0.6 to 1.0 mg/kg every 24 hours for ampho- metabolic abnormalities.3,27 Amphotericin
tericin B deoxycholate and 5 mg/kg every B has been applied topically in the orbital
24 hours for amphotericin B lipid complex. cavities to treat mucormycosis, but this
The dose of 5-flucytosine is 100 mg/kg practice is of unknown benefit.27 In addi-
orally every 6 hours, and the dose of fluco- tion to the intravenous administration of
nazole is 400 to 800 mg ever 24 hours. Li- amphotericin B for mucormycosis, some
posomal amphotericin B (3 to 5 mg/kg per have advocated its administration into the
day for 4 to 6 weeks) remains the treatment CSF and the abscess cavity.28 Posaconazole
of choice for CNS histoplasmosis, followed (800 mg/day given every 6 or 12 hours)
by itraconazole (200 mg two to three times is considered an effective salvage therapy
daily for at least 1 year).24 Azole agents for patients with mucormycosis who have
are not recommended for patients with either not responded to or become unable
life-threatening CNS histoplasmosis. CNS to tolerate amphotericin B, provided that
78
they can tolerate oral administration.29 lethargy or obtundation, a high CSF cryp-
Hyperbaric oxygen has been used as an tococcal antigen titer, a low CSF leukocyte
adjunctive treatment for mucormycosis.3 count at presentation, and infection with C.
Correction of any underlying metabolic ab- neoformans.4,18
normality is an essential aspect to treating The prognosis for patients with cerebral
the patient with mucormycosis. aspergillosis is poor, with a survival rate of
Voraconazole (8 mg/kg per day given ev- less than 5%. Death often occurs within a
ery 12 hours after a loading dose of 6 mg/kg matter of days following the onset of neu-
given twice intravenously 12 hours apart) rologic symptoms in CNS aspergillosis. A
has emerged as the antifungal treatment delay in diagnosis is often responsible for
of choice for Scedosporium brain abscess the poor outcome. A high degree of suspi-
based on clinical experience, a lack of effec- cion is often necessary to diagnose CNS as-

tive alternative treatments, and the in vitro pergillosis early in the course of the disease.
resistance of this organism to amphotericin The combination of antifungal therapy
B.3,20 In one report of 21 patients with CNS with radical surgical debridement has
scedosporiosis, a 43% therapeutic response improved the prognosis of paranasal si-
rate to voriconazole was observed.30 nus mucormycosis, with reported survival
rates of greater than 80%.31 Cerebral in-
Anticonvulsants volvement by Mucor species is associated
with a much worse prognosis than para-
Anticonvulsants should be used in the ear-
nasal involvement, particularly if the basal
ly stages of treatment of CNS fungal infec-
ganglia are involved, which removes surgi-
tions to prevent seizures.
cal debridement as a reasonable option.32
As with aspergillosis, the strongest predic-
Steroids tive factor for a poor outcome in mucormy-
Corticosteroids can be initiated in patients cosis is a delay in diagnosis and initiation
with significant surrounding cerebral ede- of treatment.4 The correction of any under-
ma causing increased intracranial pressure lying systemic metabolic disorders such as
or in patients with evidence of transten- diabetic ketoacidosis is essential for any
torial herniation. However, they should possibility of recovery.
be used sparingly, particularly in patients
who are already immunocompromised, to
avoid the detrimental effects of immune ■■ Conclusion
suppression.
The prognosis for most fungal infections of
Sequelae the CNS remains poor. Most patients who
Despite favorable survival rates in patients develop these infections have a compro-
treated for Candida meningitis, neurologic mised immune system, and discontinu-
sequelae are common, with 56% of neo- ation of the immunosuppression when
nates having psychomotor retardation and possible can help aid in recovery. Infections
50% developing hydrocephalus.6 are in the form of either a chronic menin-
goencephalitis or a brain abscess. Ampho-
tericin B or the newer lipid formulations
Prognosis
remain the primary medical treatments
The cure rates for Candida meningitis for CNS fungal infections. In the face of a
treated with amphotericin B are 71 to 100% brain abscess due to Aspergillus species or
in neonates and 67 to 89% in adults.6 Cryp- Mucor species in an immunocompromised
tococcal meningitis is difficult to eradicate patient, aggressive surgical debridement
despite aggressive treatment and carries combined with amphotericin B may be the
a mortality rate of 6%.4 Prognostic factors only possible treatment with any poten-
that have been associated with a poor out- tial for a good clinical outcome. The rapid
come in cryptococcal meningitis include identification of a CNS fungal infection and 79
the prompt initiation of treatment offer 17. W eprin BE, Hall WA, Goodman J, Adams GL. Long-
term survival in rhinocerebral mucormycosis. Case
the best chance for a positive therapeutic
report. J Neurosurg 1998;88(3):570–575 PubMed
response. The clinical condition of the pa- 18. S peed B, Dunt D. Clinical and host differences
tient at the time of diagnosis is the stron- between infections with the two varieties of
gest predictor of clinical outcome. Cryptococcus neoformans. Clin Infect Dis 1995;
21(1):28–34, discussion 35–36 PubMed
19. R uhnke M, Kofla G, Otto K, Schwartz S. CNS asper-
References gillosis: recognition, diagnosis and management.
CNS Drugs 2007;21(8):659–676 PubMed
1. H all WA, Anker L. Fungal infections in the brain.
20. B erenguer J, Diaz-Mediavilla J, Urra D, Muñoz P.
In: Batjer HH, Loftus CM, eds. Textbook of Neu-
Central nervous system infection caused by Pseu-
rological Surgery. Principles and Practice. Vol 4.
dallescheria boydii: case report and review. Rev
Philadelphia, PA: Lippincott Williams & Wilkins;
Infect Dis 1989;11(6):890–896 PubMed
2003:3157–3165
21. W alsh TJ, Anaissie EJ, Denning DW, et al; Infec-
2. Levitz SM. The ecology of Cryptococcus neofor-
tious Diseases Society of America. Treatment of
mans and the epidemiology of cryptococcosis.
aspergillosis: clinical practice guidelines of the
Rev Infect Dis 1991;13(6):1163–1169 PubMed
Infectious Diseases Society of America. Clin Infect
3. Tunkel AR. Brain abscess. In: Mandell GL, Bennett
Dis 2008;46(3):327–360 PubMed
JE, Dolin R, eds. Mandell, Douglas, and Bennett’s
22. Ikeda K, Yamashita J, Fujisawa H, Fujita S. Cere-
Principles and Practice of Infectious Diseases.
bral granuloma and meningitis caused by Can-
Philadelphia, PA: Churchill Livingstone Elsevier;
dida albicans: useful monitoring of mannan
2010:1265–1278
antigen in cerebrospinal fluid. Neurosurgery
4. Anker L, Hall WA. Fungal infections. In: Hall WA,
1990;26(5):860–863 PubMed
McCutcheon IA, eds. Infections in Neurosurgery.
23. P erfect JR. Cryptococcus neoformans. In: Mandell
Park Ridge, IL: American Association of Neuro-
GL, Bennett JE, Dolin R, eds. Mandell, Douglas,
logical Surgeons Publications; 2000: 219–235
and Bennett’s Principles and Practice of Infec-
5. Chimelli L, Mahler-Araujo MB. Fungal infections.
tious Diseases. Philadelphia, PA: Churchill Living-
Brain Pathol 1997;7(1):613–627 PubMed
stone Elsevier; 2010:3287–3303
6. Slavoski LA, Tunkel AR. Therapy of fungal men-
24. D eepe GS Jr. Histoplasma capsulatum. In: Mandell
ingitis. Clin Neuropharmacol 1995;18(2):95–
GL, Bennett JE, Dolin R, eds. Mandell, Douglas,
II Etiologic Agents
112 PubMed
and Bennett’s Principles and Practice of Infec-
7. Currie BP, Casadevall A. Estimation of the preva-
tious Diseases. Philadelphia, PA: Churchill Living-
lence of cryptococcal infection among patients
stone Elsevier; 2010:3305–3318
infected with the human immunodeficiency vi-
25. D enning DW, Stevens DA. Antifungal and surgi-
rus in New York City. Clin Infect Dis 1994;19(6):
cal treatment of invasive aspergillosis: review
1029–1033 PubMed
of 2,121 published cases. Rev Infect Dis 1990;
8. Lee SC, Dickson DW, Casadevall A. Pathology of
12(6):1147–1201 PubMed
cryptococcal meningoencephalitis: analysis of 27
26. E rdogan E, Beyzadeoglu M, Arpaci F, Celasun B.
patients with pathogenetic implications. Hum
Cerebellar aspergillosis: case report and litera-
Pathol 1996;27(8):839–847 PubMed
ture review. Neurosurgery 2002;50(4):874–876,
9. Denning DW. Invasive aspergillosis. Clin Infect
discussion 876–877 PubMed
Dis 1998;26(4):781–803, quiz 804–805 PubMed
27. T almi YP, Goldschmied-Reouven A, Bakon M, et
10. Sugar AM. Mucormycosis. Clin Infect Dis 1992;
al. Rhino-orbital and rhino-orbito-cerebral mu-
14(Suppl 1):S126–S129 PubMed
cormycosis. Otolaryngol Head Neck Surg 2002;
11. Lamaris GA, Chamilos G, Lewis RE, Safdar A, Raad
127(1):22–31 PubMed
II, Kontoyiannis DP. Scedosporium infection in a
28. Adler DE, Milhorat TH, Miller JI. Treatment of rhi-
tertiary care cancer center: a review of 25 cases
nocerebral mucormycosis with intravenous, in-
from 1989-2006. Clin Infect Dis 2006;43(12):
terstitial, and cerebrospinal fluid administration
1580–1584 PubMed
of amphotericin B: case report. Neurosurgery
12. Helbok R, Broessner G, Pfausler B, Schmutzhard
1998;42(3):644–648, discussion 648–649 PubMed
E. Chronic meningitis. J Neurol 2009;256(2):
29. v an Burik JA, Hare RS, Solomon HF, Corrado ML,
168–175 PubMed
Kontoyiannis DP. Posaconazole is effective as
13. Bennett JE. Chronic meningitis. In: Mandell GL,
salvage therapy in zygomycosis: a retrospec-
Bennett JE, Dolin R, eds. Mandell, Douglas, and
tive summary of 91 cases. Clin Infect Dis 2006;
Bennett’s Principles and Practice of Infectious
42(7):e61–e65 PubMed
Diseases. Philadelphia, PA: Churchill Livingstone
30. T roke P, Aguirrebengoa K, Arteaga C, et al; Global
Elsevier; 2010:1237–1241
Scedosporium Study Group. Treatment of scedo-
14. Nguyen MH, Yu VL. Meningitis caused by Candida
sporiosis with voriconazole: clinical experience
species: an emerging problem in neurosurgical pa-
with 107 patients. Antimicrob Agents Chemother
tients. Clin Infect Dis 1995;21(2):323–327 PubMed
2008;52(5):1743–1750 PubMed
15. Chiou CC, Wong TT, Lin HH, et al. Fungal infection
31. B litzer A, Lawson W, Meyers BR, Biller HF. Patient
of ventriculoperitoneal shunts in children. Clin
survival factors in paranasal sinus mucormycosis.
Infect Dis 1994;19(6):1049–1053 PubMed
Laryngoscope 1980;90(4):635–648 PubMed
16. Wheat LJ, Musial CE, Jenny-Avital E. Diagnosis and
32. N ussbaum ES, Hall WA. Rhinocerebral mucormy-
management of central nervous system histoplas-
cosis: changing patterns of disease. Surg Neurol
mosis. Clin Infect Dis 2005;40(6):844–852 PubMed
80 1994;41(2):152–156 PubMed
7
Parasitic Infections of the
Ali Akhaddar and Mohamed Boucetta
Man can see only what he knows.
—Johann Wolfgang von Goethe (1749–1832)
Parasitic infections of the central nervous Table 7.1 Parasitic infections that potentially involve
system (CNS) were once considered un- the central nervous system in humans
usual, if not rare. However, because of the Parasitic Groups Parasitic Infections
increase in international travel to areas
where parasitic infections are endemic and Helminth tapeworms Cysticercosisa
the migration of individuals infected with Echinococcosisa
Coenurosis
the disease, neuroparasitosis is becoming
Fascioliasis
more common worldwide. Despite this oc- Sparganosis
currence, parasitic infection is often over-
looked in the differential diagnosis of CNS Helminth flukes Schistosomiasisa
disease. Improvements in neuroimaging Paragonimiasis
and serologic assessment, as well as better Helminth roundworms Baylisascariasis
understanding of the natural progression of Filariasis
the disease and the response to antiparasit- Gnathostomiasis
ic drugs, have resulted in better treatment Angiostrongyliasis
paradigms. This chapter focuses on the most Strongyloidiasis
pertinent CNS parasitic diseases encoun- Toxocariasis
Trichinosis
tered in neurosurgical practice, especially in
immunocompetent hosts (Table 7.1). Protozoa Amebiasisa
Malaria
Toxoplasmosis
Trypanosomiasis
■■ Cysticercosis
a
ay be encountered in neurosurgical practice, especially
M
Cysticercosis is the most common parasitic in immunocompetent individuals.
disease of the CNS and is secondary to in-
fection by the larval form of the pork tape-
worm Taenia solium. Within the CNS, the
tus in parts of Latin America, India, Africa,
brain parenchyma is the most commonly
East Asia, and China.3–6 This infection is rare
affected site. CNS infection with T. solium is
in Islamic countries because of the prohibi-
a major cause of acquired epilepsy.1,2
tion of pork consumption. Neurocysticer-
cosis is becoming increasingly prevalent in
Incidence and Demographics
developed countries.5,7,8 CNS cysticercosis oc-
Neurocysticercosis is an infection with curs often in young and middle-aged adults.
worldwide prevalence and has endemic sta- Over 50 million people worldwide were af-
fected, with approximately 50,000 deaths ventricles, causing hydrocephalus by ob-
per year.4,9 Spinal forms are rare; fewer than struction of the aqueduct of Sylvius or even
200 cases have been previously reported.10,11 the fourth ventricle. Cerebral infarction is
another serious complication that results
Etiology and Pathogenesis from vasculitis of small perforating arter-
ies.12 Spinal cord involvement may cause
The life cycle of T. solium is well known, in arachnoiditis, meningitis, myelitis, or cord
which pigs are the intermediate host and compression.10,11 Most patients with intra-
humans are the definitive host. Additional- medullary cysts present with thoracic spas-
ly, humans may accidentally ingest the eggs tic paraparesis and bladder dysfunction.10
and become the intermediate host. The ova
penetrate the intestinal wall and enter the Diagnosis
bloodstream. They are then dispersed to
the skin, skeletal muscles, heart, eyes, and The peripheral white blood cell count,
most importantly, the brain.3 Involvement eosinophil count, and erythrocyte sedi-
of the CNS occurs in 60 to 90% of infected mentation rate are usually normal. Stool
patients. The most commonly involved lo- examination for T. solium eggs is positive in
cations are brain parenchyma (60%) and only 5 to 10% of patients. The cerebrospinal
the subarachnoid space (40%).4,5,12 The fluid (CSF) is also usually unremarkable ex-
spinal cord is more rarely involved (fewer cept in cases with meningeal involvement
than 6% of cases).8,10,11 After entering the (low glucose level with eosinophilia).14 En-
CNS, cysticerci elicit a scarce inflammatory zyme-linked immunosorbent assay (ELISA)
reaction in the surrounding tissues. During of the blood or CSF should be interpreted
this stage, parasites have a clear vesicular with caution. In serum, it has 50% sensi-
tivity and 65% specificity.15 Sensitivity and
II Etiologic Agents
fluid and a normal scolex (vesicular stage).

Cysticerci may remain viable or enter into specificity are higher in CSF (85 and 100%,
a process of degeneration. respectively). Enzyme-linked immunoelec-
The first stage of involution is the col- trotransfer blot (EITB) has been the gold
loidal stage, in which the vesicular fluid standard serodiagnostic assay. This test is
becomes turbid and the scolex shows signs reported to have a sensitivity of 98% and a
of degeneration. Colloidal cysticerci are sur- specificity of 100% but has only 30% sensi-
rounded by a thick collagen capsule, with tivity in the patient with a single brain le-
associated astrocytic gliosis and diffuse ce- sion.16,17 Biopsy of brain (stereotactic), skin,
rebral edema. Thereafter, the wall of the cyst or muscle can provide a definitive diagnosis
thickens, and the scolex is transformed into in an otherwise ambiguous clinical situa-
coarse, mineralized granules (nodular–gran- tion.18 At the vesicular stage, magnetic reso-
ular stage). Finally, in the calcified stage, the nance (MR) imaging demonstrates a cystic
parasite remnants appear as a mineralized lesion isointense to the CSF. The lesion con-
nodule. In the last two stages, the edema tains an eccentric scolex hyperintense to
subsides but the astrocytic changes become the CSF with no surrounding edema and
more intense. Seizures are thought to occur little or no rim enhancement after intra-
either from parenchymal irritation or gliosis venous gadolinium (Gd) administration. At
or because of active inflammation.13 the colloidal stage, MR imaging shows the
cyst with hyperintense content relative to
the CSF and mild or marked surrounding
Presentation
edema. After Gd administration, the cyst
When the lesions diffusely infect the brain wall enhances as well as the eccentric sco-
parenchyma, they produce encephalitis, lex. At the nodular–granular stage, MR im-
raised intracranial pressure, and seizures aging shows a retracted, thickened cyst with
(50 to 80% of patients).4 In the meninges, mild surrounding edema and homogeneous
they produce basal meningitis and arterial Gd enhancement. At the calcified stage,
thrombosis. The lesions may occur in the computed tomography (CT) demonstrates
82
multiple small calcified nodules with no intervention to release obstruction.24 The
surrounding edema. MR imaging shows a prognosis is better for intraparenchymal le-
small calcified lesion, better identified on sions. The mortality rate is lower than 10%.14
T2* gradient echo sequences. Cysticercosis Worse outcome is observed for extraparen-
in an intraventricular location usually pres- chymal lesions as well as cases complicated
ents as a single cyst, but on MR imaging, the by basilar arachnoiditis and vasculitis with
cyst wall and content may be difficult to subsequent cerebral ischemia.5,18 The most
identify. Gd-enhanced T1-weighted MR im- common sequelae are seizures.13,23 True
aging shows enhancement of the cyst wall disease control is achieved only by avoid-
and scolex. In the subarachnoid spaces, the ing transmission, with proper sanitary
content of the cysts appears isointense to measures (public health education and pig
7 Parasitic Infections of the Central Nervous System

the CSF.1,6,19 Spinal cysticercosis usually in- vaccination).
volves the subarachnoid space, with the for-
mation of intradural cysts or arachnoiditis. Conclusion
The intradural and intramedullary cysts are
identified on MR imaging by the same find- Neurocysticercosis remains a significant
ings as those of cerebral subarachnoid and cause of morbidity and mortality through-
intraparenchymal cysts, respectively.10,11 out the world. This disease has multiple
forms of neurologic presentation. Patients
with intraparenchymal lesions have a fa-
Treatment
vorable course and respond well to clinical
Ventricular CSF shunting is the most common treatment. Those with subarachnoid and
surgical indication for neurocysticercosis intraventricular cysts have a greater mor-
to resolve hydrocephalus. Neuroendoscopy bidity and mortality. The vast majority of
may be used for resection of some intraven- patients require anticonvulsive therapy.
tricular cysts.20 Other surgical indications Control and eradication programs are ur-
include brain biopsy and resection of mass le- gently needed in areas where the disease
sions.12,18 In cases of spinal cord involvement, is endemic.
surgery is always mandatory in the presence
of medullary compression. The two widely
accepted anticysticercal drugs are albenda- ■■ Echinococcosis
zole and praziquantel; however, albenda-
zole is superior in terms of cyst eradication, Echinococcosis is a parasitic infection
seizure control, and tolerability.21 Anticysti- caused by larvae (metacestodes) of the
cercal drugs must be used with caution in tapeworm Echinococcus. Three forms that
patients with increased intracranial pres- occur in humans: cystic (Echinococcus
sure and encephalitis.6,15 Corticosteroids are granulosus), alveolar (Echinococcus mul-
the primary form of therapy for cysticercotic tilocularis), and polycystic (Echinococcus
encephalitis, angiitis, and arachnoiditis.22 In vogeli and Echinococcus oligarthrus), which
patients with giant subarachnoid cysticerci, is rare.25 The cystic strain (cystic hydatid-
ventricular cysts, spinal cysts, and multiple osis) is the most common form to occur
parenchymal brain cysts, corticosteroids in humans.26,27 Both cerebral and spinal
must be administered before, during, and structures may be involved. This chapter
even after the course of cysticidal drugs to focuses on cystic hydatidosis because it is
avoid cerebral infarction, acute hydrocepha- the most frequent and most important CNS
lus, spinal cord swelling, and massive brain echinococcosis.
edema.8,22 Antiepileptic therapy must be ad-
ministered early.13,23 Incidence and Demographics
Outcome Although rare in western Europe and

North America, hydatidosis is a significant
A large number of patients treated with cause of morbidity and mortality in large
ventriculoperitoneal shunts require repeat geographic regions like the Middle East, 83
Mediterranean area, South America, Aus- the cyst may impinge on nerve roots and
tralia, and northwestern China. This infec- the spinal cord, causing neurologic symp-
tion is currently considered an emerging toms.32,38 Spinal hydatid cysts are classified
or reemerging disease.26–30 Annual inci- in five categories: (1) intramedullary, (2)
dence rates of diagnosed human cases vary intradural extramedullary, (3) extradu-
widely, from 1 to 200 cases per 100,000 in- ral, (4) vertebral, and (5) paravertebral le-
habitants.29 Approximately 2 to 3% of all re- sions.39 The first three categories are rare.40
ported hydatid cysts are found in the CNS. The most common sites involved are the
The brain is affected in approximately 2% lower dorsal and lumbar regions, in about
and the spine in fewer than 1% of all pa- two-thirds of cases.31,35
tients.30–33 Individuals of all ages may be af-
fected, although children and young adults Presentation
are particularly vulnerable.15,34,35
Symptoms depend on the involvement of in-
Etiology and Pathogenesis tracranial structures and may vary from sim-
ple headache to uncal herniation. Headache
The adult parasites live in the intestines is the most common presenting symptom in
of dogs and wild canids. Infective eggs, 70 to 75% of cases, followed by weakness of
passed in the feces, are ingested by inter- the extremities in 40%. Other symptoms that
mediate hosts, including sheep, cattle, and occur are epilepsy, mental changes, skull
humans. The life cycle is maintained when deformities, change in school or job perfor-
dogs ingest the carcasses of infected inter- mance, and psychotic syndromes.
mediate hosts. In humans, echinococcal Papilledema may lead to optic atrophy
infestation occurs through the fecal–oral with unilateral or bilateral blindness.31,36,41
route.3 Unilocular cysts most commonly
II Etiologic Agents
During the intraosseous phase of spinal hy-

develop in the liver (75% of cases), lungs datidosis, no symptoms are typically pres-
(15% of cases), and other organs, including ent. Thereafter, the initial symptoms are
the brain and spine.25,28 The host reacts to either radicular pain in 75% of patients or
the presence of this lesion by enveloping it muscle weakness in 20%.35,42 Trauma may
in a fibroblastic capsule (adventitial mem- produce a pathologic fracture with acute
brane), but this occurs to a much lesser neurologic signs.32 Other symptoms of sys-
degree in the brain. Occasionally, hydatid temic involvement may be associated that
cysts degenerate and die.25,26 When an em- are most often referable to involvement of
bryo of E. granulosus is lodged in the brain, the liver and lungs.
a solitary cyst develops.
Multiple cysts are rare (5%).31,36 The brain
Diagnosis
cysts are usually spherical, with a wall that
is white, smooth, soft, and elastic. The loca- Eosinophilic pleocytosis, elevated sedi-
tion of primary hydatid cysts of the brain mentation rate, and Casoni reaction are
is supratentorial in 90% of cases and sub- supportive evidence of infection but not
cortical. Intraventricular and infratentorial specific. The sensitivity of indirect agglu-
infections are unusual.31,37 A hydatid cyst is tination and indirect hemagglutination is
a slow-growing lesion (1 to 5 cm annually) high (60 to 100%); however, they have lim-
that does not invade the brain.36 In the spine, ited specificity.43 Currently, the gold stan-
the vertebral body is affected through inva- dard for diagnosis is serologic and is based
sion of the venous portovertebral shunts. on the detection of immunoglobulin G anti-
Spinal lesions are microvesicular, multiple, bodies to hydatid cyst fluid–derived native
and invasive. The parasite grows along the or recombinant antigen B subunits, either
bony intratrabecular space, then infiltrates in ELISA or in immunoblot formats.25,43 On
and destroys the bone; thereafter, it ex- CT, the brain lesion presents as a spherical,
tends into the extradural space or paraspi- well-defined, homogeneous, smooth, thin-
nal tissues. During this extraosseous stage, walled, cystic lesion isodense to the CSF
84
without surrounding cerebral edema. The through a large cranial flap and corticecto-
cyst wall is iso- or hyperdense relative to my (Fig. 7.3). The cyst is delivered by using
the brain parenchyma. Wall calcifications saline irrigation between the cyst wall and
are rare.33,36 After contrast administration, the surrounding brain with soft-tipped
there is typically no enhancement (Fig. catheters (hydrodissection).33,37,46 If the cyst
7.1a). On MR imaging, the cyst is isoin- ruptures during surgery, which occurs in
tense to CSF on T1- and T2-weighted im- approximately 20 to 25% of cases,31,36,44 lo-
ages and has a hypointense rim on T1- and cal parasiticidal solution (hypertonic saline
T2-weighted images without perilesional or oxygenic water) should be used to pre-
edema (Fig. 7.1b,c). On FLAIR (fluid-at- vent recurrence. Anaphylactic shock can
tenuated inversion recovery) images, the be observed when intraoperative spillage

fluid in the hydatid cyst is hyperintense. occurs. In the spine, different approaches
The Gd-enhanced T1-weighted MR image have been used to eradicate the vesicular
classically shows no enhancement.14,44,45 lesions, including posterior (Fig. 7.4) or
In spinal hydatidosis, CT reveals irregular anterior approaches. Spinal instability and
bony erosions of the vertebral body, neural deformity are treated when necessary to
arch, and head of the ribs. In the paraspi- prevent possible neurologic complications.
nal soft tissues, the occurrence of spherical At the completion of surgery for extradural
formations with multiple daughter cysts is lesions, the area should be irrigated with a
common. Enhancement is rare and is of- parasiticidal solution. Surgery is the main-
ten related to concomitant bacterial infec- stay of treatment for neurohydatidosis;
tion.35,42 On MR imaging, the cyst appears as however, anthelmintic treatment may be
a multiloculate, hypointense mass on T1- used before and/or after the operation to
weighted images but is brightly hyperin- prevent recurrence.32,35,36 Although their ef-
tense on T2-weighted images (Fig. 7.2). The fectiveness in neurohydatidosis is not well
alteration in signal intensity can be used to established, albendazole and mebendazole
demonstrate cyst viability. are the most frequently used anthelmintic
agents. Albendazole is a broad-spectrum
anthelmintic agent with good oral absorp-
Treatment
tion but may be hepatotoxic.47 Preoperative
In the brain, the Dowling method is fre- seizures require long-term antiepileptic
quently used and consists of the spontane- therapy. Adequate rehabilitation is crucial
ous delivery of the intact brain hydatid cyst for a successful outcome.41
a b c
Fig. 7.1a–c (a) Axial computed tomographic scan with contrast injection, (b) axial T1-weighted magnetic
resonance (MR) image, and (c) T2-weighted MR image showing a large cerebral hydatid cyst located in the left
parieto-occipital area compressing the lateral ventricle and causing shift of the midline structures. 85
b
II Etiologic Agents
a c
Fig. 7.2a–c (a) Sagittal, (b) axial, and (c) coronal T2-weighed magnetic resonance images revealing hyper-
intense, multiloculate, low-thoracic intraspinal lesions extending into the right foramina and compressing the
spinal cord.
a b
Fig. 7.3a,b (a) Operative view of the brain cyst before warm saline was injected between the cyst wall and the
86 surrounding brain to remove the cyst (Dowling technique) . (b) The hydatid cyst was extracted without rupture.
recurrence. Preventive programs must fo-
cus on breaking the parasite’s life cycle and
on educating people in areas of endemicity.
■■ Schistosomiasis
Schistosomiasis (bilharziasis) is a snail-
transmitted parasitic infection caused by
the trematode platyhelminth of the ge-
nus Schistosoma. Five species of Schisto-

soma infect humans: Schistosoma mansoni,
Schistosoma haematobium, Schistosoma ja-
Fig. 7.4 Operative view after thoracic laminectomy ponicum, Schistosoma mekongi, and Schis-
showing multivesicular hydatid cysts in the epidural tosoma intercalatum.48 CNS complications
space. usually occur in chronically infected indi-
viduals. Both the brain and spinal cord may
be involved.49
Outcome Incidence and Demographics

Rapid recovery from neurologic deficits oc- Only the first three species of Schistosoma
curs in most patients operated on for brain cause significant disease in humans and
hydatidosis. The postoperative course may are endemic in certain parts of the world:
be complicated by subdural effusion, extra- S. mansoni in Africa, Latin America, and
dural hematoma, and infection. The death some Caribbean islands; S. japonicum in
rate is less than 10%.31,36 Recurrence in the China, Indonesia, Thailand, and the Philip-
brain occurs in 10 to 20% of cases and is of- pines; and S. haematobium in Africa and the
ten due to spillage of the cyst contents at Middle East.48,49 Worldwide, 20,000 deaths
the time of its removal.31,33,41,44 When the per year are associated with the severe
spine is affected, no improvement can be consequences of this parasitic infection.
expected in patients with complete para- An estimated 600 million people are at risk
plegia. Because its eradication is nearly for infection in 79 countries where it is en-
impossible, even after repeated surgical demic.48,50 The incidence of neuroschisto-
intervention and chemotherapy, spinal hy- somiasis was estimated at approximately
datidosis has a high rate of recurrence (40 2 to 4% of persons infected systemically.51
to 100% of cases).31,35,37,38 The death rate is
approximately 4%.31,38 Hydatidosis is poten- Etiology and Pathogenesis
tially an eradicable parasitic disease, and
efforts must focus on the numerous human Schistosomes use humans and other mam-
factors that are involved in maintenance of mals as definitive hosts and aquatic snails
the parasitic cycle.26,27 as intermediate hosts. Infection is acquired
via direct contact with water contaminat-
ed by the larval form of the parasite. These
Conclusion
larvae penetrate the human skin and reach
In hydatid cyst of the brain, every attempt the vascular system, where they mature.
should be made to deliver the cyst unrup- Adult parasites localize in the venous sys-
tured. Spinal hydatidosis is highly likely to tem, draining the colon (S. mansoni and S.
recur, leading to progressive destruction of japonicum) or the urinary tract (S. haema-
the vertebral column and neurologic de- tobium). Other organs, such as the lungs,
terioration. Anthelmintic treatment must liver, and CNS, may be involved.48,49,52 Af-
also be considered to control the disease ter the eggs die, circumscribed granulo-
locally, avoid systemic spread, and prevent mas form around the degenerating eggs. 87
Ultimately, the only residue of disease is eloradicular (55%), and conus–cauda equina
fibrosis surrounding a zone of necrosis.53 syndrome (18%).63 Because of the location of
The eggs of S. japonicum have a tendency parasitic infestation, sensory disturbances
to calcify. CNS involvement is uncommon; rarely ascend higher than the T9 level.61
cerebral lesions most frequently occur in
cases of S. japonicum infection, whereas Diagnosis
S. mansoni and S. haematobium infections
may involve the spinal cord.49 A tumor- Laboratory changes, such as eosinophilia,
like presentation can develop as a result and evidence of eggs in the urine or feces
of slowly expanding intracranial lesions.54 may or may not be present. Rectal biopsy
The granulomas are rimmed by a zone has an important sensitivity, allowing
of reactive astrocytosis. The adult worm identification of the eggs in 95 to 100% of
may be present within blood vessels in the cases.64 CSF examination generally shows
brain, inducing vasculitis with rupture of an inflammatory pattern. Antibody detec-
blood vessels and secondary hemorrhage.54 tion (indirect hemagglutination, indirect
Schistosome-induced myelopathy results immunofluorescence tests, or ELISA) in
from the inflammatory reaction accompa- samples of blood or CSF is useful in only a
nying the deposition of ova in the venules few specific circumstances. The existence
located in and around the lower part of the of other forms of visceral involvement is
spinal cord. The ova, which normally are important.48,57,65 Definitive diagnosis re-
deposited in the inferior mesenteric vein quires the pathologic demonstration of
of the portal system, reach the spinal veins parasitic eggs in brain, spinal cord, or spi-
via the Batson plexus.55–58 nal nerve root tissue obtained at biopsy.66
On MR imaging, the tumorlike lesion is
II Etiologic Agents
Presentation heterogeneous, isointense to the gray mat-

ter on T1-weighted, and hyperintense on
S. japonicum infection is almost always as- T2-weighted imaging. It is most commonly
sociated with cerebral manifestations, and located in the cerebellum, less often in the
S. mansoni and S. haematobium infection thalamus and hemispheres. After Gd ad-
with a myeloradicular syndrome. Symp- ministration, MR imaging may reveal either
toms of cutaneous allergic response, fe- homogeneous nodular enhancement of the
ver, hematuria, hepatosplenomegaly, and mass or a punctate pattern of enhance-
peripheral eosinophilia may be present ment with multiple enhancing nodules
before the neurologic symptoms appear.57 distributed throughout the mass.19,58,66–68 In
Young men, teenagers, and children are the spinal cord, the most frequent findings
mostly affected. are medullary enlargement (particularly
Cerebral lesions may be unique or mul- the lower spinal cord) and thickening of the
tiple and have presented with headache, sei- spinal roots (especially the cauda equina)
zures, and focal neurologic deficits, whereas on T1-weighted imaging, signal hyperin-
nausea, vomiting, ataxia, and brain hernia- tensity on T2-weighted imaging, and a het-
tion are more common in posterior fossa erogeneous pattern of Gd enhancement.56,62
schistosomiasis.57,58 The seizure semiology
consists mainly of motor seizures.57,59 Acute
Treatment
cerebral schistosomiasis can provoke en-
cephalitis and strokelike symptoms due to Surgical treatment should be considered for
cerebral vasculitis. Spinal cord schistoso- brain involvement when the lesion causes
miasis has a spectrum of severity ranging a mass effect, the neurologic signs and
from asymptomatic egg deposits to severe symptoms progress despite clinical treat-
acute transverse myelitis. Patients present ment, or the diagnosis is uncertain. De-
with back pain as the first symptom in 79 to compression for the posterior fossa lesions
100% of cases.60–62 Classically, there are three is often necessary to prevent the develop-
clinical forms: medullary (27% of cases), my- ment of hydrocephalus.51,58 Praziquantel
88
and oxamniquine are the antischistosomal tic medication, or diagnostic uncertainty
agents recommended for treatment.59,64 exists. Cerebral involvement is associated
These agents destroy the adult worms with a better outcome than disease affect-
and thereby prevent further oviposition.64 ing the spinal cord. Preventive campaigns
Corticosteroids are utilized to diminish are urgently needed in areas of endemicity
granulomatous inflammation and edema. to reduce this disease.
In addition, there is some evidence that
corticosteroids reduce ova deposition by
adult worms.63,69 The therapeutic decision ■■ Amebiasis
for patients with the new onset of seizures
should be made based on the type of sei- Amebiasis is a widespread parasitic dis-

zures.57,59 In spinal cord involvement, No- ease caused by the protozoa Entamoeba
bre et al reported that 22% of their patients histolytica, Naegleria fowleri, Acantham-
exhibited a full response to medical treat- oeba species, and Balamuthia species.70,71
ment, 57% had a partial response without E. histolytica is a causative agent of ame-
functional limitations, and 17% had par- bic dysentery and invasive extraintestinal
tial improvement with limitations or no amebiasis. CNS infections are rare but have
response to treatment.62 With intracranial been uniformly fatal.70,72–75 The various clin-
lesions, if there is no clinical improvement icopathologic entities associated with CNS
after the institution of antischistosomal amebiasis include the following: (1) ame-
medications or if neurologic deterioration bic abscess (AMA) due to E. histolytica, (2)
occurs, surgical decompression and biopsy granulomatous amebic encephalitis (GAE)
sampling should be considered. due to Acanthamoeba species and Bala-
muthia mandrillaris (order Leptomyxida),
Outcome (3) primary amebic meningoencephalitis
(PAM) due to N. fowleri, and (4) necrotizing
Outcome is largely dependent on early
hemorrhagic encephalitis due to Sappinia
treatment, particularly with spinal cord in-
diploidea, which is rare.53,71,76
volvement, and is better for cerebral schisto-
somiasis. Improvement is usually progressive
Incidence and Demographics
and more rapid at the onset of corticosteroid
and antischistosomal drug treatment.69 For Amebiasis is a global disease, although
some authors, microsurgery is effective for most cases are seen in developing countries
the total resection of lesions and can assist in the tropics.72,76 E. histolytica is a major
in protection of the brain, increasing the cure human pathogen that is estimated to cause
rate.51,58 A significant degree of disability is more than 100,000 deaths per year.77,78.
common following spinal schistosomiasis The incidence of amebic brain abscesses
and may require prolonged rehabilitation.61,65 due to Entamoeba species in patients with
Signs and symptoms can recur in patients confirmed amebic liver abscesses varies
who do not receive adequate antiparasitic from 0.6 to 8.1%.77,78 More than 200 cases
chemotherapy.64 of GAE have been reported worldwide, and
approximately 300 cases of PAM.70,73 CNS
Conclusion amebiasis has been reported to represent
0.27% of all mass lesions of the brain.74 Both
Correlation of the clinical, epidemiologic,
immunocompetent and immunocompro-
and neuroimaging features together with
mised hosts may be involved.70,79–82
the demonstration of eggs in the urine or
feces and positive serology may be helpful
Etiology and Pathogenesis
in diagnosing neuroschistosomiasis. Surgi-
cal treatment should be considered when Usually, humans acquire amebiasis by in-
the lesion causes a mass effect, the signs gesting cysts of E. histolytica in contami-
and symptoms worsen despite anthelmin- nated food, by drinking contaminated
89
water, or by swimming in the infested competent individuals and children.74,81,84
water of lakes. E. histolytica and B. man- Many patients with GAE present with
drillaris reach the brain by hematogenous typical skin lesions, such as a purple nod-
spread from the colon through the hepatic, ule.70,75,80,83 N. fowleri can produce a fulmi-
pulmonary, or vertebral veins or ascend nant PAM resembling bacterial meningitis,
directly along the nasal mucosa, olfactory with death occurring within 72 hours after
nerves, or traumatized skin (mainly in the presentation.76 Victims tend to be young
case of B. mandrillaris) to the brain, lead- and healthy, typically with a recent history
ing to cerebral vasculitis, hemorrhagic of swimming in a warm body of water.71
necrosis, meningoencephalitis, or intra-
parenchymal abscess.74,80,83,84 Abscesses are Diagnosis
usually in the distribution of the middle
cerebral artery. The abscess consists of a Diagnosis is made by culture, serology,
central area of necrosis that contains ame- or immunofluorescence of CSF or brain
bic trophozoites in the periphery.73,76 specimens to demonstrate the trophozo-
Acanthamoeba infection reaches the CNS ites.73,75 Recently, the usefulness of molecu-
via the bloodstream from a site of pulmo- lar analysis and polymerase chain reaction
nary involvement or skin lesions. The brain in diagnosing CNS amebiasis has been re-
shows reactive gliosis, acute and chronic ported.86 Skin biopsy and liver abscess with
inflammation, and areas of necrosis sur- granulomatous infection would aid in the
rounded by trophozoites and cysts.53,84 Al- diagnosis.75,76,86 In cases of GAE, the CSF
though typical granulomas are not seen, profile may reveal mildly low to normal
several multinucleated giant cells of the glucose concentrations. Pleocytosis with
foreign body or Langhans type are found. a predominant lymphocytosis and high
II Etiologic Agents
In PAM, hemorrhagic necrosis is seen in- protein levels are commonly seen.75 The
volving the inferior frontal lobe along the immune status of the patient should be
olfactory nerve.71 investigated. Amebic encephalitis involves
the cerebral hemispheres, mainly the fron-
Presentation tal and parietal lobes and basal ganglia. On
MR imaging, T1-weighted imaging demon-
In cerebral abscess due to E. histolytica, strates a centrally hypointense mass with
most symptoms results from increased in- surrounding cerebral edema and hetero-
tracranial pressure, local mass effect, and geneous or ring enhancement after Gd in-
meningismus, with fever an uncommon jection. T2-weighted imaging can show a
finding. Liver abscesses may be associated centrally hyperintense lesion with possible
with brain abscesses.85,86 Infections with hemorrhage that is surrounded by hyperin-
Acanthamoeba are more indolent and of- tense edema.19,85,88 On diffusion-weighted
ten occur in both immunocompetent and imaging, a slight area of restricted diffusion
immunocompromised hosts, resulting in a and increased signal on the FLAIR sequence
subacute granulomatous encephalitis.70,79,82 may be seen.75 To establish a definitive di-
The patient often presents with nonspecific agnosis, stereotactic biopsy is preferred for
symptoms of fever, malaise, and headache. multiple and small lesions.
As the disease progresses, seizures, nau-
sea, vomiting, lethargy, and an altered level
Treatment
of consciousness result.71,83 As is the case
with brain abscess, signs and symptoms In rare cases, excision of the brain lesion
of a space-occupying lesion develop in pa- may be curative if the infection is localized
tients with large granulomatous lesions.87 and the disease has not evolved into diffuse
Infections due to B. mandrillaris can also encephalitis.70 A decompressive frontal lo-
cause chronic granulomatous meningoen- bectomy has been performed with success.79
cephalitis, occurring mostly in immuno- CSF diversion is necessary for patients with
90
symptomatic hydrocephalus, although the References
shunt tubing may become obstructed by in- 1. Del Brutto OH, Rajshekhar V, White AC Jr, et al.
flammatory debris. Except for brain abscess Proposed diagnostic criteria for neurocysticerco-
due to E. histolytica (metronidazole therapy), sis. Neurology 2001;57(2):177–183 PubMed
2. Garcia HH, Del Brutto OH; Cysticercosis Work-
treatment of cerebral amebiasis is usually ing Group in Peru. Neurocysticercosis: updated
late and nonspecific. After the diagnosis has concepts about an old disease. Lancet Neurol
been confirmed, aggressive treatment with 2005;4(10):653–661 PubMed
intravenous (and/or intrathecal) amphoteri- 3. King CH, Fairley J. Cestodes (tapeworms). In: Man-
dell GL, Bennett JE, Dolin R, eds. Bennett’s Principles
cin B, miconazole, rifampin, sulfa drugs, and and Practice of Infectious Diseases. Philadelphia, PA:
tetracycline in combination should be start- Elsevier Churchill Livingstone; 2010:3607–3616
ed.89 However, only rare survivors have been 4. Hawk MW, Shahlaie K, Kim KD, Theis JH. Neuro-

cysticercosis: a review. Surg Neurol 2005;63(2):
reported with Naegleria meningoencepha-
123–132, discussion 132 PubMed
litis.90 Acanthamoeba infection of the CNS 5. White AC Jr. Neurocysticercosis: updates on epi-
has been treated with sulfadiazine and other demiology, pathogenesis, diagnosis, and manage-
sulfa drugs with also fatal outcomes.79 Treat- ment. Annu Rev Med 2000;51:187–206 PubMed
6. Diaz Vasquez PP. Parasitoses of the central ner-
ment of CNS Balamuthia infection is empiric. vous system: cysticercosis. In: Sindou M, ed.
There are reports of treatment with flucyto- Practical Handbook of Neurosurgery. Vol 1. Vi-
sine, pentamidine, fluconazole, sulfadiazine, enna, Austria: Springer-Verlag; 2009:483–498
and a macrolide.81 Corticosteroids have been 7. Wallin MT, Kurtzke JF. Neurocysticercosis in the
United States: review of an important emerging in-
used by some investigators to blunt the pre- fection. Neurology 2004;63(9):1559–1564 PubMed
viously described intense inflammatory re- 8. García HH, Gonzalez AE, Evans CAW, Gilman
action.91 Prophylactic anticonvulsants may RH; Cysticercosis Working Group in Peru. Tae-
nia solium cysticercosis. Lancet 2003;362(9383):
be used if appropriate. 547–556 PubMed
9. Psarros TG, Zouros A, Coimbra C. Neurocysticer-
Outcome cosis: a neurosurgical perspective. South Med J
2003;96(10):1019–1022 PubMed
Cerebral amebiasis is the second most com- 10. A hmad FU, Sharma BS. Treatment of intramedul-
mon cause of death from parasites and lary spinal cysticercosis: report of 2 cases and re-
view of literature. Surg Neurol 2007;67(1):74–77,
accounts for 4.2 to 8.5% of deaths due to discussion 77 PubMed
amebiasis.19,72,76 Although brain abscesses 11. M ohanty A, Venkatrama SK, Das S, Das BS, Rao
due to E. histolytica have a relatively good BR, Vasudev MK. Spinal intramedullary cysticer-
cosis. Neurosurgery 1997;40(1):82–87 PubMed
prognosis,85,86 most cases of PAM and GEA 12. E scobedo F. Neurosurgical aspects of cysticerco-
are fatal.74,82–84 Only rare survivors have been sis. In: Schmidek HH, Sweet WH, eds. Operative
reported, even in previously healthy pa- Neurosurgical Techniques. Indications, Methods,
tients.79,81 Prevention of amebiasis through and Results. Vol 1. Orlando, FL: Grune & Stratton;
1988:93–102
improved public health education and ad- 13. Rajshekhar V, Jeyaseelan L. Seizure outcome in pa-
equate management of dysentery is an im- tients with a solitary cerebral cysticercus granulo-
portant goal. ma. Neurology 2004;62(12):2236–2240 PubMed
14. G askill SJ, Marlin AE. Tuberculosis and fungal and
parasitic infections of the central nervous sys-
Conclusion tem. In: Leland A, Pollack I, Adelson P, eds. Princi-
ples and Practice of Pediatric Neurosurgery. 2nd
CNS amebiasis is rare and difficult to diag- ed. New York, NY: Thieme; 2008:1182–1195
nose. This infection should be considered 15. R amos-Kuri M, Montoya RM, Padilla A, et al.
in any patient with subacute and/or chron- Immunodiagnosis of neurocysticercosis. Dis-
appointing performance of serology (enzyme-
ic meningoencephalitis without evidence linked immunosorbent assay) in an unbiased
of bacterial involvement. Except for E. his- sample of neurological patients. Arch Neurol
tolytica, all other species cause disease that 1992;49(6):633–636 PubMed
16. W ilson M, Bryan RT, Fried JA, et al. Clinical
is difficult to treat and commonly fatal.
evaluation of the cysticercosis enzyme-linked
Early aggressive multidrug therapy offers immunoelectrotransfer blot in patients with
the best chance of survival and the best neurocysticercosis. J Infect Dis 1991;164(5):
possible outcome. 1007–1009 PubMed
91
17. Prabhakaran V, Rajshekhar V, Murrell KD, Oom- 33. A rana-Iniguez R. Echinococcus. In: Vinken PJ,
men A. Taenia solium metacestode glycoproteins Bruyn GW, eds. Infections of the Nervous System.
as diagnostic antigens for solitary cysticercus Part III. Handbook of Clinical Neurology 1978;
granuloma in Indian patients. Trans R Soc Trop 35:175–208
Med Hyg 2004;98(8):478–484 PubMed 34. Akhaddar A, Gourinda H, el Alami Z, el Madhi T,
18. Sinha S, Sharma BS. Neurocysticercosis: a review Miri A. Hydatid cyst of the sacrum. Report of a case.
of current status and management. J Clin Neuro- Rev Rhum Engl Ed 1999;66(5):289–291 PubMed
sci 2009;16(7):867–876 PubMed 35. A khaddar A, Gourinda H, Aghoutane M, El Alami
19. Hourani RG, Tamraz JC. Imaging of parasitic diseas- FZ, El Madhi T, Miri A. L’hydatidose vertébrale
es of the central nervous system. In: Haddad MC, chez l’enfant. A propos de 4 cas avec revue de la
Abd El Baji ME, Tamraz JC, eds. Imaging of Parasitic littérature. Rachis (Clichy) 1999;11:215–220
Diseases. Berlin, Germany: Springer; 2008:7–31 36. K haldi M, Mohamed S, Kallel J, Khouja N. Brain
20. Rangel-Castilla L, Serpa JA, Gopinath SP, Graviss hydatidosis: report on 117 cases. Childs Nerv Syst
EA, Diaz-Marchan P, White AC Jr. Contemporary 2000;16(10-11):765–769 PubMed
neurosurgical approaches to neurocysticercosis. 37. L imaiem F, Bellil S, Bellil K, et al. Primary hyda-
Am J Trop Med Hyg 2009;80(3):373–378 PubMed tidosis of the central nervous system: a retro-
21. Cruz M, Cruz I, Horton J. Albendazole versus pra- spective study of 39 Tunisian cases. Clin Neurol
ziquantel in the treatment of cerebral cysticerco- Neurosurg 2010;112(1):23–28 PubMed
sis: clinical evaluation. Trans R Soc Trop Med Hyg 38. K hazim R, Fares Y, Heras-Palou C, Ruiz Barnes
1991;85(2):244–247 PubMed P. Posterior decompression of spinal hydatido-
22. Del Brutto OH, Sotelo J, Roman GC. Therapy for sis: long term results: Fundacion Jimenez Diaz,
neurocysticercosis: a reappraisal. Clin Infect Dis Madrid, Spain. Clin Neurol Neurosurg 2003;
1993;17(4):730–735 PubMed 105(3):209–214 PubMed
23. Del Brutto OH. Prognostic factors for seizure re- 39. B raithwaite PA, Lees RF. Vertebral hydatid dis-
currence after withdrawal of antiepileptic drugs ease: radiological assessment. Radiology 1981;
in patients with neurocysticercosis. Neurology 140(3):763–766 PubMed
1994;44(9):1706–1709 PubMed 40. C hakir N, Akhaddar A, El Quessar A, et al. [Prima-
24. Suastegui Roman RA, Soto-Hernandez JL, Sotelo ry intradural extramedullary hydatidosis. Case
J. Effects of prednisone on ventriculoperitoneal report and review of the literature]. J Neuroradiol
shunt function in hydrocephalus secondary to 2002;29(3):177–182 PubMed
cysticercosis: a preliminary study. J Neurosurg 41. C iurea AV, Fountas KN, Coman TC, et al. Long-
II Etiologic Agents
1996;84(4):629–633 PubMed term surgical outcome in patients with intracra-

25. Eckert J, Deplazes P. Biological, epidemiological, nial hydatid cyst. Acta Neurochir (Wien) 2006;
and clinical aspects of echinococcosis, a zoonosis 148(4):421–426 PubMed
of increasing concern. Clin Microbiol Rev 2004; 42. A bbassioun K, Amirjamshidi A. Diagnosis and
17(1):107–135 PubMed management of hydatid cyst of the central ner-
26. Craig P, Budke CM, Schantz PM, et al. Human vous system. Part 2. Hydatid cysts of the skull,
echinococcosis: a neglected disease? Trop Med orbit and spine. Neurosurg Q 2001;11:10–16
Internat Health 2007;35:283–292 43. Lorenzo C, Ferreira HB, Monteiro KM, et al.
27. Dakkak A. Echinococcosis/hydatidosis: a severe Comparative analysis of the diagnostic perfor-
threat in Mediterranean countries. Vet Parasitol mance of six major Echinococcus granulosus an-
2010;174(1-2):2–11 PubMed tigens assessed in a double-blind, randomized
28. da Silva AM. Human echinococcosis: a ne- multicenter study. J Clin Microbiol 2005;43(6):
glected disease. Gastroenterol Res Pract 2010; 2764–2770 PubMed
2010:583297 PubMed 44. Abbassioun K, Amirjamshidi A. Diagnosis and
29. Pawlowski Z, Eckert J, Vuitton D, et al. Echinococ- management of hydatid cyst of the central nervous
cosis in humans: clinical aspects, diagnosis and system. Part 1. General considerations and hydatid
treatment. In: Eckert J, Gemmel MA, Meslin FX, disease of the brain. Neurosurg Q 2001;11:1–9
Pawlowski ZS, eds. WHO/OIE Manual on Echino- 45. Abdel Razek AAK, El-Shamam O, Abdel Wa-
coccosis in Humans and Animals: a Public Health hab N. Magnetic resonance appearance of ce-
Problem of Global Concern. Paris, France: World rebral cystic echinococcosis: World Health
Health Organization and World Organization for Organization (WHO) classification. Acta Radiol
Animal Health; 2001:20–66 2009;50(5):549–554 PubMed
30. Nourbakhsh A, Vannemreddy P, Minagar A, To- 46. Izci Y, Tüzün Y, Seçer HI, Gönül E. Cerebral hydatid
ledo EG, Palacios E, Nanda A. Hydatid disease of cysts: technique and pitfalls of surgical manage-
the central nervous system: a review of literature ment. Neurosurg Focus 2008;24(6):E15 PubMed
with an emphasis on Latin American countries. 47. Falagas ME, Bliziotis IA. Albendazole for the
Neurol Res 2010;32(3):245–251 PubMed treatment of human echinococcosis: a review of
31. Altinörs N, Bavbek M, Caner HH, Erdogan B. Cen- comparative clinical trials. Am J Med Sci 2007;
tral nervous system hydatidosis in Turkey: a co- 334(3):171–179 PubMed
operative study and literature survey analysis of 48. Ross AG, Bartley PB, Sleigh AC, et al. Schistosomiasis.
458 cases. J Neurosurg 2000;93(1):1–8 PubMed N Engl J Med 2002;346(16):1212–1220 PubMed
32. Pamir MN, Ozduman K, Elmaci I. Spinal hydatid 49. Pittella JE. Neuroschistosomiasis. Brain Pathol
disease. Spinal Cord 2002;40(4):153–160 PubMed 1997;7(1):649–662 PubMed
92
50. World Health Organization. Prevention and Con- 68. S anelli PC, Lev MH, Gonzalez RG, Schaefer PW.
trol of Schistosomiasis and Soil-Transmitted Hel- Unique linear and nodular MR enhancement pat-
minthiasis: Report of a WHO Expert Committee. tern in schistosomiasis of the central nervous
Geneva, Switzerland: WHO; 2002. Technical Re- system: report of three patients. AJR Am J Roent-
port Series No. 912 genol 2001;177(6):1471–1474 PubMed
51. Shu K, Zhang S, Han L, Lei T. Surgical treatment 69. F owler R, Lee C, Keystone JS. The role of corti-
of cerebellar schistosomiasis. Neurosurgery costeroids in the treatment of cerebral schis-
2009;64(5):941–943, discussion 943–944 PubMed tosomiasis caused by Schistosoma mansoni:
52. Lucas S, Bell J, Chimelli L. Parasitic and fungal case report and discussion. Am J Trop Med Hyg
infections. In: Love S, Louis DN, Ellison DW, eds. 1999;61(1):47–50 PubMed
Greenfield’s Neuropathology. London, England: 70. Deol I, Robledo L, Meza A, Visvesvara GS, Andrews
Hodder Arnold; 2008:1447–1487 RJ. Encephalitis due to a free-living amoeba (Bala-
53. Chacko G. Parasitic diseases of the central ner- muthia mandrillaris): case report with literature
vous system. Semin Diagn Pathol 2010;27(3): review. Surg Neurol 2000;53(6):611–616 PubMed

167–185 PubMed 71. Seidel JS. Naegleria, Acanthamoeba, and Balamuth-
54. Mackenzie IR, Guha A. Manson’s schistosomiasis ia. In: Feigin R, Cherry JS, Demmler GJ, Kaplan SL,
presenting as a brain tumor. Case report. J Neuro- eds. Textbook of Pediatric Infectious Diseases. Vol
surg 1998;89(6):1052–1054 PubMed 2. Philadelphia, PA: Saunders; 2004:2748–2755
55. Olson S, Rossato R, Guazzo E. Spinal schistosomi- 72. Marciano-Cabral F, Puffenbarger R, Cabral GA. The
asis. J Clin Neurosci 2002;9(3):317–320 PubMed increasing importance of Acanthamoeba infections.
56. K amel MH, Murphy M, Kelleher M, Aquilina K, Lim J Eukaryot Microbiol 2000;47(1):29–36 PubMed
C, Marks C. Schistosomiasis of the spinal cord pre- 73. M artinez AJ, Visvesvara GS. Free-living, am-
senting as progressive myelopathy. Case report. J phizoic and opportunistic amebas. Brain Pathol
Neurosurg Spine 2005;3(1):61–63 PubMed 1997;7(1):583–598 PubMed
57. Lei T, Shu K, Chen X, Li L. Surgical treatment of 74. G alarza M, Cuccia V, Sosa FP, Monges JA. Pe-
epilepsy with chronic cerebral granuloma caused diatric granulomatous cerebral amebiasis: a
by Schistosoma japonicum. Epilepsia 2008;49(1): delayed diagnosis. Pediatr Neurol 2002;26(2):
73–79 PubMed 153–156 PubMed
58. Braga MH, de Carvalho GT, Brandão RA, et al. Pseu- 75. M cKellar MS, Mehta LR, Greenlee JE, et al. Fa-
dotumoral form of cerebral Schistosoma man- tal granulomatous Acanthamoeba encephalitis
soni. World Neurosurg 2011;76(1-2):200–207, mimicking a stroke, diagnosed by correlation of
discussion 84–86 PubMed results of sequential magnetic resonance imag-
59. Betting LE, Pirani C Jr, de Souza Queiroz L, Damasce- ing, biopsy, in vitro culture, immunofluorescence
no BP, Cendes F. Seizures and cerebral schistosomia- analysis, and molecular analysis. J Clin Microbiol
sis. Arch Neurol 2005;62(6):1008–1010 PubMed 2006;44(11):4265–4269 PubMed
60. Junker J, Eckardt L, Husstedt I. Cervical intrame- 76. P etri WA Jr, Haque R. Amebiasis. In: Mandell GL,
dullar schistosomiasis as a rare cause of acute Bennett JE, Dolin R, eds. Bennett’s Principles and
tetraparesis. Clin Neurol Neurosurg 2001;103(1): Practice of Infectious Diseases. Philadelphia, PA:
39–42 PubMed Elsevier Churchill Livingstone; 2010:3411–3427
61. Ferrari TC, Moreira PR, Cunha AS. Spinal cord 77. Campbell S. Amebic brain abscess and me-
schistosomiasis: a prospective study of 63 cases ningoencephalitis. Semin Neurol 1993;13(2):
emphasizing clinical and therapeutic aspects. 153–160 PubMed
J Clin Neurosci 2004;11(3):246–253 PubMed 78. L ombardo L, Alonso P, Saenzarroyo L, Brandt H,
62. Nobre V, Silva LC, Ribas JG, et al. Schistosomal Humbertomateos J. Cerebral amebiasis-report of
myeloradiculopathy due to Schistosoma man- 17 cases. J Neurosurg 1964;21:704–709 PubMed
soni: report on 23 cases. Mem Inst Oswaldo Cruz 79. Fung KT, Dhillon AP, McLaughlin JE, et al. Cure of
2001;96(Suppl):137–141 PubMed Acanthamoeba cerebral abscess in a liver transplant
63. Ferrari TCA, Moreira PR, Cunha AS. Clinical patient. Liver Transpl 2008;14(3):308–312 PubMed
characterization of neuroschistosomiasis due to 80. S chuster FL, Visvesvara GS. Free-living amoebae
Schistosoma mansoni and its treatment. Acta Trop as opportunistic and non-opportunistic patho-
2008;108(2-3):89–97 PubMed gens of humans and animals. Int J Parasitol
64. Ferrari MLA, Coelho PMZ, Antunes CMF, Tavares 2004;34(9):1001–1027 PubMed
CAP, da Cunha AS. Efficacy of oxamniquine and 81. D eetz TR, Sawyer MH, Billman G, Schuster FL,
praziquantel in the treatment of Schistosoma Visvesvara GS. Successful treatment of Balamuth-
mansoni infection: a controlled trial. Bull World ia amoebic encephalitis: presentation of 2 cases.
Health Organ 2003;81(3):190–196 PubMed Clin Infect Dis 2003;37(10):1304–1312 PubMed
65. Carod-Artal FJ. Neurological complications of 82. V elho V, Sharma GK, Palande DA. Cerebrospinal
Schistosoma infection. Trans R Soc Trop Med Hyg acanthamebic granulomas. Case report. J Neuro-
2008;102(2):107–116 PubMed surg 2003;99(3):572–574 PubMed
66. Mehta A, Teoh SK, Schaefer PW, Chew FS. Ce- 83. W hite JM, Barker RD, Salisbury JR, et al.
rebral schistosomiasis. AJR Am J Roentgenol Granulomatous amoebic encephalitis. Lancet
1997;168(5):1322 PubMed 2004;364(9429):220 PubMed
67. P reidler KW, Riepl T, Szolar D, Ranner G. Cerebral 84. R ecavarren-Arce S, Velarde C, Gotuzzo E, Cabrera
schistosomiasis: MR and CT appearance. AJNR Am J. Amoeba angeitic lesions of the central nervous
J Neuroradiol 1996;17(8):1598–1600 PubMed system in Balamuthia mandrilaris amoebiasis.
Hum Pathol 1999;30(3):269–273 PubMed
93
85. De Villiers JP, Durra G. Case report: amoebic findings. AJNR Am J Neuroradiol 2006;27(6):
abscess of the brain. Clin Radiol 1998;53(4): 1217–1221 PubMed
307–309 PubMed 89. G
askill SJ, Marlin AE. Tuberculosis and fungal
86. Solaymani-Mohammadi S, Lam MM, Zunt JR, Pe- and parasitic infections of the central nervous
tri WA Jr. Entamoeba histolytica encephalitis di- system. In: Albright AL, Pollack IF, Adelson PD.
agnosed by PCR of cerebrospinal fluid. Trans R Soc Principles and Practice of Pediatric Neurosurgery.
Trop Med Hyg 2007;101(3):311–313 PubMed 2nd ed. New York, NY: Thieme; 2008:1182–1195
87. Akhaddar A, Elouennass M, Baallal H, Boucetta M. 90. S
harma PP, Gupta P, Murali MV, Ramachan-
Focal intracranial infections due to Actinomyces dran VG. Primary amebic meningoencephalitis
species in immunocompetent patients: diagnos- caused by Acanthamoeba: successfully treated
tic and therapeutic challenges. World Neurosurg with cotrimoxazole. Indian Pediatr 1993;30(10):
2010;74(2-3):346–350 PubMed 1219–1222 PubMed
88. Singh P, Kochhar R, Vashishta RK, et al. Ame- 91. M
arciano-Cabral F, Cabral G. Acanthamoeba spp.
bic meningoencephalitis: spectrum of imaging as agents of disease in humans. Clin Microbiol
Rev 2003;16(2):273–307 PubMed
II Etiologic Agents
94
8
Bacterial Brain Abscess
Bacterial brain abscess is a life-threatening and chemotherapy, increases, reports of

entity encountered in a wide variety of clin- bacterial brain abscess secondary to atypical
ical settings. The condition is often lethal if etiologic agents appear to be on the rise.
not treated, but excellent outcomes may be
achieved with proper management. With
aggressive multimodal treatment, mortality ■■ Etiologic Agent
has fallen but remains at about 10%. Diag-
nosis is at times elusive, and management The most likely etiologic agent depends on
requires the nuanced use of surgery, anti- the risk factors of the patient. In neonates,
biotics, and supportive care. Furthermore, Proteus and Citrobacter species are the most
numerous complications can occur. In this frequently cultured organisms,2,3 whereas
chapter, the epidemiology, pathophysiol- in older children and adult patients, the
ogy, diagnosis, and management of bac- most common isolates in reported series
terial brain abscesses are reviewed. Brain are Streptococcus species, in particular
abscesses caused by nonbacterial agents are Streptococcus milleri.4,5 Staphylococcal in-
discussed elsewhere in this volume. fections are most common among intrave-
nous drug users as well as after craniotomy
and trauma, as a result of inoculation from
■■ Epidemiology contaminated skin. Bacteroides species
(Fig. 8.1), which are anaerobic gram-nega-
Brain abscesses are not uncommon and oc- tive bacilli that are part of the normal flora
cur in the United States at a rate of approxi- within the digestive system, are also not
mately 2,500 per year.1 The prevalence is infrequently isolated.5
highest in young men, and increased rates Aerobic gram-negative bacilli, includ-
are also observed in young children and neo- ing Escherichia coli, Haemophilus influen-
nates; each of these groups exhibits different zae, Pseudomonas aeruginosa, and Klebsiella
risk factors and therefore different microbial pneumoniae, are also isolated from brain ab-
profiles. Worldwide, the prevalence prob- scesses with some frequency—the latter of-
ably varies significantly as the percentage ten in association with diabetes mellitus as
of populations with immunocompromise, a risk factor.6 Nocardia species are atypical
immunization rates, and prevalence of other bacteria that form branching filaments (Fig.
risk factors vary. As the number of patients 8.2) and can cause brain abscess, particu-
with immunocompromise due to human larly in immunocompromised patients. No-
immunodeficiency virus (HIV) and to iatro- cardia brain abscesses are generally difficult
genic causes, such as solid-organ transplant to treat, and mortality rates are higher than
Fig. 8.2 Modified Brown-Brenn stain showing the
fine, filamentous bacterium Nocardia asteroides in a
cardiac transplant recipient with a brain abscess (mag-
nification ×160).
Immunocompromised patients are at a

higher risk for brain abscesses. HIV infec-
tion is in particular a risk factor for bacterial
Fig. 8.1 Contrast-enhanced axial computed tomo- brain abscess; however, in this population,
graphic scan of the brain shows a left occipital Bacteroi- CNS lymphoma, Toxoplasma gondii (Fig.
des fragilis brain abscess that, until the biopsy yielded 8.3) abscess, and metastatic disease are
II Etiologic Agents
pus, was thought to represent a brain metastasis in a also relatively common. The evaluation of
patient with a long history of smoking. a ring-enhancing lesion in this population
is therefore particularly challenging. Iatro-
genic causes of immunocompromise, such
as cancer chemotherapy and immunosup-
those for other bacterial brain abscesses.7,8 pression after solid-organ transplant, are
Spread of Nocardia to the brain is most often also risk factors for brain abscess devel-
hematogenous. Propionibacterium acnes can opment. Transplant patients have an in-
cause brain abscess, and as with other cases creased risk for developing nocardial brain
of Propionibacterium acnes CNS involve- abscesses,14–17 which may be part of dis-
ment, such infections tend to be less severe seminated infection. Diabetes mellitus and
and may occur in a delayed fashion.9,10 cystic fibrosis result in an increased risk for
A significant percentage of brain ab- systemic infections and for brain abscess.
scesses are polymicrobial. Most series also Anatomic risk factors include the pres-
contain a significant number of brain ab- ence of cyanotic heart disease and heredi-
scesses that are sterile when cultured,5,6,11,12 tary hemorrhagic telangiectasia (HHT). HHT
which may be due to prior treatment with results in a dramatically increased risk for
antibiotics13 or to issues related to the han- brain abscess, which is likely the result of
dling of collected samples. paradoxical emboli from pulmonary ar-
teriovenous malformations (Fig. 8.4) and
most often due to Streptococcus species.18 A
■■ Risk Factors higher mortality rate has been reported for
brain abscess associated with HHT.19,20 Cya-
Risk factors for the development of brain notic heart disease is a specific risk factor for
abscess may be divided into those resulting pediatric patients.21,22 Dermoid cysts may
from immunologic factors, those due to an- contain a sinus tract in communication with
atomic issues, and those due to increased the skin that can result in abscess formation,
exposure to pathogens. particularly within the cerebellum.23,24
96
Fig. 8.3 Toxoplasma gondii bradyzoite isolated from a Fig. 8.4 Contrast-enhanced computed tomographic
brain abscess in a patient with acquired immunodefi- scan of the chest demonstrating an arteriovenous mal-
ciency syndrome (AIDS) stained with hematoxylin and formation in the posterior aspect of the left lung in a
eosin (magnification ×160). patient with hereditary hemorrhagic telangiectasia.
Risk factors that derive from increased lobes. Their origin is often within the white
exposure to pathogens include intravenous matter adjacent to the cerebral cortex. Ab-
drug use, a history of intracranial surgery scesses that result from direct extension
(including a history of cervical traction or of sinus infection are located in the fron-
8 Bacterial Brain Abscess

halo pin placement), a history of meningi- tal lobe, and the temporal lobe is often the
tis, dental surgery, and a history of recur- site of abscesses that are the result of mas-
rent sinusitis and otitis media. Otitis media toiditis (Fig. 8.5). Cerebellar abscesses can
and sinusitis account for the majority of have an otogenic origin. Abscesses of the
abscesses in several series.25 Odontogenic brainstem are rare33 but do occur, and as
abscesses are frequently mentioned in case expected, they carry a poor prognosis.
reports,26 although the frequency of their The stages of brain abscess develop-
true causality is uncertain. ment, from inoculation of the brain paren-
Brain abscess after a neurosurgical pro- chyma to capsule development, have been
cedure is a rare but well-known complica- described.34 These stages include the early
tion. Two large retrospective studies have and late cerebritis stages followed by the
been performed and found similar rates of early and late capsule stages. During the
brain abscess after craniotomy that were early cerebritis stages, inflammation and
just under 0.2%.27,28 Similarly low rates have edema develop in response to the presence
been described after transnasal endoscopic of an infectious inoculum. An area of cen-
skull base surgery.29 Among neurosurgical tral necrosis starts to form, with fibroblast
procedures, the placement of halo pins, deposition of reticulin along the margin
such as those used for cervical immobili- during the late cerebritis phase. The for-
zation, is associated with numerous case mation of a ring-enhancing margin defines
reports of brain abscess formation, and the capsule stages (Fig. 8.6); it starts as a
the risk may be increased by retightening vascular, gliotic structure (early) and then
pins that have become loose after original is sequestered within a completed collagen
placement.30–32 border (late).
A murine model of staphylococcal brain
abscess has suggested that despite the fact
■■ Pathophysiology that the purulent material is sequestered
from the rest of the brain, localized in-
Brain abscesses may occur anywhere with- flammation mediated by tumor necrosis
in the brain, although the most frequent factor-α (TNF-α), interleukin-1b (IL-1b),
sites are the frontal, temporal, and parietal and macrophage inflammatory protein-2
97
Fig. 8.5 Axial contrast-enhanced T1-weighted mag-
netic resonance image of the brain demonstrating
Streptococcus species mastoiditis with direct extension
into the posterior fossa, resulting in a brain abscess in
Fig. 8.6 Contrast-enhanced T1-weighted magnetic
the left cerebellar hemisphere.
resonance image of the brain shows a brain abscess
in the late capsular stage with a completed collagen
II Etiologic Agents
border. The abscess was dental in origin and grew an

anaerobic Streptococcus species on culture.
(MIP-2) may contribute to damage of the

adjacent parenchyma.35 This inflammation,
however, may be necessary for an optimal
host response because animals deficient in cause of the immune-privileged nature of
TNF-α or IL-1 exhibit reduced survival after the CNS and the size limitations of the in-
experimental abscess, the latter of which tracranial space, brain abscesses most fre-
may be mediated downstream by the che- quently present with signs and symptoms
mokines CXCL13 and CCL9.36 A member of of a mass lesion. As such, headache, nausea,
the toll-like receptor family, toll-like recep- vomiting, lethargy, and focal neurologic
tor-2 (TLR-2), which is expressed on neu- deficits may be seen. Fever and meningis-
trophils and macrophages and recognizes mus are often absent.28 Papilledema is oc-
molecular motifs associated with Staphy- casionally present and adds urgency to
lococcus species and other pathogens, ap- the patient assessment. Careful evaluation
pears to be a pathway of inflammatory for the presence of risk factors is crucial
initiation.37 in leading to the correct diagnosis. In neo-
nates, signs of abscess may include seizures,
enlarging head circumference, decreased
■■ Diagnosis feeding, and respiratory difficulties.2
Because the presentation is often es-
The diagnosis of brain abscesses is often de- sentially that of a mass lesion, clues that
layed because of the nonspecific nature of distinguish the clinical picture from that
the presentation. One of the pitfalls in rec- of a patient presenting with a brain tumor
ognition is the incorrect assumption that should be sought. A history of intravenous
a patient with a brain abscess will present drug use, immunocompromise, or relevant
with signs and symptoms of infection. Be- infection is important, and the physical ex-
98
amination then focuses on signs of dental ■■ Imaging
or otologic infection. A history of previ-
ous malignancy or tobacco exposure or a Computed tomography (CT) is often the first
strong family history of cancer is similarly imaging study obtained and shows evidence
more suggestive that a ring-enhancing le- of a mass lesion with surrounding cerebral
sion may be a neoplasm. Finally, the time edema. On CT, peripheral rim enhancement
course is occasionally a clue because intra- is seen on contrast studies with a central
parenchymal brain abscesses often have a area of hypodensity (Fig. 8.8). Magnetic
shorter time course than do malignancies. resonance (MR) imaging similarly reveals a
Laboratory investigations may reveal an contrast-enhancing lesion with surround-
elevated white blood cell count and inflam- ing edema (see Fig. 8.6). Contrast enhance-
matory markers, in particular C-reactive ment may be more prominent along the
protein. Serum chemistries should also be region closer to the ventricle, although this
obtained to assess for the presence of elec- finding is not consistent among patients.
trolyte imbalances, and the coagulation The presence of restricted diffusion within
profile should be obtained in anticipation the enhancing ring is strongly suggestive of
of surgical intervention. a pyogenic abscess.38 MR spectroscopy can
Once the diagnosis of brain abscess is distinguish abscess from a neoplastic lesion
suspected, obtaining material for culture is by the presence of increased amino acids
critical in determining appropriate antibi- and acetate38; however, treatment should
otic therapy. Blood cultures should be ob- not be delayed to obtain this test.
tained in any patient suspected of having a

brain abscess, although these are positive in
a minority of cases. Lumbar puncture should
not be attempted because it carries a risk for
neurologic deterioration when performed12
and is often nondiagnostic. Aspiration of the
lesion (as described in the section on treat-
ment) is often necessary to obtain positive
cultures (Fig. 8.7). Ideally, empiric antibiotic
therapy should be delayed until a definitive
culture is obtained because sterile cultures
may otherwise occur.
Fig. 8.8 Axial contrast-enhanced computed tomo-

graphic scan of the brain shows a brain abscess with
central hypodensity that represents pus and cerebral
Fig. 8.7 Intraoperative photograph shows a stereotac- edema that surrounds a well-established late-stage
tic aspiration of a brain abscess. Note the purulent mate- capsule. The abscess, in a patient who had received a
rial filling the syringe as a result of gentle aspiration. heart transplant, grew Nocardia asteroides.
99
■■ Treatment
Bacterial brain abscesses are treated with
antibiotics, which should be started as
soon as an adequate specimen is obtained
for culture. Prolonged treatment with in-
travenous antibiotics should be anticipat-
ed and arrangements can be made, such as
placement of an intravenous catheter for
extended use. Empiric antibiotic treatment
with broad coverage (e.g., vancomycin,
metronidazole, and cefotaxime) is usually
started at the time cultures are obtained.
The antibiotic regimen is then tailored to
the specific pathogen once sensitivities
are determined. Anticonvulsant drugs are
administered prophylactically to prevent
seizures. In most situations, corticoste-
roids are avoided because of the belief that
their presence will diminish the immune
response and stabilize the blood–brain
barrier, thereby decreasing antibiotic pen-
etration. Corticosteroids can effectively
reduce intracerebral swelling secondary to Fig. 8.9 Significant cerebral edema can develop sur-
II Etiologic Agents
the vasogenic edema associated with brain rounding a brain abscess, as is apparent on this axial
abscesses (Fig. 8.9). Experimental models T2-weighted magnetic resonance image of the brain.
have differed on whether dexamethasone The ring-shaped area of decreased signal represents
significantly alters the local immune re- the abscess capsule.
sponse to bacterial pathogens.39,40 Dexa-
methasone is often administered before it
has been determined that the intracranial
lesion is an abscess, and occasionally in the the abscess. Stereotactic drainage offers a
presence of a known pyogenic brain ab- less invasive surgical approach that is bet-
scess to treat life-threatening edema with ter suited for deep-seated lesions (see Fig.
mass effect and impending herniation. 8.7). In cases in which surgery is primarily
Medical therapy alone may be contem- for diagnostic purposes, stereotactic aspi-
plated for patients with smaller lesions ration may be preferable to craniotomy.
that are generally less than 2.5 cm in diam- Kondziolka et al have described good re-
eter, particularly if the lesion is deep-seat- sults with stereotactic drainage, with the
ed within the brain or if multiple lesions failures of this technique occurring in cases
are present. For lesions with a diameter that had inadequate antibiotic treatment
larger than 2.5 cm, surgical treatment is or insufficient aspiration and in larger ab-
recommended if feasible. The goals of sur- scesses that did not undergo any form of
gery include definitive identification of the drainage.41 Open surgery is preferable for
causative agent and removal of as much lesions located in the cerebellum and for
purulent material as possible. Open sur- the treatment of recurrent abscesses. Great
gery and stereotactic aspiration have both care must be taken at the time of surgery
been advocated. The advantage of open not to inoculate the ventricular system
surgery, via craniotomy and corticectomy, with infectious material. Unless grossly in-
is the ability to perform a more extensive fected or in the presence of osteomyelitis,
removal of infectious material while open- the bone flap may be replaced at the time
ing any loculated compartments within of surgery.
100
For patients with signs of hydrocepha- ■■ Complications
lus or with posterior fossa abscesses ex-
erting mass effect on the fourth ventricle Seizures
(Fig. 8.10), an external ventricular drain
Seizures can frequently complicate the
should be placed to alleviate or prevent
treatment of bacterial brain abscess either
cerebrospinal fluid (CSF) obstruction. The
early or later in the course of the disease.
ventriculostomy will be either gradually
The use of prophylactic antiepileptic drugs
withdrawn over time and removed or re-
is appropriate, although strong evidence
placed by a shunt at a later time. Permanent
for their benefit is lacking and there is no
shunt hardware is not placed until it has
consensus on the duration of treatment.
been demonstrated that the CSF is sterile
Any patient with an unexplained decline
on multiple cultures.
in mental function should receive intensive
Supportive treatment for the patient
care unit–based electroencephalographic
includes intubation and mechanical ven-
monitoring for 24 hours once intraventric-
tilation when necessary and the correc-
ular rupture and sepsis have been excluded.
tion of any electrolyte imbalances when
present. Patients often present after an ex-
tended period of anorexia, and aggressive Ventriculitis
fluid resuscitation is necessary to optimize Purulent ventriculitis is one of the most
care. Withdrawal from recreational drugs feared complications of brain abscess and
that include alcohol must also be identi- is the most common cause of death after
fied and treated appropriately when pres-

surgery for brain abscess.11 Intraventricu-
ent because hospitalization may represent lar extension may occur either sponta-
an extended absence of such agents. If an neously or as a complication of surgical
infectious source is identified, it must be intervention. Abscess rupture into the ven-
treated aggressively, as well. tricle often presents as a sudden deterio-
ration in neurologic function or may be
heralded by signs and symptoms of men-
ingismus or sepsis. Once intraventricular
rupture does occur, the mortality rate is as
high as 80%.42 Intraventricular purulence
should be treated with the placement of
an external ventricular drain, the intra-
thecal administration of antibiotics, and
the surgical treatment or re-treatment of
the primary abscess if appropriate. With
aggressive multimodal treatment, lower
mortality rates have been reported for
brain abscess.43
Hydrocephalus
Hydrocephalus occurs occasionally as a
complication of brain abscesses, in par-
ticular in those patients who survive ven-
tricular involvement. Hydrocephalus is
also fairly frequently observed in neonates
with brain abscesses because many of
Fig. 8.10 Axial T1-weighted contrast-enhanced mag- these occur in conjunction with meningi-
netic resonance image of the brain shows a cerebellar tis. Hydrocephalus in this setting is usually
brain abscess that caused acute hydrocephalus, requir-
communicating in nature and therefore
ing emergent placement of an external ventricular
drain to relieve cerebrospinal fluid obstruction. should be treated with shunt placement as
101
opposed to an endoscopic third ventricu- their successful culture is key to optimizing
lostomy. The shunt is placed after sterile the medical arm of management. Patients
CSF cultures and benign CSF profiles have at risk for bacterial brain abscess often
been demonstrated. Loculi may be present present additional challenges by virtue of
in the ventricles, particularly in survivors their medical comorbidities, socioeconom-
of ventriculitis, and in these cases a single ic issues, and neonatal age. Complications
ventricular catheter may not be sufficient such as hydrocephalus, epilepsy, and intra-
to treat the resultant hydrocephalus. En- ventricular rupture of the abscess can all
doscopic fenestration may be an option in result in the rapid clinical deterioration of
such complicated cases. a previously stable patient. Despite these
challenges, aggressive, appropriate mul-
Recurrent Abscesses tispecialty care is often rewarded with an
excellent long-term patient outcome.
Successful treatment of bacterial brain
abscesses requires vigilance for recurrent References
disease. Abscesses may recur in a delayed
fashion after ostensibly successful treat- 1. Hall WA, Truwit CL. The surgical management
of infections involving the cerebrum. Neuro-
ment. For this reason, patients treated surgery 2008;62(Suppl 2):519–530, discussion
for bacterial brain abscess are followed 530–531 PubMed
with surveillance MR imaging every 4 to 6 2. Renier D, Flandin C, Hirsch E, Hirsch JF. Brain ab-
scesses in neonates. A study of 30 cases. J Neuro-
weeks until the lesions have resolved com- surg 1988;69(6):877–882 PubMed
pletely. Outpatient follow-up should be for 3. Goodkin HP, Harper MB, Pomeroy SL. Intracere-
a minimum of 1 year. Predisposing factors bral abscess in children: historical trends at Chil-
that are modifiable must be addressed on a dren’s Hospital Boston. Pediatrics 2004;113(6):
1765–1770 PubMed
long-term basis.
II Etiologic Agents
4. de Louvois J, Gortavai P, Hurley R. Bacteriology of

abscesses of the central nervous system: a mul-
ticentre prospective study. BMJ 1977;2(6093):
981–984 PubMed
■■ Outcome 5. Hakan T, Ceran N, Erdem I, Berkman MZ, Göktaş
P. Bacterial brain abscesses: an evaluation of 96
The survival for brain abscess has improved cases. J Infect 2006;52(5):359–366 PubMed
with the development of more potent anti- 6. Kao PT, Tseng HK, Liu CP, Su SC, Lee CM. Brain
abscess: clinical analysis of 53 cases. J Microbiol
biotics and a refinement of surgical tech- Immunol Infect 2003;36(2):129–136 PubMed
nique. Mortality in most modern series is 7. Kilincer C, Hamamcioglu MK, Simsek O, et al. No-
approximately 10%. Survivors of neonatal cardial brain abscess: review of clinical manage-
ment. J Clin Neurosci 2006;13(4):481–485 PubMed
brain abscess often have significant cogni- 8. Sabuncuoğlu H, Cibali Açikgo ZZ, Caydere M, Ustün
tive deficits.2 This impairment may be due H, Semih Keskil I. Nocardia farcinica brain abscess:
to previous meningitis, postinfectious epi- a case report and review of the literature. Neuro-
lepsy, or both. Adult patients with bacterial cirugia (Astur) 2004;15(6):600–603 PubMed
9. Chung S, Kim JS, Seo SW, et al. A case of brain
brain abscess whose course was compli- abscess caused by Propionibacterium acnes 13
cated by intraventricular rupture are also months after neurosurgery and confirmed by
often severely disabled. In our experience, 16S rRNA gene sequencing. Korean J Lab Med
2011;31(2):122–126 PubMed
excellent outcomes in otherwise uncom-
10. K ranick SM, Vinnard C, Kolson DL. Propionibac-
plicated cases are possible with appropri- terium acnes brain abscess appearing 10 years
ate treatment. after neurosurgery. Arch Neurol 2009;66(6):
793–795 PubMed
11. Beller AJ, Sahar A, Praiss I. Brain abscess. Review of
89 cases over a period of 30 years. J Neurol Neuro-
■■ Conclusion surg Psychiatry 1973;36(5):757–768 PubMed
12. N athoo N, Nadvi SS, Narotam PK, van Dellen JR.
Brain abscess: management and outcome analysis
Brain abscess is a life-threatening disease of a computed tomography era experience with
entity that is challenging both to diagnose 973 patients. World Neurosurg 2011;75(5-6):
and to treat. A wide array of pathogens 716–726, discussion 612–617 PubMed
may be responsible for the infection, and 13. M ampalam TJ, Rosenblum ML. Trends in the
102 management of bacterial brain abscesses: a re-
view of 102 cases over 17 years. Neurosurgery 30. K ono Y, Prevedello DM, Snyderman CH, et al.
1988;23(4):451–458 PubMed One thousand endoscopic skull base surgical
14. Jimenez-Galanes Marchan S, Meneu Díaz JC, Caso procedures demystifying the infection potential:
Maestro O, et al. Disseminated nocardiosis: a rare incidence and description of postoperative men-
infectious complication following non-heart-beat- ingitis and brain abscesses. Infect Control Hosp
ing donor liver transplantation. Transplant Proc Epidemiol 2011;32(1):77–83 PubMed
2009;41(6):2495–2497 PubMed 31. Q uiñones-Hinojosa A, Chi JH, Manley GT. Emer-
15. Kalokhe AS, Kraft CS, Lyon GM, Lim P, Wang J. A gent placement of halo orthosis after a traumatic
35-year-old woman with prior renal transplanta- cervical injury leading to a cerebral abscess. J
tion admitted with a temporal brain abscess. Clin Trauma 2007;62(6):E11–E13 PubMed
Infect Dis 2011;53(8):843–844, 797 PubMed 32. S aeed MU, Dacuycuy MA, Kennedy DJ. Halo pin
16. M oon JH, Cho WS, Kang HS, Kim JE. Nocardia brain insertion-associated brain abscess: case re-
abscess in a liver transplant recipient. J Korean port and review of literature. Spine 2007;32(8):
Neurosurg Soc 2011;50(4):396–398 PubMed E271–E274 PubMed
17. Belhocine W, Purgus R, Almasalma M, et al. Nocar- 33. S uzer T, Coskun E, Cirak B, Yagci B, Tahta K. Brain
dia carnea infection in a kidney transplant recipient. stem abscesses in childhood. Childs Nerv Syst
Transplant Proc 2010;42(10):4359–4360 PubMed 2005;21(1):27–31 PubMed
18. Sell B, Evans J, Horn D. Brain abscess and he- 34. B ritt RH, Enzmann DR, Placone RC Jr, Obana WG,
reditary hemorrhagic telangiectasia. South Med Yeager AS. Experimental anaerobic brain abscess.
J 2008;101(6):618–625 PubMed Computerized tomographic and neuropatho-
19. Hall WA. Hereditary hemorrhagic telangiectasia logical correlations. J Neurosurg 1984;60(6):
(Rendu-Osler-Weber disease) presenting with 1148–1159 PubMed
polymicrobial brain abscess. Case report. J Neu- 35. Baldwin AC, Kielian T. Persistent immune activation
rosurg 1994;81(2):294–296 PubMed associated with a mouse model of Staphylococcus
20. Dong SL, Reynolds SF, Steiner IP. Brain abscess in aureus-induced experimental brain abscess. J Neu-
patients with hereditary hemorrhagic telangiec- roimmunol 2004;151(1-2):24–32 PubMed
tasia: case report and literature review. J Emerg 36. K ielian T, Bearden ED, Baldwin AC, Esen N. IL-1

Med 2001;20(3):247–251 PubMed and TNF-alpha play a pivotal role in the host
21. Goodman ML, Nelson PB. Brain abscess compli- immune response in a mouse model of Staphy-
cating the use of a halo orthosis. Neurosurgery lococcus aureus-induced experimental brain
1987;20(1):27–30 PubMed abscess. J Neuropathol Exp Neurol 2004;63(4):
22. Kao KL, Wu KG, Chen CJ, et al. Brain abscesses 381–396 PubMed
in children: analysis of 20 cases presenting at a 37. Kielian T, Haney A, Mayes PM, Garg S, Esen N. Toll-
medical center. J Microbiol Immunol Infect 2008; like receptor 2 modulates the proinflammatory mi-
41(5):403–407 PubMed lieu in Staphylococcus aureus-induced brain abscess.
23. Mehnaz A, Syed AU, Saleem AS, Khalid CN. Clini- Infect Immun 2005;73(11):7428–7435 PubMed
cal features and outcome of cerebral abscess in 38. L ai PH, Ho JT, Chen WL, et al. Brain abscess and
congenital heart disease. J Ayub Med Coll Abbot- necrotic brain tumor: discrimination with pro-
tabad 2006;18(2):21–24 PubMed ton MR spectroscopy and diffusion-weighted
24. Akhaddar A, Jiddane M, Chakir N, El Hassani imaging. AJNR Am J Neuroradiol 2002;23(8):
R, Moustarchid B, Bellakhdar F. Cerebellar ab- 1369–1377 PubMed
scesses secondary to occipital dermoid cyst with 39. N euwelt EA, Lawrence MS, Blank NK. Effect of
dermal sinus: case report. Surg Neurol 2002; gentamicin and dexamethasone on the natural
58(3-4):266–270 PubMed history of the rat Escherichia coli brain abscess
25. Roche M, Humphreys H, Smyth E, et al. A twelve- model with histopathological correlation. Neuro-
year review of central nervous system bacterial surgery 1984;15(4):475–483 PubMed
abscesses; presentation and aetiology. Clin Mi- 40. Schroeder KA, McKeever PE, Schaberg DR, Hoff JT.
crobiol Infect 2003 Aug;9(8):804–809 Effect of dexamethasone on experimental brain
26. Karagöz Güzey F, Bas NS, Sencer A, et al. Posterior abscess. J Neurosurg 1987;66(2):264–269 PubMed
fossa dermoid cysts causing cerebellar abscesses. 41. K ondziolka D, Duma CM, Lunsford LD. Factors
Pediatr Neurosurg 2007;43(4):323–326 PubMed that enhance the likelihood of successful stereo-
27. Corson MA, Postlethwaite KP, Seymour RA. Are tactic treatment of brain abscesses. Acta Neuro-
dental infections a cause of brain abscess? Case chir (Wien) 1994;127(1-2):85–90 PubMed
report and review of the literature. Oral Dis 42. Z eidman SM, Geisler FH, Olivi A. Intraventricular
2001;7(1):61–65 PubMed rupture of a purulent brain abscess: case report.
28. McClelland S III, Hall WA. Postoperative central Neurosurgery 1995;36(1):189–193, discussion
nervous system infection: incidence and associ- 193 PubMed
ated factors in 2111 neurosurgical procedures. 43. Takeshita M, Kawamata T, Izawa M, Hori T. Pro-
Clin Infect Dis 2007;45(1):55–59 PubMed dromal signs and clinical factors influencing out-
29. Yang SY. Brain abscess: a review of 400 cases. J come in patients with intraventricular rupture of
Neurosurg 1981;55(5):794–799 PubMed purulent brain abscess. Neurosurgery 2001;48(2):
310–316, discussion 316–317 PubMed
103
III
CNS Locations for Infection
9
Meningeal Infections
Manika Suryadevara and Joseph B. Domachowske
The clinical presentation of fever, head- demiologic and surveillance studies from
ache, and stiff neck raises the clinical suspi- the United States, Europe, Brazil, Israel,
cion of meningeal infection in most cases, and Canada show that bacterial meningitis
while biochemical, cellular, and microbio- is less common in developed parts of the
logical analysis of the cerebrospinal fluid world but is generally caused by the same
(CSF) confirms the presence of inflamma- groups of microorganisms found in under-
tory cells and biochemical perturbations developed regions.
and identifies the etiologic agent. Acute The development and implementation
bacterial meningitis is a medical emergen- of vaccines to prevent infections caused
cy, and before the antibiotic era it was al- by the three most common agents of bac-
most always a fatal infection. The incidence terial meningitis (Haemophilus influenzae
and demographics of meningeal infections type B [HIB], Streptococcus pneumoniae,
vary by age and geographic location. Many and Neisseria meningitidis) have had pro-
of these differences are the direct result of found effects on the epidemiology of men-
effective immunization measures for the ingitis in children from all regions of the
common causes of bacterial meningitis world where these vaccines are routinely
that have been introduced across the de- available.
veloped world.
■■ Etiology and Pathogenesis

■■ Incidence and Demographics
Most cases of bacterial meningitis result
Bacterial meningitis is a significant global from hematogenous seeding of the menin-
health problem with dramatic differences ges. Direct extension of a bacterial infection
in infection rates when developed coun- from the sinuses, middle ear, or mastoid
tries are compared with underdeveloped air cells is another route of spread. Such a
regions of the world. In Senegal, Africa, the source is immediately obvious on neuroim-
average incidence of bacterial meningitis aging. The most common microbiological
during the 1970s was 50 cases per 100,000 causes and pathogenesis of bacterial men-
people, with an alarming 1 in 250 children ingitis differ based on the age of the affect-
developing meningitis during their first ed patient (Table 9.1). Common etiologic
year of life.1–3 Sub-Saharan Africa is com- agents of bacterial meningitis in the first
monly referred to as the meningitis belt week of life include Streptococcus agalac-
because of epidemics of meningococcal tiae (group B streptococci), Escherichia coli,
meningitis, with incidence rates as high and Listeria monocytogenes.6–10 Late-onset
as 100 cases per 100,000 people.4,5 Epi- neonatal meningitis occurs after the first
Table 9.1 Common infecting pathogens and recommended empiric antimicrobial therapy for acute bacterial
meningitis by age group
Recommended empiric antibiotic therapy pending

Age group Most common pathogens culture result
Neonates and Group B streptococci, ampicillina + cefotaximea

infants up to Escherichia coli, Listeria OR
3 mo monocytogenes ampicillina + gentamicina
Older infants, Streptococcus pneumoniae, vancomycin (60 mg/kg/ d divided every 6 h in children)
children, and Neisseria meningitidis vancomycin (45 mg/kg/d divided every 8 h in adults)
adults younger PLUS
than 50 years cefotaxime (300 mg/kg/ d up to 12 g/d divided every 6 h)
OR
ceftriaxone (100 mg/kg/d up to 4 g/d divided every 12 h)
Adults older S. pneumoniae, N. meningitidis, ampicillin (12 g/d divided every 4 h)

than 50 years L. monocytogenes, gram- +
negative bacilli vancomycin + cefotaxime or ceftriaxone as above
a
ntibiotic dosing in neonates depends on age and weight. From birth to 7 days, the doses for ampicillin and cefotaxime
A
are the same and are 150 mg/kg per day divided every 8 hours. From days 8 through 28, they are 200 mg/kg per day di-
vided every 6 hours, and after 28 days they are 300 mg/kg per day divided every 6 hours. The gentamicin dose from birth
to 7 days is 5 mg/kg per day divided every 12 hours. After 7 days, the dose of gentamicin is 7.5 mg/kg per day divided
every 8 hours with therapeutic drug monitoring.
week of life and up to 3 months of age and with uncomplicated bacterial meningitis
may be caused by the agents listed above, will usually demonstrate leptomeningeal
other enteric gram-negative bacilli, Pasteu- enhancement (Fig. 9.1) if a contrast image
rella after animal exposure,11 pneumococci, is performed.
meningococci, and staphylococci.12
During late infancy and early child-
hood, S. pneumoniae and N. meningitidis
account for 80% of cases of bacterial men-
ingitis.13–16 The remaining 20% are caused
by L. monocytogenes, Streptococcus pyo-
genes (group A streptococci), S. agalactiae
(group B streptococci), H. influenzae (type
B and nontypeable isolates), E. coli, and
other enteric gram-negative rods (includ-
ing Salmonella species). Bacterial menin-
gitis in adolescents and younger adults is
usually caused by either S. pneumoniae or
N. meningitidis17–19; however, after the age
of 50 years, L. monocytogenes becomes
more prevalent.20 In elderly individuals, S.
pneumoniae, N. meningitidis, and L. mono-
cytogenes remain the more common mi-
crobiological etiologic agents21; however,
a broad array of other pathogens has been
described, depending on the presence of
comorbidities, travel, and unusual expo-
sures.22 Neuroimaging studies of patients Fig. 9.1 Diffuse leptomeningeal enhancement seen on
a contrast-enhanced magnetic resonance image from a
4-month-old girl with meningococcal meningitis.
108
Haemophilus influenzae Type B Disease Control and Prevention, showed a
Meningitis 59% decline in pneumococcal meningitis in
children younger than 2 years of age,27 and
HIB is a gram-negative organism that in- Nationwide Inpatient Sample data showed
vades via the respiratory tract. The pri- that the incidence rate fell by 33% in chil-
mary virulence factor is the polysaccharide dren younger than 5 years of age (from 0.8
capsule, which allows it to evade the host’s to 0.55 cases per 100,000 population).28
innate immune defenses. Other encapsu-
lated types of H. influenzae (types A, C, D, Meningococcal Meningitis
E, and F) and nontypeable, or unencapsu-
lated, forms of the bacterial species are rare N. meningitidis is a gram-negative diplo-
causes of meningitis, usually seen in pa- coccus. Major virulence factors include
tients with humoral immune deficiencies. the presence of lipopolysaccharide (endo-
A primary site of infection, such as the lung toxin), expression of an immunoglobulin
or middle ear, may precede the bacteremia A protease, and the presence of a poly-
that is ultimately responsible for hematog- saccharide capsule that allows the organ-
enous seeding of the meninges. Once the ism to evade the host’s innate immune
most common bacterial form of meningi- response. The 12 serogroups of N. menin-
tis during childhood, HIB infection is now gitidis known to infect humans are charac-
a rare occurrence in countries where vac- terized by the polysaccharide expressed on
cination programs are in place. A diagno- the capsule: A, B, C, 29-E, H, I, K, L, W-135,
sis of HIB meningitis in a vaccinated child X, Y, and Z. Clinically, the most relevant and
merits special attention. Although primary most prevalent serogroup types are A, B, C,
9 Meningeal Infections
vaccine failure with breakthrough infec- Y, and W-135. Invasive disease caused by
tion can occur, every such child should be the other types is unusual. Asymptomatic
evaluated for the possibility of an immu- nasopharyngeal carriage of the bacterium
nodeficiency condition. Based on the enor- is relatively common. In the United States,
mous success of HIB vaccination programs carrier prevalence in the general popula-
in children, HIB meningitis has become a tion is estimated to be between 5 and 10%.
disease found predominately in adults in During adolescence, this prevalence can
the United States and Europe.23–25 increase to as high as 35%. In situations
of close contact, such as military barracks
and college dormitories, carriage rates may
Pneumococcal Meningitis
approach 100%.29 The balance between
S. pneumoniae is now the leading cause of carriage and the development of disease is
bacterial meningitis in the United States affected by a combination of host and en-
and Europe, accounting for more than 60% vironmental factors, along with the char-
of all cases.26 The polysaccharide capsule acteristics of the infecting organism.30,31
functions as a primary virulence factor, and Several social factors may also increase
more than 90 different capsular serotypes risk, such as close contact with an infected
have been described. The serotypes differ person and living or working in crowded
in prevalence and their tendency for anti- conditions. It would appear that changes in
biotic resistance. Some serotypes are more behavior are the driving force behind the
likely to cause invasive disease, including increased risk for meningococcal carriage
meningitis. Like HIB meningitis, pneumo- in adolescents, particularly with regard to
coccal meningitis is usually secondary to smoking and alcohol consumption.32,33
hematogenous seeding of the meninges, The proportion of cases of meningococ-
with a primary focus in the sinopulmonary cal disease caused by individual serogroups
tract. After introduction of the conjugate A, B, C, W-135, and Y varies by geographic
vaccine in 2000, U.S. population–based region. In developed countries, serogroup
data from the Active Bacterial Core surveil- distribution also differs within regions. In
lance (ABCs), published by the Centers for Great Britain, for example, serogroups B and
109
C account for over 90% of cases, whereas Meningitis Caused by Streptococcus
in New Zealand, serogroup B alone causes pyogenes (Group A Streptococci)
87% of all cases. In contrast, meningococcal
meningitis diagnosed in the African men- S. pyogenes accounts for approximately 1%
ingitis belt is usually caused by serogroup of all cases of bacterial meningitis in chil-
A. Attack rates during epidemics in Africa dren and adults.48 Primary infection of the
approach 1% of the population.34–36 In Saudi middle ear, lung, or sinuses is the rule, with
Arabia, where serogroup W-135 predomi- bacteremic spread to the central nervous
nates, attack rates have been described at system (CNS), but cases also occur following
25 cases per 100,000 population during the recent head injury, after neurosurgical pro-
Hajj.37–40 The country of Niger has recently cedures, in the presence of a neurosurgical
experienced the emergence of serogroup device, and in patients with CSF leaks.49,50
X, where it caused half of 1,139 cases in Reported mortality rates vary from 4 to 27%,
2006.41 In the United States, between 1,200 with neurologic sequelae in 28%. Common
and 3,500 cases of meningococcal disease complications in children include learn-
occur annually (0.9 to 1.5 cases per 100,000 ing difficulties and other cognitive deficits,
population). Data for 2006 through 2008 visual field defects, and hearing loss.51 The
show that serogroups B, Y, and C account largest published adult series demonstrated
for most of the U.S. cases.42 a rate of neurologic sequelae (43%) higher
than that reported in children.48
Meningitis Caused by Streptococcus

Meningitis Caused by
agalactiae (Group B Streptococci)
Staphylococcus aureus
Group B streptococci are gram-positive or-
Unlike the community-acquired meningitis
ganisms possessing several virulence fac-
caused by H. influenzae, pneumococci, me-
tors, including a polysaccharide capsule,
ningococci, and group A streptococci, S. aure-
several adherence proteins, and cytolytic
us meningitis is almost always a nosocomial
toxins. The organism remains a common
infection, occurring most commonly after a
cause of meningitis in newborns, with
neurosurgical procedure, such as CSF shunt
more than two-thirds of these infections
placement.52,53 In the unusual circumstance
occurring during the first 3 months of life.43
of community-acquired S. aureus meningi-
Several studies have shown that adminis-
tis, the patient should be questioned about
tration of intravenous antibiotics to wom-
possible intravenous drug use and assessed
en in labor who are known to be colonized
for the presence of an underlying immuno-
by group B streptococci is highly effective
deficiency. In addition, patients with staph-
at reducing subsequent neonatal coloniza-
ylococcal endocarditis frequently develop
tion. A meta-analysis of seven clinical tri-
metastatic infection of the CNS, including
als demonstrated a 30-fold reduction of
brain abscess and meningeal infection.54,55
neonatal group B streptococcal invasive
The mortality rate for nosocomial S. aureus
disease when antibiotics were delivered in
meningitis is approximately 14%.56 Mortality
this manner.44 In the United States during
secondary to community-acquired S. aureus
the decade of the 1990s, the incidence of
meningitis exceeds 50% because of underly-
neonatal group B streptococcal infection
ing, predisposing diseases.54
dropped from 1.7 to 0.6 cases per 1,000
live births, likely as a result of the increased
Meningitis Caused by
use of peripartum antibiotics in women in
Listeria monocytogenes
labor.45,46 By 2004, rates dropped further,
to approximately 0.3 per 1,000 following L. monocytogenes is a food-borne bacteri-
the implementation of formal obstetric um responsible for causing meningitis and
screening guidelines.47 Meningitis caused other serious invasive illness in humans and
by group B streptococci is unusual beyond other animals. L. monocytogenes is a gram-
infancy but has been described. positive bacillus with the unusual ability
110
to thrive intracellularly based on a host of Lyme Meningitis
characterized virulence factors.57 L. mono-
Lyme disease is an infection caused by the
cytogenes causes approximately 2% of all
spirochete Borrelia burgdorferi. This infec-
cases of meningitis in the United States, a
tion is transmitted via an infected tick bite
proportion that has grown smaller in recent
in areas of endemicity. The pathogenesis of
years, likely as a result of a decrease in the
Lyme meningitis is secondary to spirochet-
contamination of ready-to-eat foods.58 In-
emia during the early disseminated stage
fection is often associated with the presence
of infection.
of infectious foci in the brain parenchyma,
especially in the brainstem.59 The organism
remains one of the principal causes of bac- Tuberculous Meningitis
terial meningitis in neonates.60–63 Worldwide, tuberculous meningitis re-
mains a serious health threat, particularly
Meningitis Caused by Enteric in children residing in resource-poor areas
Gram-Negative Bacteria of the world. Morbidity among survivors
is the rule; death occurs in approximately
E. coli, Klebsiella species, Acinetobacter
60% of patients.71 The agent of tuberculosis,
baumannii, Pseudomonas aeruginosa, and
Mycobacterium tuberculosis, is an extreme-
other aerobic gram-negative bacteria have
ly common cause of pulmonary infection.
been shown to cause meningitis follow-
CNS complications occur following dis-
ing head trauma or neurosurgical proce-
semination in the highest-risk groups, in-
dures.64–67 Meningitis caused by members
cluding children and patients infected with
of this group of organisms tends to occur
HIV. Prediction of outcome early in the ill-
late after surgery, with a median time until
ness is difficult because the infection runs
presentation of 12 days. Some infections
a protracted course. Clinical indices such as
may be detected more than a month after
cranial nerve palsy or other focal findings,
craniotomy. Community-acquired menin-
seizures, and coma at the time of presen-
gitis caused by aerobic gram-negative rods
tation have been assessed as predictors of
is unusual in adults but can occur in the
long-term morbidity. Radiologic findings
context of immune-compromising condi-
of hydrocephalus, cerebral infarction, or
tions such as human immunodeficiency
tuberculomas65 may offer a more realistic
virus (HIV) infection. In contrast, enteric
predictive value for long-term sequelae,
gram-negative bacteria as a group are sec-
particularly among children.72–75
ond in frequency to group B streptococci
during the neonatal period.68 Most of these
infections are caused by E. coli, Klebsiella
species, and Citrobacter species. Citrobac- ■■ S
pecific Risk Factors for the
ter koseri infections are almost universally Development of Bacterial
complicated by the development of paren- Meningitis
chymal abscesses. Young infants may also
develop meningitis caused by Pasteurella Alcoholism, diabetes mellitus, asplenia, can-
multocida, almost always after direct or cer, and other secondary immune compro-
indirect exposure to cats or dogs in the mising conditions all increase the risk for
household.11 Salmonella species have also invasive CNS infections, including meningi-
been shown to cause meningitis. Approxi- tis. Other risk factors for the development
mately 15% of pediatric and adult patients of meningitis can be divided into two broad
who develop bacteremia during gastroin- categories: anatomic and immunologic. Pa-
testinal salmonellosis will develop a meta- tients who present with recurrent bacterial
static infection of the joints, bone, or CNS. meningitis need to be evaluated for underly-
CNS seeding may cause meningitis but can ing factors because direct surgical or medi-
also be complicated by subdural empyema cal intervention for the underlying cause
and brain abscess.69,70 may be required to prevent further episodes.
111
Anatomic Risk Factors (2) an enlarged vestibule with normal
semicircular canals; and (3) an enlarged
Anatomic abnormalities that predispose pa- vestibular aqueduct containing a dilated
tients to bacterial meningitis include neural endolymphatic sac77 (Fig. 9.2). In most
tube defects, epidermoid cysts, dermoid cases, Mondini dysplasia is associated with
cysts, dermal sinus tracts, neurenteric cysts, some degree of hearing impairment and
and congenital inner ear malformation, in- can be associated with CSF otorrhea and
cluding Mondini defects.76 Most of these meningitis.78,79 It is thought that a fistula
defects become evident during a careful between the CSF spaces and the middle ear
physical examination and/or fairly routine predisposes patients to the development
neuroimaging; however, the detection of in- of meningitis. The underlying CSF fistula
ner ear malformations requires specialized in some patients with Mondini defects can
high-resolution images when suspicion is occur in such places as through a deficient
strong. oval window or stapes footplate.
Mondini Dysplasia Cochlear Implant

The Mondini defect consists of three main In most cases of meningitis in patients with
features: (1) instead of a cochlea with the a cochlear implant, the initial infection is
normal two and one-half turns, a cochlea acute otitis media on the side of the implant.
with one and one-half turns, comprising Bacteria enter the inner ear through the sur-
a normal basal turn and a cystic apex in gical cochleostomy. Pathways of bacterial
place of the distal one and one-half turns; access to the CSF from the inner ear include
a b
c d
Fig. 9.2a–d High-resolution computed tomography comparing the appearance of a normal cochlea, with 2.5
turns (a) and a vestibule (c), with the abnormal findings seen in Mondini dysplasia; (b) shows a dilated cochlea
with only 1.5 turns, and (d) shows a dilated vestibule. There is superimposed mastoiditis in this patient, who
developed pneumococcal meningitis secondary to the anatomic defect.
112
entry into the labyrinth, infiltration of the Hypogammaglobulinemia
cochlea along the implanted electrode, and/
Patients with humoral immunodeficiencies
or perivascular pathways into the internal
are especially prone to develop sinopulmo-
auditory canal to the meninges.80 In a case-
nary infections and meningitis caused by
control study performed in children young-
encapsulated bacterial pathogens (pneu-
er than 6 years of age, 26 cases of meningitis
mococci, meningococci, H. influenzae).
were identified among 4,264 patients with
Although patients with hypogammaglobu-
cochlear implants.81 During a 2-year follow-
linemia have no increased susceptibility to
up of the same cohort, an additional 12 epi-
most viral infections, there is one exception.
sodes of meningitis occurred.82 This finding
Although immunologically normal indi-
represents a more than 30-fold increase in
viduals develop a self-limited “aseptic men-
the risk for meningitis compared with the
ingitis” when enteroviruses infect the CNS,
general population. The mortality rate of
patients with hypogammaglobulinemia
meningitis in the context of a cochlear im-
can develop chronic meningoencephali-
plant is approximately 16%. Not surpris-
tis.96 Enterovirus-directed therapies are not
ingly, S. pneumoniae is the most commonly
available, and despite aggressive supportive
identified etiologic agent of implant-associ-
care, many of these patients lose substantial
ated bacterial meningitis.
neurologic function, and some die.
Immunologic Risk Factors IRAK-4 and MyD88 Deficiency

Primary immune deficiencies, particularly Impairments in innate immune respons-
those that impair humoral immunity, and
es are also known to increase the risk for
secondary immune deficiencies resulting developing meningitis. The autosomal re-
from alcoholism, HIV infection, diabetes mel- cessive interleukin-1 receptor–associated
litus, asplenia, the use of immunosuppressive kinase (IRAK)-4 and myeloid differentia-
medications, and malignancy all increase a tion (MyD) factor 88 deficiencies impair
patient’s risk for developing an invasive sys- toll-like receptor (TLR)–mediated and in-
temic infection, including meningitis.83–85 The terleukin-1 receptor–mediated immunity.
most common infecting bacterial pathogen in These defects lead to a predisposition to the
patients with immunodeficiency is S. pneu- development of recurrent life-threatening
moniae,86 but other bacterial, viral, fungal, bacterial diseases, especially during infan-
and even parasitic opportunistic infections cy and early childhood. In the single largest
must be considered based on the degree of clinical report of infections in patients with
the patient’s immunocompromised state. these deficiencies, approximately half of all
Specifically, HIV-infected individuals have up invasive bacterial infections were menin-
to a 324-fold higher risk for invasive pneumo- gitis, although the frequency and types of
coccal infection.87–89 Even following therapy long-term sequelae were similar to those
with highly active antiretroviral medications, seen in immunocompetent patients.97 In-
when HIV replication is controlled, the risk fecting agents included S. pneumoniae, HIB,
for developing pneumococcal meningitis re- S. aureus, and group B streptococci.
mains approximately 35-fold higher than that
in the general population.90,91 This increased
Complement Deficiency
risk has a profound public health effect in
the underdeveloped world, where up to 95% Complement deficiencies are rare disor-
of patients with pneumococcal meningitis ders of immune function afflicting 0.03% of
are also infected with HIV.92–95 Opportunistic the population. Because complement acti-
infections are seen more frequently in those vation pathways converge at the activation
individuals with severe immunodeficiencies, of C3, patients who are deficient in C3 have
but some immune defects are directly asso- serious deficiencies in complement-medi-
ciated with an increased risk for specific of- ated opsonization, phagocyte recruitment,
fending organisms. and bacteriolysis. Such patients are prone
113
to invasive infection caused by encapsulat- Other symptoms that are seen include a pete-
ed bacteria such as pneumococci, menin- chial or purpuric rash, change in muscle tone,
gococci, and H. influenzae. Most infections vomiting, and decreased oral intake. Of note,
in patients with C3 deficiency involve the a change in a child’s state of alertness is one
sinopulmonary tract (otitis, sinusitis, and of the most important signs of meningitis, al-
pneumonia), but C3-deficient patients are though the finding may be subtle.102
also predisposed to the development of A nationwide study in the Netherlands
sepsis and meningitis.98 An increased in- prospectively evaluated 696 episodes of
cidence of invasive meningococcal disease community-acquired bacterial meningitis
has been observed in patients with defi- in adults. They found that the classic triad
ciencies or defects in terminal complement of fever, neck stiffness, and altered men-
components C5–C9 and dysfunctional pro- tal status was present in only 44% of the
perdin.99–101 Any patient who presents with episodes. However, when headache was
recurrent infections (including meningitis) added to this list, 95% of the patients had at
caused by Neisseria species should be eval- least two of the four symptoms.19 The clas-
uated for a terminal complement defect. sic triad was more likely to be present in
pneumococcal meningitis than in menin-
gococcal meningitis.19,111 Rash was present
■■ Clinical Presentation in 26% of cases and focal neurologic defi-
cit in 33%. Seizures were present in 5% of
The clinical presentation of acute bacterial patients.19 Neurologic abnormalities seen

meningitis varies by patient age and imon presentation in adults with meningitis
mune status as well as the etiology of the can include generalized deficits, such as
infection.102 The classic triad of fever, neck confusion, lethargy, and unresponsiveness,
stiffness, and altered mental status is not as well as focal neurologic signs, such as
always present. Only in patients with se- cranial nerve palsies, hemiparesis, aphasia,
vere meningeal inflammation (white blood and visual field defects.17,112
cell [WBC] count ≥ 1,000/mL of CSF) is nu- Elderly patients are another group
chal rigidity 100% sensitive and specific for whose clinical diagnosis can be challenging.
the diagnosis of acute meningitis.103 Presenting signs and symptoms are quite
Neonatal meningitis is difficult to iden- variable and are often nonspecific.22 It is im-
tify because newborns tend to present with portant to note that nuchal rigidity can be
nonspecific symptoms, including tem- present for reasons other than meningitis in
perature instability, respiratory distress, elderly patients, such as previous cerebro-
jaundice, poor suck, and lethargy.102,104,105 vascular accidents, Parkinson disease, and
Approximately 50 to 88% of neonates pres- cervical spondylosis.113 The elderly are more
ent with fever, two-thirds with irritability likely to present with depressed mental
and/or a bulging fontanelle, one-third with status, hemiparesis, and seizures than with
lethargy, and 25 to 40% with seizures be- headache, nausea, vomiting, and nuchal
fore admission.102,104,105 The presence of a rigidity.20,113 Acute complications of pyo-
bulging fontanelle is strongly predictive of genic bacterial meningitis include the de-
neonatal meningitis.106 velopment of cerebritis with parenchymal
Infants beyond the neonatal period and infarcts, subdural empyema, ventriculitis,
children younger than 5 years of age with and hydrocephalus (Fig. 9.3). Neuroimaging
meningitis present with fever, irritability, should not be delayed because emergent
altered mental status, and decreased oral in- surgical intervention may be necessary.
take.104,107–109 Seizures occur in 42 to 81% of Unlike the other common types of bac-
these children.104,107 Other symptoms may terial meningitis, Lyme disease is associ-
include neck stiffness, headache, vomiting, ated with aseptic meningitis, more closely
lethargy, “staring eyes,” and rash.104,107–109 Chil- mimicking mild forms of viral meningitis
dren older than 5 years of age are more likely rather than fulminant, pyogenic bacte-
to present with classic meningismus.104,110 rial meningitis. One study showed that the
114
■■ Diagnosis
In patients with suspected meningitis, a
lumbar puncture is indicated to obtain
CSF for biochemical, cellular, and micro-
biological evaluation. At the time of lum-
bar puncture, an opening pressure should
be obtained, and CSF should be collected
and analyzed for cell count and differential,
protein and glucose concentrations, Gram
stain, and bacterial culture.120 Additional
diagnostic tests may also be considered
based on the clinical suspicion for viral,
fungal, or parasitic infection. In neonates,
CSF glucose concentrations are normally
lower than ranges typically observed in
older children and adults because of the
immaturity of the glucose transport mech-
Fig. 9.3 Contrast-enhanced computed tomographic
scan of the brain demonstrating several severe com- anisms and the increased permeability of
plications of pneumococcal meningitis. The patchy the blood–brain barrier. In healthy older
enhancement of the leptomeninges is often seen dur- children and adults, CSF glucose concen-
ing bacterial meningitis. The areas of hypodensity, trations should remain higher than two-
most pronounced in the two frontal and the left pa- thirds of the serum glucose.102,121 CNS
rietal lobes, represent diffuse cerebritis with second-
bacterial infections alter glucose transport
ary areas of infarction. The pronounced dilatation of
the ventricular system is obvious. Finally, an extra-axial
across the blood–brain barrier, thereby
ring-enhancing lesion overlying the left cerebral con- decreasing CSF concentrations. Effective
vexity represents a subdural empyema. antimicrobial treatment of the infection
results in rapid normalization of the glu-
cose concentration, usually days before the
protein concentration normalizes, and the
duration of headache secondary to Lyme CSF pleocytosis resolves.
meningitis was three times longer, lasting Ranges for normal CSF protein concen-
on average for more than a week.114 More trations are age-dependent. The normal
than half of adults with Lyme meningitis mean CSF protein concentration is 90 mg/
will exhibit symptoms of parenchymal in- dL in full-term infants and 115 mg/dL in
volvement, such as somnolence, memory premature infants. Normal CSF protein
loss, poor concentration, emotional labil- concentrations decrease to approximately
ity, and behavioral changes. In contrast, 40 mg/dL by the second month of life.102,121
a series in children with CNS Lyme infec- Infections of the CNS disrupt the tight
tion showed that most young patients junctions between the endothelial cells of
have a fairly benign, mild course of asep- the venules, resulting in an increased pres-
tic meningitis.115 Seventh nerve palsy is ence of protein in the CSF.
seen in approximately half of patients The presence of leukocytes in the CSF
with Lyme meningitis but can also be an should raise suspicion for meningitis. The
isolated neurologic finding of Borrelia in- WBC count in CSF from healthy neonates is
fection.116 Rare complications and some approximately 8/mm3, with upper limits of
less common presentations of CNS Lyme normal ranging from 22 to 26/mm3.102,121–123
infection include other cranial nerve pal- By 1 month of age, the upper limit of nor-
sies, particularly cranial nerves III and VI, mal decreases to less than 10/ mm3.102,122
pseudotumor cerebri, chorea, cerebellar In general, bacterial meningitis results in a
ataxia, mononeuritis multiplex, myelitis, substantial CSF pleocytosis (leukocyte count
and opsoclonus-mycolonus.117–119 ranging from 100/mm3 to 10,000/mm3), gen-
115
erally higher than leukocyte counts in pa- Tuberculous meningitis is confirmed
tients with aseptic meningitis. The leukocyte by a positive mycobacterial culture or CSF
differential count in cases of bacterial men- polymerase chain reaction result in a pa-
ingitis shows a predominance of neutrophils, tient with specific risk factors for tubercu-
whereas aseptic meningitis has a lympho- losis. A Mantoux skin test (purified protein
cytic predominance.124 Table 9.2 compares derivative [PPD]) should be placed and a
the classic CSF findings in bacterial, viral, chest radiograph obtained. The diagnosis
Lyme disease, and tuberculous meningitis. of tuberculous meningitis requires a high
CSF Gram stain is positive in 50 to 90% index of suspicion and early initiation of
of cases of community-acquired bacterial empiric therapy because PPD testing is un-
meningitis. Culture is positive in 70 to 85% reliable in this clinical situation, and myco-
of untreated patients with bacterial men- bacterial culture results are often delayed
ingitis, but up to 48 hours may be required for weeks.128
for organism identification.125,126 Some pa-
tients who present with meningitis have
already received antibiotics (particularly ■■ Treatment
oral antibiotics) before lumbar puncture
and CSF analysis. Pretreatment with anti- Empiric antibiotic therapy must be initi-
biotics will not normalize CSF perturba- ated promptly even if the lumbar puncture
tions immediately; however, the yield of cannot be performed in a timely manner
positive Gram stains decreases by approxi- because any delay can be associated with
mately 20%, and CSF cultures may be ster- progressive neurologic complications and
ilized. Therefore, patients who have been increased mortality.125,126,129,130
pretreated with antibiotics and whose Empiric antibiotic choices are deter-
clinical picture and CSF analysis are con- mined by the patient’s age, immune status,
sistent with bacterial meningitis, yet who and risk factors and by local antimicro-
have negative CSF cultures, should receive bial resistance rates.125,126,131 A summary of
a complete course of empiric parenteral recommended empiric antibiotic therapy
antibiotics.121,125,126 for community-acquired meningitis is in-
CSF findings in Lyme meningitis typi- cluded in Table 9.1. Previously healthy
cally include a leukocyte count of 100 to children and adults should be treated with
200/mm3, with a predominance of mono- vancomycin and a third-generation cepha-
nuclear cells (lymphocytes), and a modest losporin. Neonates, who are at higher risk
elevation in CSF protein. Serologic testing is for infection with L. monocytogenes and
performed to confirm the diagnosis.127 gram-negative bacilli, should be treated
Table 9.2 Cerebrospinal fluid findings in bacterial, viral, and tuberculous meningitis
Bacterial Viral (Aseptic) Tuberculous

Meningitis Meningitis Lyme Meningitis Meningitis
Opening pressure Elevated Normal to elevated Normal to elevated Elevated
WBC count ≥ 100–10,000 10–300 100–200 50–500

(cells/mm3)
WBC differential Predominance of Predominance of Predominance of Predominance of

neutrophils lymphocytes lymphocytes lymphocytes
Glucose (mg/dL) Low Normal Normal Low
Protein (mg/dL) Elevated Normal to high Mildly elevated Elevated
116 Abbreviation: WBC, white blood cell

with both ampicillin and a third-genera- Once a pathogen has been identified as
tion cephalosporin (or gentamicin). Adults the cause of meningitis, it is important that
past the age of 50 require the combination susceptibility testing be performed before
of ampicillin, vancomycin, and a third-gen- the antimicrobial regimen is de-escalated.
eration cephalosporin.19,22,102,126,132 Optimizing antibiotic therapy requires an
In 1988, studies from the United States understanding of antibiotic susceptibilities
showed that children with HIB meningitis and the ability of the chosen medication
who were treated with adjunctive dexa- to penetrate the blood–brain barrier and
methasone were less likely to develop achieve a sufficiently high concentration
hearing loss as a complication of meningi- in the CSF. Alternative antimicrobial regi-
tis,133 an observation that was supported in mens for antibiotic-resistant bacteria or for
later studies.134 Adjunctive dexamethasone patients allergic to penicillins and cepha-
has also been studied in the context of losporins might include meropenem, tri-
pneumococcal meningitis. In 1997, a meta- methoprim-sulfamethoxazole, and other
analysis of 10 clinical trials was the first to newer classes of drugs. Such cases should
show borderline benefit in reducing neu- be managed with the help of an infectious
rologic sequelae, including hearing loss.134 disease expert.
Subsequently, a multicenter adult trial per- Seven days of parenteral therapy with
formed in Europe showed that dexametha- penicillin G or ceftriaxone is sufficient
sone prevented serious sequelae.135 Among for the treatment of meningococcal men-
the most impressive observations was a ingitis. Infections due to a β-lactamase–
reduction in mortality from 34 to 14%. In negative H. influenzae can be treated with
direct contrast, two large clinical trials ampicillin for 7 days; however, if the or-
were performed in patients from Malawi ganism produces β-lactamase, a third-
with pneumococcal meningitis. These tri- generation cephalosporin should be used.
als failed to demonstrate any reduction in Uncomplicated meningitis due to S. pneu-
mortality or neurologic sequelae following moniae should be treated for 10 to 14 days.
pediatric or adult pneumococcal meningi- Infections due to group B streptococci, L.
tis.2,136 A Cochrane meta-analysis of trials monocytogenes, or gram-negative bacilli
showing beneficial effects of adjunctive require longer treatment of at least 14 to
corticosteroids in high-income countries 21 days. Ampicillin plus gentamicin is the
but not in resource-poor countries sug- combination of choice for group B strep-
gested that differences in baseline charac- tococcal meningitis, whereas ampicillin
teristics could explain the variable results alone is recommended for treatment of lis-
found in clinical trials done in different teriosis.102,125,126,131,132 Lyme meningitis, un-
regions of the world.137 Current guidelines like other manifestations of Lyme disease,
from the Infectious Diseases Society of requires therapy with 2 weeks of intrave-
America, the European Federation of Neu- nous ceftriaxone.128
rological Sciences, and the British Infection Tuberculous meningitis requires com-
Society all recommend adjunctive dexa- bination therapy for a year or more. Treat-
methasone for patients with suspected or ment should begin as soon as the infection
proven pneumococcal meningitis.138–140 is suspected because of high morbidity and
The use of adjunctive dexamethasone has mortality rates with untreated infection. It
also been studied in the context of menin- is important to determine antibiotic sus-
gococcal meningitis. A 2004 meta-analysis ceptibility results from infecting isolates
showed no decrease in mortality in dexa- because of the increasing prevalence of
methasone-treated adult patients.141 When drug-resistant strains. The recommended
used, dexamethasone should be adminis- first-line antibiotic regimen for M. tuber-
tered before or with the first dose of antibi- culosis meningitis includes isoniazid, ri-
otics at a dose of 0.15 mg/kg intravenously fampin, pyrazinamide, and ethambutol
every 6 hours for 4 days.126,132 or streptomycin. This combination can be
117
altered once the results of antimicrobial niation. Independent predictors for an un-
susceptibility testing are available. Cortico- favorable outcome include a low Glasgow
steroids given as adjunctive therapy for tu- Coma Score on presentation, cranial nerve
berculous meningitis have been shown to palsies, a CSF leukocyte count of less than
decrease neurologic sequelae and improve 1,000/mm3, and elevated CSF protein.21
survival.120,128,142 Neurologic sequelae occur in up to half of all
survivors. Permanent consequences include
deafness, focal neurologic deficits, seizure
■■ C
omplications, Sequelae, disorders, and cognitive impairment.21,147,156
and Prognosis The loss of cognitive speed appears stable
over time; however, early physical impair-
Despite the availability of preventive vac- ments generally regress with time.157
cines and effective antibiotics, bacterial
meningitis remains a significant cause of Sequelae of Meningococcal Meningitis
morbidity and mortality in both devel-
The highest number of cases of meningo-
oped and resource-poor areas of the world.
coccal infection occurs in infants, but mor-
A spectrum of sequelae has been noted in
tality in this age group is less than 5%. A
survivors of meningitis, including seizure
second peak in the number of cases occurs
disorders, focal neurologic deficits, hear-
in adolescents and young adults between
ing loss, vision loss, and impaired cognitive
15 and 24 years old, in whom mortality

function.143 Sequelae vary based on the etio-
rates are higher than 20%.158 Case-fatality
logic agent and age of the infection, but tak-
rates are also higher in patients with se-
en together, roughly one in four patients will
rogroup C than in those with serogroup
experience moderate to severe long-term
B disease. Mortality is higher among pa-
consequences of bacterial meningitis.144
tients with meningococcal septicemia than
in those with meningococcal meningitis159
Sequelae of Haemophilus influenzae
and is usually the result of endotoxic shock
Type B Meningitis
with cardiovascular collapse. As many as
Reported mortality rates for HIB meningitis 19% of survivors experience serious sequel-
range from 3 to 42%.15,145,146 A meta-analysis ae, including sensorineural hearing loss,
of studies done in children showed a mor- skin and soft tissue necrosis requiring am-
tality rate of 4%,147 while mortality in adults putation, seizures, ataxia, hemiplegia, and
is generally reported to be higher.54,145,148,149 septic or immune complex arthritis.160–162
The most common sequela of HIB meningi-
tis is sensorineural hearing loss, which has Sequelae of Listeria Meningitis
been described in up to 16% of children and
Listeria meningitis is usually a very severe
between 10 and 25% of adults.54,145
infection in adults. Mean mortality rates
are 30% or higher despite early antibiotic
Sequelae of Pneumococcal Meningitis
treatment.163,164 The mortality of late-onset
Pneumococcal meningitis has a higher mor- neonatal listeriosis is slightly lower (10 to
tality rate than HIB meningitis. In children, 20%), but survivors of infection may have
mortality is between 8 and 37%, with the sequelae such as hydrocephalus and psy-
highest mortality rates seen in the poor- chomotor retardation.165
est areas of the world.15,147,150,151 Adults fare
worse, with mortality rates between 20 and
37% in developed countries and as high as ■■ Conclusion
51% in parts of Africa.3,151–155 Causes of death
in patients with pneumococcal meningitis Bacterial meningitis remains a major public
include cardiovascular failure, stroke, status health problem in both developed and un-
epilepticus, and cerebral edema with her- derdeveloped parts of the world. The three
118
most common causes of acute bacterial 10. M ulder CJ, Zanen HC. Listeria monocytogenes
neonatal meningitis in The Netherlands. Eur J
meningitis, S. pneumoniae, N. meningitidis,
Pediatr 1986;145(1-2):60–62 PubMed
and HIB, are largely vaccine-preventable in 11. K obayaa H, Souki RR, Trust S, Domachowske JB.
areas of the world that are able to imple- Pasteurella multocida meningitis in newborns
ment effective public health programs. The after incidental animal exposure. Pediatr Infect
Dis J 2009;28(10):928–929 PubMed
diagnostic approach and treatment regimens 12. Pong A, Bradley JS. Bacterial meningitis and
are largely straightforward, but challenges the newborn infant. Infect Dis Clin North Am
emerge when patients have received prior 1999;13(3):711–733, viii PubMed
antibiotics or when the infection is caused 13. Franco-Paredes C, Lammoglia L, Hernández I,
Santos-Preciado JI. Epidemiology and outcomes
by unusual or antibiotic-resistant bacteria. of bacterial meningitis in Mexican children: 10-
Despite the availability of safe and effective year experience (1993-2003). Int J Infect Dis
antibiotics, and major progress in supportive 2008;12(4):380–386 PubMed
14. N igrovic LE, Kuppermann N, Malley R; Bacterial
care for patients with serious CNS infections, Meningitis Study Group of the Pediatric Emer-
the morbidity and mortality associated with gency Medicine Collaborative Research Com-
meningitis remain substantial. Future efforts mittee of the American Academy of Pediatrics.
at more effective prevention, better access to Children with bacterial meningitis presenting to
the emergency department during the pneumo-
existing vaccines, and further understanding coccal conjugate vaccine era. Acad Emerg Med
on how to best avoid long-term complica- 2008;15(6):522–528 PubMed
tions continue to be explored. 15. Pelkonen T, Roine I, Monteiro L, et al. Risk factors for
death and severe neurological sequelae in child-
hood bacterial meningitis in sub-Saharan Africa.
References Clin Infect Dis 2009;48(8):1107–1110 PubMed
1. G reenwood BM. The epidemiology of acute bac- 16. S
áez-Llorens X, McCracken GH Jr. Bacterial
terial meningitis in tropical Africa. In: Williams meningitis in children. Lancet 2003;361(9375):
JD, Burnie J, eds. Bacterial Meningitis. London, 2139–2148 PubMed
England: Academic Press; 1987:93–113 17. D
urand ML, Calderwood SB, Weber DJ, et al.
2. Scarborough M, Gordon SB, Whitty CJ, et al. Cor- Acute bacterial meningitis in adults. A review
ticosteroids for bacterial meningitis in adults in of 493 episodes. N Engl J Med 1993;328(1):
sub-Saharan Africa. N Engl J Med 2007;357(24): 21–28 PubMed
2441–2450 PubMed 18. S
igurdardóttir B, Björnsson OM, Jónsdóttir KE,
3. Scarborough M, Thwaites GE. The diagnosis Erlendsdóttir H, Gudmundsson S. Acute bacte-
and management of acute bacterial meningitis rial meningitis in adults. A 20-year overview.
in resource-poor settings. Lancet Neurol 2008; Arch Intern Med 1997;157(4):425–430 PubMed
7(7):637–648 PubMed 19. v
an de Beek D, de Gans J, Spanjaard L, Weisfelt
4. Campagne G, Schuchat A, Djibo S, Ousséini A, M, Reitsma JB, Vermeulen M. Clinical features
Cissé L, Chippaux JP. Epidemiology of bacterial and prognostic factors in adults with bacte-
meningitis in Niamey, Niger, 1981-96. Bull World rial meningitis. N Engl J Med 2004;351(18):
Health Organ 1999;77(6):499–508 PubMed 1849–1859 PubMed
5. Decosas J, Koama JB. Chronicle of an outbreak 20. C
abellos C, Verdaguer R, Olmo M, et al. Com-
foretold: meningococcal meningitis W135 in munity-acquired bacterial meningitis in elderly
Burkina Faso. Lancet Infect Dis 2002;2(12): patients: experience over 30 years. Medicine
763–765 PubMed (Baltimore) 2009;88(2):115–119 PubMed
6. Andersen J, Christensen R, Hertel J. Clinical fea- 21. C
hoi C. Bacterial meningitis in aging adults. Clin
tures and epidemiology of septicaemia and men- Infect Dis 2001;33(8):1380–1385 PubMed
ingitis in neonates due to Streptococcus agalactiae 22. W
eisfelt M, van de Beek D, Spanjaard L, Reits-
in Copenhagen County, Denmark: a 10 year sur- ma JB, de Gans J. Community-acquired bacte-
vey from 1992 to 2001. Acta Paediatr 2004; rial meningitis in older people. J Am Geriatr Soc
93(10):1334–1339 PubMed 2006;54(10):1500–1507 PubMed
7. Heath PT, Nik Yusoff NK, Baker CJ. Neonatal 23. Brouwer MC, van de Beek D, Heckenberg SG,
meningitis. Arch Dis Child Fetal Neonatal Ed Spanjaard L, de Gans J. Community-acquired
2003;88(3):F173–F178 PubMed Haemophilus influenzae meningitis in adults. Clin
8. Hristeva L, Booy R, Bowler I, Wilkinson AR. Pro- Microbiol Infect 2007;13(4):439–442 PubMed
spective surveillance of neonatal meningitis. Arch 24. D
workin MS, Park L, Borchardt SM. The changing
Dis Child 1993;69(1 Spec No):14–18 PubMed epidemiology of invasive Haemophilus influen-
9. May M, Daley AJ, Donath S, Isaacs D; Austral- zae disease, especially in persons > or = 65 years
asian Study Group for Neonatal Infections. Early old. Clin Infect Dis 2007;44(6):810–816 PubMed
onset neonatal meningitis in Australia and New 25. F
arhoudi D, Löfdahl M, Giesecke J. Invasive Hae-
Zealand, 1992-2002. Arch Dis Child Fetal Neona- mophilus influenzae type b disease in Sweden
tal Ed 2005;90(4):F324–F327 PubMed 1997-2003: epidemiological trends and pat-
119
terns in the post-vaccine era. Scand J Infect Dis meningitidis serogroup W135: estimates of the
2005;37(10):717–722 PubMed attack rate in a defined population and the risk
26. Arda B, Sipahi OR, Atalay S, Ulusoy S. Pooled anal- of invasive disease developing in carriers. Clin
ysis of 2,408 cases of acute adult purulent men- Infect Dis 2003;36(6):679–683 PubMed
ingitis from Turkey. Med Princ Pract 2008;17(1): 41. B oisier P, Nicolas P, Djibo S, et al. Meningococ-
76–79 PubMed cal meningitis: unprecedented incidence of se-
27. Whitney CG, Farley MM, Hadler J, et al; Active rogroup X-related cases in 2006 in Niger. Clin
Bacterial Core Surveillance of the Emerging In- Infect Dis 2007;44(5):657–663 PubMed
fections Program Network. Decline in invasive 42. C enters for Disease Control and Prevention. Ac-
pneumococcal disease after the introduction tive Bacterial Core surveillance (ABCs) Report:
of protein-polysaccharide conjugate vaccine. N Neisseria meningitidis, 2009. http://www.cdc.
Engl J Med 2003;348(18):1737–1746 PubMed gov/abcs/reports-findings/survreports/me-
28. Tsai CJ, Griffin MR, Nuorti JP, Grijalva CG. Chang- ning09.html. Accessed December 17, 2012
ing epidemiology of pneumococcal meningitis 43. Phares CR, Lynfield R, Farley MM, et al; Active Bac-
after the introduction of pneumococcal conju- terial Core surveillance/Emerging Infections Pro-
gate vaccine in the United States. Clin Infect Dis gram Network. Epidemiology of invasive group B
2008;46(11):1664–1672 PubMed streptococcal disease in the United States, 1999-
29. van Deuren M, Brandtzaeg P, van der Meer JW. 2005. JAMA 2008;299(17):2056–2065 PubMed
Update on meningococcal disease with empha- 44. A llen UD, Navas L, King SM. Effectiveness of
sis on pathogenesis and clinical management. intrapartum penicillin prophylaxis in prevent-
Clin Microbiol Rev 2000;13(1):144–166 PubMed ing early-onset group B streptococcal infection:
30. Caugant DA, Tzanakaki G, Kriz P. Lessons from results of a meta-analysis. CMAJ 1993;149(11):
meningococcal carriage studies. FEMS Microbiol 1659–1665 PubMed
Rev 2007;31(1):52–63 PubMed 45. S chrag S, Gorwitz R, Fultz-Butts K, Schuchat A.
31. Dull PM, Abdelwahab J, Sacchi CT, et al. Neis- Prevention of perinatal group B streptococcal
seria meningitidis serogroup W-135 carriage disease. Revised guidelines from CDC. MMWR
among US travelers to the 2001 Hajj. J Infect Dis Recomm Rep 2002;51(RR-11):1–22 PubMed
2005;191(1):33–39 PubMed 46. S chrag SJ, Zywicki S, Farley MM, et al. Group B
32. MacLennan J, Kafatos G, Neal K, et al; United streptococcal disease in the era of intrapar-
Kingdom Meningococcal Carriage Group. Social tum antibiotic prophylaxis. N Engl J Med 2000;
behavior and meningococcal carriage in Brit- 342(1):15–20 PubMed
ish teenagers. Emerg Infect Dis 2006;12(6): 47. Johri AK, Paoletti LC, Glaser P, et al. Group B
950–957 PubMed Streptococcus: global incidence and vaccine
33. Imrey PB, Jackson LA, Ludwinski PH, et al. Me- development. Nat Rev Microbiol 2006;4(12):
ningococcal carriage, alcohol consumption, and 932–942 PubMed
campus bar patronage in a serogroup C me- 48. v an de Beek D, de Gans J, Spanjaard L, Sela S,
ningococcal disease outbreak. J Clin Microbiol Vermeulen M, Dankert J. Group A streptococcal
1995;33(12):3133–3137 PubMed meningitis in adults: report of 41 cases and a re-
34. Pinner RW, Gellin BG, Bibb WF, et al; Menin- view of the literature. Clin Infect Dis 2002;34(9):
gococcal Disease Study Group. Meningococcal e32–e36 PubMed
disease in the United States—1986. J Infect Dis 49. P erera N, Abulhoul L, Green MR, Swann RA.
1991;164(2):368–374 PubMed Group A streptococcal meningitis: case report
35. Moore PS. Meningococcal meningitis in sub-Sa- and review of the literature. J Infect 2005;51(2):
haran Africa: a model for the epidemic process. E1–E4 PubMed
Clin Infect Dis 1992;14(2):515–525 PubMed 50. B araldés MA, Domingo P, Mauri A, et al. Group
36. Moore PS, Reeves MW, Schwartz B, Gellin BG, A streptococcal meningitis in the antibiotic
Broome CV. Intercontinental spread of an epi- era. Eur J Clin Microbiol Infect Dis 1999;18(8):
demic group A Neisseria meningitidis strain. 572–578 PubMed
Lancet 1989;2(8657):260–263 PubMed 51. Arnoni MV, Berezin EN, Sáfadi MA, Almeida FJ,
37. Rosenstein NE, Perkins BA, Stephens DS, Popovic Lopes CR. Streptococcus pyogenes meningitis in
T, Hughes JM. Meningococcal disease. N Engl J children: report of two cases and literature review.
Med 2001;344(18):1378–1388 PubMed Braz J Infect Dis 2007;11(3):375–377 PubMed
38. Pollard AJ. Global epidemiology of meningococ- 52. F ederico G, Tumbarello M, Spanu T, et al. Risk
cal disease and vaccine efficacy. Pediatr Infect factors and prognostic indicators of bacterial
Dis J 2004;23(12, Suppl):S274–S279 PubMed meningitis in a cohort of 3580 postneurosur-
39. Wilder-Smith A, Barkham TMS, Ravindran S,
gical patients. Scand J Infect Dis 2001;33(7):
Earnest A, Paton NI. Persistence of W135 Neis- 533–537 PubMed
seria meningitidis carriage in returning Hajj 53. Jensen AG, Espersen F, Skinhøj P, Rosdahl
pilgrims: risk for early and late transmission to VT, Frimodt-Møller N. Staphylococcus aureus
household contacts. Emerg Infect Dis 2003;9(1): meningitis. A review of 104 nationwide, con-
123–126 PubMed secutive cases. Arch Intern Med 1993;153(16):
40. Wilder-Smith A, Goh KT, Barkham T, Paton NI. 1902–1908 PubMed
Hajj-associated outbreak strain of Neisseria
120
54. Brouwer MC, Keizerweerd GD, De Gans J, Span- dragons in a foster home. J Pediatr 2010;156(2):
jaard L, Van De Beek D. Community acquired 322–323 PubMed
Staphylococcus aureus meningitis in adults. 70. M ahapatra AK, Pawar SJ, Sharma RR. Intracranial
Scand J Infect Dis 2009;41(5):375–377 PubMed Salmonella infections: meningitis, subdural col-
55. Pintado V, Meseguer MA, Fortún J, et al. Clini- lections and brain abscess. A series of six sur-
cal study of 44 cases of Staphylococcus aureus gically managed cases with follow-up results.
meningitis. Eur J Clin Microbiol Infect Dis 2002; Pediatr Neurosurg 2002;36(1):8–13 PubMed
21(12):864–868 PubMed 71. K ent SJ, Crowe SM, Yung A, Lucas CR, Mijch AM.
56. Korinek AM, Golmard JL, Elcheick A, et al. Risk Tuberculous meningitis: a 30-year review. Clin
factors for neurosurgical site infections after Infect Dis 1993;17(6):987–994 PubMed
craniotomy: a critical reappraisal of antibiotic 72. Hosoglu S, Geyik MF, Balik I, et al. Predictors of
prophylaxis on 4,578 patients. Br J Neurosurg outcome in patients with tuberculous meningitis.
2005;19(2):155–162 PubMed Int J Tuberc Lung Dis 2002;6(1):64–70 PubMed
57. Vázquez-Boland JA, Kuhn M, Berche P, et al.
73. U ysal G, Köse G, Güven A, Diren B. Magnetic
Listeria pathogenesis and molecular virulence resonance imaging in diagnosis of childhood
determinants. Clin Microbiol Rev 2001;14(3): central nervous system tuberculosis. Infection
584–640 PubMed 2001;29(3):148–153 PubMed
58. Voetsch AC, Angulo FJ, Jones TF, et al; Centers for 74. Y asar KK, Pehlivanoglu F, Sengoz G. Predictors
Disease Control and Prevention Emerging Infec- of mortality in tuberculous meningitis: a mul-
tions Program Foodborne Diseases Active Sur- tivariate analysis of 160 cases. Int J Tuberc Lung
veillance Network Working Group. Reduction in Dis 2010;14(10):1330–1335 PubMed
the incidence of invasive listeriosis in foodborne 75. S pringer P, Swanevelder S, van Toorn R, van
diseases active surveillance network sites, 1996- Rensburg AJ, Schoeman J. Cerebral infarction
2003. Clin Infect Dis 2007;44(4):513–520 PubMed and neurodevelopmental outcome in childhood
59. Nieman RE, Lorber B. Listeriosis in adults: a
tuberculous meningitis. Eur J Paediatr Neurol
changing pattern. Report of eight cases and re- 2009;13(4):343–349 PubMed
view of the literature, 1968-1978. Rev Infect Dis 76. T ebruegge M, Curtis N. Epidemiology, etiol-
1980;2(2):207–227 PubMed ogy, pathogenesis, and diagnosis of recur-
60. Lorber B. Listeriosis. Clin Infect Dis 1997;24(1): rent bacterial meningitis. Clin Microbiol Rev
1–9, quiz 10–11 PubMed 2008;21(3):519–537 PubMed
61. Rocourt J, Brosch R. Human listeriosis 1990.
77. M ondini C. Minor works of Carlo Mondini: the
Document WHO/ HPP/FOS/92.4. Geneva, Swit- anatomical section of a boy born deaf. Am J Otol
zerland: World Health Organization; 1992 1997;18(3):288–293 PubMed
62. Schuchat A, Swaminathan B, Broome CV. Epide- 78. L o WW. What is a ‘Mondini’ and what differ-
miology of human listeriosis. Clin Microbiol Rev ence does a name make? AJNR Am J Neuroradiol
1991;4(2):169–183 PubMed 1999;20(8):1442–1444 PubMed
63. Synnott MB, Morse DL, Hall SM. Neonatal men- 79. O hlms LA, Edwards MS, Mason EO, Igarashi M,
ingitis in England and Wales: a review of rou- Alford BR, Smith RJ. Recurrent meningitis and
tine national data. Arch Dis Child 1994;71(2): Mondini dysplasia. Arch Otolaryngol Head Neck
F75–F80 PubMed Surg 1990;116(5):608–612 PubMed
64. Kim BN, Peleg AY, Lodise TP, et al. Management 80. Arnold W, Bredberg G, Gstöttner W, et al.
of meningitis due to antibiotic-resistant Aci- Meningitis following cochlear implantation:
netobacter species. Lancet Infect Dis 2009;9(4): pathomechanisms, clinical symptoms, conserva-
245–255 PubMed tive and surgical treatments. ORL J Otorhinolar-
65. Reichert MC, Medeiros EA, Ferraz FA. Hospital- yngol Relat Spec 2002;64(6):382–389 PubMed
acquired meningitis in patients undergoing cra- 81. R eefhuis J, Honein MA, Whitney CG, et al. Risk
niotomy: incidence, evolution, and risk factors. of bacterial meningitis in children with co-
Am J Infect Control 2002;30(3):158–164 PubMed chlear implants. N Engl J Med 2003;349(5):
66. Tang LM, Chen ST. Klebsiella ozaenae meningi- 435–445 PubMed
tis: report of two cases and review of the litera- 82. B iernath KR, Reefhuis J, Whitney CG, et al. Bac-
ture. Infection 1994;22(1):58–61 PubMed terial meningitis among children with cochlear
67. Tang LM, Chen ST. Klebsiella oxytoca meningitis: implants beyond 24 months after implantation.
frequent association with neurosurgical proce- Pediatrics 2006;117(2):284–289 PubMed
dures. Infection 1995;23(3):163–167 PubMed 83. M ourtzoukou EG, Pappas G, Peppas G, Fala-
68. Unhanand M, Mustafa MM, McCracken GH Jr, gas ME. Vaccination of asplenic or hyposplenic
Nelson JD. Gram-negative enteric bacillary men- adults. Br J Surg 2008;95(3):273–280 PubMed
ingitis: a twenty-one-year experience. J Pediatr 84. M uller LM, Gorter KJ, Hak E, et al. Increased risk
1993;122(1):15–21 PubMed of common infections in patients with type 1
69. Tabarani CM, Bennett NJ, Kiska DL, Riddell SW, and type 2 diabetes mellitus. Clin Infect Dis
Botash AS, Domachowske JB. Empyema of pre- 2005;41(3):281–288 PubMed
existing subdural hemorrhage caused by a rare 85. Nelson S, Kolls JK. Alcohol, host defence and soci-
Salmonella species after exposure to bearded ety. Nat Rev Immunol 2002;2(3):205–209 PubMed
121
86. Brouwer MC, van de Beek D, Heckenberg SG, consequences of neisserial and other infections
Spanjaard L, de Gans J. Community-acquired in an immune deficiency. Medicine (Baltimore)
Listeria monocytogenes meningitis in adults. Clin 1984;63(5):243–273 PubMed
Infect Dis 2006;43(10):1233–1238 PubMed 101. Sjöholm AG, Kuijper EJ, Tijssen CC, et al. Dys-
87. Bliss SJ, O’Brien KL, Janoff EN, et al. The evidence functional properdin in a Dutch family with me-
for using conjugate vaccines to protect HIV-in- ningococcal disease. N Engl J Med 1988;319(1):
fected children against pneumococcal disease. 33–37 PubMed
Lancet Infect Dis 2008;8(1):67–80 PubMed 102. Klein JO, Feigin RD, McCracken GH Jr. Report

88. Frankel RE, Virata M, Hardalo C, Altice FL, Fried- of the task force on diagnosis and manage-
land G. Invasive pneumococcal disease: clinical ment of meningitis. Pediatrics 1986;78(5 Pt 2):
features, serotypes, and antimicrobial resistance 959–982 PubMed
patterns in cases involving patients with and 103. Thomas KE, Hasbun R, Jekel J, Quagliarello VJ.
without human immunodeficiency virus infec- The diagnostic accuracy of Kernig’s sign, Brudz-
tion. Clin Infect Dis 1996;23(3):577–584 PubMed inski’s sign, and nuchal rigidity in adults with
89. Janoff EN, Breiman RF, Daley CL, Hopewell PC. suspected meningitis. Clin Infect Dis 2002;35(1):
Pneumococcal disease during HIV infection. Epide- 46–52 PubMed
miologic, clinical, and immunologic perspectives. 104. Molyneux E, Walsh A, Phiri A, Molyneux M.

Ann Intern Med 1992;117(4):314–324 PubMed Acute bacterial meningitis in children admitted
90. Grau I, Pallares R, Tubau F, et al; Spanish Pneumo- to the Queen Elizabeth Central Hospital, Blan-
coccal Infection Study Network (G03/103). Epi- tyre, Malawi in 1996-97. Trop Med Int Health
demiologic changes in bacteremic pneumococcal 1998;3(8):610–618 PubMed
disease in patients with human immunodefi- 105. Chang CJ, Chang WN, Huang LT, et al. Neonatal
ciency virus in the era of highly active antiret- bacterial meningitis in southern Taiwan. Pediatr
roviral therapy. Arch Intern Med 2005;165(13): Neurol 2003;29(4):288–294 PubMed
1533–1540 PubMed 106. Berkley JA, Versteeg AC, Mwangi I, Lowe BS,

91. Heffernan RT, Barrett NL, Gallagher KM, et al. Newton CR. Indicators of acute bacterial menin-
Declining incidence of invasive Streptococcus gitis in children at a rural Kenyan district hospi-
pneumoniae infections among persons with tal. Pediatrics 2004;114(6):e713–e719 PubMed
AIDS in an era of highly active antiretroviral 107. Chinchankar N, Mane M, Bhave S, et al. Diagno-
therapy, 1995-2000. J Infect Dis 2005;191(12): sis and outcome of acute bacterial meningitis
2038–2045 PubMed in early childhood. Indian Pediatr 2002;39(10):
92. Gordon SB, Chaponda M, Walsh AL, et al. Pneu- 914–921 PubMed
mococcal disease in HIV-infected Malawian 108. Weber MW, Herman J, Jaffar S, et al. Clinical
adults: acute mortality and long-term survival. predictors of bacterial meningitis in infants and
AIDS 2002;16(10):1409–1417 PubMed young children in The Gambia. Trop Med Int
93. Gordon SB, Walsh AL, Chaponda M, et al. Bacte- Health 2002;7(9):722–731 PubMed
rial meningitis in Malawian adults: pneumococ- 109. Lehmann D, Yeka W, Rongap T, et al. Aetiology and
cal disease is common, severe, and seasonal. Clin clinical signs of bacterial meningitis in children
Infect Dis 2000;31(1):53–57 PubMed admitted to Goroka Base Hospital, Papua New
94. Klugman KP, Madhi SA, Feldman C. HIV and Guinea, 1989-1992. Ann Trop Paediatr 1999;
pneumococcal disease. Curr Opin Infect Dis 19(1):21–32 PubMed
2007;20(1):11–15 PubMed 110. Curtis S, Stobart K, Vandermeer B, Simel DL, Klas-
95. Molyneux EM, Tembo M, Kayira K, et al. The sen T. Clinical features suggestive of meningitis
effect of HIV infection on paediatric bacterial in children: a systematic review of prospective
meningitis in Blantyre, Malawi. Arch Dis Child data. Pediatrics 2010;126(5):952–960 PubMed
2003;88(12):1112–1118 PubMed 111. Wiberg K, Birnbaum A, Gradon J. Causes and
96. Cunningham CK, Bonville CA, Ochs HD, et al. presentation of meningitis in a Baltimore
Enteroviral meningoencephalitis as a complica- community hospital 1997-2006. South Med J
tion of X-linked hyper IgM syndrome. J Pediatr 2008;101(10):1012–1016 PubMed
1999;134(5):584–588 PubMed 112. Weisfelt M, van de Beek D, Spanjaard L, Reitsma
97. Picard C, von Bernuth H, Ghandil P, et al. Clini- JB, de Gans J. Clinical features, complications,
cal features and outcome of patients with IRAK- and outcome in adults with pneumococcal men-
4 and MyD88 deficiency. Medicine (Baltimore) ingitis: a prospective case series. Lancet Neurol
2010;89(6):403–425 PubMed 2006;5(2):123–129 PubMed
98. Figueroa JE, Densen P. Infectious diseases associ- 113. Miller LG, Choi C. Meningitis in older patients:
ated with complement deficiencies. Clin Micro- how to diagnose and treat a deadly infection.
biol Rev 1991;4(3):359–395 PubMed Geriatrics 1997;52(8):43–44, 47–50, 55 PubMed
99. Fijen CA, Kuijper EJ, Tjia HG, Daha MR, Dankert J. 114. Avery RA, Frank G, Glutting JJ, Eppes SC. Predic-
Complement deficiency predisposes for meningi- tion of Lyme meningitis in children from a Lyme
tis due to nongroupable meningococci and Neis- disease-endemic region: a logistic-regression
seria-related bacteria. Clin Infect Dis 1994;18(5): model using history, physical, and laboratory
780–784 PubMed findings. Pediatrics 2006;117(1):e1–e7 PubMed
100. Ross SC, Densen P. Complement deficiency states 115. Belman AL, Iyer M, Coyle PK, Dattwyler R. Neu-
and infection: epidemiology, pathogenesis and rologic manifestations in children with North
122
American Lyme disease. Neurology 1993; 132. H offman O, Weber RJ. Pathophysiology and
43(12):2609–2614 PubMed treatment of bacterial meningitis. Ther Adv
116. Clark JR, Carlson RD, Sasaki CT, Pachner AR,
Neurol Disord 2009;2(6):1–7 PubMed
Steere AC. Facial paralysis in Lyme disease. La- 133. Lebel MH, Freij BJ, Syrogiannopoulos GA, et al.
ryngoscope 1985;95(11):1341–1345 PubMed Dexamethasone therapy for bacterial men-
117. Peter L, Jung J, Tilikete C, Ryvlin P, Mauguiere F. Op- ingitis. Results of two double-blind, placebo-
soclonus-myoclonus as a manifestation of Lyme controlled trials. N Engl J Med 1988;319(15):
disease. J Neurol Neurosurg Psychiatry 2006; 964–971 PubMed
77(9):1090–1091 PubMed 134. McIntyre PB, Berkey CS, King SM, et al. Dexa-
118. Sarff LD, Platt LH, McCracken GH Jr. Cerebrospi- methasone as adjunctive therapy in bacte-
nal fluid evaluation in neonates: comparison of rial meningitis. A meta-analysis of randomized
high-risk infants with and without meningitis. J clinical trials since 1988. JAMA 1997;278(11):
Pediatr 1976;88(3):473–477 PubMed 925–931 PubMed
119. Raucher HS, Kaufman DM, Goldfarb J, Jacobson 135. de Gans J, van de Beek D; European Dexa-
RI, Roseman B, Wolff RR. Pseudotumor cerebri methasone in Adulthood Bacterial Meningitis
and Lyme disease: a new association. J Pediatr Study Investigators. Dexamethasone in adults
1985;107(6):931–933 PubMed with bacterial meningitis. N Engl J Med 2002;
120. Bamberger DM. Diagnosis, initial management, 347(20):1549–1556 PubMed
and prevention of meningitis. Am Fam Physician 136. Molyneux EM, Walsh AL, Forsyth H, et al. Dexa-
2010;82(12):1491–1498 PubMed methasone treatment in childhood bacterial
121. Bonadio WA. The cerebrospinal fluid: physiolog- meningitis in Malawi: a randomised controlled
ic aspects and alterations associated with bacte- trial. Lancet 2002;360(9328):211–218 PubMed
rial meningitis. Pediatr Infect Dis J 1992;11(6): 137. van de Beek D, de Gans J, McIntyre P, Prasad K. Corti-
423–431 PubMed costeroids for acute bacterial meningitis. Cochrane
122. Chadwick SL, Wilson JW, Levin JE, Martin JM. Ce- Database Syst Rev 2007;(1):CD004405 PubMed
rebrospinal fluid characteristics of infants who 138. Chaudhuri A, Martinez-Martin P, Kennedy PG, et
present to the emergency department with fe- al; EFNS Task Force. EFNS guideline on the man-
ver: establishing normal values by week of age. agement of community-acquired bacterial men-
Pediatr Infect Dis J 2011;30(4):e63–e67 PubMed ingitis: report of an EFNS Task Force on acute
123. Darras BT, Annunziato D, Leggiadro RJ. Lyme
bacterial meningitis in older children and adults.
disease with neurologic abnormalities. Pediatr Eur J Neurol 2008;15(7):649–659 PubMed
Infect Dis 1983;2(1):47–49 PubMed 139. Heyderman RS, Lambert HP, O’Sullivan I, Stuart
124. Lee BE, Chawla R, Langley JM, et al. Paediatric In- JM, Taylor BL, Wall RA. Early management of
vestigators Collaborative Network on Infections suspected bacterial meningitis and meningo-
in Canada (PICNIC) study of aseptic meningitis. coccal septicaemia in adults. J Infect 2003;46(2):
BMC Infect Dis 2006;6:68 PubMed 75–77 PubMed
125. Lin AL, Safdieh JE. The evaluation and manage- 140. Tunkel AR, Hartman BJ, Kaplan SL, et al. Prac-
ment of bacterial meningitis: current practice guidelines for the management of bacte-
tice and emerging developments. Neurologist rial meningitis. Clin Infect Dis 2004;39(9):
2010;16(3):143–151 PubMed 1267–1284 PubMed
126. Tunkel AR, Hartman BJ, Kaplan SL, et al. Prac- 141. van de Beek D, de Gans J, McIntyre P, Prasad K.
tice guidelines for the management of bacte- Steroids in adults with acute bacterial men-
rial meningitis. Clin Infect Dis 2004;39(9): ingitis: a systematic review. Lancet Infect Dis
1267–1284 PubMed 2004;4(3):139–143 PubMed
127. Eppes SC, Nelson DK, Lewis LL, Klein JD. Char- 142. Sinner SW. Approach to the diagnosis and man-
acterization of Lyme meningitis and compari- agement of tuberculous meningitis. Curr Infect
son with viral meningitis in children. Pediatrics Dis Rep 2010;12(4):291–298 PubMed
1999;103(5 Pt 1):957–960 PubMed 143. Mace SE. Acute bacterial meningitis. Emerg Med
128. Ginsberg L, Kidd D. Chronic and recurrent men- Clin North Am 2008;26(2):281–317, viii PubMed
ingitis. Pract Neurol 2008;8(6):348–361 PubMed 144. Chandran A, Herbert H, Misurski D, Santosham
129. Proulx N, Fréchette D, Toye B, Chan J, Kravcik S. M. Long-term sequelae of childhood bacterial
Delays in the administration of antibiotics are as- meningitis: an underappreciated problem. Pedi-
sociated with mortality from adult acute bacteri- atr Infect Dis J 2011;30(1):3–6 PubMed
al meningitis. QJM 2005;98(4):291–298 PubMed 145. Pedersen TI, Howitz M, Ostergaard C. Clinical
130. Namani S, Koci R, Dedushi K. The outcome of characteristics of Haemophilus influenzae menin-
bacterial meningitis in children is related to gitis in Denmark in the post-vaccination era. Clin
the initial antimicrobial therapy. Turk J Pediatr Microbiol Infect 2010;16(5):439–446 PubMed
2010;52(4):354–359 PubMed 146. Anh DD, Kilgore PE, Kennedy WA, et al. Hae-
131. DE Gaudio M, Chiappini E, Galli L, DE Martino M. mophilus influenzae type B meningitis among
Therapeutic management of bacterial meningitis children in Hanoi, Vietnam: epidemiologic pat-
in children: a systematic review and comparison terns and estimates of H. Influenzae type B dis-
of published guidelines from a European perspec- ease burden. Am J Trop Med Hyg 2006;74(3):
tive. J Chemother 2010;22(4):226–237 PubMed 509–515 PubMed
123
147. B araff LJ, Lee SI, Schriger DL. Outcomes of bacte- the focus of infection. BMC Infect Dis 2005;5:93
rial meningitis in children: a meta-analysis. Pe- PubMed
diatr Infect Dis J 1993;12(5):389–394 PubMed 157. Hoogman M, van de Beek D, Weisfelt M, de Gans
148. Domingo P, Pericas R, Mirelis B, Nolla J, Prats G. J, Schmand B. Cognitive outcome in adults after
Haemophilus influenzae meningitis in adults: bacterial meningitis. J Neurol Neurosurg Psychi-
analysis of 12 cases [in Spanish]. Med Clin (Barc) atry 2007;78(10):1092–1096 PubMed
1998;111(8):294–297 PubMed 158. Sharip A, Sorvillo F, Redelings MD, Mascola L,
149. Schuchat A, Robinson K, Wenger JD, et al; Ac- Wise M, Nguyen DM. Population-based analy-
tive Surveillance Team. Bacterial meningi- sis of meningococcal disease mortality in the
tis in the United States in 1995. N Engl J Med United States: 1990-2002. Pediatr Infect Dis J
1997;337(14):970–976 PubMed 2006;25(3):191–194 PubMed
150. Arditi M, Mason EO Jr, Bradley JS, et al. 159. Kaplan SL, Schutze GE, Leake JAD, et al. Multi-
Three-year multicenter surveillance of pneu- center surveillance of invasive meningococcal
mococcal meningitis in children: clinical char- infections in children. Pediatrics 2006;118(4):
acteristics, and outcome related to penicillin e979–e984 PubMed
susceptibility and dexamethasone use. Pediat- 160. Weisfelt M, van de Beek D, Spanjaard L, de Gans
rics 1998;102(5):1087–1097 PubMed J. Arthritis in adults with community-acquired
151. Casado-Flores J, Aristegui J, de Liria CR, Mar- bacterial meningitis: a prospective cohort study.
tinón JM, Fernández C; Spanish Pneumococcal BMC Infect Dis 2006;6:64 PubMed
Meningitis Study Group. Clinical data and fac- 161. Erickson L, De Wals P. Complications and se-
tors associated with poor outcome in pneumo- quelae of meningococcal disease in Quebec,
coccal meningitis. Eur J Pediatr 2006;165(5): Canada, 1990-1994. Clin Infect Dis 1998;26(5):
285–289 PubMed 1159–1164 PubMed
152. Kornelisse RF, Westerbeek CM, Spoor AB, et al. 162. Harrison LH, Pass MA, Mendelsohn AB, et al. In-
Pneumococcal meningitis in children: prog- vasive meningococcal disease in adolescents and
nostic indicators and outcome. Clin Infect Dis young adults. JAMA 2001;286(6):694–699 PubMed
1995;21(6):1390–1397 PubMed 163. McLauchlin J. Human listeriosis in Britain, 1967-
153. Stanek RJ, Mufson MA. A 20-year epidemiologi- 85, a summary of 722 cases. 1. Listeriosis during
cal study of pneumococcal meningitis. Clin In- pregnancy and in the newborn. Epidemiol Infect
fect Dis 1999;28(6):1265–1272 PubMed 1990;104(2):181–189 PubMed
154. Weightman NC, Sajith J. Incidence and out- 164. McLauchlin J. Human listeriosis in Britain, 1967-
come of pneumococcal meningitis in north- 85, a summary of 722 cases. 2. Listeriosis in
ern England. Eur J Clin Microbiol Infect Dis non-pregnant individuals, a changing pattern of
2005;24(8):542–544 PubMed infection and seasonal incidence. Epidemiol In-
155. Weisfelt M, van de Beek D, Spanjaard L, Reitsma fect 1990;104(2):191–201 PubMed
JB, de Gans J. Clinical features, complications, 165. Evans JR, Allen AC, Bortolussi R, Issekutz TB,

and outcome in adults with pneumococcal men- Stinson DA. Follow-up study of survivors of fetal
ingitis: a prospective case series. Lancet Neurol and early onset neonatal listeriosis. Clin Invest
2006;5(2):123–129 PubMed Med 1984;7(4):329–334 PubMed
156. Østergaard C, Konradsen HB, Samuelsson S. Clin-
ical presentation and prognostic factors of Strep-
tococcus pneumoniae meningitis according to
124
10
Epidural and Subdural Infections
Sandi Lam and Peter C. Warnke
Subdural empyema is a focal purulent in- sult from the infection of subdural effusions
fection between the dura mater and arach- associated with meningitis.4 Local spread of
noid mater. More than 95% of cases of infection most commonly occurs from fron-
subdural empyema occur in the intracra- tal, ethmoid, or sphenoid sinusitis; osteo-
nial space rather than the spinal neuraxis.1 myelitis; and retrograde thrombophlebitis
Subdural empyemas make up 15 to 22% of of the valveless diploic veins.
focal intracranial infections. The histori- Rarely do mastoid infections lead to
cally high mortality rate of more than 80% epidural abscess or subdural empyema.
before the widespread availability of anti- The vascularity of the diploic system is at
biotics was reduced to 15.6 to 41% after the its most prominent in men in their second
advent of antimicrobial therapy.1 Once an and third decades of life. The frontal sinus
empyema is established within the subdu- also continues to develop during this pe-
ral space, there are few anatomic barriers to riod. Most cases of complicated sinusitis
the spread of infection. From 70 to 80% of occur in otherwise healthy men in this age
these cases occur over the cerebral convexi- group. There is a predisposition for subdu-
ties, although they can also have a parafal- ral empyema to develop in males, with a
cine, tentorial, or infratentorial location. male-to-female ratio of 3:1.2,4,6–8
Concomitant intracerebral abscess is pres- Direct extension of infection into the
ent in up to 6 to 22% of cases, whereas epi- subdural space occurs in chronic otitis
dural abscess is found in 9 to 17% of cases.2–4 media and rarely as a consequence of mas-
Epidural abscess develops between the toiditis. Infection can be introduced after
skull and the dura mater. The adherence the application of cranial pins and traction
of the dura mater to the calvaria can limit devices, neurosurgical or otolaryngologic
the expansion of an intracranial epidural procedures, and penetrating head trauma.
abscess. Autopsy studies reveal evidence Infection can also occur as a complication
of the spread of epidural infection into the of preexisting subdural collections and
subdural space in 80% of cases.5 with rare pulmonary and hematogenous
diseases. Tuberculous subdural empyema
has been reported.1,4,5,8–11
■■ E
pidemiology and Like subdural empyema, epidural ab-
Pathophysiology scesses occur most frequently in males
during the second and third decades of life,
A majority of cases of subdural empyema de- corresponding to the population with the
velop by the direct local extension of infec- highest likelihood of developing complicat-
tion rather than by hematogenous spread. In ed sinusitis. Intracranial epidural abscesses
infants, most cases of subdural empyema re- arise from direct extension in association
with sinusitis, osteomyelitis, cranial pin and ■■ Work-Up and Diagnosis
traction device placement, penetrating head
trauma, or postoperative infection.4,5,8,10 Laboratory Studies
The focus of this chapter is limited to
Laboratory studies apply to both subdu-
intracranial epidural abscess and subdural
ral empyema and epidural abscess. They
empyema. However, it is important to note
include complete blood counts, which re-
that the spine, in contrast to the intracrani-
veal a leukocytosis with a predominance
al compartment, provides a relatively large
of polymorphonuclear neutrophils. Ab-
space that can allow significant extension
normalities of the erythrocyte sedimenta-
of a spinal epidural abscess. The spread can
tion rate and C-reactive protein level are
be hematogenous by direct extension of a
nonspecific findings, with an ESR that is
contiguous local infection, and the patho-
elevated but generally less than 100 mm/
physiology of spinal epidural abscess is
h.4,12–14 Blood, urine, and sputum should be
different from that of intracranial epidural
cultured to identify potential organisms
abscess. Epidural abscess is estimated to
and sources of infection. A metabolic panel
occur nine times more frequently in the
should be obtained to allow correction of
spine than intracranially.5
any electrolyte abnormalities, such as hy-
ponatremia, and to screen for underlying
metabolic dysfunction in light of medi-
■■ Clinical Features
cal and antibiotic treatment.1,14,15 Lumbar

puncture is typically not recommended
In cases of subdural empyema, the most
for subdural empyema or intracranial epi-
common presenting features are fever and
dural abscess because of the risk for brain
headache. Clinical symptoms of sinusitis or a
herniation due to increased intracranial
history of sinusitis may or may not be pres-
pressure. Cerebrospinal fluid (CSF) studies
ent. Altered mental status is frequent. Other
are often nonspecific and show a moder-
presenting features of subdural empyema
ate pleocytosis with predominantly poly-
include meningismus, hemiparesis, nausea,
morphonuclear neutrophils, moderately
vomiting, sinus tenderness, local swelling/in-
elevated protein, and normal to low glu-
flammation, speech difficulty, homonymous
cose levels. Gram stain and CSF studies are
hemianopsia, decreased visual acuity, photo-
negative in over 75% cases of both epidural
phobia, cranial nerve palsies, and papillede-
abscess and subdural empyema. Normal
ma. Seizures occur in 8 to 20%. Neurologic
or sterile CSF samples do not exclude the
symptoms are typically due to inflammation
diagnosis of intracranial epidural abscess
of the cerebrum and meninges, mass effect,
or subdural empyema.4,12 Causative organ-
and thrombophlebitis of the cerebral venous
isms vary with the etiology of the primary
drainage. Focal deficits and seizures develop
infection (Tables 10.1 and 10.2). Sterile in-
as disease progression increases the mass ef-
traoperative cultures are reported in up to
fect or causes cerebritis.1,12
50% of cases of epidural abscess and subdu-
Patients with intracranial epidural abscess
ral empyema, presumably as a result of the
generally present with signs and symptoms of
preoperative administration of antibiotics.
infection and an expanding extra-axial intra-
For this reason, empiric administration of
cranial mass. These may include fever, head-
antibiotics before the collection of a speci-
ache, altered mental status, malaise, nausea,
men for culture should be avoided.4,12–14
vomiting, focal neurologic deficits, seizures,
sinus tenderness, or local inflammation. In
Imaging
cases of postoperative infection after crani-
otomy, over 90% of patients with epidural ab- Although magnetic resonance (MR) imag-
scess have evidence of a wound infection.5,12 ing is recognized to be more sensitive for
Compared with that of subdural empyema, showing morphological detail, detect-
the clinical presentation of intracranial epi- ing intraparenchymal abnormalities, and
dural abscess is generally described as more delineating the extent of infection, com-
126
indolent, although cases may vary.12 puted tomography (CT) is still the imag-
Table 10.1 Common causative organisms: subdural empyema
Associated Source Organisms
Paranasal sinusitis (frontal, ethmoid, sphenoid) α-Hemolytic streptococci
Staphylococci
Anaerobic/microaerophilic streptococci
Aerobic gram-negative bacilli
Bacteroides species
Otitis media/mastoiditis Aerobic and anaerobic streptococci
Pseudomonas aeruginosa
Bacteroides species
Enterobacter species
10 Epidural and Subdural Infections

Staphylococci
Postoperative infection Staphylococci
P. aeruginosa
Propionibacterium species
Penetrating head trauma Staphylococci
Clostridium species
Meningitis (neonate) Group B streptococci
Listeria monocytogenes
Meningitis (child) Streptococcus pneumoniae
Haemophilus influenzae
Neisseria meningitidis
Escherichia coli
ing modality most widely available and ment, particularly along the medial border
accessible in a timely manner. CT is most of the lesion at the pial surface, inward dis-
helpful when obtained with and without placement of the gray–white junction, and
intravenous contrast, allowing differentia- effacement of the ventricles, cortical sulci,
tion between chronic subdural or epidural and basal cisterns (Fig. 10.1). Mass effect is
hematoma, postoperative changes, and often caused more by edema than by the
infectious processes. CT findings for sub- empyema collection itself. Vasogenic ede-
dural empyema typically demonstrate a ma is prominent in cases of subdural em- 127
hypodense subdural lesion with enhance- pyema that are complicated by cerebritis,
Table 10.2 Common causative organisms: epidural abscess
Associated Source Organisms
Paranasal sinusitis (frontal, ethmoid, sphenoid) α-Hemolytic streptococci
Staphylococci
Anaerobic/microaerophilic streptococci
Bacteroides species
Otitis media/mastoiditis Aerobic and anaerobic streptococci
Pseudomonas aeruginosa
Bacteroides species
Staphylococci
Postoperative infection Staphylococci

P. aeruginosa
Propionibacterium species
Penetrating head trauma Staphylococci
Clostridium species
Fig. 10.1 Computed tomographic scan with contrast

associated cerebral abscess, or cortical ve- of left frontal and interhemispheric subdural empyema
nous thrombosis, which may further lead in a 15-year-old boy with frontal and ethmoid sinusitis.
to venous infarction.13,14,16 Note the hypodense subdural collection with enhance-
ment along the pial surface, underlying effacement of
Early in the disease course, CT may be un-
the cortical sulci, and mass effect from the purulent
revealing, but if clinical suspicion of infec- lesion and from cerebral edema.
tion persists, repeat imaging with CT with
and without contrast or MR imaging with
and without contrast is warranted. In cas-
es associated with sinusitis, CT of the head
may show sinus opacification, air–fluid lev-
els, or bony erosion.4 Epidural abscess on CT
typically appears as a crescentic or lenticu-
lar hypodense, enhancing extra-axial lesion.
MR imaging of the brain with and without
gadolinium contrast is more sensitive than
CT and may provide more detail in delineat-
ing the extent of infection. The extradural
lesion is frequently contiguous to an area
128
sinusitis, skull osteomyelitis, compound isms after a specimen is obtained. These
skull fracture, or craniotomy defect.6,8,13,16 should subsequently be tailored accord-
On MR imaging, subdural empyemas gen- ing to culture and sensitivity results. Ini-
erally appear hypointense or variable on tial empiric antimicrobial therapy should
T1-weighted images and hyperintense on provide coverage for gram-positive cocci,
T2-weighted images; they have high signal gram-negative bacilli, and anaerobes. The
on diffusion-weighted images, indicating standard recommended empiric antibiotic
restricted diffusion. Rim enhancement is regimen includes vancomycin, metronida-
seen following gadolinium administration. zole, and a third-generation cephalosporin.
Intracranial epidural abscesses exhibit hy- The duration of antibiotic therapy is typi-
perintensity on T2-weighted images, vari- cally recommended to be 4 to 6 weeks and
able intensity on T1-weighted images, and is extended to 6 to 8 weeks or longer in the
restricted diffusion, and they most often presence of osteomyelitis. For neonates
demonstrate contrast enhancement at the and children, empiric antibiotic choices
periphery1,4,13,17 (Fig. 10.2). may vary according to local rates of mi-
crobial resistance; particularly in cases of
subdural empyema, they may mirror the
Treatment and Management

antibiotic regimens that are used for men-
For both subdural empyema and epidural ingitis treatment.4,10,14,15,18 Prophylaxis for
abscess, broad-spectrum antibiotics should seizures is recommended, and anticonvul-
be administered as soon as possible with sants are mandatory if seizure activity is
coverage for aerobic and anaerobic organ- observed.4,12,18
a b
Fig. 10.2a,b Computed tomographic (CT) scan with contrast and magnetic resonance (MR) image (T1-weight-
ed image with contrast, T2-weighted image, and diffusion-weighted image sequence) of right frontal epidural
abscess and of left frontal and parietal subdural empyema in a 19-year-old man with associated frontal sinusitis
and subgaleal abscess. This patient had a history of surgical cosmetic craniofacial reconstruction for congenital
craniofacial abnormalities. (a) CT scan with contrast shows an enhancing lenticular extra-axial mass represent-
ing the left frontal epidural abscess. The right frontal area harbors multiple subdural hypodense collections with
enhancement, particularly along the pial surfaces, representing the subdural empyemas. Note also the subga-
leal collection of pus. (b) MR T1-weighted image with contrast shows the enhancing lesions and delineates the 129
anatomy and extent of disease involvement with more detail than the CT scan. (Continued on page 130)
c d
e f
Fig. 10.2c–f (Continued) (c) MR T2-weighted image and (d) diffusion-weighted image sequence shows hyper-
intense signal within the purulent areas. (e) Postoperative MR T1-weighted image with contrast and (f) CT scan
of the head with bone windows. (f) After surgical drainage of the right frontal epidural abscess and left fronto-
parietal subdural empyema as well as right frontal sinus exenteration, image shows evacuation of the purulent
material and the craniotomy sites repaired with titanium mesh.
130
Surgical management is indicated in al- abscess.4,5 Unfavorable prognostic indica-
most all cases of subdural empyema for ce- tors include age older than 60 years, poor
rebral decompression, drainage of purulent neurologic status at the time of presenta-
material, and identification of the caus- tion, rapid disease progression, delay in ini-
ative organism(s). There is no consensus tiating antibiotics, and subdural empyema
regarding the optimal surgical approach. resulting from trauma or surgery. Mortal-
Interventions include burr hole drain- ity in treated cases of subdural empyema
age, stereotactic drainage for deep-seated reaches 5 to 20%. Up to half of patients have
parafalcine or tentorial empyemas, and neurologic deficits at the time of discharge
craniotomy for irrigation, débridement, from the hospital, with 15 to 35% having
and drainage. Purulent material tends to hemiparesis and up to 30% having persis-
be in a fluid state early in the disease pro- tent seizures.1,4,12,13
cess and may produce loculate as time
passes. Repeat surgical procedures may be
required. Burr holes or craniotomy for de- ■■ Conclusion
compression with irrigation, débridement,
and drainage is warranted in a majority of Intracranial epidural abscess and subdu-

cases of epidural abscess. A delay in surgi- ral empyema are surgical emergencies
cal intervention has been associated with that carry significant morbidity, even in
higher morbidity and mortality rates. Re- the context of prompt appropriate treat-
peat surgical procedures may be necessary ment. Recognition of risk factors and a
in cases of persistent or recurrent suppu- strong degree of suspicion aid in the diag-
rative infection.2,12,15,18–21 For both subdural nosis. In both of these entities, treatment
empyema and epidural abscess, definitive with broad-spectrum antibiotics should
surgical management of complicated si- be started as soon as a sample for culture
nusitis should also be undertaken in con- is obtained. Surgery is performed in most
junction with the otolaryngology service.4 cases with the goal of treating mass effect
Surgery per se is not curative, but it is and reducing the size of purulent collec-
an essential component of treatment in tions to optimize antibiotic penetration.
the vast majority of cases to create those
pharmacokinetic conditions (reduced dif- References
fusion distance, sink effect, and improved 1. Lam S, Nguyen T. Subdural empyema. In: Lisak
perfusion) that will allow antibiotics to R, Truong D, Carroll W, Bhidayasiri R, eds. Inter-
penetrate the infected areas, helping to national Neurology: a Clinical Approach. Oxford,
provide curative therapy.14,15,19 In a lim- England: Blackwell Publishing; 2009:245–247
2. Bok AP, Peter JC. Subdural empyema: burr holes
ited number of scenarios, subdural empy- or craniotomy? A retrospective computerized to-
ema and epidural abscess can be managed mography-era analysis of treatment in 90 cases. J
nonoperatively. This treatment strategy is Neurosurg 1993;78(4):574–578 PubMed
3. Dill SR, Cobbs CG, McDonald CK. Subdural empy-
usually not considered except for patients
ema: analysis of 32 cases and review. Clin Infect
with very limited disease extension, no Dis 1995;20(2):372–386 PubMed
mass effect, no neurologic symptoms or 4. Osborn MK, Steinberg JP. Subdural empyema and
deficits, and an early favorable response to other suppurative complications of paranasal si-
nusitis. Lancet Infect Dis 2007;7(1):62–67 PubMed
antibiotics.2–4,12 5. Lam S, Nguyen T. Epidural abscess. In: Lisak R,
Truong D, Carroll W, Bhidayasiri R, eds. Interna-
Prognosis tional Neurology: a Clinical Approach. Oxford,
England: Blackwell Publishing; 2009:248–249
Neurologic status at the time of presenta- 6. Kombogiorgas D, Seth R, Athwal R, Modha J, Singh
J. Suppurative intracranial complications of si-
tion is a predictor of neurologic outcome.
nusitis in adolescence. Single institute experience
Delays in diagnosis or treatment are asso- and review of literature. Br J Neurosurg 2007;
ciated with increased morbidity and mor- 21(6):603–609 PubMed
tality. Mortality is estimated to be 10% in 7. Nathoo N, Nadvi SS, van Dellen JR, Gouws E.
Intracranial subdural empyemas in the era of
patients with treated intracranial epidural
131
computed tomography: a review of 699 cases. 15. A mar AP, Ghosh S, Apuzzo ML. Treatment of
Neurosurgery 1999;44(3):529–535, discussion central nervous system infections: a neurosurgi-
535–536 PubMed cal perspective. Neuroimaging Clin N Am 2000;
8. Pradilla G, Ardila GP, Hsu W, Rigamonti D. Epi- 10(2):445–459 PubMed
dural abscesses of the CNS. Lancet Neurol 2009; 16. Foerster BR, Thurnher MM, Malani PN, Petrou
8(3):292–300 PubMed M, Carets-Zumelzu F, Sundgren PC. Intracranial
9. Hlavin ML, Kaminski HJ, Fenstermaker RA, White infections: clinical and imaging characteristics.
RJ. Intracranial suppuration: a modern decade of Acta Radiol 2007;48(8):875–893 PubMed
postoperative subdural empyema and epidural 17. B aum PA, Dillon WP. Utility of magnetic reso-
abscess. Neurosurgery 1994;34(6):974–980, dis- nance imaging in the detection of subdural em-
cussion 980–981 PubMed pyema. Ann Otol Rhinol Laryngol 1992;101(10):
10. Krauss WE, McCormick PC. Infections of the 876–878 PubMed
dural spaces. Neurosurg Clin N Am 1992;3(2): 18. H all WA, Truwit CL. The surgical management
421–433 PubMed of infections involving the cerebrum. Neuro-
11. van Dellen A, Nadvi SS, Nathoo N, Ramdial PK. In- surgery 2008;62(Suppl 2):519–530, discussion
tracranial tuberculous subdural empyema: case re- 530–531 PubMed
port. Neurosurgery 1998;43(2):370–373 PubMed 19. F euerman T, Wackym PA, Gade GF, Dubrow T. Cra-
12. Tunkell A. Subdural empyema, epidural abscess, niotomy improves outcome in subdural empy-
and suppurative intracranial thrombophlebitis. ema. Surg Neurol 1989;32(2):105–110 PubMed
In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, 20. Z iai WC, Lewin JJ III. Advances in the manage-
Douglas, and Bennett’s Principles and Practices ment of central nervous system infections in the
of Infectious Diseases. Philadelphia, PA: Elsevier ICU. Crit Care Clin 2006;22(4):661–694, abstract
Churchill Livingstone; 2005:1165–1168 viii–ix PubMed
13. Anslow P. Cranial bacterial infection. Eur Radiol 21. Ziai WC, Lewin JJ III. Update in the diagnosis and
2004;14(Suppl 3):E145–E154 PubMed management of central nervous system infections.
14. Bernardini GL. Diagnosis and management of Neurol Clin 2008;26(2):427–468, viii PubMed
brain abscess and subdural empyema. Curr Neu-
rol Neurosci Rep 2004;4(6):448–456 PubMed
132
11
Infectious Intracranial Aneurysms
Hoon Choi, Walter A. Hall, and Eric M. Deshaies
The earliest published case of an infec- ■■ Epidemiology

tious aneurysm dates back to 1869, when
Church described a 13-year-old boy with The autopsy review of Fearnsides in 1916
left hemiparesis who was found to have a estimated that 30% of all intracranial an-
ruptured right middle cerebral artery aneurysms were infectious in origin.35 More
eurysm and mitral valve endocarditis.1 The recent reviews have put the estimate at 2
term mycotic aneurysm was introduced by to 6%.36–38 This decrease in the incidence is
Sir William Osler in 1885 to describe an likely due to the introduction of antibiotic
aortic aneurysm in the setting of bacterial therapy. The difficulty in estimating the
endocarditis.2 This term was subsequently true incidence of IIA stems from the some-
used to describe all intra- and extracranial what protean natural history of the disease.
aneurysms of an infectious etiology. Be- Bacterial IIAs have been observed to form
cause of the inaccuracy of this term in de- and regress spontaneously with antibi-
scribing a condition most commonly due to otic therapy, whereas IIAs associated with
bacterial involvement, several alternative fungal and tuberculous infections have
terms have been suggested, such as infect- been observed to be more persistent than
ed, infectious, infective, inflammatory, sep- bacterial infections.20,35,39–42 The increasing
tic, bacterial, and microbial. More recently, number of patients immunocompromised
the term infectious intracranial aneurysm as a consequence of acquired immunode-
(IIA) has gained popularity. For this chap- ficiency syndrome (AIDS), steroid therapy,
ter, we reviewed the literature and found a chemotherapeutic regimens, or organ
total of 303 patients with 390 aneurysms transplant presents a potential source for
from 1966 to 2008 that were associated an increase in the number of IIAs in sus-
with infection3–34 (Table 11.1). These cas- ceptible populations.
es will help to illustrate the pathogenesis, Although intracranial aneurysms are
presentation, microbiology, aneurysmal less common in children than in adults,
characteristics, natural history, and treat- those diagnosed in children are more likely
ment strategies for IIA. to be infectious. Approximately 10% of an-
134
Table 11.1 List of case reviews and reports included in the analysis
No. of No. of Medical Surgical Endovascular

Case Series or Report Year Patients Aneurysms Mean Age Therapy Therapy Therapy NR Mortality
Ojemann et al24 1966 1 4 46 1
Suwanwela32 1972 6 12 13 5 1 1
Bingham6 1977 2 5 19.5 2
Bohmfalk et al7 1978 4 6 32.8 3 1 2
Frazee et al14 1980 13 19 40 8 5 6
Day12 1981 2 2 44 2
Mielke et al22 1981 1 1 58 1 1
Pootrakul and Carter27 1982 1 1 40 1
Rout et al29 1984 6 6 20.5 4 2
Kikuchi et al18 1985 1 4 61 1 1

16
Hart et al 1987 2 2 25.5 1 1 1
Salgado et al30 1987 68 68 31.4 66 2 NR
Hadley et al15 1988 1 1 28 1
Monsuez et al23 1989 12 12 30.7 7 5 3
Barrow and Prats4 1990 12 15 26.5 6 6 4
Brust et al8 1990 17 29 35 5 12 4

Lee et al20 1990 1 2 7 mo 1
3
Aspoas and de Villiers 1993 25 33 23 3 21 1 1
Kurino et al19 1994 1 1 63 ` 1 1
Corr et al11 1995 14 18 27.3 6 8 1
Lin and Vieco21 1995 1 1 35 1
Scotti et al31 1996 3 4 40 3 1
Powell and Rijhsinghani28 1997 1 Multiple 38 1
Piastra et al26 2000 1 1 2 mo 1 1
Venkatesh et al34 2000 17 22 29.7 12 5 2
Chun et al10 2001 20 27 33.5 5 10 5 2

5
Bartakke et al 2002 1 1 5 1
Chapot et al9 2002 14 18 43.6 14
Phuong et al25 2002 16 29 48.9 4 10 2a 3
Kannoth et al17 2007 25 29 24.8 10 11 4 8
Dhomne et al13 2008 13 14 33.8 13 2
Trivedi et al33 2008 1 1 35 1
Total 303 390+ 34.3 151 110 35 7 45
Abbreviations: NR, not reported

a
One patient died before receiving any treatment.
11 Infectious Intracranial Aneurysms
135
eurysms in children are estimated to be vasculature. Showers of septic emboli can
infectious in origin.43–47 Endocarditis, espe- lead to the formation of multiple IIAs, seen
cially left-sided valve disease, is frequently in 17% of the reviewed cases (Table 11.3).
associated with IIA. In the present analysis, This result was consistent with the previ-
76% of patients with IIA had a diagnosis ously reported rate of 20%.48
of infective endocarditis (Table 11.2). Ex-
travascular infections, such as meningitis, Intravascular
orbital cellulitis, and postcraniotomy infec-
tions, have been reported to lead to IIA. In 1887, Eppinger49 described the infec-
tious and inflammatory processes leading
to weakening of the arterial wall and sub-
■■ Pathogenesis sequent aneurysm formation. He observed
that the inflammation involved the adven-
The pathogenesis of IIA can be conceptual- titia initially and then spread inward to the
ized into three different processes: intra- internal elastic membrane. This notion was
vascular, extravascular, and cryptogenic. confirmed in a mongrel dog model involv-
The intravascular mechanism is the most ing silicone rubber emboli.50,51 Although
common, involves septic emboli, and is vasa vasorum play a role in aortic aneu-
commonly secondary to bacterial endo- rysm formation after infection in a dog
carditis. IIAs due to septic emboli are often model,52 vasa vasorum are rarely present
located at vessel branch points in the distal in intracranial vessels.53 Molinari and col-
Table 11.2 Associated infections Table 11.3 Aneurysm location
Associated Infection Number Percentage Aneurysm Location Number Percentage
IE 231 76 MCA 167 43
Mitral IE 84 28 PCA 37 9
Aortic IE 23 8 ACA 30 8
Septal defect 4 1 ICA 23 6
Tricuspid IE 2 0.7 BA 8 2
Meningitis 31 10 PICA 8 2
CST 19 6 SCA 6 1.5
Dental infection 12 4 VA 4 1
Orbital cellulitis 11 3.6 AICA 1 0.3
Abscess 5 1.7 Other 10 2.5
UTI 3 1 NR 96 25
Vasculitis 2 0.7 Total aneurysms 390 100
Post-craniotomy 2 0.7 No. of patients with 52 17

multiple aneurysms
Cellulitis 1 0.3
Abbreviations: ACA, anterior cerebral artery; AICA, anterior
DVT phlebitis 1 0.3 inferior cerebellar artery; BA, basilar artery; ICA, internal
cerebral artery; MCA, middle cerebral artery; NR, not
Abbreviations: CST, cavernous sinus thrombosis; reported; PCA, posterior cerebral artery; PICA, posterior
DVT, deep vein thrombosis; IE, infective endocarditis; inferior cerebellar artery; SCA, superior cerebellar artery;
136 UTI, urinary tract infection VA, vertebral artery
leagues have suggested that in the absence and pharyngitis (see Table 11.2). Orbital
of vasa vasorum, bacteria can escape from cellulitis, sinusitis (Fig. 11.1), and skull
the lumen of the vessel through the oc- base infections often lead to cavernous si-
cluded origins of the thin-walled penetrat- nus thrombosis, which in turn can lead to
ing vessels into the Virchow-Robin space the formation of cavernous internal carotid
and from there to the adventitia of the oc- artery aneurysms. The histologic changes
cluded vessel. that develop are similar to the changes
In the experimental model by Molinari seen after septic embolic occlusion. There
et al,51 aneurysm formation occurred at is a progressive infiltration of the adventi-
the proximal end of the occluded segment, tia and media by polymorphonuclear leu-
overlapping the embolus and the adjacent kocytes, followed by prominent intimal
segment with a patent lumen, indicating inflammation (Fig. 11.2). There is often
the importance of arterial pulse pressure thrombosis of the involved arteries and
in the dilation of the diseased, weakened venous structures. The infective arteritis
arterial wall. Chronic aneurysms were also results in a weakened vessel wall, leading
induced by subtherapeutic doses of antibi- to aneurysm formation and rupture. Upon
otics. These aneurysms were found to be macroscopic examination, the aneurysm

firmly adherent to both the leptomeninges wall is very friable and often adherent to
and pachymeninges and had intact, indu- the adjacent brain parenchyma.
rated, fibrotic walls. Inadequate antibiotic
treatment permitted microorganisms to Cryptogenic
disseminate through penetrating vessels
into the infarcted intraparenchymal area, The third type of IIA is described as cryp-
causing brain abscess. togenic or primary IIA. This category rep-
resents a presumptive diagnosis based on
the clinical situation and angiographic
Extravascular
appearance of the abnormality.54 These
IIAs can also form as a result of primary ex- aneurysms occur in the absence of an ob-
travascular infections, such as meningitis, vious inflammatory process in the rest of
postcraniotomy infections, orbital celluli- the body, and blood cultures are frequently
tis, skull osteomyelitis, sinusitis, tonsillitis, negative.
Fig. 11.1 Axial computed tomographic scan with Fig. 11.2 Photomicrograph showing inflammatory
contrast shows maxillary sinusitis (arrow) due to As- cells infiltrating the wall of an infectious intracranial
pergillus fumigatus in a patient with diabetes mellitus. aneurysm (magnification unknown). 137
■■ Microbiology thrombosis of the neighboring arteries
could be seen in some cases of fungal IIA.
In the present analysis of 303 patients These patients were often afebrile at pre-
with IIAs spanning more than 42 years, the sentation and had a more indolent clini-
most common causative organisms were cal course. A combination of difficulty in
Streptococcus species, present in 102 pa- making a diagnosis, poor response to an-
tients (Table 11.4). Of these patients, 40 timicrobial treatment, proximal location
were found to have Streptococcus viridans of fungal IIA, adjacent thrombosis, immu-
(S. sanguinis, S. mutans, and S. mitis). The nosuppression, medical comorbidities, and
second most common causative organisms often a friable arterial wall led to a poor
were Staphylococcus species, found in 48 outcome compared with patients who had
patients (16%). Of the 48 patients, 41 were bacterial IIA. The mortality rate for fungal
found to be infected with S. aureus. Entero- IIA was 92%. Aspergillus fumigatus, Candida
coccus species were seen in 10 patients. albicans, and Mucor species are the three
Gram-negative bacteria were rare, isolated most common IIA-causing fungi (Fig. 11.3).
in only four cases, three of which were Other reported fungi include Petriellidium
Pseudomonas aeruginosa. Mycobacterium boydii, Pseudallescheria boydii, and organ-
species were isolated in four patients. Other isms causing chromoblastomycosis.4,22,54,55
bacteria isolated in patients with IIA have Blood cultures were positive in only 55%
included Staphylococcus epidermidis, Strep- of the reviewed cases (Table 11.5). Oje-
tococcus pneumoniae, Streptococcus bovis, mann’s review found negative blood cul-
Streptococcus pyogenes, α- and γ-hemolytic tures in 12.5%, which was comparable with
streptococci, Peptostreptococcus, Klebsiella the 10% in the review of Bohmfalk et al.7,37
species, Escherichia coli, Diphtheria species, The high rate of negative blood cultures in
and Serratia marcescens. the present review may be due to the lack
A true mycotic (fungal) etiology was of information on the absence of growth
verified in 13 of 303 patients with IIA (4%). from blood cultures. In two cases in which
At least seven of these patients were im- the cerebrospinal fluid culture was positive
munocompromised. Fungal IIA tended to for Staphylococcus species in the presence
involve more proximal segments of the of negative blood cultures, the result was
arterial vasculature, and an associated likely due to early antibiotic treatment.29,32
In one case, the only positive culture result
was from a sputum sample, which grew
Table 11.4 Causative microorganisms
Klebsiella pneumoniae and E. coli.29
Microorganism Number Percentage
Streptococcus 102 34
Viridans group 40 13
Enterococcus 10 3
Staphylococcus 48 16
S. aureus 41 14
Fungi 13 4
Candida 4 1
Gram-negative rods 4 1
Pseudomonas 3 1 Fig. 11.3 Gomori methenamine silver stain showing

the fungal hyphae of Aspergillus fumigatus within the
Mycobacterium 4 1
138 wall of a mycotic aneurysm (magnification unknown).
Table 11.5 Presentation Table 11.6 Predisposing factors
Presentation Number Percentage Predisposing Factor Number Percentage
Positive blood culture 168 55 Valvular disease 83 27
Fever 156 51 Rheumatic heart 46 15

disease
Headache 99 33
Congenital heart 16 5
Malaise 84 28 disease
Motor deficit 83 27 Intravenous drug use 20 7
LOC/MS change 46 15 Immunocompromise 9 3
Seizure 39 13
Nausea, vomiting 35 12
Cranial nerve palsy 34 11

cases of IIA. Conditions found to be associ-

Meningitis 31 10 ated with fungal IIA included intravenous
drug use (20 cases) and immunosuppres-
Behavioral change 25 8 sion (9 cases).
Petechiae 12 4 Headache was part of the initial presen-
tation in 99 patients (33%) (see Table 11.5).
Speech deficit 9 3 Loss of consciousness or altered mental
Abbreviations: LOC, loss of consciousness; MS, mental
status was present in 46 cases (15%). Thir-
status ty-nine patients (13%) presented with sei-
zures. Motor deficit was present in 83 cases
(27%), followed by cranial nerve palsy in 34
(11%) and speech deficit in 9 (3%).
Of 303 patients in the present analysis,
■■ Presentation 208 (69%) experienced aneurysmal rupture
(Table 11.7). Thirty-one percent of these
Of 303 patients with IIA found in the lit-
erature review, 146 (48%) were female, and
the average age was 34.5 years (see Table
11.1). The most common clinical finding
Table 11.7 Aneurysmal rupture and intracranial
was fever, which was present in 156 pa- hemorrhage on presentation
tients (51%). Blood cultures were positive
in 168 patients (55%) (see Table 11.5). A Presentation Number Percentage
total of 231 (76%) patients had a concur- Ruptured aneurysm 208 69
rent diagnosis of infective endocarditis
(see Table 11.2). The mitral valve was the SAH 64 21
most commonly involved site, with evi-
IPH 78 26
dence of documented vegetations in 84
patients, followed by the aortic valve in 23 IVH 15 5
patients. Evidence of preexisting valvular
disease was present in 83 patients (27%) EDH 1 0.3
(Table 11.6). The most common cause of an Unruptured 84 28
underlying valvular abnormality was rheu-
matic heart disease, which was reported NR 11 3
in 46 cases. Congenital heart disease was
Abbreviations: EDH, epidural hemorrhage; IPH, intraparen-
documented in 16 patients and was found chymal hemorrhage; IVH, intraventricular hemorrhage;
to be an important factor in the pediatric NR, not reported; SAH, subarachnoid hemorrhage
139
patients had subarachnoid hemorrhage Patients with IIA arising from an extra-
(Fig. 11.4). Seventy-eight patients experi- vascular source had a different clinical pre-
enced intraparenchymal hemorrhage (Fig. sentation than those with an intravascular
11.5); a majority of these cases were the etiology. Articles by Rout et al and by Su-
result of aneurysmal rupture, but a small wanwela et al describe IIA associated with
number were the result of hemorrhagic cavernous sinus thrombosis resulting from
transformation after an ischemic stroke local infection, such as orbital cellulitis.29,32
due to septic emboli. Intraventricular These patients presented predominantly
hemorrhage was seen in 15 patients. The with ocular pain, ophthalmoplegia, pro-
presence of infarction was not consistently ptosis, fever, and meningismus and tended
documented throughout the 303 reviewed to have unruptured cavernous internal ca-
cases. In Ojemann’s review of 81 patients rotid artery aneurysms.
from 1959 and 1980, the clinical presenta-
tion was hemorrhage in 52%, infarction in
20%, infarction followed by hemorrhage in ■■ Location
6%, and headache in 2%.37
There were 45 deaths, all but three of A total of 390 IIAs were found in 303 pa-
which occurred in the patients with rup- tients in the current review (see Table 11.3).
tured aneurysm (see Table 11.1). Of 303 Of these IIAs, 167 were located on the mid-
IIA cases, 84 (28%) had no aneurysmal dle cerebral artery (43%). Of the reviewed
rupture (see Table 11.7). Generally, these IIAs, 9.5% were located on the posterior
patients had better outcomes than the pa- cerebral artery, followed closely by 8% on
tients with ruptured IIA. the anterior cerebral artery and 6% on the
internal carotid artery. Most of these aneu-
rysms were located distally, consistent with
their pathogenesis, in which septic emboli
Fig. 11.4 Axial computed tomographic scan showing Fig. 11.5 Axial computed tomographic scan showing
a subarachnoid hemorrhage to the right of the brain- an intracerebral hemorrhage presumed to be due to a
stem that was due to the rupture of a basilar trunk my- mycotic aneurysm in a patient with systemic aspergillosis.
cotic aneurysm caused by Aspergillus species.
140
lodge within the blood vessel. Proximally diagnosed aneurysms.56 Depending on the
located aneurysms were seen in cavernous degree of inflammation, virulence of the
sinus thrombosis, tuberculous meningitis causative organism, and whether there has
(Fig. 11.6), and locally angioinvasive fungal been antibiotic treatment, the natural his-
infections. Posterior circulation aneurysms tory of IIA can be variable. Antibiotic ad-
that involved the vertebrobasilar artery and ministration interferes with the efforts to
posterior and anterior inferior cerebellar ar- determine the incidence rates accurately
teries occurred in 7%. Fox reported on 175 and limits clinical projections. In Oje-
bacterial aneurysms in 140 patients and mann’s retrospective review of 27 patients
found that 64% of these were located on the with IIA who were subjected to serial angi-
middle cerebral artery, 11% on the anterior ography with concurrent antibiotic treat-
cerebral artery, 11% on the internal carotid ment, 30% of the aneurysms resolved, 19%
artery, 8% on the posterior cerebral artery, diminished in size, 15% did not change in
and 6% on the vertebrobasilar arteries.50 size, and 22% enlarged; new aneurysms
Multiple aneurysms were seen in 52 of 303 developed in 15%.57 Other series have not-
patients (17%) in the present analysis, con- ed similar general outcome patterns with
sistent with Fox’s finding of 18%. Informa- variations that would be expected given

tion on the morphology of the aneurysms the differences in patient populations and
was not readily available, but when it was specific treatment algorithms.
described, the numbers of fusiform and sac- The overall mortality rate in the pres-
cular aneurysms appeared to be similar. ent review was 15% (45 of 303 patients)
(see Table 11.1). Of 208 patients with rup-
tured IIA, 42 (20%) died, which was an un-
■■ Natural History derestimate because of the lack of data on
mortality in 68 patients from the review
Autopsy reports and clinical series have by Salgado et al.30 With this study elimi-
varying incidence rates of IIA because of nated, the mortality rate in patients with
the presence of clinically dormant and unruptured IIA increased to 27%. This rate is
in contrast to the rate in patients with un-
ruptured IIA, in whom the mortality rate
was 3.6%. Bohmfalk et al noted that 42% of
patients presenting to the hospital with
evidence of subarachnoid hemorrhage due
to an intracranial bacterial aneurysm died.7
Patients with fungal IIA had the worst out-
come, with 12 of 13 cases progressing to
death.4,10,17–19,22,26 These results are consis-
tent with the reported fungal mortality
rate of greater than 90% despite medical or
surgical treatment.36 This mortality rate is
likely influenced by the immunocompro-
mised status of these patients.
■■ Treatment
In patients with IIA, it is imperative to start
appropriate antibiotic therapy as early as
Fig. 11.6 Contrast-enhanced axial computed tomo- possible. The animal experiments by Mo-
graphic scan in a child with tuberculous meningitis. linari et al revealed that within 24 hours
Notice the presence of severe hydrocephalus. after the administration of septic emboli,
141
intense inflammation and disruption of ganism. Unruptured aneurysms should be
the adventitia and muscularis occurred.51,52 initially treated conservatively with anti-
Of 303 patients, 151 (50%) in this analysis biotic therapy unless the aneurysms fail
received only medical treatment (Table to resolve or enlarge after at least 6 weeks
11.8), whereas 110 patients (36%) received of treatment.4,39,57,58 Conservative medical
medical treatment and underwent surgi- treatment may be the only safe option if the
cal intervention. Endovascular techniques, patient is medically unstable for surgery or
which became available for patients who the location and morphology of the IIA do
were treated in the later years covered by not permit safe surgery. Serial angiography
our review, were performed in conjunc- is important in monitoring the progression
tion with antibiotic therapy in 35 patients of the aneurysm (Fig. 11.7). The presence of
(12%). Of the 45 deaths in the current fungal IIA is a relative indication for conser-
analysis, 29 occurred in the patients who vative, nonsurgical management.58
received medical treatment (19%), 5 in
patients who received surgical treatment
(4.5%), 4 in patients who had endovascu-
lar treatment (11%), 6 in patients with un-
known treatment, and 1 in a patient who
was untreated. These numbers are likely
influenced by the fact that the medically
unstable patients were deemed unsuitable

for surgical intervention or died before sur-
gical intervention could be performed.
Medical treatment can result in com-
plete resolution of aneurysms in approxi-
mately 30% of cases.7,11,37,58 Broad-spectrum
antibiotic treatment, covering Streptococ-
cus species and Staphylococcus species,
should be started as early as possible. Pa-
tients should be receive at least 6 weeks of
therapy, although there is no prospective
randomized clinical trial to determine the
optimal duration of treatment. The anti-
biotic of choice should be governed by its Fig. 11.7 Cerebral angiogram illustrating an aneu-
ability to cross the blood–brain barrier and rysm of the basilar artery in a patient with Aspergillus
the sensitivity results of the causative or- fumigatus pneumonia.
Table 11.8 Management
Management Number Percentage Mortality, No. Mortality, %
Medical 151 50 29 19
Surgical 110 36 5 4.5
Endovascular 35 12 4 11
NR 6 2 6 100
No treatment 1 0.3 1 100
Abbreviations: NR, died before treatment

142
Surgical intervention may initially be tively treated by means of latex balloons
indicated in patients with ruptured IIA for and coils. Follow-up angiography showed
the treatment of intracranial hypertension stable occlusion of 16 aneurysms and re-
and herniation syndromes. Surgery for the filling of 2, which were subsequently suc-
purpose of definitively treating aneurysms cessfully treated. Chun et al demonstrated
was performed in 36% of patients in the a multimodality approach to IIA treatment,
current analysis (see Table 11.8). Surgery with 5 of 27 aneurysms treated by endo-
was more likely to be performed if there vascular means.10 In the 4 surviving pa-
was an enlargement or persistence of the tients, follow-up angiography showed no
IIA despite appropriate antibiotic therapy, aneurysmal recurrence.
aneurysms were located distally, or neuro-
logic decline was noted. Antibiotic therapy
can help reduce the risk for surgical com- ■■ Conclusion
plications because antimicrobials can lead
to reparative fibrosis in aneurysm walls, IIAs are a relatively rare entity. They are
making them less likely to rupture.4,40 Be- most commonly due to septic emboli, of-
cause of the friable nature of the IIA, clip ten in association with infective endocar-

ligation may not always be possible. In this ditis, that lodge in the distal vasculature,
case, wrapping the aneurysm dome is a where they cause inflammation and dis-
surgical treatment option, as is trapping ruption of the arterial wall from the ad-
the parent artery. Another therapeutic al- ventitia inward. A majority of patients
ternative is surgical excision of the aneu- with IIA present with signs of infection and
rysm and a segment of the parent vessel, aneurysmal rupture, although the clinical
which has the advantage of removing the presentation may vary for those with an
intracranial nidus of infection.12 This pro- extravascular source of infection. The most
cedure can be combined with a primary common causative microorganisms are
vascular anastomosis, such as an extra- Streptococcus species, followed by Staphy-
cranial–intracranial bypass.15 For proximal lococcus species. Patients with immuno-
lesions, such as intracavernous internal suppression are at risk for fungal IIA and
carotid artery aneurysms, carotid ligation have a mortality rate of over 90%. Multiple
with distal revascularization is an option.29 aneurysms may be present, but this has
Multiple aneurysms should be closely not been proven to be a negative prognos-
monitored with serial angiography, then tic indicator. The middle cerebral artery is
managed in the same manner as solitary by far the most frequently affected intra-
aneurysms. Consideration should be given cranial blood vessel. Management strategy
to the treatment of the aneurysm that has should begin with the early institution of
most likely bled and any other easily acces- antibiotic therapy (Fig. 11.8). Serial angi-
sible adjacent lesions. ography should be performed to monitor
The sophistication and efficacy of endo- the progression of the aneurysms closely.
vascular options for aneurysm treatment When unruptured aneurysms do not re-
have increased over the last two decades. spond to conservative therapy, or when
Chapot et al treated all 18 IIAs in 14 pa- the patient displays signs of intracranial
tients with endovascular methods.9 Distal hypertension, surgery should be consid-
or fusiform aneurysms were treated with ered. Ruptured IIAs should be treated with
parent vessel occlusion in which cyano- appropriate antibiotics and either surgical
acrylate, autologous clot, polyvinyl alco- or endovascular intervention to prevent re-
hol microparticles, or a combination of a bleeding. Endovascular options should be
straight coil and cyanoacrylate was used; explored when open surgical treatment is
proximal saccular aneurysms were selec- being considered.
143
Fig. 11.8 Management algorithm for infectious intracranial aneurysms. IIA, infectious intracranial aneurysm
References 8. B rust JC, Dickinson PC, Hughes JE, Holtzman RN. The
diagnosis and treatment of cerebral mycotic aneu-
1. C hurch WS. Aneurysm of the right cerebral ar- rysms. Ann Neurol 1990;27(3):238–246 PubMed
tery in a boy of thirteen. Trans Pathol Soc London 9. Chapot R, Houdart E, Saint-Maurice JP, et al. En-
1869;20:109–110 dovascular treatment of cerebral mycotic aneu-
2. Osler W. Gulstonian lecture on malignant endo- rysms. Radiology 2002;222(2):389–396 PubMed
carditis. BMJ 1885;1(1264):577–579 PubMed 10. C hun JY, Smith W, Halbach VV, Higashida RT, Wil-
3. Aspoas AR, de Villiers JC. Bacterial intracranial aneu- son CB, Lawton MT. Current multimodality man-
rysms. Br J Neurosurg 1993;7(4):367–376 PubMed agement of infectious intracranial aneurysms.
4. Barrow DL, Prats AR. Infectious intracranial aneu- Neurosurgery 2001;48(6):1203–1213, discussion
rysms: comparison of groups with and without 1213–1214 PubMed
endocarditis. Neurosurgery 1990;27(4):562–572, 11. Corr P, Wright M, Handler LC. Endocarditis-
discussion 572–573 PubMed related cerebral aneurysms: radiologic changes
5. Bartakke S, Kabde U, Muranjan MN, Bavdekar SB. with treatment. AJNR Am J Neuroradiol 1995;
Mycotic aneurysm: an uncommon cause for intra- 16(4):745–748 PubMed
cranial hemorrhage. Indian J Pediatr 2002;69(10): 12. D ay AL. Extracranial-intracranial bypass graft-
905–907 PubMed ing in the surgical treatment of bacterial aneu-
6. Bingham WF. Treatment of mycotic intracranial an- rysms: report of two cases. Neurosurgery 1981;
eurysms. J Neurosurg 1977;46(4):428–437 PubMed 9(5):583–588 PubMed
7. Bohmfalk GL, Story JL, Wissinger JP, Brown WE 13. D homne S, Rao C, Shrivastava M, Sidhartha W, Li-
Jr. Bacterial intracranial aneurysm. J Neurosurg maye U. Endovascular management of ruptured
1978;48(3):369–382 PubMed cerebral mycotic aneurysms. Br J Neurosurg 2008;
22(1):46–52 PubMed
144
14. Frazee JG, Cahan LD, Winter J. Bacterial intra- 32. S uwanwela C, Suwanwela N, Charuchinda S, Hong-
cranial aneurysms. J Neurosurg 1980;53(5): saprabhas C. Intracranial mycotic aneurysms of
633–641 PubMed extravascular origin. J Neurosurg 1972;36(5):
15. Hadley MN, Spetzler RF, Martin NA, Johnson PC. 552–559 PubMed
Middle cerebral artery aneurysm due to Nocardia 33. T rivedi MP, Carroll C, Rutherford S. Infective en-
asteroides: case report of aneurysm excision and docarditis complicated by rupture of intracranial
extracranial-intracranial bypass. Neurosurgery mycotic aneurysm during pregnancy. Int J Obstet
1988;22(5):923–928 PubMed Anesth 2008;17(2):182–187 PubMed
16. Hart RG, Kagan-Hallet K, Joerns SE. Mechanisms 34. V enkatesh SK, Phadke RV, Kalode RR, Kumar S,
of intracranial hemorrhage in infective endocar- Jain VK. Intracranial infective aneurysms pre-
ditis. Stroke 1987;18(6):1048–1056 PubMed senting with haemorrhage: an analysis of angio-
17. Kannoth S, Iyer R, Thomas SV, et al. Intracranial in- graphic findings, management and outcome. Clin
fectious aneurysm: presentation, management and Radiol 2000;55(12):946–953 PubMed
outcome. J Neurol Sci 2007;256(1-2):3–9 PubMed 35. Fearnsides EG. Intracranial aneurysms. Brain
18. Kikuchi K, Watanabe K, Sugawara A, Kowada M. 1916;39:224
Multiple fungal aneurysms: report of a rare case 36. K ojima Y, Saito A, Kim I. The role of serial angiog-
implicating steroid as predisposing factor. Surg raphy in the management of bacterial and fungal
Neurol 1985;24(3):253–259 PubMed intracranial aneurysms—report of two cases and
19. Kurino M, Kuratsu J, Yamaguchi T, Ushio Y. My- review of the literature. Neurol Med Chir (Tokyo)
cotic aneurysm accompanied by aspergillotic 1989;29(3):202–216 PubMed
granuloma: a case report. Surg Neurol 1994; 37. O jemann RG. Infectious intracranial aneurysms.

42(2):160–164 PubMed In: Ojemann RG, Ogilvy CS, Crowell RM, Heros
20. Lee KS, Liu SS, Spetzler RF, Rekate HL. Intracranial RC, eds. Surgical Management of Cerebrovascu-
mycotic aneurysm in an infant: report of a case. lar Disease. 3rd ed. Baltimore, MD: Williams &
Neurosurgery 1990;26(1):129–133 PubMed Wilkins; 1995:369–375
21. Lin BH, Vieco PT. Intracranial mycotic aneu- 38. S tengel A, Wolforth CC. Mycotic (bacterial) an-
rysm in a patient with endocarditis caused by eurysms of intravascular origin. Arch Intern Med
Cardiobacterium hominis. Can Assoc Radiol J 1923;31:527–554
1995;46(1):40–42 PubMed 39. B aldwin HZ, Zabramski JM, Spetzler RF. Infectious
22. Mielke B, Weir B, Oldring D, von Westarp C. Fun- intracranial aneurysms. In: Carter LP, Spetzler RF,
gal aneurysm: case report and review of the liter- Hamilton MG, eds. Neurovascular Surgery. New
ature. Neurosurgery 1981;9(5):578–582 PubMed York, NY: McGraw-Hill; 1998:777–778
23. Monsuez JJ, Vittecoq D, Rosenbaum A, et al. 40. C antu RC, LeMay M, Wilkinson HA. The impor-
Prognosis of ruptured intracranial mycotic an- tance of repeated angiography in the treatment
eurysms: a review of 12 cases. Eur Heart J 1989; of mycotic-embolic intracranial aneurysms. J
10(9):821–825 PubMed Neurosurg 1966;25(2):189–193 PubMed
24. Ojemann RG, New PF, Fleming TC. Intracranial 41. M cDonald CA, Jorb M. Intracranial aneurysms.
aneurysms associated with bacterial meningitis. Arch Neurol Psychiatry 1939;42:298–328
Neurology 1966;16(12):1222–1226 PubMed 42. R oach MR, Drake CG. Ruptured cerebral aneu-
25. Phuong LK, Link M, Wijdicks E. Management of ryms caused by micro-organisms. N Engl J Med
intracranial infectious aneurysms: a series of 16 1965;273:240–244
cases. Neurosurgery 2002;51(5):1145–1151, dis- 43. Daltroff G, Lamit J, Bichet J, Chague D, Jacquet G,
cussion 1151–1152 PubMed Portha C. Intracranial septic aneurysm in an infant.
26. Piastra M, Chiaretti A, Tortorolo L. Ruptured intra- Apropos of a case and review of the literature [in
cranial mycotic aneurysm presenting as cerebral French]. Pediatrie 1984;39(2):125–132 PubMed
haemorrhage in an infant: case report and review 44. H acker RJ. Intracranial aneurysms of childhood:
of the literature. Childs Nerv Syst 2000;16(3): a statistical analysis of 500 cases from the world
190–193 PubMed literature. Neurosurgery 1982;10:775
27. Pootrakul A, Carter LP. Bacterial intracranial an- 45. H umphreys RP. Aneurysms and arteriovenous
eurysm: importance of sequential angiography. malformations of the brain. In: Hoffman HJ, Ep-
Surg Neurol 1982;17(6):429–431 PubMed stein F, eds. Disorders of the Developing Nervous
28. Powell S, Rijhsinghani A. Ruptured bacterial in- System. Boston, MA: Blackwell Scientific; 1986:
tracranial aneurysm in pregnancy. A case report. 46. M azza C, Pasqualin A, Da Pian R, Pezzotta S. In-
J Reprod Med 1997;42(7):455–458 PubMed tracranial aneurysms and subarachnoid hemor-
29. Rout D, Sharma A, Mohan PK, Rao VR. Bacterial rhage in children and adolescents [in Italian].
aneurysms of the intracavernous carotid artery. J Minerva Med 1986;77(25):1145–1151 PubMed
Neurosurg 1984;60(6):1236–1242 PubMed 47. P asqualin A, Mazza C, Cavazzani P, Scienza R, Da-
30. Salgado AV, Furlan AJ, Keys TF. Mycotic aneurysm, Pian R. Intracranial aneurysms and subarachnoid
subarachnoid hemorrhage, and indications for hemorrhage in children and adolescents. Childs
cerebral angiography in infective endocarditis. Nerv Syst 1986;2(4):185–190 PubMed
Stroke 1987;18(6):1057–1060 PubMed 48. S hibuya S, Igarashi S, Amo T, Sato H, Fukumitsu
31. Scotti G, Li MH, Righi C, Simionato F, Rocca A. T. Mycotic aneurysms of the internal carotid
Endovascular treatment of bacterial intracra- artery. Case report. J Neurosurg 1976;44(1):
nial aneurysms. Neuroradiology 1996;38(2): 105–108 PubMed
186–189 PubMed 49. E ppinger. Arch f Klin Chir, Berlin, Bd. xxxv. 5.156
145
50. Molinari GF, Smith L, Goldstein MN, Satran R. 54. Barker WF. Mycotic aneurysms. Ann Surg
Brain abscess from septic cerebral embolism: an 1954;139(1):84–89 PubMed
experimental model. Neurology 1973;23(11): 55. W eir B. Aneurysms Affecting the Nervous Sys-
1205–1210 PubMed tem. Baltimore, MD: Williams & Wilkins; 1987
51. Molinari GF, Smith L, Goldstein MN, Satran R. 56. Yao KC, Bederson JB. Infectious intracranial an-
Pathogenesis of cerebral mycotic aneurysms. eurysms. In: Winn HR, ed. Youman’s Neurologi-
Neurology 1973;23(4):325–332 PubMed cal Surgery. 5th ed. Philadelphia, PA: Saunders;
52. Nakata Y, Shionoya S, Kamiya K. Pathogenesis 2003:2101–2106
of mycotic aneurysm. Angiology 1968;19(10): 57. O jemann RG. Surgical management of bacterial
593–601 PubMed intracranial aneurysms. In: Schmidek HH, Sweet
53. Clare CE, Barrow DL. Infectious intracranial an- WH, eds. Operative Neurosurgical Techniques.
eurysms. Neurosurg Clin N Am 1992;3(3):551– New York, NY: Grune & Stratton; 1988:997–1001
566 PubMed
146
12
Vertebral Column Infections
Kyle I. Swanson and Daniel K. Resnick
Vertebral column infections involve bone spontaneous diskitis include intravenous

(osteomyelitis), intervertebral disk(s) (dis- drug use, alcoholism, diabetes mellitus,
kitis), or a combination of both (spondyl- malignancy, immunosuppression, human
odiskitis). Spontaneous infection results immunodeficiency virus (HIV) infection,
from the spread of organisms from other endocarditis, renal failure, and cirrhosis.1,2,6
parts of the body to the vertebral column. Similar risk factors are associated with
Infections resulting in instability or neuro- spontaneous vertebral osteomyelitis.5,7,8
logic deficit are treated with a combination Some fungal and atypical bacterial in-
of antibiotics and surgery, whereas verte- fections are endemic in certain areas.
bral column infections without instability Blastomycosis is more common around
or deficit are frequently treated with anti- the Great Lakes and Ohio and Mississippi
biotics alone. When infections are identi- River basins. Coccidioidomycosis is local-
fied early and treated appropriately, the ized to the southwestern United States and
prognosis is generally favorable. The rela- Central America.9 In countries around the
tively nonspecific signs and symptoms of Mediterranean Sea, brucellosis comprises a
vertebral column infections are frequently sizable portion of vertebral column infec-
missed, however, resulting in considerable tions. Spinal tuberculosis, also known as
delay in diagnosis. Untreated infection can Pott disease, is more common in Southeast
result in chronic pain, spinal deformity, Asia and Africa (Fig. 12.1).10
neurologic deficits, and death. The overall rate of infection after spine
surgery is 2.1% (range, 0.5 to 12%), with
the procedure type a main determinant
■■ Incidence and Demographics of the postoperative infection rate.11–20 In
general, longer procedures and operations
Spontaneous diskitis has an incidence of with instrumentation have higher rates of
0.2 to 2.4 per 100,000, with a bimodal dis- infection. The incidence of infection after
tribution that peaks in early childhood and procedures involving intervertebral disks is
again at around 60 to 70 years of age.1,2 The relatively low, at 0.5 to 1%.21,22 Simple lami-
overall incidence of spontaneous verte- nectomy without bony fusion has an in-
bral osteomyelitis is approximately 2.4 per fection rate of approximately 1.5 to 2%.22,23
100,000, with an incidence that increases With the addition of instrumentation and
with age. The incidence is 0.3 per 100,000 in grafting, the rate of infection increases
those younger than 20 years of age and 6.5 significantly to 2.8 to 6%.22–25 The infection
per 100,000 in those older than 70 years of rate is increased still further if the surgery
age.3 Vertebral column infection has a male is done in the setting of spine trauma, with
predominance.3–5 Patient risk factors for a reported risk of 10%.26
b
a c d
Fig. 12.1a–d A 24-year-old Vietnamese man presented with long-standing thoracic back pain and worsening
kyphotic deformity. Lateral radiograph (a) revealed a gibbous deformity centered on T11. Contrasted T1-weight-
ed magnetic resonance images revealed enhancement consistent with osteomyelitis involving predominantly
T10–T12, with an associated large paravertebral abscess and a small epidural abscess (b,c). The patient un-
derwent T10–T12 corpectomies and drainage of the paravertebral abscess via a thoracolumbar approach, with
use of a titanium cage and autograft, and a T6–L3 posterior instrumented fusion (d). Intraoperative cultures
confirmed the diagnosis of tuberculosis.
A large number of patient characteris- gery.20,23,24,26–35 The presence of three or

tics have been associated with an increased more comorbidities further increases the
risk for spine surgical site infections: obe- risk for postoperative infection.20
sity, malnutrition, increased age, steroid
use, tobacco abuse, alcoholism, diabetes
mellitus, malignancy, concomitant urinary ■■ Etiology and Pathogenesis
tract infection, prior surgery, prior infec-
tion, prior radiation therapy, prolonged Infections of vertebral column are most of-
preoperative hospitalization, trauma, and ten the result of direct implantation during
148 complete neurologic deficit before sur- invasive procedures and surgery. A much
less common source of direct implantation disk space but are much more likely to in-
is penetrating trauma.36,37 Spontaneous volve the vertebrae. Patients with sickle
infections are usually caused by hematog- cell disease have an increased risk for in-
enous spread from a remote infection, such fection with Salmonella species and Hae-
as endocarditis, dental abscess, skin infec- mophilus influenzae.6
tion, or urinary tract infection. This hema- Spontaneous vertebral osteomyelitis gen-
togenous spread can be either arterial or erally begins at the vascular vertebral body
venous. The paravertebral venous plexus end plates; therefore, the vertebral body is
(Batson plexus) is a valveless venous sys- almost always involved, whereas the poste-
tem that connects the internal vertebral rior elements are only rarely involved (3 to
plexus to the deep pelvic and thoracic 12%).41 The most common source for spon-
veins, thus allowing a conduit for the dis- taneous vertebral osteomyelitis is urinary
tant spread of infection to the vertebral col- tract infection, followed by skin infection.5
umn.38 Finally, infection may spread to the As with diskitis, the most frequent or-
vertebral column from contiguous infected ganism causing vertebral osteomyelitis is S.
structures, such as overlying infected skin aureus, followed by gram-negative rod spe-
and decubitus ulcers, as well as deep infec- cies, especially Escherichia coli.5 Pseudomo-
tions, such as pyelonephritis, mediastinitis, nas aeruginosa is relatively more common
and pharyngeal abscesses. in intravenous drug users, but even in this
12 Vertebral Column Infections

The bimodal distribution of ages seen in patient population S. aureus is the most
patients with spontaneous diskitis is likely frequent causative organism.7 Tuberculosis
due to the differences in vascular anatomy remains an important cause of osteomyeli-
between children and adults. During child- tis in many developing regions of the world
hood, end-arteries penetrate the nucleus and in certain at-risk populations, such as
pulposus of the intervertebral disk, provid- patients with HIV infection. Brucellosis is
ing a direct channel through which bacte- another atypical bacterial cause of osteo-
ria can enter the disk. Also, the vertebral myelitis that is found in the Mediterra-
end plates have more arterial anastomoses nean region and is associated with animal
in children, allowing better bacterial clear- contact or the ingestion of unpasteurized
ance. By adulthood, the arterial supply milk.42 Other causes of spontaneous ver-
reaches only the annulus fibrosus, decreas- tebral osteomyelitis include various fungal
ing the likelihood of direct bacterial embo- infections, such as candidiasis, aspergil-
lization into the disk, whereas involvement losis, coccidioidomycosis, histoplasmosis,
of the vertebral end plates increases. The and blastomycosis, and rarely parasitic in-
rate of diskitis increases again in late adult- fections such as echinococcosis.9,40,43
hood because of the increase of comorbidi- The distribution of the involved spinal
ties with age.1,39 segments is similar for both diskitis and
Staphylococcus aureus is the most com- osteomyelitis, with the lumbar spine most
mon organism to cause diskitis, followed by frequently involved (60%), followed by the
gram-negative rods, Streptococcus species, thoracic spine (30%) and the cervical spine
and Enterococcus species.2,4 The likelihood (10%).1,4,5 Usually, one spinal level is in-
of gram-negative rod diskitis increases in volved, but multilevel involvement is seen
patients with gastrointestinal or genito- in 5 to 18% of pyogenic cases and 20% of
urinary infection, diabetes mellitus, intra- tuberculosis cases.1 Vertebral osteomyeli-
venous drug use, or a suppressed immune tis is frequently associated with adjacent
system.6 Fungal diskitis is uncommon but paravertebral abscesses (26%) and epidural
is more likely in patient populations that abscesses (17%).8
are immunocompromised, neutropenic, Postoperative vertebral column infec-
critically ill, on multiple antibiotics, or that tions are caused by the direct spread of
have indwelling central venous catheters.40 bacteria into the surgical wound from sur-
Atypical bacteria, such as those causing gical instruments, the surgeon’s hands, or
tuberculosis or brucellosis, can involve the airborne transmission. For early-onset in-
149
fections, the most common organism is S. an environment conducive for bacterial
aureus, which accounts for 50 to 75% of cas- growth. This may explain in part why pos-
es, followed by Staphylococcus epidermidis, terior spinal surgeries, which require the
gram-negative rod species, and polymi- extensive use of retractors, have a signifi-
crobial infections.22,23 S. epidermidis, Propi- cantly higher rate of infection than ante-
onibacterium acnes, and Corynebacterium rior spinal surgeries.26,51 Retraction should
species are often the cause of late-onset in- be periodically relaxed during prolonged
fections associated with instrumentation.44 surgery. The gentle handling of tissues and
Decreasing exposure of the surgical meticulous reapproximation of skin edges
wound to bacterial contamination aids in will also aid in healing.
preventing postoperative infection. Ade- Finally, perioperative intravenous pro-
quate cleansing of the skin before the start phylactic antibiotics can decrease bacte-
of surgery is vitally important. Randomized rial viability and prevent postoperative
controlled trials have demonstrated that infections.52,53 The appropriate use of pro-
chlorhexidine-alcohol is superior to povi- phylactic antibiotics decreases the rate of
done-iodine for preoperative skin cleans- postoperative spine infections from 5.9 to
ing.45 Likewise, chlorhexidine-based scrubs 2.2%.54 Prophylactic antibiotics should be
and alcohol rubs are superior to povidone- given just before incision, should be dosed
iodine–based scrubs for decolonizing hands again during long procedures, and should
before surgery.46 The practice of double be continued for no more than 24 hours.
gloving reduces the incidence of glove per- Topical prophylactic antibiotics applied to
forations that can result in cross-contami- the wound bed may also help prevent post-
nation.47 Vertical laminar airflow decreases operative infections. Gentamicin-soaked
the exposure of surgical wounds to airborne collagen sponges placed in the disk space
contamination and decreases the rate of in- may decrease the rate of postoperative dis-
fection in posterior spine fusions.48 Frequent kitis, and vancomycin powder applied to
irrigation decreases the bacterial burden in the surgical wound before closure has been
direct contact with the wound. shown to decrease infections in instru-
During any surgery there will be some mented spine fusions; however, irrigation
bacterial contamination because perfect with antibiotic-containing saline has not
sterility is not possible. Any factor that pro- been proven to have additional benefit over
longs surgery will theoretically increase irrigation with normal saline alone.52,55–58
exposure to contamination and increase
the risk for infection. Operative times lon-
ger than 3 hours increase postoperative in- ■■ Clinical Presentation
fection rates.49 Multilevel surgical fusions
also increase the risk for infection, in part The major presenting symptom of both
because of the prolonged operative time, spontaneous diskitis and osteomyelitis is
although the addition of a foreign body localized pain, with approximately 90% of
likely also plays a role.50 patients reporting back or neck pain, de-
The ability of the body to defend itself pending on the region involved.1,8 The pain
against infection also plays an important caused by a vertebral column infection is
role in determining whether a postopera- less likely to decrease with rest or recum-
tive infection will develop. This is governed bency than back or neck pain caused by
in large part by underlying patient condi- degenerative conditions and is often more
tions, as described previously. Surgical fac- resistant to analgesic medications. Radicu-
tors that influence the immune response lar pain related to irritation or compression
are also critical. A large volume of blood of adjacent nerve roots can occasionally
loss that is greater than 1 L or requires occur. Patients with lumbar involvement
blood transfusion has been associated with may have pain elicited with a straight leg
increased rates of infection.24,32 Prolonged raise test. The pain associated with diski-
retraction can devitalize tissue and provide tis in children can present as a refusal to
150
walk or bear weight.39 Osteomyelitis may initial postoperative relief of preoperative
also present with a sudden, severe worsen- symptoms and worsening localized pain re-
ing of pain associated with vertebral body mote from the time of surgery are concern-
fracture. Localized tenderness to percus- ing for infection. Diskitis can present as just
sion or palpation occurs in approximately worsening pain, more than a month after
one-fifth of patients with osteomyelitis.59 diskectomy, in a patient with a well-healed
Another common symptom of spontane- incision and no fevers. Recurrent disk herni-
ous vertebral column infection is fever. The ation is sometimes mistakenly diagnosed, or
association of back or neck pain with fever the patient may be wrongly accused of ma-
should always raise the possibility of spine lingering. An evaluation for infection should
infection; however, fever is not universally be considered in patients with recent spine
present. Only 60 to 70% of patients with surgery and worsening pain.
diskitis and 35 to 60% of those with osteo- Fever is frequently, but not always, pres-
myelitis report fever.2,8,59 Other, less fre- ent in postoperative vertebral column in-
quent systemic findings include chills, night fections. Moreover, several other common
sweats, general malaise, and anorexia.59 causes for fever postoperatively must be
Neurologic deficits, including weakness, considered, including atelectasis, pneumo-
difficulty walking, sensory abnormality, uri- nia, urinary tract infection, drug reaction,
nary incontinence or retention, fecal incon- and deep vein thrombosis.

tinence, and reflex abnormality, can all occur Wound drainage is the most common
and are reported in approximately one-third sign of postoperative spine infections and
of osteomyelitis cases.59 Neurologic deficits can be the only sign or symptom in some
are less likely in diskitis. Paralysis or rap- patients. Approximately 93% of patients
idly progressing deficits are concerning for with postoperative spine infection have
concurrent spinal epidural abscess. Chronic drainage. Other external signs of infection
osteomyelitis may present as a worsening include erythema, swelling, tenderness,
kyphosis, most pronounced in the sharply and wound dehiscence. The time from
angled gibbous deformity, which can also surgery to initial presentation of a postop-
cause spinal cord compression and neuro- erative spine infection is around 2 weeks.
logic deficits.8 Chronic vertebral osteomyeli- Infection with aggressive organisms like
tis may present with a draining sinus tract.10 Clostridium perfringens, however, can pres-
Vertebral column infections are often ent in days, and infection with indolent
initially misdiagnosed because the most organisms like P. acnes can present years
common presenting symptom, pain, is after surgery.22
nonspecific. The mean time to diagnosis The development of new neurologic
for vertebral osteomyelitis is 1.8 months. In deficits not initially present postopera-
one series, the diagnosis of vertebral osteo- tively should warrant urgent evaluation
myelitis was considered in only a quarter of to rule out abscess causing spinal cord or
patients at initial evaluation.8 The differen- nerve root compression. Treatment of an
tial diagnosis of vertebral column infection abscess causing spinal cord compression
includes infections of the spinal canal, ver- is a neurosurgical emergency because de-
tebral column fracture, degenerative disk lay in treatment may dramatically increase
disease or herniated disk, metastatic or morbidity or mortality.61
primary malignancy, inflammatory spon-
dyloarthopathies, neuropathic arthropathy,
sarcoidosis, psoas abscess, pancreatitis, and ■■ Diagnosis
pyelonephritis.60
Laboratory
Worsening pain is also a frequent symp-
tom in postoperative vertebral column infec- Laboratory markers of inflammation play
tions. Differentiation between the expected an important role in the diagnosis of ver-
pain of surgery and the pain caused by infec- tebral column infections, especially when
tion can be difficult. Pain that returns after the clinical signs and symptoms are not
151
specific. An elevated white blood cell count at different locations and times should be
with neutrophilia is frequently present in collected. Collecting the sample while the
spontaneous diskitis and vertebral osteo- patient is febrile increases the yield. Ap-
myelitis, as well as in postoperative infec- proximately half of all patients with dis-
tions, but a significant number of cases will kitis or osteomyelitis will have positive
have no leukocytosis and a normal white blood cultures that can be used to guide
blood cell differential. Approximately two- treatment.4,5 Echocardiography is usually
thirds of patients with vertebral osteomy- warranted in patients with bacteremia,
elitis will have an elevated white blood cell especially S. aureus bacteremia, as endo-
count, and about a third will have neutro- carditis is present in a significant number
philia.62 In some series, fewer than half of of patients with spontaneous diskitis and
patients with diskitis have a leukocytosis.63 vertebral osteomyelitis. Similarly, patients
The absence of leukocytosis does not rule with the new onset of back pain in the set-
out the possibility of infection. ting of known endocarditis should be eval-
An elevated C-reactive protein (CRP) uated for vertebral column infection.66
level and erythrocyte sedimentation rate If blood cultures demonstrate no growth
(ESR) are much more sensitive markers for after 2 days, a computed tomography (CT)–
infection than the white blood cell count guided percutaneous biopsy is warranted
but are nonspecific, and these parameters as the next step in the evaluation of spon-
can be elevated in the setting of many dif- taneous vertebral column infections. The
ferent types of inflammation. The CRP level diagnostic yield for CT-guided biopsy is
and ESR will be elevated in most cases of between 60 and 70%, and a repeat percuta-
vertebral column infection.62–64 The likeli- neous biopsy can increase the yield further
hood of infection in a patient with a nor- if the initial biopsy is negative.4,63 Biopsy
mal white blood cell count, CRP level, and specimens should be routinely sent for
ESR is quite low, although not impossible. aerobic and anaerobic bacterial cultures
Because the CRP level and ESR are normal- and fungal culture. Sensitivities should
ly elevated after surgery, caution must be be performed on any identified organism.
exercised when they are used to diagnose Histopathology samples should be evalu-
infections postoperatively. After surgery, ated with Gram stain and fungal stains. In
the ESR will be maximal around postoper- patients with risk factors associated with
ative day 5 and will often remain elevated tuberculosis or brucellosis, appropriate
for weeks. The CRP level has a much ear- cultures should be obtained, and histopa-
lier peak, at around 2 days, and will usu- thology should be evaluated for granulo-
ally normalize within 5 to 14 days after mas and acid-fast bacilli.60 Blood cultures
surgery.64,65 The CRP level can be especially should also be repeated a few hours after
useful in diagnosing late postoperative percutaneous biopsy.1 Open biopsy is war-
infections that present with nonspecific ranted if both blood cultures and percuta-
symptoms, such as pain. The quicker re- neous biopsy fail to yield a diagnosis and
sponse time of the CRP level also makes it a infection is still suspected. The yield of
more accurate gauge of treatment success open biopsy is 77% (range, 47 to 100%).5
or failure than the ESR.64 Serologic testing for specific fungal, para-
The proper diagnosis and treatment of sitic, or atypical bacterial causes of vertebral
vertebral column infections depends on column infections, such as brucellosis and
identifying the causative organism. Cul- cat-scratch fever (Bartonella henselae), may
tures should be obtained before antibiotics be warranted in patients who are from re-
are started to maximize yield. All patients gions where these diseases are endemic or
with suspected infection should have who have environmental exposures.39,67 An-
blood cultures collected because blood cul- tigen testing is another adjunct for the diag-
ture is a minimally invasive procedure that nosis of vertebral column infections caused
frequently identifies the causative organ- by certain fungi, such as candidiasis, asper-
ism. Ideally, three blood cultures obtained gillosis, and cryptococcosis. A tuberculin skin
152
test should be performed in patients sus- changes and has markedly increased ana-
pected of having tuberculous spondylitis.10 tomic detail. CT is the best study for eval-
Blood cultures should also be obtained uating the features of bony involvement
from patients with suspected postopera- and is vital for preoperative planning in
tive vertebral column infections. A major- vertebral column infections requiring sur-
ity of patients with surgical site infections gical fixation (Fig. 12.2a). Some soft tissue
will need surgical débridement, so cultures details are also discernible on CT, such as
are best obtained at the time of surgery. the presence of paravertebral fluid collec-
Occasionally, percutaneous needle aspira- tions. The administration of intravenous
tion is used in postoperative infections to iodinated contrast will usually result in
drain an abscess or to obtain a diagnosis the enhancement of infected disk and bone
in situations for which surgery is not in- as well as rim enhancement of associated
dicated, such as isolated diskitis. Cultures abscesses. Contrasted CT is particularly
from late-onset infections in the setting of useful for the imaging guidance of percu-
instrumentation should be allowed to in- taneous biopsies or abscess drainage. Al-
cubate for a prolonged period of time, up though contrasted CT is not as sensitive or
to 7 to 15 days, to increase the likelihood specific for vertebral column infections as
of identifying slow-growing organisms like contrasted magnetic resonance (MR) imag-
P. acnes.44 Cultures taken from the incision ing, it can often provide adequate diagnos-

site or from external drainage are often tic images in patients who are unable to
misleading because they will grow skin undergo MR imaging because of implanted
flora that may not be related to the under- devices or morbid obesity.68
lying infection. Myelography is generally avoided be-
cause of the availability of adequate nonin-
vasive techniques and the risk for seeding
Imaging
the cerebrospinal fluid by performing a
Plain radiographs are not particularly sensi- lumbar puncture in the setting of infection.
tive or specific for the diagnosis of vertebral MR imaging combined with gadolinium
column infections, and findings may be nor- contrast administration is the most reliable
mal for weeks after the onset of infection. imaging modality for diagnosing spontane-
Paravertebral soft tissue swelling, which is ous vertebral column infections. On non-
more noticeable in the cervical region, can contrasted T1-weighted images, diskitis
sometimes be the first radiographic sign of and osteomyelitis will demonstrate hy-
vertebral column infection. Disk space nar- pointensity of the disk and vertebral bod-
rowing generally takes between 7 and 10 ies, as opposed to normal hyperintensity
days to develop but is common in degen- in the vertebral bone marrow due to the
erative spine disease as well. Vertebral end presence of fat (Fig. 12.2b). Intravenous
plate erosion and vertebral body rarefaction gadolinium will enhance regions of inflam-
take weeks to develop. Vertebral fracture mation, especially the vertebral end plates
or collapse can develop late and is some- and associated abscesses (Fig. 12.2c).68 The
times confused with osteoporotic fracture. involved bone and disk will usually be hy-
In patients with kyphotic deformity in the perintense on T2-weighted images because
setting of vertebral osteomyelitis, the com- of increased edema (Fig. 12.2d). With diski-
parison of recumbent and standing radio- tis, there is usually a loss of the intranuclear
graphs can aid in the determination of overt cleft and decreased disk space height.69 End
instability. In general, plain radiographs plate destruction, frank vertebral collapse,
may be useful as an initial screening study and kyphotic deformities are late findings
and can also be used as a follow-up study of vertebral column infections. With iso-
to monitor for new or worsening kyphotic lated diskitis, MR imaging has a sensitivity
deformity (Fig. 12.2e,f). and specificity of over 90%, and with ver-
CT information is similar to that of plain tebral osteomyelitis, the sensitivity is 96%
radiographs but is more sensitive to early and the specificity is 93%.68,70 Imaging the
153
a b c
d e f
Fig. 12.2a–f A 63-year-old woman on dialysis with diabetes mellitus, end-stage renal disease, and obesity pre-
sented with 2 months of right upper quadrant pain. She was found to have methicillin-sensitive Staphylococcus
aureus mitral valve endocarditis and bacteremia. Three days later, she developed thoracic back pain. Thoracic
computed tomography (a) revealed diskitis and osteomyelitis at T7 and T8. Thoracic magnetic resonance imag-
ing confirmed the diagnosis, with the involved area demonstrating hypointensity on T1-weighted images (b),
enhancement on T1-weighted images with contrast (c), and focal hyperintensity on T2-weighted images (d).
The patient developed progressive kyphosis on follow-up radiographs (e) despite appropriate antibiotics and
bracing. She underwent corpectomies of T7 and T8 via a costotransversectomy approach, with use of a titanium
expandable cage and autograft, and a T4–T11 posterior instrumented fusion (f). The patient recovered well from
the surgery but died 2 months later from complications of endocarditis.
entire spine is recommended by some au- rely on increased uptake of various ra-
thors because of the possibility of concomi- dioactive tracers in metabolically active
tant distant vertebral column infection.71 regions, such as infection, but will also la-
Radionuclide studies are sometimes bel inflammation in general. They are less
useful when MR imaging is either not pos- sensitive than MR imaging but more sensi-
sible or nondiagnostic, such as in the set- tive than contrasted CT. Gallium-67 single-
ting of hardware-induced artifact.68 They photon emission computed tomography
154
(SPECT) and combined gallium-67/tech- alone is successful in a majority of patients
netium-99 (bone) SPECT have the highest with tuberculous vertebral osteomyelitis.75
reported sensitivity (91%) and specificity Postoperative vertebral column infections,
(92%). SPECT scans are more accurate than on the other hand, are treated in most cas-
scintigraphy.54 Labeled leukocyte imaging, es with a combination of targeted antibiot-
although useful in the diagnosis of osteo- ics and surgical débridement.
myelitis elsewhere in the body, has been
found to be less effective for the diagnosis Surgical Treatment
of vertebral osteomyelitis. [18F]Fluorode-
oxyglucose positron emission tomography Surgical treatment is indicated for the fol-
(FDG-PET) is another modality that has, in lowing reasons: failure to obtain diagnostic
preliminary studies, identified vertebral cultures via less invasive means, débride-
osteomyelitis with good accuracy.72 ment of infected tissue and drainage of
Postoperative vertebral column infec- associated abscesses in the setting of per-
tions have many of the same radiologic sistent or recurrent infection despite ad-
characteristics mentioned above, but the equate antimicrobial treatment or in the
interpretation of imaging is often made setting of overt sepsis, intractable pain,
more difficult because surgery itself causes decompression of the spinal cord or spi-
inflammatory changes that can mimic in- nal nerve roots in the setting of severe or

fection.73 Contrasted CT and MR imaging worsening neurologic deficits, and stabili-
can both identify enhancing fluid collec- zation of the spine or correction of signifi-
tions concerning for abscess, although care cant deformity.76
must be taken not to confuse abscesses Early treatment of kyphosis caused by
with other postoperative fluid collections, tuberculous vertebral osteomyelitis should
such as hematomas and seromas. A plain be considered in patients with risk factors
radiograph can be useful for ruling out re- for progression of deformity: kyphotic an-
tained foreign body. Both radiographs and gle of more than 30 degrees, loss of more
CT scans can demonstrate the loosening than 1.5 times the vertebral body height,
of implants, which can be associated with involvement of greater than three verte-
late-onset infections.74 bral bodies, overt radiographic instability,
involvement of both anterior and posterior
elements, and onset of disease during spi-
nal immaturity.77
■■ Treatment
Approaches
The goal of the treatment of vertebral col-
umn infections is to eliminate infection Surgery for isolated diskitis is rarely re-
permanently while maintaining spinal sta- quired and is most frequently used for
bility and neurologic function. In spontane- identification of the causative organism. In
ous infections, the mainstay of treatment is the lumbar spine, the standard posterior
tailored antibiotics, with surgical interven- microdiskectomy approaches may be uti-
tion reserved for selected indications, such lized. In the cervical spine, anterior cervi-
as instability or neurologic compression. In cal diskectomy approaches are preferred.
isolated diskitis, more than three-quarters For isolated diskitis in the thoracic spine, a
of patients can be treated nonoperatively posterolateral approach, such as the trans-
with appropriate antibiotics.1 Although pedicular approach or the transfacet pedi-
disease is usually more extensive in ver- cle-sparing approach, can be used. A lateral
tebral osteomyelitis, the majority of cases approach, such as the lateral extracavitary
can still be successfully treated without approach or costotransversectomy, is also
surgery. A systematic review found that an option. Associated paravertebral ab-
only 42% of patients with pyogenic osteo- scesses can be drained percutaneously.
myelitis required surgery in addition to an- The surgical treatment of vertebral os-
tibiotics.5 Furthermore, medical treatment teomyelitis, when necessary, requires more 155
extensive débridement and usually concur- ated psoas abscess.10 The upper sacral spine
rent stabilization. With adequate surgical can be accessed ventrally via similar routes.
débridement and antibiotics, there does The correction of severe, fixed kyphotic
not seem to be an increased risk for recur- deformity often requires complex poste-
rence of infection when autograft, allograft, rior surgical techniques utilizing wedge
or instrumentation is used in the setting of osteotomies and posterior instrumented
acute infection, even in an immunocom- fixation. These deformity correction sur-
promised patient population.72,78–81 Ante- geries can have a relatively high level of as-
rior surgical approaches are often preferred sociated operative morbidity.75
because vertebral osteomyelitis most often The treatment of postoperative vertebral
involves the vertebral bodies, with only column infections involves exploration of
rare involvement of the posterior elements. the wound with meticulous débridement of
Approaching anteriorly allows a more com- all necrotic and infected material. Sutures
plete débridement of infected tissue and from the prior surgery should be removed.
direct reconstruction of the compromised In early-onset postoperative infections,
portion of the vertebral column. intact spinal instrumentation and viable
Vertebral osteomyelitis involving the bone graft should be left in situ to increase
upper cervical spine at C1 and C2 is quite the chance of fusion.12–14,22,25,50,51,74,89–91 The
rare and may require transoral resection wound should be copiously irrigated with
and supplemental posterior instrumented liters of normal saline or antibiotic-con-
fusion (Fig. 12.3). Subaxial cervical verte- taining saline.22,74 Pulse-lavage irrigation
bral column infections are treated via an- may enhance débridement.
terior cervical diskectomy or corpectomy The wound can be closed primarily with
with the use of an autologous graft or cage, a drain in place. Alternatively, the wound
with or without ventral plating. Complica- can initially be left open to heal by sec-
tions associated with plating in this setting ondary intention, or it can be closed in a
have been reported.71 delayed fashion. Vacuum-assisted closure
The thoracic spine presents a particular (VAC) dressings can decrease nursing re-
challenge for the surgical treatment of ver- quirements and may help the healing
tebral osteomyelitis because of the difficulty process, although the benefit of VAC dress-
of anterior approaches. The cervicothoracic ings over traditional gauze packing has
junction can be approached ventrally via yet to be definitively demonstrated.92–94
cervical exposure, partial sternotomy, or An irrigation-suction system for continu-
manubrial resection.82 Posterolateral ap- ous irrigation has been reported for the
proaches have also been used to access this postoperative treatment of infected spine
region and include the transpedicular, lateral instrumentation.51 In patients with severe
extracavitary, and parascapular extrapleural infections, sepsis, extensive associated ne-
approaches.83–85 Posterior instrumented fu- crosis, or polymicrobial infections, repeat
sion is often used in conjunction with the débridement 2 to 3 days after the initial
anterior surgery to prevent cervicothoracic operation may provide additional bene-
instability.80,86 The midthoracic spine can be fit.22,25,74 Nonabsorbable monofilament su-
approached anteriorly via a thoracotomy, ture is recommended for skin closure.
or it can be accessed posterolaterally by ei- When patients with instrumented spine
ther a costotransversectomy or a lateral ex- fusions present with late-onset postop-
tracavitary approach (Fig. 12.2).83,84,87 The erative infection, they should be treated
lower thoracic spine and thoracolumbar with removal of hardware, in addition to
junction can be reached ventrally via a tho- the usual débridement and irrigation.91,95,96
racoabdominal approach (Fig. 12.1).88 These late postoperative infections are
The lumbar spine is approached ante- often caused by organisms capable of
riorly by either a retroperitoneal or trans- creating a glycocalyx covering on instru-
peritoneal approach. The retroperitoneal mentation that increases resistance to an-
approach also allows drainage of any associ- tibiotic therapy.96 Leaving the hardware
156
a b c

d
e f g
Fig. 12.3a–g A 44-year-old man with a history of tobacco abuse presented with 2 months of neck stiffness.
The patient described an episode of violent choking, caused by a fish bone, a few weeks before the onset of
neck symptoms. His erythrocyte sedimentation rate and C-reactive protein level were elevated, but he was afe-
brile without leukocytosis. Radiographs revealed erosion of the odontoid process of C2 and 10 mm of anterior
displacement of C1 relative to the body of C2 (a). The patient was placed in a halo brace for initial stabilization.
Contrasted T1-weighted magnetic resonance images revealed enhancement consistent with osteomyelitis in-
volving the odontoid process and the anterior arch of C1, and a paravertebral abscess (b,d). The paravertebral
abscess demonstrated marked T2-weighted hyperintensity (c,e). The patient underwent a transoral resection
(f), followed by a posterior fusion involving C1 lateral mass screws and C2 translaminar screws, with wire fixation
of an iliac crest autograft between C1 and C2 (g). The infection was polymicrobial, consistent with contamination
from a penetrating foreign body.
in place significantly increases the risk for Medical Treatment

infection relapse.91 These patients should
be monitored closely for worsening defor- The cornerstone of medical management
mity that might indicate a need for repeat for vertebral column infections is antibiotic
instrumented fusion, although they often therapy tailored to the causative organism
have already achieved stable fusion. and drug sensitivities. Empiric antibiotics 157
should be withheld if possible until adequate to β-lactam antibiotics, empiric coverage
cultures have been obtained. Consultation should generally also have activity against
with infectious disease specialists is advised methicillin-resistant S. aureus (MRSA). One
to help guide antibiotic selection and dura- viable combination is vancomycin and cef-
tion. Spinal immobilization via orthosis or triaxone. In patients at high risk for P. ae-
short-term bed rest can aid in pain control. ruginosa infections, such as intravenous
Physical rehabilitation may also be benefi- drug users, ceftriaxone can be switched
cial. Proper nutrition is vital to the successful for a cephalosporin with antipseudomonal
treatment of vertebral column infections.27,74 coverage, such as cefepime or ceftazidime.
Medical comorbidities, such as diabetes mel- High-dose nafcillin or oxacillin is the
litus and HIV infection, should be adequately preferred treatment for methicillin-sensi-
treated. Steroids are not used in the treat- tive S. aureus (MSSA). Vancomycin is used
ment of vertebral column infections. for MRSA and coagulase-negative Staphy-
lococcus species. P. aeruginosa is usually
treated with ceftazidime or cefepime, and
Antimicrobial Therapies
in seriously ill patients it is combined ini-
For pyogenic diskitis, intravenous antibiot- tially with either an aminoglycoside or
ics are usually continued for 4 to 6 weeks, ciprofloxacin. Nonpseudomonal gram-
although some recent reports suggest negative rod bacteria, such as E. coli, are
that a 12-week course of antibiotics, with usually treated with either ceftriaxone or
a switch to oral antibiotics after 6 weeks, ciprofloxacin. Penicillin G is the first-line

may decrease the risk for recurrence.1,6 A treatment for Streptoccocus species. An-
6-week course of antibiotics is usually rec- aerobic infections can be covered by either
ommended for the treatment of pyogenic clindamycin or metronidazole.100
vertebral osteomyelitis, although reported The first-line regimen for the treat-
courses range from 4 weeks to 3 months.97 ment of tuberculosis is a combination of
In patients with vertebral osteomyelitis, isoniazid, rifampicin, ethambutol, and
there is an increased risk for relapse with pyrazinamide for 2 months. This is subse-
regimens that are less than 4 weeks.98 Suc- quently pared down to just isoniazid and
cessful treatment of vertebral osteomyelitis rifampicin to complete a 6- to 9-month
with a completely oral regimen (fluoroqui- total course of treatment.101 Susceptibil-
nolones and rifampin) has been reported.99 ity testing is important given the rise of
For patients with postoperative verte- multidrug-resistant tuberculosis. Brucel-
bral column infections who do not have losis is often treated with a combination of
implanted hardware, intravenous antibiot- doxycycline and rifampicin for 6 months,
ics are continued for 4 to 6 weeks. Postop- although streptomycin or gentamicin may
erative infections involving instrumented be added for the first 2 to 3 weeks.10 Am-
fusions are treated with at least 6 weeks of photercin B is the first-line treatment of
antibiotics. For patients who have implant- many serious fungal infections, including
ed hardware, the addition of oral antibi- candidiasis and blastomycosis, although
otic suppression therapy, started after the voriconazole is now preferred for the treat-
initial intravenous antibiotic course and ment of invasive aspergillosis.10,100
continued for a minimum of 6 months and Patients should be monitored closely for
occasionally indefinitely, has been found to evidence of therapy failure. A lack of symp-
decrease the risk for late recurrence.91 tomatic improvement, continued fevers, or
Empiric antibiotics can be started in persistent elevation of the CRP level after 4
seriously ill patients after adequate cul- weeks are all suggestive of treatment fail-
tures have been obtained. Any empiric ure.64 Regular laboratory testing is usually
regimen should have good gram-positive indicated to monitor for antimicrobial tox-
cocci coverage, especially against S. aure- icity. Repeat MR imaging is a poor predictor
us, as well as gram-negative rod coverage. of outcome after treatment has started and
Given the increasing resistance of S. aureus may initially appear worse than pretreat-
158
ment imaging. New MR imaging may be infusion, postoperative infection increased
dicated in the setting of neurologic decline the mortality rate from 0.5 to 1.06%.104
to rule out new or worsening abscess.60,102
Serial radiographs can be used to monitor
for progressive kyphosis. ■■ Conclusion
Vertebral column infection should be con-
■■ Outcome sidered in any patient with back or neck
pain and associated fever, elevated inflam-
The reported recurrence rate after an matory markers, or bacteremia. Contrasted
initial course of antibiotics for pyogenic MR imaging is the most sensitive and spe-
spondylodiskitis is 8% (range, 1 to 22%).1,63 cific test to evaluate for vertebral column
Recurrence is usually within 6 months, but infection. Obtaining diagnostic cultures is
infection can return years later. Vertebral of paramount importance for the proper
osteomyelitis relapse is more likely in the treatment of both spontaneous and post-
setting of an associated paravertebral ab- operative infections. Antibiotics should
scess, a chronically draining sinus tract, be held until cultures are obtained. Post-
or recurrent bacteremia. With adequate operative infections are typically treated
treatment, pyogenic vertebral column in- with a combination of surgery and tailored

fections will generally progress to fusion antibiotics. Spontaneous vertebral column
across the involved disk spaces over the infections can often be treated with antibi-
course of 6 to 24 months, although pseud- otics alone. Surgery is indicated to obtain
arthrosis can develop.1 In patients with diagnostic cultures, decompress neural
tuberculosis, 65 to 79% of cases develop a structures, treat spinal instability, and dé-
solid fusion with medical therapy alone. bride infected and necrotic material when
Chronic pain is the most likely compli- infection persists or worsens in the face of
cation associated with vertebral column appropriate antibiotics.
infections, with 64% of patients treated
conservatively reporting residual back References
pain, versus 26% of patients treated opera- 1. Cottle L, Riordan T. Infectious spondylodiscitis. J
tively.103 In a systematic review of pyogenic Infect 2008;56(6):401–412 PubMed
vertebral osteomyelitis case series, over 2. Hopkinson N, Stevenson J, Benjamin S. A case
ascertainment study of septic discitis: clinical,
a quarter of patients had a complication
microbiological and radiological features. QJM
that significantly worsened their quality of 2001;94(9):465–470 PubMed
life, including 28% with chronic pain, 16% 3. Grammatico L, Baron S, Rusch E, et al. Epidemi-
with persistent weakness, and 7% with ology of vertebral osteomyelitis (VO) in France:
analysis of hospital-discharge data 2002-2003.
bowel or bladder dysfunction.5 Postopera- Epidemiol Infect 2008;136(5):653–660 PubMed
tive vertebral column infections signifi- 4. Legrand E, Flipo RM, Guggenbuhl P, et al; Rheu-
cantly increase the cost of spine surgery, matology Network Organization. Management
the length of hospitalization, and the num- of nontuberculous infectious discitis. Treat-
ments used in 110 patients admitted to 12 teach-
ber of complications, including neurologic ing hospitals in France. Joint Bone Spine 2001;
deficits.11,20,104 68(6):504–509 PubMed
Worse outcomes are associated with 5. Mylona E, Samarkos M, Kakalou E, Fanourgiakis
P, Skoutelis A. Pyogenic vertebral osteomyelitis: a
motor weakness or complete paralysis at systematic review of clinical characteristics. Se-
presentation, delay of diagnosis beyond 2 min Arthritis Rheum 2009;39(1):10–17 PubMed
months, and hospital-acquired infections.8 6. Grados F, Lescure FX, Senneville E, Flipo RM,
Mortality for spontaneous pyogenic spon- Schmit JL, Fardellone P. Suggestions for manag-
ing pyogenic (non-tuberculous) discitis in adults.
dylodiskitis is approximately 6% (range, Joint Bone Spine 2007;74(2):133–139 PubMed
2 to 12%).1,5 Mortality is usually related 7. Patzakis MJ, Rao S, Wilkins J, Moore TM, Harvey PJ.
to sepsis, endocarditis, or an underlying Analysis of 61 cases of vertebral osteomyelitis. Clin
Orthop Relat Res 1991;(264):178–183 PubMed
medical condition.2,63 In a series of patients
8. McHenry MC, Easley KA, Locker GA. Vertebral
undergoing surgical decompression and osteomyelitis: long-term outcome for 253 pa- 159
tients from 7 Cleveland-area hospitals. Clin In- 27. K
lein JD, Hey LA, Yu CS, et al. Perioperative nutri-
fect Dis 2002;34(10):1342–1350 PubMed tion and postoperative complications in patients
9. Kim CW, Perry A, Currier B, Yaszemski M, Garfin undergoing spinal surgery. Spine 1996;21(22):
SR. Fungal infections of the spine. Clin Orthop 2676–2682 PubMed
Relat Res 2006;444:92–99 PubMed 28. T
enney JH, Vlahov D, Salcman M, Ducker TB.
10. Skaf GS, Kanafani ZA, Araj GF, Kanj SS. Non-pyo- Wide variation in risk of wound infection follow-
genic infections of the spine. Int J Antimicrob ing clean neurosurgery. Implications for peri-
Agents 2010;36(2):99–105 PubMed operative antibiotic prophylaxis. J Neurosurg
11. Calderone RR, Garland DE, Capen DA, Oster H. 1985;62(2):243–247 PubMed
Cost of medical care for postoperative spinal 29. A ndreshak TG, An HS, Hall J, Stein B. Lumbar
infections. Orthop Clin North Am 1996;27(1): spine surgery in the obese patient. J Spinal Dis-
171–182 PubMed ord 1997;10(5):376–379 PubMed
12. A
bbey DM, Turner DM, Warson JS, Wirt TC, Scalley 30. C apen DA, Calderone RR, Green A. Periopera-
RD. Treatment of postoperative wound infections tive risk factors for wound infections after lower
following spinal fusion with instrumentation. J back fusions. Orthop Clin North Am 1996;27(1):
Spinal Disord 1995;8(4):278–283 PubMed 83–86 PubMed
13. G
lassman SD, Dimar JR, Puno RM, Johnson JR. 31. Patel N, Bagan B, Vadera S, et al. Obesity and spine
Salvage of instrumental lumbar fusions com- surgery: relation to perioperative complications.
plicated by surgical wound infection. Spine J Neurosurg Spine 2007;6(4):291–297 PubMed
1996;21(18):2163–2169 PubMed 32. H o C, Sucato DJ, Richards BS. Risk factors for the
14. K
eller RB, Pappas AM. Infection after spinal fu- development of delayed infections following
sion using internal fixation instrumentation. Or- posterior spinal fusion and instrumentation in
thop Clin North Am 1972;3(1):99–111 PubMed adolescent idiopathic scoliosis patients. Spine
15. K
ostuik JP, Israel J, Hall JE. Scoliosis surgery 2007;32(20):2272–2277 PubMed
in adults. Clin Orthop Relat Res 1973;(93): 33. Simpson JM, Silveri CP, Balderston RA, Simeone
225–234 PubMed FA, An HS. The results of operations on the lumbar

16. Lonstein J, Winter R, Moe J, Gaines D. Wound spine in patients who have diabetes mellitus. J Bone
infection with Harrington instrumentation and Joint Surg Am 1993;75(12):1823–1829 PubMed
spine fusion for scoliosis. Clin Orthop Relat Res 34. R echtine GR, Bono PL, Cahill D, Bolesta MJ, Chrin
1973;(96):222–233 PubMed AM. Postoperative wound infection after instru-
17. R
oberts FJ, Walsh A, Wing P, Dvorak M, Schweigel J. mentation of thoracic and lumbar fractures. J
The influence of surveillance methods on surgical Orthop Trauma 2001;15(8):566–569 PubMed
wound infection rates in a tertiary care spinal sur- 35. S ponseller PD, LaPorte DM, Hungerford MW, Eck
gery service. Spine 1998;23(3):366–370 PubMed K, Bridwell KH, Lenke LG. Deep wound infections
18. W
est JL III, Ogilvie JW, Bradford DS. Complica- after neuromuscular scoliosis surgery: a multi-
tions of the variable screw plate pedicle screw center study of risk factors and treatment out-
fixation. Spine 1991;16(5):576–579 PubMed comes. Spine 2000;25(19):2461–2466 PubMed
19. Balderston RA, Blumberg KD, eds. Infection 36. H ales DD, Duffy K, Dawson EG, Delamarter R.
in spine surgery. In Balderston RA, An HS, eds. Lumbar osteomyelitis and epidural and paraspi-
Complications in Spinal Surgery. Philadelphia, nous abscesses. Case report of an unusual source
PA: Saunders; 1991:157–168 of contamination from a gunshot wound to the
20. Olsen MA, Mayfield J, Lauryssen C, et al. Risk fac- abdomen. Spine 1991;16(3):380–383 PubMed
tors for surgical site infection in spinal surgery. J 37. Schulze CJ, Mayer HM. Exogenous lumbar spon-
Neurosurg 2003;98(2, Suppl):149–155 PubMed dylodiscitis following a stabwound injury and
21. B
ongartz EB, Ulrich P, Fidler M, Bernucci C. Re- vertebral fracture. A case report and review of the
operation in the management of post-opera- literature. Eur Spine J 1995;4(6):357–359 PubMed
tive disc space infection. Zentralbl Neurochir 38. B atson OV. The function of the vertebral veins
1994;55(2):120–124 PubMed and their role in the spread of metastases. Ann
22. Weinstein MA, McCabe JP, Cammisa FP Jr. Post- Surg 1940;112(1):138–149 PubMed
operative spinal wound infection: a review of 39. Fernandez M, Carrol CL, Baker CJ. Discitis and
2,391 consecutive index procedures. J Spinal vertebral osteomyelitis in children: an 18-year re-
Disord 2000;13(5):422–426 PubMed view. Pediatrics 2000;105(6):1299–1304 PubMed
23. Massie JB, Heller JG, Abitbol JJ, McPherson D,
40. C hia SL, Tan BH, Tan CT, Tan SB. Candida spon-
Garfin SR. Postoperative posterior spinal wound dylodiscitis and epidural abscess: management
infections. Clin Orthop Relat Res 1992;(284): with shorter courses of anti-fungal therapy in
99–108 PubMed combination with surgical debridement. J Infect
24. W
immer C, Gluch H, Franzreb M, Ogon M. Pre- 2005;51(1):17–23 PubMed
disposing factors for infection in spine surgery: a 41. Babinchak TJ, Riley DK, Rotheram EB Jr. Pyogenic
survey of 850 spinal procedures. J Spinal Disord vertebral osteomyelitis of the posterior elements.
1998;11(2):124–128 PubMed Clin Infect Dis 1997;25(2):221–224 PubMed
25. Sasso RC, Garrido BJ. Postoperative spinal 42. Katonis P, Tzermiadianos M, Gikas A, Papagelo-
wound infections. J Am Acad Orthop Surg 2008; poulos P, Hadjipavlou A. Surgical treatment of spi-
16(6):330–337 PubMed nal brucellosis. Clin Orthop Relat Res 2006;444:
26. Blam OG, Vaccaro AR, Vanichkachorn JS, et al. 66–72 PubMed
Risk factors for surgical site infection in the 43. Schnepper GD, Johnson WD. Recurrent spinal
patient with spinal injury. Spine 2003;28(13): hydatidosis in North America. Case report and
160 1475–1480 PubMed
review of the literature. Neurosurg Focus 2004; 59. P
riest DH, Peacock JE Jr. Hematogenous vertebral
17(6):E8 PubMed osteomyelitis due to Staphylococcus aureus in the
44. Haidar R, Najjar M, Der Boghossian A, Tabbarah adult: clinical features and therapeutic outcomes.
Z. Propionibacterium acnes causing delayed post- South Med J 2005;98(9):854–862 PubMed
operative spine infection: review. Scand J Infect 60. Z
immerli W. Clinical practice. Vertebral osteo-
Dis 2010;42(6-7):405–411 PubMed myelitis. N Engl J Med 2010;362(11):1022–
45. D
arouiche RO, Wall MJ Jr, Itani KMF, et al. 1029 PubMed
Chlorhexidine-alcohol versus povidone-iodine 61. R
igamonti D, Liem L, Sampath P, et al. Spinal
for surgical-site antisepsis. N Engl J Med 2010; epidural abscess: contemporary trends in etiol-
362(1):18–26 PubMed ogy, evaluation, and management. Surg Neurol
46. T
anner J, Swarbrook S, Stuart J. Surgical hand an- 1999;52(2):189–196, discussion 197 PubMed
tisepsis to reduce surgical site infection. Cochrane 62. Jensen AG, Espersen F, Skinhøj P, Frimodt-Møller
Database Syst Rev 2008;(1):CD004288 PubMed N. Bacteremic Staphylococcus aureus spondylitis.
47. T
anner J, Parkinson H. Double gloving to reduce Arch Intern Med 1998;158(5):509–517 PubMed
surgical cross-infection. Cochrane Database Syst 63. Friedman JA, Maher CO, Quast LM, McClelland RL,
Rev 2006;3(3):CD003087 PubMed Ebersold MJ. Spontaneous disc space infections in
48. G
ruenberg MF, Campaner GL, Sola CA, Ortolan adults. Surg Neurol 2002;57(2):81–86 PubMed
EG. Ultraclean air for prevention of postop- 64. K
han MH, Smith PN, Rao N, Donaldson WF. Se-
erative infection after posterior spinal fusion rum C-reactive protein levels correlate with clin-
with instrumentation: a comparison between ical response in patients treated with antibiotics
surgeries performed with and without a verti- for wound infections after spinal surgery. Spine J
cal exponential filtered air-flow system. Spine 2006;6(3):311–315 PubMed
2004;29(20):2330–2334 PubMed 65. T helander U, Larsson S. Quantitation of C-reac-
49. W
immer C, Gluch H. Management of postop- tive protein levels and erythrocyte sedimenta-

erative wound infection in posterior spinal tion rate after spinal surgery. Spine 1992;17(4):
fusion with instrumentation. J Spinal Disord 400–404 PubMed
1996;9(6):505–508 PubMed 66. Le Moal G, Roblot F, Paccalin M, et al. Clinical and
50. Picada R, Winter RB, Lonstein JE, et al. Postop- laboratory characteristics of infective endocarditis
erative deep wound infection in adults after when associated with spondylodiscitis. Eur J Clin
posterior lumbosacral spine fusion with instru- Microbiol Infect Dis 2002;21(9):671–675 PubMed
mentation: incidence and management. J Spinal 67. G
raveleau J, Grossi O, Lefebvre M, et al. Verte-
Disord 2000;13(1):42–45 PubMed bral osteomyelitis: an unusual presentation of
51. Levi AD, Dickman CA, Sonntag VK. Management of Bartonella henselae infection. Semin Arthritis
postoperative infections after spinal instrumenta- Rheum 2011;41(3):511–516 PubMed
tion. J Neurosurg 1997;86(6):975–980 PubMed 68. K
othari NA, Pelchovitz DJ, Meyer JS. Imaging of
52. Brown EM, Pople IK, de Louvois J, et al; British So- musculoskeletal infections. Radiol Clin North
ciety for Antimicrobial Chemotherapy Working Am 2001;39(4):653–671 PubMed
Party on Neurosurgical Infections. Spine update: 69. B
oden SD, Davis DO, Dina TS, Sunner JL, Wiesel
prevention of postoperative infection in patients SW. Postoperative diskitis: distinguishing early
undergoing spinal surgery. Spine 2004;29(8): MR imaging findings from normal postopera-
938–945 PubMed tive disk space changes. Radiology 1992;184(3):
53. W
atters WC III, Baisden J, Bono CM, et al; North 765–771 PubMed
American Spine Society. Antibiotic prophylaxis in 70. P alestro CJ, Love C, Miller TT. Infection and mus-
spine surgery: an evidence-based clinical guide- culoskeletal conditions: imaging of musculoskel-
line for the use of prophylactic antibiotics in spine etal infections. Best Pract Res Clin Rheumatol
surgery. Spine J 2009;9(2):142–146 PubMed 2006;20(6):1197–1218 PubMed
54. B
arker FG II. Efficacy of prophylactic antibi- 71. Shousha M, Boehm H. Surgical treatment of cer-
otic therapy in spinal surgery: a meta-analysis. vical spondylodiscitis: a review of 30 consecutive
Neurosurgery 2002;51(2):391–400, discussion patients. Spine 2012;37(1):E30–E36 PubMed
400–401 PubMed 72. C
arragee E, Iezza A. Does acute placement of
55. R
ohde V, Meyer B, Schaller C, Hassler WE. instrumentation in the treatment of vertebral
Spondylodiscitis after lumbar discectomy. In- osteomyelitis predispose to recurrent infection:
cidence and a proposal for prophylaxis. Spine long-term follow-up in immune-suppressed pa-
1998;23(5):615–620 PubMed tients. Spine 2008;33(19):2089–2093 PubMed
56. O’Neill KR, Smith JG, Abtahi AM, et al. Reduced 73. R
oss JS, Zepp R, Modic MT. The postopera-
surgical site infections in patients undergoing tive lumbar spine: enhanced MR evaluation of
posterior spinal stabilization of traumatic injuries the intervertebral disk. AJNR Am J Neuroradiol
using vancomycin powder. Spine J 2011;11(7): 1996;17(2):323–331 PubMed
641–646 PubMed 74. Beiner JM, Grauer J, Kwon BK, Vaccaro AR. Post-
57. Sweet FA, Roh M, Sliva C. Intrawound application of operative wound infections of the spine. Neuro-
vancomycin for prophylaxis in instrumented thora- surg Focus 2003;15(3):E14 PubMed
columbar fusions: efficacy, drug levels, and patient 75. Khoo LT, Mikawa K, Fessler RG. A surgical re-
outcomes. Spine 2011;36(24):2084–2088 PubMed visitation of Pott distemper of the spine. Spine J
58. H
aines SJ. Topical antibiotic prophylaxis in 2003;3(2):130–145 PubMed
neurosurgery. Neurosurgery 1982;11(2):250– 76. Butler JS, Shelly MJ, Timlin M, Powderly WG,

253 PubMed O’Byrne JM. Nontuberculous pyogenic spinal
infection in adults: a 12-year experience from 161
a tertiary referral center. Spine 2006;31(23): 91. K owalski TJ, Berbari EF, Huddleston PM, Steckel-
2695–2700 PubMed berg JM, Mandrekar JN, Osmon DR. The manage-
77. Rajasekaran S, Soundarapandian S. Progression ment and outcome of spinal implant infections:
of kyphosis in tuberculosis of the spine treated contemporary retrospective cohort study. Clin
by anterior arthrodesis. J Bone Joint Surg Am Infect Dis 2007;44(7):913–920 PubMed
1989;71(9):1314–1323 PubMed 92. Ploumis A, Mehbod AA, Dressel TD, Dykes DC,
78. Przybylski GJ, Sharan AD. Single-stage autogenous Transfeldt EE, Lonstein JE. Therapy of spinal wound
bone grafting and internal fixation in the surgical infections using vacuum-assisted wound closure:
management of pyogenic discitis and vertebral risk factors leading to resistance to treatment. J
osteomyelitis. J Neurosurg 2001;94(1, Suppl): Spinal Disord Tech 2008;21(5):320–323 PubMed
1–7 PubMed 93. Y uan-Innes MJ, Temple CL, Lacey MS. Vacuum-
79. Schuster JM, Avellino AM, Mann FA, et al. Use of assisted wound closure: a new approach to
structural allografts in spinal osteomyelitis: a re- spinal wounds with exposed hardware. Spine
view of 47 cases. J Neurosurg 2000;93(1, Suppl): 2001;26(3):E30–E33 PubMed
8–14 PubMed 94. U bbink DT, Westerbos SJ, Evans D, Land L, Ver-
80. Rath SA, Neff U, Schneider O, Richter HP. Neu- meulen H. Topical negative pressure for treating
rosurgical management of thoracic and lumbar chronic wounds. Cochrane Database Syst Rev
vertebral osteomyelitis and discitis in adults: a re- 2008;(3):CD001898 PubMed
view of 43 consecutive surgically treated patients. 95. V iola RW, King HA, Adler SM, Wilson CB. Delayed
Neurosurgery 1996;38(5):926–933 PubMed infection after elective spinal instrumentation
81. Stone JL, Cybulski GR, Rodriguez J, Gryfinski ME, and fusion. A retrospective analysis of eight cas-
Kant R. Anterior cervical debridement and strut- es. Spine 1997;22(20):2444–2450, discussion
grafting for osteomyelitis of the cervical spine. J 2450–2451 PubMed
Neurosurg 1989;70(6):879–883 PubMed 96. C lark CE, Shufflebarger HL. Late-developing in-
82. Karikari IO, Powers CJ, Isaacs RE. Simple method fection in instrumented idiopathic scoliosis.
for determining the need for sternotomy/manu- Spine 1999;24(18):1909–1912 PubMed

briotomy with the anterior approach to the cer- 97. R oblot F, Besnier JM, Juhel L, et al. Optimal du-
vicothoracic junction. Neurosurgery 2009;65(6, ration of antibiotic therapy in vertebral osteo-
Suppl):E165–E166, discussion E166 PubMed myelitis. Semin Arthritis Rheum 2007;36(5):
83. Benzel EC. The lateral extracavitary approach to 269–277 PubMed
the spine using the three-quarter prone position. 98. Sapico FL, Montgomerie JZ. Pyogenic verte-
J Neurosurg 1989;71(6):837–841 PubMed bral osteomyelitis: report of nine cases and re-
84. Larson SJ, Holst RA, Hemmy DC, Sances A Jr. Lat- view of the literature. Rev Infect Dis 1979;1(5):
eral extracavitary approach to traumatic lesions 754–776 PubMed
of the thoracic and lumbar spine. J Neurosurg 99. S chrenzel J, Harbarth S, Schockmel G, et al; Swiss
1976;45(6):628–637 PubMed Staphylococcal Study Group. A randomized
85. F
essler RG, Dietze DD Jr, Millan MM, Peace D. Lat- clinical trial to compare fleroxacin-rifampicin
eral parascapular extrapleural approach to the with flucloxacillin or vancomycin for the treat-
upper thoracic spine. J Neurosurg 1991;75(3): ment of staphylococcal infection. Clin Infect Dis
349–355 PubMed 2004;39(9):1285–1292 PubMed
86. A
rnold PM, Baek PN, Bernardi RJ, Luck EA, Larson SJ. 100. G
ouliouris T, Aliyu SH, Brown NM. Spondylo-
Surgical management of nontuberculous thoracic discitis: update on diagnosis and management.
and lumbar vertebral osteomyelitis: report of 33 J Antimicrob Chemother 2010;65(Suppl 3):
cases. Surg Neurol 1997;47(6):551–561 PubMed iii11–iii24 PubMed
87. McCormick PC. Retropleural approach to the
101. A
merican Thoracic Society; CDC; Infectious Dis-
thoracic and thoracolumbar spine. Neurosurgery eases Society of America. Treatment of tuber-
1995;37(5):908–914 PubMed culosis. MMWR Recomm Rep 2003;52(RR-11):
88. Anderson TM, Mansour KA, Miller JI Jr. Thoracic 1–77 PubMed
approaches to anterior spinal operations: anterior 102. A
n HS, Seldomridge JA. Spinal infections: diag-
thoracic approaches. Ann Thorac Surg 1993;55(6): nostic tests and imaging studies. Clin Orthop
1447–1451, discussion 1451–1452 PubMed Relat Res 2006;444:27–33 PubMed
89. M
ok JM, Guillaume TJ, Talu U, et al. Clinical out- 103. H
adjipavlou AG, Mader JT, Necessary JT, Muf-
come of deep wound infection after instrument- foletto AJ. Hematogenous pyogenic spinal in-
ed posterior spinal fusion: a matched cohort fections and their surgical management. Spine
analysis. Spine 2009;34(6):578–583 PubMed 2000;25(13):1668–1679 PubMed
90. Stambough JL, Beringer D. Postoperative wound 104. V
eeravagu A, Patil CG, Lad SP, Boakye M. Risk fac-
infections complicating adult spine surgery. J tors for postoperative spinal wound infections
Spinal Disord 1992;5(3):277–285 PubMed after spinal decompression and fusion surgeries.
Spine 2009;34(17):1869–1872 PubMed
162
13
Spinal Canal Infections
Ian E. McCutcheon
Although uncommon, infections of the ■■ Spinal Epidural Abscess

spinal canal have profound clinical im-
plications and pose a risk for paralysis. Infections in the epidural space can be iso-
Their early diagnosis and prompt, effective lated but are often associated with infection
treatment are therefore very important in in the vertebral body, disk space, or both.
maintaining neurologic function and qual- Thus, an anatomic distinction is somewhat
ity of life. Improvements in radiographic artificial and not the principal factor in de-
imaging, most notably the widespread termining therapy, although an important
availability of magnetic resonance (MR) distinction is that the medical cure of osteo-
imaging, allow such conditions to be local- myelitis requires a longer duration of anti-
ized because they typically cause the gross biotic administration than does infection of
structural abnormality of an abscess rather the disk or epidural space. The first patho-
than the more subtle microscopic findings logic description of a bacterial vertebral
of meningitis. These infections have actu- osteomyelitis was published in 1820 by Ber-
ally become more common in recent de- gamaschi. By the 1890s, surgery had been
cades as a consequence of the increasing reported for pyogenic vertebral infections
number of patients with chronic or immu- by Ollier and Chipault; in 1896, Makins and
nosuppressive illness whose life expectan- Abbott associated vertebral infection with
cy modern medicine has extended. epidural suppuration and advocated both
The spectrum of such disorders falls into removal of the infected bone and evacua-
three categories: (1) spinal epidural abscess tion of the epidural pus.1 This concept was
(SEA), typically bacterial in origin and the also promoted by Ramsay Hunt in 1904 in
most common of the three; (2) spinal sub- the first paper devoted to establishing epi-
dural abscess, which is much less common; dural abscess as a separate entity.2 The first
and (3) intramedullary abscess of the spinal attempt at surgical drainage of an isolated
cord, which is also rare, although more of- SEA without vertebral involvement was
ten reported than subdural abscess in the performed by Delorme in 1892; the pa-
spinal compartment. Each of these infec- tient succumbed to bacterial endocarditis
tions is generally pyogenic (i.e., producing quickly thereafter, and functional recovery
a purulent and mainly neutrophilic infil- after successful drainage was first reported
trate), but infections caused by mycobac- in 1901 by Barth.3 These early papers pro-
teria, fungi, and Nocardia species are also moted SEA as a distinct condition and be-
occasionally seen. This chapter specifically gan the trend toward surgical drainage of
excludes discussion of focal infection of the such abscesses, which continues to this day.
vertebrae, known as vertebral osteomyeli- Because such abscesses are now frequently
tis, which is addressed in a separate chapter. diagnosed in immunocompromised and el-
derly patients, many of whom are medically promotes the formation of SEAs in the tho-
fragile, there has been a reassessment of the racolumbar area. However, the distribution
need for surgery in all cases and a reconsid- of SEAs is relatively even along the spine.
eration of medical treatment in selected pa- Epidural abscesses found in the anterior
tients, which is now performed with some epidural space are almost always associ-
success (Table 13.1). ated with diskitis or vertebral osteomyelitis
extending past the posterior longitudinal
Anatomy ligament into the epidural compartment.
Because the anterior dural attachments are
The spinal epidural space under normal stronger, epidural abscesses in the anterior
conditions is filled with fat, a loose areo- space tend to be more limited in extent,
lar connective tissue network, and an whereas those in the posterior aspect of the
exuberant venous plexus. This space sits canal extend over more segments. A typi-
between the spinal dura and the bony ring cal SEA covers three to five segments, but
that forms the vertebral canal. The dura is many more can be involved.
relatively adherent to the posterior longi-
tudinal ligament in the anterior aspect of
Epidemiology
the canal, and thus the dorsal and lateral
components of the epidural space are more The incidence of SEA has risen in recent
prominent and are the typical sites for ab- years, likely through a combination of in-
scess. Because of the larger diameter of the creased detection, increased life expec-
spinal cord in the cervical spine, the space tancy for immunocompromised patients,
is minimal in the neck; however, it enlarges and aging of the population. The incidence
in the midthoracic region (T4–T8), where is variously reported as between 0.2 and
it has a depth of 5 to 7 mm, then narrows 2 cases per 10,000 hospital admissions.4,5
gradually to accommodate the lumbar cord The elderly are prone to such infections,
enlargement, with progressive widening with the peak incidence in the sixth and
caudal to L2 until the dura ends at S2. It has seventh decades; SEAs are also relatively
been suggested that this anatomic variation uncommon in the pediatric age range. The
two most common correlates are frequent
bacteremia and significant impairment of
immune function. Both acquired immu-
Table 13.1 Risk factors for spinal epidural abscess in nodeficiency syndrome (AIDS) and intra-
a general hospital
venous drug use are thus very significant
Risk Factora Percentage risk factors for SEA, as are diabetes mellitus,
end-stage renal disease, and hepatic cirrho-
Intravenous drug use 37 sis. In addition, any medical treatment that
Diabetes mellitus 29 uses immunosuppression to a therapeutic
end or provokes it as a side effect (including
Multiple medical illnesses 23 long-term steroid therapy, chemotherapy,
and suppression of the antigraft response in
Trauma 17
transplant recipients) can promote SEA.6,7
Prior spinal surgery 15 In such patients, the spontaneous bacte-
remia that all people harbor from time to
Morbid obesity 9
time (and that is cleared by competent im-
HIV infection 9 mune mechanisms) is more likely to prog-
ress unchecked, resulting in SEA.
End-stage renal disease 8
Spinal nerve block 7 Microbiology
Abbreviation: HIV, human immunodeficiency virus

The most common causative organism is
Risk factors add up to more than 100% because of over-
a Staphylococcus aureus,8 which in conjunc-
164 lapping conditions in many patients. tion with other gram-positive microbes
(e.g., Staphylococcus epidermidis, Strepto- Both bone and disk can act as sources of in-
coccus pneumoniae, Streptococcus viridans, fection in the neighboring epidural space.
Enterococcus, and Propionibacterium acnes) Some infections may emanate from the
causes most epidural abscesses. Gram-neg- epidural veins alone, thus allowing involve-
ative species are less often cultured from ment of several spinal segments without
SEAs, but abscesses containing Escherichia concomitant infection of bone or disk.
coli, Pseudomonas aeruginosa, Salmonella, Bacterial contamination can occur di-
Klebsiella, and other species are sometimes rectly in patients undergoing open surgery
found after infection of the urinary or gas- with exposure of the epidural space. The
trointestinal tract. Anaerobes rarely cause dead space left after instrumentation is a
spinal epidural infections in the general particularly suitable environment for the
population but sometimes cause infection growth of bacteria implanted at the time
in intravenous drug abusers. Unfortunate- of surgery. Foreign bodies placed in the
ly, 10 to 20% of patients show no growth on disk space (e.g., epidural stimulators or
culture of the abscess material, even in the catheters) can also carry bacteria into this
absence of prior antibiotic therapy.6,7 compartment, as can penetrating injuries
Streptococcus species are the second or direct breakdown, as occurs in a decu-
most common bacteria (after Staphylo- bitus ulcer.
coccus species) to cause SEA and are often The development of neurologic deficits
seen in association with recent pneumonia follows the onset of SEA in 5 to 50% of pa-
or after dental procedures. The gram-neg- tients. Such deficits occur through direct
13 Spinal Canal Infections

ative species dominate in intravenous drug compression caused by an expanding ab-
abusers, while Mycobacterium tuberculosis scess; this is further exacerbated when
is quite common in Asia and Africa, and spinal deformity occurs as a consequence
such cases are starting to seep into North of biomechanical impairment of the spine
America as well. Fungal infections are also as infected bone leads to vertebral wedg-
becoming slightly more common. ing. It has long been noted, however, that
cord dysfunction on a clinical level is often
Mechanisms of Pathogenesis significantly more evident than the degree
of compression alone should cause. Some
The venous route of infection from pelvis patients acquire a central cord syndrome
to vertebral column, proposed by Batson that is hard to explain as a result of mass
in 1957, has had much traction over the effect.4 In addition, the rapidity and oc-
years but is now largely discredited. Hema- casional irreversibility of the neurologic
togenous dissemination of bacteria likely deterioration associated with the onset of
occurs most often through arterial trans- SEA suggests that a vascular mechanism
fer, particularly to the metaphyseal area underlies these clinical phenomena.
near the anterior longitudinal ligament. Autopsy studies by Russell et al showed
Abscesses in the epidural space can arise thrombosis of the epidural arteries and
through bacterial embolization to this part veins as well as venous infarction and
of the vertebral body with secondary prop- edema within the cord in patients with
agation into the adjacent epidural space, or SEA.10 However, experimental model sys-
through direct spread to the epidural space tems (as exemplified by the rabbit model
posteriorly. Adjacent foci of infection, such of Feldenzer et al) show an explicit lack
as pulmonary, retropharyngeal, or intra- of microangiopathy in the cord except in
abdominal abscess, are also occasional animals with severely compressive lesions,
sources of SEA.9 Infection and thrombosis and they found no thrombosis or venous
of the nutrient metaphyseal artery pro- occlusion.11–13 Such findings argue in favor
duce avascular necrosis of bone and thus of the compressive theory, yet the clinical
create a nidus for infection. Ischemia of the course of the disease in humans does not
disk occurs through the same mechanism, fully support it. This contradiction may
rendering it more susceptible to infection. simply reflect the limits of the experimen-
165
tal rabbit model in mimicking the human About 75% of patients have signs of spi-
clinical situation, as well as the heteroge- nal cord or nerve root dysfunction when
neity of such infections in their microbial the diagnosis is made. Monoparesis is
pathogenesis and the underlying clinical common, and paraparesis or quadriparesis
conditions that predispose patients to SEA. is occasionally seen. Patients with severe
Unfortunately, this ambiguity of etiology back pain or encephalopathy may be more
and of substrate has prevented a consen- difficult to examine, and confusion is noted
sus on the appropriate method of therapy in 15 to 35% of patients. Loss of bowel or
across all groups. bladder control and sensory deficit can
also occur, but a complete loss of sensation
Clinical Features below a sensory level is usually seen only
with profound and often irreversible loss
A broad range of symptoms can signify an
of motor function. In patients with urinary
SEA, and classic features are not always
retention or incontinence, measuring post-
present. The diagnosis can be missed un-
void residual volumes with subsequent
less the index of suspicion is high.14 Al-
Foley catheter placement provides clarity
though a very small fraction of patients
as to bladder function.17
with back pain harbor a spinal infection, a
The presence of fever and back pain,
pattern can be gleaned that should point
particularly in immunocompromised pa-
to the diagnosis of epidural abscess and
tients or in those with a history of intrave-
drive the performance of studies to de-

nous drug abuse, should prompt testing for
termine whether one is present. The first
SEA, especially when recent bacteremia is
symptom of an SEA is isolated back pain,
documented.
and more generalized infection is often ab-
Secondary extraspinal infection is occa-
sent. Because the symptoms are clarified
sionally seen in people with SEA. Infection
over time, it is typical for patients to seek
in a vertebra can seep into the adjacent
medical attention repeatedly before the
fascial layers to cause abscess in the psoas
diagnosis is made. Symptoms usually prog-
or paraspinal muscles, can cause retropha-
ress through four stages: (1) an aching pain
ryngeal abscess, and sometimes provokes a
in the spine, (2) root pain or radiculopathy,
sympathetic pleural effusion.
(3) weakness, and (4) paralysis.11 Usually,
a patient’s symptoms do not follow this
pattern perfectly and may consist either of Diagnosis
local pain manifestations or systemic signs Laboratory Studies
of infection (fever, malaise, night sweats).
The interval between the onset of pain and Serum markers of acute inflammation are
the onset of neurologic deficit also var- helpful in screening patients for SEA. It is
ies.4,15,16 The combination of fever and back important to remember, however, that at
pain in a patient with immunocompromise least 10% of patients later proven to have
or a history of drug abuse should lead to an epidural abscess show no inflammatory
the suspicion of SEA. The back pain is not markers. The three markers generally used
always associated with local tenderness of are the white blood cell count, the eryth-
the spine, and the pain is usually severe. rocyte sedimentation rate (ESR), and the C-
Fever is often slight and may be masked reactive protein (CRP) level. Most sensitive
by the patient’s use of analgesics for the is the ESR, elevated in 90% of patients with
back pain or through the prior use of an- spinal infection, often dramatically so.18
tibiotics. In some, septicemia occurs, and This readily available test can be used to
this can be the primary presentation. One- monitor response to therapy, and it should
third of patients are neurologically intact always be measured during initial evalua-
at presentation. The rate of progression of tion. However, it is not particularly specific,
the neurologic deficits varies greatly, with and some patients have an elevated basal
some advancing slowly and others causing ESR from other causes even before onset of
166 paralysis within hours. the infection. One such example would be a
patient with hepatic cirrhosis. Such patients choice. Many patients will have had preced-
are prone to acquiring SEA; however, their ing plain X-rays or computed tomography
ESR elevations do not correct even when (CT) scans. CT is most useful when it in-
treatment of the infection is successful. The cludes three-dimensional reconstructions
CRP level is less sensitive but somewhat of the spinal anatomy. The main findings
better in the detection of early infections of SEA on plain films are indirectly associ-
because serum levels rise within hours af- ated anomalies of the bone or disk, includ-
ter the initiation of a bacterial infection. It ing narrowing of the disk space, erosion of
is also useful in the postoperative setting in the vertebral end plate, and lytic erosion of
patients suspected of having an SEA after the vertebral bodies. Plain films can also
spinal surgery. Both the ESR and the CRP show spinal alignment and thus may be
level rise after spine surgery, but the CRP useful to establish a baseline status. Bone
level returns to normal more quickly and scans (radionuclide scintigraphy) are not
thus may have more utility in the work-up very specific and have a sensitivity of only
of patients in the postoperative period. The 70%,15 although they sometimes show early
ESR can take 2 to 3 months to normalize af- foci of osteomyelitis before plain films do.
ter successful treatment (Fig. 13.1). Lumbar Gallium 67 and technetium 99 tracers both
puncture is not usually performed when have reasonable sensitivity, with gallium
an epidural infection is suspected because slightly more specific than technetium as a
it may inoculate infected material into the tracer, but neither has high specificity over
subarachnoid space and because the cere- all. Sensitivity can be raised by performing

brospinal fluid (CSF) from most patients a tagged white blood cell scan, but even
with SEA demonstrates evidence of a non- this shows a lack of sensitivity that impairs
specific parameningeal process, with a high its utility. Other markers, including biotin
protein level and a mild leukocytosis. labeled with indium-111, are now being
investigated as more specific indicators
of infection.19 Plain films and CT show no
Imaging
change during the earliest stages of infec-
Confirmation of the presence of infection tion. It takes several weeks for a disk to lose
and determination of its site in the spine height and for trabecular erosion to occur
are usually achieved by MR imaging. The on either side of a disk from which infec-
multiplanar capacity of MR imaging and its tion will ultimately spread to the epidural
ability to distinguish infection from other space. Vertebral collapse and loss of lordo-
pathology make it the imaging method of sis occur only when infection is advanced.
Fig. 13.1 Restoration of a normal

erythrocyte sedimentation rate (ESR)
occurs gradually after surgical evacu-
ation of spinal epidural abscess. In
this patient, the ESR took 3½ months
to normalize. The y-axis shows the
ESR, and the x-axis shows time in
weeks after surgery. Antibiotics were
given for 10 weeks after surgery.
167
CT is most often used in guiding the per- of gadolinium will provide images that are
cutaneous aspiration of disk spaces, verte- sufficient to distinguish between different
bral bodies, or paraspinal fluid collections pathologies and to determine their location.
to provide microbiological identification of T1-weighted images before contrast show
infection. CT myelography is still occasion- bone infection as a hypointense signal, with
ally needed for patients in whom metallic particular focus on the end plates, as well as
implants degrade the quality of MR im- loss of the normal hyperintensity caused by
ages. With the advent of open MR imaging, fat in the vertebral marrow. On T2-weighted
the previous contraindication of obesity is images, hyperintensity represents edema in
no longer as important in driving patients the disk space, which is sometimes found in
toward CT. The absence of ionizing radia- the vertebra and paravertebral region as well.
tion in MR imaging is another advantage of In post-contrast studies, T1-weighted images
this modality compared with CT. show enhancement of the vertebral body, its
Contrast-enhanced MR imaging should end plates, the paravertebral soft tissues, and
thus be performed in all patients suspected the epidural space20 (Fig. 13.2). Because spi-
of having an SEA unless contraindications nal infections are sometimes multifocal, the
exist. Imaging before and after the infusion entire spine should be imaged.
a b
Fig. 13.2a–c Epidural abscess. This 51-year-old man

in remission from prior acute myelogenous leukemia
developed severe neck pain 1 year later. The pain ra-
diated into both shoulders and was associated with
dysphagia. Post-contrast magnetic resonance imag-
ing showed osteomyelitis of C4 and C5 with involve-
ment of the intervening disk space and a contiguous
enhancing epidural mass anterior to the thecal sac,
consistent with epidural abscess. Both sagittal (a) and
axial (b) images reveal the lesion. The patient under-
went biopsy and culture of the C5 vertebral body and
the C4–5 disk, which confirmed osteomyelitis due to
Staphylococcus epidermidis. He was treated with intra-
venous antibiotics for 10 days and then oral antibiot-
ics. Because of persistent elevation of the erythrocyte
sedimentation rate, he continued oral therapy for 9
months. He ultimately experienced complete resolu-
tion of the infection and likely fusion of C4 and C5 with
168 c this prolonged medical therapy (c).
Identifying the Pathogen The heterogeneity of the clinical course in
SEA makes it difficult to standardize treat-
Once imaging has suggested an epidural ab-
ment decisions. Delay in treatment can be
scess, the causative agent(s) must be identi-
entertained only when neurologic deficits
fied to direct the antibiotic choices. Because
are minimal or when comorbidities such
hematogenous spread from other infected
as sepsis and coagulopathy require correc-
sites is the usual cause of SEA, cultures of
tion before surgery. Careful and frequent
urine and septum should be obtained, as
monitoring should be used for any patient
should blood cultures in multiple sets. Ide-
undergoing medical management alone
ally, blood cultures should be done during
because deficits can progress rapidly and
a septicemic phase or when temperature
so may require a surgical strategy instead.
spikes occur. Blood cultures identify the
Planning surgery requires consideration
organism in only half of cases, however,
of the level or levels of spinal involvement,
so needle biopsy of the involved vertebral
the degree of cord compression, the loca-
body or disk space should be carried out
tion of the abscess within the spinal canal
under radiographic control. Once this is
(anterior versus posterior), and the physical
done, broad-spectrum antibiotic coverage
nature of the material compressing the cord.
of the usual pathogens (Staphylococcus spe-
The strategies for dealing with pus and ret-
cies and Streptococcus species) should be
ropulsed bone are quite different. In addi-
initiated. Percutaneous biopsy yields ma-
tion, simple laminectomy may be effective
terial for successful culture in 60 to 80% of
for washing out a posteriorly or posterolat-
cases. When percutaneous attempts fail to

erally situated phlegmon and for provid-
yield a positive specimen, open biopsy is
ing cord decompression, but it may also
the next step and has a similar rate of suc-
worsen spinal instability when vertebral
cess. Withholding antibiotics until all nec-
involvement is profound at the same level.
essary material has been taken for culture
The goals of surgery are decompression of
will maximize the success of such cultures.
neural structures, including cord and roots;
If cultures are negative in the face of obvi-
removal of purulent material from the epi-
ous clinical infection, broad-range poly-
dural space; removal of any granulation
merase chain reaction (PCR) techniques can
tissue present; and, when necessary, cor-
be used to enhance the sensitivity of detec-
rection of deformity and instability caused
tion.20 When no bacterial organism can be
by disruption of the vertebral column.
identified after several attempts, mycobac-
The great majority of patients are still
terial and fungal infections should also be
treated primarily with surgery, with anti-
considered, particularly in at-risk patients.
biotic therapy to follow for a period of sev-
eral weeks.21 In general, the probability of
Treatment success is maximized by the removal of as
Surgery much infectious material as possible. Do-
ing this may induce or worsen instability;
The mainstay of treatment for SEA has tra- therefore, the surgeon must be prepared
ditionally been surgery, and it remains so to restabilize the spine at the same sitting.
despite inroads that have been made by Tissue adherent to the dura should not be
medical therapy in recent years.6,7 Factors removed too vigorously because breaching
to be considered in the choice of treat- the dura may allow the infected material to
ment (surgical versus medical) include be introduced into the subarachnoid space,
degree of sepsis, neurologic status, extent resulting in meningitis. Once the solid ma-
of cord compression, degree of vertebral terial has been removed from the epidural
destruction, and presence of spinal insta- compartment, copious irrigation with an-
bility. Most epidural abscesses require ur- tibiotic solutions is performed. With ante-
gent although not emergent care; however, rior decompression, a fusion will typically
any patient with significant myelopathy be required, which is commonly done with
should receive prompt surgical treatment. an interposition autograft or allograft.
169
When necessary, reconstruction and sta- ed, and thus a full corpectomy is commonly
bilization can be delayed to a second-stage performed with reconstruction thereafter.
procedure. It is also important to remem- When patients have significant com-
ber that in patients with only a slight loss pression of the cord and thus a clinical
of lordosis or slight kyphosis, fusion may myelopathy, steroid administration is con-
occur over time during antibiotic therapy sidered both safe and useful at high doses.
without instrumentation. Therefore, when Current studies suggest that the spine
it is not certain that instrumentation is can be reconstructed and stabilized with
necessary, delaying a decision on its place- safety and effectiveness even within a
ment (and using an external brace in the surgical wound contaminated by an epi-
meantime) is reasonable. dural infection. As long as necrotic bone
Further treatment difficulties arise and infectious material are removed to the
when the abscess is largely ventral. In the maximum degree, bone grafts can be used
cervical spine, a ventrally placed abscess as either autografts or allografts and can
without adjacent bony involvement can fuse to native bone. By putting the fusion
usually be treated safely by laminectomy construct under compression, the place-
with maintenance of the facet joints. When ment of plates, rods, and screws as needed
vertebral body involvement is more exten- promotes bone fusion in this circumstance.
sive, the best option is generally a formal As long as the infectious material is well
diskectomy and vertebrectomy via an an- removed and a sufficiently long course of
terior approach, followed by bone grafting antibiotics is given, it is rarely necessary to

or cage placement with anterior plating. reoperate to remove infected or colonized
Trough corpectomies can be used to limit instrumentation or bone graft.17,23–26
bone removal and preserve the biome-
chanical stability in cases of ventral SEA.22
Medical Therapy
In the thoracic spine, a transpedicular or
lateral extracavitary approach to an anteri- Some patients can be managed with medi-
or phlegmon may be preferable, often with cal therapy alone and can thus avoid surgi-
posterior instrumentation being necessary. cal intervention.6,7,27,28 This choice must be
Anterior infections within the midthoracic made carefully and with due consideration
or low thoracic spine respond well to trans- given to the MR imaging characteristics
thoracic approaches performed through a of the epidural lesion and the neurologic
thoracotomy, but the lateral extracavitary status of the patient. Collections that are
approach can be utilized in these cases as fluid and thus easily drained tend to be hy-
well. A laminectomy alone for ventral tho- perintense on T2-weighted images and to
racic disease is not advisable. enhance only peripherally around a cen-
Ventral abscesses of the lower thoracic tral core of hypointensity. More solid, or-
and upper lumbar spine generally require ganized lesions (granulation tissue) tend
débridement by a thoracoabdominal ap- to enhance throughout and to appear iso-
proach, which allows bone or cage recon- or hypointense on T2-weighted images.
struction with plating as well as removal of When such a phlegmon is present and the
the phlegmon. Those patients with infec- patient is neurologically intact, medical
tion in the midlumbar or low lumbar spine therapy can be considered. When a patient
can undergo decompression via a retro- has radiographic signs of a fluid collec-
peritoneal approach when the infection is tion but lacks any neurologic compromise,
anteriorly placed, with the reconstruction the decision is more controversial. Cer-
similar to that used at higher levels. Below tainly abscesses below the conus are less
L2, a posterior approach is generally used. surgically compelling, whereas those in
When infection persists despite antibi- the cervical and thoracic spine pose more
otics or when it recurs, reoperation may be danger for a sudden neurologic decline
necessary. In this scenario, a search for se- and thus are better managed with an op-
questered and devascularized bone is need- erative strategy. Neurologic recovery can
170
occur after surgery even in patients with elevations in the face of clinical improve-
abscesses extending over many segments, ment.18 In such cases, it is reasonable to
and even in those presenting with several extend the length of antibiotic treatment
days of complete paralysis.29,30 Any patient and, if the ESR elevation persists, to repeat
treated conservatively must be frequently imaging and perform a biopsy to clarify the
reassessed, and a low threshold for surgical clinical situation.
intervention must be maintained. Because the most common bacterial
The risk for deterioration while a pa- species causing SEA are staphylococcal and
tient is on medical therapy is not trivial. streptococcal species, the most commonly
Khanna et al showed that 19% of patients used antibiotics are cephalosporins, van-
who had been selected for medical thera- comycin, and β-lactams. Vancomycin and
py alone because of their relatively intact cephalosporins penetrate infected bone
neurologic status and identifiable organ- and disk inefficiently, and when bone dis-
ism eventually required surgery because ease is extensive, a second agent (rifampin
of neurologic decline while they were on or a fluoroquinolone) may be valuable.
medical therapy.16 A similar rate of neuro- When cultures are negative and no sensi-
logic progression was cited by Darouiche et tivity typing can be meaningful, empiric
al and other authors.6,15 Nevertheless, not therapy must be used. If treatment fails,
all patients with SEA are good candidates then reimaging and repeat culturing are
for surgery, and the absence of spinal insta- indicated and should include a search for
bility in neurologically intact patients may less common causative agents, such as fun-

make medical therapy attractive. gi and mycobacteria. Usually, those receiv-
Medical therapy requires both the ad- ing intravenous antibiotics are restricted to
ministration of intravenous antibiotics (as bed for 2 weeks and thereafter are mobi-
determined by bacterial sensitivity pro- lized with a fitted orthosis to prevent spi-
filing) and immobilization of the affected nal deformity and pain.
portion of the spine, which helps control
pain and may promote fusion. The dura-
tion of therapy has not been standardized, ■■ Outcome
but in general, the SEAs of patients with
lesser degrees of bone infection and who The best predictor of outcome is the clinical
are immunocompetent can clear with 6 to and neurologic condition of the patient at
8 weeks of antibiotic therapy. When osteo- the time of surgery. Neurologic deficits can
myelitis is present or when the patient is decrease after decompression and washout
immunocompromised, 8 weeks of antibi- of the abscess, and indeed patients do bet-
otic therapy or longer is the recommended ter after surgery for SEA than after surgery
duration.31 The route of administration is for other extrinsic compressive causes of
generally intravenous, with supplemental myelopathy. In one series, surgical inter-
oral antibiotics used in some cases. Relaps- vention within 24 hours of the onset of
es generally occur within 6 months after paralysis resulted in neurologic improve-
the conclusion of therapy and affect up to ments in 6 of 14 patients (42%).15 The prog-
15% of patients.32 The route of administra- nosis for recovery is worse in patients who
tion is generally intravenous. Supplemen- present with established and extensive
tal oral antibiotics are used in some cases; deficits due to delays in treatment, or in
however, there is no evidence that oral an- those in whom sudden and profound de-
tibiotics are helpful, and they may be sup- cline from spinal vascular occlusion has
pressive rather than curative. occurred. In addition, those who present
The effectiveness of such therapy is with overt sepsis do poorly.
gauged by reductions in pain and fever and Factors influencing outcome as de-
by a decrease in the ESR. However, the ESR termined by Khanna et al are discussed
is not entirely reliable as a marker for in- below.16 Those who do better are neurologi-
fection, and some patients show sustained cally intact at presentation, younger than 60
171
years of age, have less than 50% spinal canal Nocardia asteroides is a gram-positive
compromise, have a lumbosacral location of aerobe with a filamentous structure. This
the abscess, and undergo surgery within 72 organism typically produces pulmonary
hours. Those in whom the SEA comprises infection in patients with immunocompro-
pus rather than phlegmon also have better mise and only rarely involves the spine. The
prognosis. It is likely that multiple comor- mechanism of spread to the spine is thought
bidities and a complete sensory or motor to be either through direct extension from
deficit predispose to a poorer outcome. Sig- a thoracic infection or by hematogenous
nificant recovery from a profound neurolog- routes. Treatment usually includes some
ic deficit does occur, with one study of the combination of penicillin, cephalosporin,
effectiveness of rehabilitation in SEA after and aminoglycoside, and treatment may
surgery showing 5 of 11 patients recover- be prolonged. Surgical treatment is simi-
ing from plegia to full function over time.33 lar to that used in SEA caused by other
With medical management, the prognosis pathogens.36,37
depends on the patient’s age, on the rate of Actinomyces israelii is a gram-positive
decrease in the ESR, and on the presence of bacterium that also has a filamentous struc-
immunocompromise. Although the elderly ture. It typically results in a chronic drain-
have a poor outcome in general, when they ing infection containing “sulfur granules,”
are managed with aggressive surgery, they which are not sulfur but clumps of the ac-
can do well.7,34 tual organism. This microbe commonly af-
Other measures of outcome include fects the oral cavity and paranasal sinuses
mortality, which ranges from 3 to 23% in and thus may extend into the soft tissues
several series of SEA.6,7 When it occurs, of the neck. Involvement of the spine usu-
death usually stems from a missed diag- ally is the result of contiguous spread from
nosis or from a severe coexisting illness either the retropharyngeal area or the
outside the nervous system. Another im- lungs. This bacterium usually causes ver-
portant measure of outcome is mainte- tebral destruction or deformity. Surgical
nance of sagittal balance in the spine over intervention is used only in patients with
time. Thus, spontaneous fusion of contigu- neurologic compromise. Medical treatment
ous affected levels is a positive outcome, as includes intravenous penicillin G, ciproflox-
is radiographic incorporation of the bone acin, or rifampin.38,39
graft after surgical treatment. The best Brucellosis is uncommon in the United
predictors of a successful outcome relate States but remains epidemic in countries
to clinical status of the patient, and in par- bordering the Mediterranean Sea and in
ticular the disappearance of fever and pre- Central and South America. Human infec-
treatment laboratory abnormalities as well tion comes through contact with livestock
as the relief of spinal and radicular pain. or from consumption of unpasteurized milk.
MR imaging findings in SEA take months to In 25% of cases, osteoarticular complica-
resolve, and serial imaging correlates poor- tions arise, half of which involve the spine.
ly with clinical improvement.35 Thus, vertebral infections occur in 10 to 12%
of cases and produce a subacute clinical
scenario similar to that seen in spinal infec-
■■ U
nusual Bacteria Causing tions caused by other microbes. Spinal de-
Epidural Abscess formity is rarely seen, and cure occurs with
antibiotic therapy in 90% of patients. Antibi-
Very occasionally, bacterial pathogens oth- otics used include tetracycline, aminoglyco-
er than the usual species (Staphylococcus, sides, and trimethoprim-sulfamethoxazole.
Streptococcus, and Enterococcus species, E. Surgery is not typically necessary but oc-
coli, Pseudomonas aeruginosa, and Proteus casionally is required for decompression or
species) act as the causative agents for epi- correction of deformity.40–42
dural abscess. Most notable of these are No- Tuberculosis remains an important pub-
cardia, Brucella, and Actinomyces species. lic health hazard throughout the world,
172
particularly in less developed countries. whom progressive neurologic symptoms
The causative organism is highly preva- stem from cord compression. The role of
lent in Russia, the Indian subcontinent, and surgical drainage of extraspinal collections
eastern and central Africa because of the or of débridement of involved bone in
high incidence of human immunodeficien- helping to clear infection remains unclear.
cy virus (HIV) infection in those regions. However, the confirmed indications of spi-
Poor nutrition and crowded living condi- nal instability, pronounced deformity, and
tions also predispose to cultivation of the neurologic deficit still apply as reasons to
disease, as does inappropriate antibiotic perform surgery.43–47
treatment leading to resistant strains of
mycobacterial species. Involvement of the
Fungal Pathogens
bones and joints occurs in 3 to 5% of pa-
tients with tuberculosis and rises to 60% in Fungal infection of the spine is rarely seen
those with coexisting HIV infection. Half of and is generally associated with immuno-
the cases affecting bone occur in the spine suppression resulting from lengthy ste-
and have a propensity to create deformity roid use, diabetes mellitus, HIV infection,
and thus paraplegia. Although involvement or intravenous drug abuse or occurring
at the thoracolumbar junction is most in conjunction with severe systemic ill-
common, any level can be affected. As with nesses. The most common fungal infection
actinomycosis, tubercular involvement of is candidiasis, which presents in immuno-
the spine occurs both from hematogenous compromised patients as an opportunistic

spread and by direct extension from an in- infection but in which vertebral involve-
fected lung. Tuberculosis tends to be more ment is not common. SEA occurs typically
indolent than other infections of the spine, in the setting of disseminated candidiasis,
more commonly involves the posterior ele- and its clinical features are not particularly
ments of the vertebral body, and produces different from those seen with classic bac-
deformity more often. Paraspinal phleg- terial SEA. Treatment is also similar, and
mon or abscess is frequent. Although initial amphotericin B is the standard medical
inflammation leads to abscess formation therapy. Osteomyelitis responds in 85% of
with liquid pus, in later stages caseous ma- the patients thus treated, but mortality is
terial forms, and both bony necrosis and high because of the comorbid conditions
ligamentous disruption contribute to spi- usually present in other organ systems.48,49
nal deformity. As the acute infection fades, Other fungal infections include coccidi-
a chronic infection with a fibrous reaction oidomycosis, aspergillosis, and blastomy-
improves but does not typically restore cosis. Although infection with Coccidioides
complete spinal stability. Tuberculosis of immitis is relatively benign and usually
the spine may be associated with calcifi- occurs in the respiratory tract, it can dis-
cation and even ossification, which when seminate. Rarely, infections within the
exuberant produces a chronic compression spine occur, usually within the vertebral
of the cord. body and commonly extending into the
The standard treatment of spinal tuber- epidural space. In the United States, such
culosis is by medical therapy with multiple cases are seen mainly in the southwestern
agents for a prolonged period of time. The quadrant. They are treated surgically in the
most common regimen includes isoniazid, fashion usual for other forms of SEA and
rifampin, and pyrazinamide for 12 months then with lifelong antifungal therapy.50,51
or more. Although some authors recom- Aspergillosis occurs in patients similar to
mend bed rest in the initial management those affected by Candida species and has
of spinal tuberculosis, this is impractical in a very similar treatment profile. Aspergillus
many of the countries where the disease is species involve the spine more commonly
most prevalent. As with other forms of SEA, than coccidioidomycosis does and rarely
surgical treatment is valuable in patients afflict immunocompetent patients.52,53
with instability of the spine or in those in Blastomycosis, which is epidemic in the
173
southeastern United States and the Mid- ly with the risk for wound infection. We
west, produces a granuloma presenting routinely give intravenous antibiotics for
as a cutaneous or respiratory infection. prophylaxis within the 60 minutes before
Dissemination may produce bony involve- surgery and continue them at scheduled
ment, particularly within the spine. The intervals throughout the case and for 24
typical situation involves a destructive hours afterward. We also routinely irrigate
vertebral lesion associated with a paraspi- copiously with antibiotic-containing saline
nal mass that is treated with amphotericin to prevent intraoperative contamination.
B or newer drugs, such as itraconazole. Epi- The causative organisms in postopera-
dural involvement is exceptionally unusual tive infections are typically skin flora, usu-
but has been reported.54 ally S. aureus or S. epidermidis. The diagnosis
is largely a clinical one, prompted by find-
Parasitic Infection ing drainage from a wound between 2 days
and 2 weeks after surgery. Interpretation
Occasional reports in the literature de-
of the ESR or CRP level can be problematic
scribe epidural involvement with parasitic
because each is elevated by surgery in gen-
infections of the spine. Parasitic infestation
eral; the CRP level returns to normal more
of the spinal canal is very rare in developed
quickly, but without a baseline value (often
countries and is usually treated surgically.
not previously obtained), a trend cannot
Examples include cases of Echinococcus
be ascertained. CT or MR imaging usually
granulosus (hydatid disease),55 Schistosoma

shows a shaggy subincisional space, and
mansonii (bilharziasis),56 and dracunculia-
although strong peripheral enhancement
sis (guinea worm).57 Like schistosomiasis,
of this cavity may denote infection, false-
cysticercosis is usually a parenchymal dis-
positive results are common. If it appears
ease of the spinal cord or occurs in the sub-
that infection is only superficial, we treat
arachnoid space, yet cysticercosis can also
with antibiotics alone. With frank drain-
form masses or collections that occupy the
age and particularly if purulent material
epidural space, producing neural compro-
extrudes from the wound, reexploration
mise.58 In general, patients with parasitic
is indicated. This involves washout of the
involvement of the epidural space still re-
wound with large amounts of antibiotic
quire systemic therapy because of the dis-
solution and débridement of the depths of
seminated nature of such infections.
the wound to remove any necrotic tissue
Epidural Abscess after or granulation tissue. The epidural compo-
Therapeutic Intervention nent of these abscesses may require gentle
scraping of granulation tissue from the du-
Postoperative infections in spinal operative ral surface. As this may provoke a CSF leak,
wounds typically do provoke an epidural care must be exercised while such material
abscess as well as an overlying cellulitis. is physically removed from the epidural
Because most spinal procedures involve space. After wound washout, antibiotics
a laminectomy with dural exposure, any are continued intravenously for several
collection of purulent material within the days, and conversion to oral administration
surgical site tends to track down to the takes place when and if sensitivities allow.
dura. The incidence of wound infection The total duration of antibiotic therapy de-
after spinal surgery averages 2%, but more pends on the severity of the infection but
infections occur in reoperative procedures may extend for 3 to 4 weeks.
or in those patients in whom prior irra- When instrumentation has been placed,
diation, chemotherapy, or steroid therapy a larger dead space is created that pro-
has been used. In addition, patients with motes infection through the buildup of
poor nutrition, impaired mobility, diabe- epidural hematoma, an increase in necro-
tes mellitus, or a history of smoking are all sis of the overlying paraspinal muscles, and
at increased risk for SEA. The duration of tissue ischemia caused by prolonged re-
surgery also appears to correlate positive- traction. The presence of a large hematoma
174
around the instrumentation also provides pain occurs a few days after the procedure
a good culture medium for the growth of with elevation of the ESR and CRP level, and
microorganisms. Usually, infections af- a local inflammatory process can be visible
ter spinal instrumentation surgery take 2 on MR imaging, particularly on the post-
to 6 weeks to become clinically apparent. contrast images. Treatment is medical, and
A scenario of wound breakdown within the patient may also require external brac-
this time frame does suggest an infec- ing with a period of immobilization if the
tion within the wound, as does more focal pain is severe. The use of needles with a
drainage. The principles of treatment are stylet helps prevent this complication but
the same as those described above for sim- does not completely eliminate it.60,61
pler spinal operations, and it is generally Epidural catheter placement can also
not necessary to remove the instrumenta- provide a route of access for bacteria into
tion. If methylmethacrylate has been used, the epidural space. Here again, the usual
it should be removed; however, metallic causative bacteria are staphylococcal spe-
implants resist infection well, and as long cies, reflecting skin flora. The incidence
as isolated soft tissue has been removed of such infections rises with the length
from within the various crevices of the in- of time the catheter is in place, with an
strumentation system, a good resolution of overall incidence of 0.2 to 0.77 per 1,000
the infection usually occurs. When neces- catheter-days.62,63 Thus, patients receiving
sary to relieve tension on the overlying skin longer-term epidural catheters for control
and subcutaneous tissue, plastic surgical of cancer pain face a higher infectious risk.

flaps can be rotated to offer better cover- In such cases, therefore, the practice is to
age of the wound and promote its ultimate implant an indwelling subcutaneous sys-
healing. When loose bone graft is present tem including a refillable pump attached
within an infected area, it too should be to a completely internalized epidural cath-
removed because it is devitalized tissue eter after a percutaneous trial to ensure
and can provide a nidus for recurrence of effectiveness. The early signs of infection
the infection. Delayed infections occurring in this scenario include pain around the
several months after surgery are usually catheter insertion site, superficial infection
caused by more indolent microorganisms, at that site, and in some cases blockage of
including Propionibacterium acnes, Coryne- the catheter. The formation of an epidural
bacterium species, and S. epidermidis. We abscess around the catheter within the
do not recommend hardware removal as nonlaminectomized portion of the spine
some authors have done.59 Rather, we strip eventually leads to a neurologic deficit. MR
the glycocalyx polysaccharide shell that imaging can provide a fairly certain diag-
usually coats the instrumentation, and we nosis.63 When infection is mild, catheter re-
do so in meticulous manner with a copious moval with subsequent antibiotic therapy
washout with antibiotic solution. If such a will usually clear the infection. Successful
procedure fails to eliminate the infection, clearance of infection with medical ther-
then only do we consider hardware remov- apy alone (and without catheter removal)
al. This allows as much time as possible for has been reported but is not recommend-
bony fusion to occur and thus permits re- ed for most patients.28 When a neurologic
moval of the instrumentation without re- deficit has developed, surgical interven-
introducing spinal instability. tion is necessary. The catheter tip should
be cultured immediately on removal to al-
low identification of the organism and the
Infections after Other Spinal Procedures
determination of its antibiotic sensitivi-
Diskography is not done now as commonly ties. Occasional cases of sepsis with seri-
as it once was. Infections do occur after ous consequences have been reported after
diskography, and these include diskitis, catheter-related epidural abscess. We rec-
epidural abscess, and subdural abscess if ommend tunneling the catheter whenever
the dura has been penetrated. Severe local possible as a way of preventing infection.
175
With the advent of percutaneous verte- relate to the absence of air sinuses in the
broplasty and kyphoplasty as methods of spine and to the more voluminous epidural
treating pain caused by spinal compression space located there. Half of the cases in-
fractures, a new source of epidural abscess volve S. aureus, and the others are due to
has joined the list of those associated with the same diverse species found from time
foreign body placement in and around to time in SEA (E. coli, M. tuberculosis, oth-
the spine. The technique involves the in- ers). Most patients with a spinal subdural
jection of methylmethacrylate into the abscess carry at least one factor predispos-
cancellous center of a collapsed vertebral ing them to infection. These include diabe-
body. Although infection is uncommon, tes mellitus, alcoholism, and HIV infection.
occasional reports are now appearing as a Many patients who develop such abscesses
consequence of the widespread use of this have had recent spinal surgery, and many
technique in the elderly, in patients with have concurrent or recent infections else-
osteoporosis, and in those with metastatic where. In 20% of cases, the abscess occurs
cancer.64,65 Because methylmethacrylate is because of a spinal tap or a diskogram gone
a porous, avascular substance, it is a very awry.67 Another quarter of the cases ema-
retentive harbor for microorganisms once nate from cutaneous infections or defects,
they are introduced. Therefore, simple an- such as cellulitis, congenital dermal sinus-
tibiotic therapy is usually unsuccessful in es, and furuncles68,69 (Fig. 13.3). Only 15% of
clearing infections associated with such these abscesses occur outside the thoracic
vertebral augmentation. The recommend- and lumbar spine.

ed treatment for an infected vertebroplas- The symptoms usually include back pain
ty or kyphoplasty site, particularly when at the affected level, fever, and neurologic
it involves an epidural abscess, is removal deficits appropriate to the site and degree
of the involved vertebral segment with of compression exerted by the phlegmon.
its methylmethacrylate, copious washout
with antibiotic solution, and appropriate
reconstruction and instrumentation.
Spinal Subdural Abscess

A subdural empyema contained focally
within the intradural extramedullary space
of the spinal canal is exceptionally rare.
The literature contains approximately 65
reports, with S. aureus the most common
bacterial source and the thoracolumbar
spine the most commonly affected region.
As with other spinal infections, MR imaging
is the diagnostic procedure of choice. The
first spinal subdural empyema was report-
ed in 1927.66 There is no clear pattern for
gender or age. Whereas the epidural space
has anatomic barriers, described previous-
ly, that limit the spread of an abscess from Fig. 13.3 Epidural abscess developing in associa-
its point of origin, no such constraints apply tion with a congenital dermal sinus tract in an infant.
within the subdural space, and thus the in- This T2-weighted sagittal magnetic resonance im-
age shows significant cord compression from a well-
fectious process can extend along multiple
defined abscess. The arrows show both the dorsally
segments of the spinal canal. The incidence placed globular lesion and the immediately adjacent
of spinal subdural infection is much lower sinus tract coursing cephalad from its origin on the
than that of cranial subdural empyema; the skin. The abscess was surgically drained and the sinus
reasons for this are speculative but likely tract excised, with normal development thereafter.
176
Disturbance of consciousness can occur if Because the subdural space is the cen-
the abscess generalizes into a diffuse spinal tral compartment sandwiched between
meningitis leading to meningoencephali- the epidural space and the spinal cord, it
tis. Spinal tenderness is present in only 20 is possible for a subdural spinal abscess
to 30% of patients, so it cannot be used as also to involve either of the two contiguous
a feature to differentiate a subdural infec- compartments by crossing the dural or pial
tion from an epidural abscess. Meningitis barrier.73,74 Involvement of all three has not
is common in these cases, and more of the as yet been reported.
patients are ill at presentation than those
with SEA; the progression of the disease is
Spinal Intramedullary Abscess
usually quite rapid. Diagnosis is generally
made by reviewing the MR images. If lum- Spinal intramedullary abscess is rare but
bar puncture is done because of meningeal somewhat more common than a subdu-
signs and fever and pus is demonstrated, ral abscess of the spine. Cases tend to arise
then spinal subdural empyema should either in young people (younger than 25
be suspected. Intraspinal gas on imaging years of age) or in older adults (older than
should lead to inclusion in the differen- 50 years of age). The usual route of dis-
tial diagnosis of spinal subdural empyema semination is hematogenous in adults, and
caused by a gas-forming microorganism. occasional correlation with patent foramen
Both aerobic and anaerobic microbes can ovale has been reported.75,76 In children,
produce gases, including hydrogen, nitro- spinal intramedullary abscess may be as-

gen, hydrogen sulfide, and methane, which sociated with a dermal sinus tract.77
accumulate because of their low degree of Staphylococcus species, Streptococcus
aqueous solubility.70 species, and gram-negative bacilli are re-
The treatment of choice for spinal sub- sponsible for most intramedullary abscess-
dural abscess is surgical drainage of the ab- es from which bacteria can be cultured. The
scess. The mortality rate is much higher in most common finding, however, is a sterile
patients treated with medical therapy alone culture, seen in 25 to 40% of cases. Polymi-
(80%) than in those treated with surgery crobial infections account for up to 21% of
(18%).71 Like intracranial subdural empy- cases.78,79 Less common pathogens can also
emas, spinal cases should be considered as cause intramedullary infection and include
surgical emergencies because patients can Listeria, Brucella, Actinomyces, Nocardia,
become paralyzed within hours after the Candida, and Toxoplasma. In the work-up
onset of the deficit due to vascular throm- before surgery, post-contrast MRI is the di-
bosis induced by the infection. Because of agnostic test of choice. This study may show
the intradural location of the abscess, du- a nodular pattern of enhancement rather
ral opening is required, and closure in such than ring enhancement, which with a lack
cases should be done with monofilament of pleocytosis in any CSF sampled helps to
suture, such as polypropylene (Prolene; distinguish an abscess from a metastatic tu-
Ethicon 360), rather than braided suture, mor in the cord. A typical example is shown
such as nylon (Nurolon; Ethicon 360) or in Fig. 13.4. Cord edema with variable and
silk. In cases extending over multiple lev- heterogeneous enhancement may signify
els, it may be possible to do a more lim- early myelitis as a precursor to an abscess,
ited laminectomy and use a lavage system which takes 7 to 15 days to form after local
within the subdural space.72 During drain- bacterial inoculation. It has been suggested
age of the intradural pus, preservation of that enhancement at the poles of the le-
the arachnoid is ideal but usually not pos- sion and a peri-ependymal pattern should
sible. After surgery, intravenous antibiotics raise the suspicion for an intramedullary
appropriately chosen from culture results abscess.80 The same authors report that
are given for 4 to 6 weeks. The role of dexa- pial and arachnoidal enhancement can re-
methasone in preventing or moderating oc- flect perimedullary venous dilatation rep-
clusive thrombolysis remains controversial. resenting thrombosed veins and may offer
177
b
a
Fig. 13.4a–c Intramedullary abscess. A 54-year-old

man with the onset of hemiparesis 8 months after
removal of an adenocarcinoma of the gastroesopha-
geal junction. In the interim, he had had two episodes
of empyema at a chest tube site; the first occurred 5
weeks after surgery and the second 5 months after
the first. With the earlier episode of empyema, he had
generalized sepsis. Six weeks after the later episode,
neurologic decline began. He was afebrile with leuko-
cytosis to 13,200/mm3 and a left shift. Post-contrast
magnetic resonance imaging showed an intramedul-
lary ring-enhancing lesion at C2–3 (a) that was eccen-
tric within the cord (b) and associated with significant
edema extending from the cervicomedullary junction
to C6 on T2-weighted images (c). The bacterium cul-
tured from the abscess at surgery was Streptococcus
milleri, and the patient regained significant neurologic
function while completing 4 weeks of intravenous
antibiotics. He died of pulmonary embolism 7 weeks
c after surgery.
evidence of an infectious etiology for any as anaerobes, but coverage should be tai-
ring-enhancing lesion in the cord. lored to the causative pathogens once they
A high index of suspicion, early diagnosis, have been identified. Although no data ex-
and prompt surgical evacuation in conjunc- ist on antibiotic penetration into the spinal
tion with appropriate intravenous antibi- cord (as opposed to the brain, where much
otics given for up to 8 weeks constitute the evidence has been gathered), it seems logi-
best strategy for treating an intramedul- cal to choose drugs that penetrate the blood–
lary abscess. The initial antibiotic coverage brain and blood–CSF barriers. We tend to
178 should be broad enough to treat gram-pos- use a combination of vancomycin, ceftazi-
itive and gram-negative organisms as well dime, and metronidazole as initial therapy
for this disorder. Penicillin should be added monofilament sutures, and then he or she
or substituted to cover Listeria if the patient is placed on antibiotics for 6 to 8 weeks. Al-
is immunocompromised or has a history of though the mortality rate (unlike that in epi-
alcohol abuse, hepatic cirrhosis, or diabetes dural or subdural abscesses) is quite low, the
mellitus.81 Antibiotic treatment alone is oc- neurologic recovery tends to be incomplete.
casionally successful if the infection is chron- As in any spinal cord procedure, neurologic
ic, the pathogen known, the abscess small, outcome depends mainly on the preopera-
and neurologic deficits absent, and myelitis tive level of function of the patient.
without defined abscess formation is usually
treated with antibiotics alone.75,79,80 The use References
of perioperative steroids must be carefully 1. Makins GH, Abbott FC. II. On acute primary os-
individualized, with the benefits of reducing teomyelitis of the vertebrae. Ann Surg 1896;
cord edema balanced against the immuno- 23(5):510–539 PubMed
2. Ramsay Hunt J. Acute infectious osteomyelitis of
suppressive and other potentially harmful
the spine and acute suppurative perimeningitis.
properties of such medications. Med Record 1904;65:641–650
Early recognition optimizes the chances 3. Walker AE. A History of Neurological Surgery.
for functional recovery, with the best re- Baltimore, MD: Williams & Wilkins; 1951
4. Hlavin ML, Kaminski HJ, Ross JS, Ganz E. Spinal
sults occurring when treatment begins epidural abscess: a ten-year perspective. Neuro-
within 3 days after the onset of symptoms. surgery 1990;27(2):177–184 PubMed
Once treatment concludes, the overall rate 5. Rigamonti D, Liem L, Sampath P, et al. Spinal
of residual neurologic impairment is 70%, epidural abscess: contemporary trends in etiol-

ogy, evaluation, and management. Surg Neurol
and prolonged antibiotic therapy is recom- 1999;52(2):189–196, discussion 197 PubMed
mended because these lesions have a pro- 6. Darouiche RO. Spinal epidural abscess. N Engl J
pensity to recur.79,82 Med 2006;355(19):2012–2020 PubMed
7. Pradilla G, Nagahama Y, Spivak AM, Bydon A,
The pathogenesis of spinal intramed- Rigamonti D. Spinal epidural abscess: current
ullary abscess recapitulates that of an in- diagnosis and management. Curr Infect Dis Rep
tracerebral abscess. The bacterial nidus is 2010;12(6):484–491 PubMed
first infiltrated by polymorphonuclear leu- 8. Chen SH, Chang WN, Lu CH, et al. The clinical
characteristics, therapeutic outcome, and prog-
kocytes. Suppurative myelitis follows, then nostic factors of non-tuberculous bacterial spinal
the development of a necrotic center with epidural abscess in adults: a hospital-based study.
liquefaction.83 Spreading along the white Acta Neurol Taiwan 2011;20(2):107–113 PubMed
9. Smith C, Kavar B. Extensive spinal epidural ab-
matter tracts, the average lesion extends
scess as a complication of Crohn’s disease. J Clin
over three to six spinal segments. Ulti- Neurosci 2010;17(1):144–146 PubMed
mately, the central pus is circumscribed 10. R ussell NA, Vaughan R, Morley TP. Spinal epi-
by the development of fibrous granulation dural infection. Can J Neurol Sci 1979;6(3):
325–328 PubMed
tissues. All levels of the cord are equally af- 11. R ankin RM, Flothow PG. Pyogenic infection of the
fected. The lesions can be acute, subacute, spinal epidural space. West J Surg Obstet Gynecol
or chronic in nature. An acute intramedul- 1946;54:320–323 PubMed
lary abscess presents with back pain, fever, 12. F eldenzer JA, McKeever PE, Schaberg DR, Camp-
bell JA, Hoff JT. Experimental spinal epidural ab-
and neurologic deficits in a fashion simi- scess: a pathophysiological model in the rabbit.
lar to that of an acute transverse myelitis. Neurosurgery 1987;20(6):859–867 PubMed
A chronic abscess more closely mimics an 13. Feldenzer JA, McKeever PE, Schaberg DR, Campbell
JA, Hoff JT. The pathogenesis of spinal epidural ab-
intramedullary tumor, with the absence of scess: microangiographic studies in an experimental
fever, a gradually developing back pain, and model. J Neurosurg 1988;69(1):110–114 PubMed
the slow onset of neurologic deficit. Most 14. Davis DP, Salazar A, Chan TC, Vilke GM. Prospective
patients have motor impairment and blad- evaluation of a clinical decision guideline to diag-
nose spinal epidural abscess in patients who pres-
der impairment, pain, and often sensory ent to the emergency department with spine pain.
loss. Interestingly, only half are febrile.75 J Neurosurg Spine 2011;14(6):765–770 PubMed
Surgical treatment generally involves lam- 15. Darouiche RO, Hamill RJ, Greenberg SB, Weathers
SW, Musher DM. Bacterial spinal epidural abscess.
inectomy with a midline myelotomy to gain
Review of 43 cases and literature survey. Medi-
access to the abscess cavity, which tends to be cine (Baltimore) 1992;71(6):369–385 PubMed
relatively central within the cord. After gentle 16. K hanna RK, Malik GM, Rock JP, Rosenblum ML.
Spinal epidural abscess: evaluation of factors 179
irrigation, the patient’s wound is closed with
influencing outcome. Neurosurgery 1996;39(5): myelitis. Semin Arthritis Rheum 2007;36(5):
17. Lifeso RM. Pyogenic spinal sepsis in adults. Spine 33. Koo DW, Townson AF, Dvorak MF, Fisher CG. Spinal
1990;15(12):1265–1271 PubMed epidural abscess: a 5-year case-controlled review
18. Carragee EJ, Kim D, van der Vlugt T, Vittum D. The of neurologic outcomes after rehabilitation. Arch
clinical use of erythrocyte sedimentation rate in Phys Med Rehabil 2009;90(3):512–516 PubMed
pyogenic vertebral osteomyelitis. Spine 1997; 34. C ahill DW, Love LC, Rechtine GR. Pyogenic osteo-
22(18):2089–2093 PubMed myelitis of the spine in the elderly. J Neurosurg
19. Lazzeri E, Erba P, Perri M, et al. Scintigraphic im- 1991;74(6):878–886 PubMed
aging of vertebral osteomyelitis with 111in-bio- 35. Kowalski TJ, Layton KF, Berbari EF, et al. Follow-up
tin. Spine 2008;33(7):E198–E204 PubMed MR imaging in patients with pyogenic spine infec-
20. Fuursted K, Arpi M, Lindblad BE, Pedersen LN. tions: lack of correlation with clinical features. AJNR
Broad-range PCR as a supplement to culture for Am J Neuroradiol 2007;28(4):693–699 PubMed
detection of bacterial pathogens in patients with 36. A talay B, Azap O, Cekinmez M, Caner H, Haberal
a clinically diagnosed spinal infection. Scand J In- M. Nocardial epidural abscess of the thoracic spi-
fect Dis 2008;40(10):772–777 PubMed nal cord and review of the literature. J Infect Che-
21. Boström A, Oertel M, Ryang Y, et al. Treatment strate- mother 2005;11(3):169–171 PubMed
gies and outcome in patients with non-tuberculous 37. W est KR, Mason RC, Sun M. Nocardia spinal epi-
spinal epidural abscess—a review of 46 cases. Minim dural abscess: 14-year follow-up. Orthopedics
Invasive Neurosurg 2008;51(1):36–42 PubMed 2012;35(1):e128–e131 PubMed
22. Deshmukh VR. Midline trough corpectomies for 38. Y ung BC, Cheng JC, Chan TT, Loke TK, Lo J, Lau
the evacuation of an extensive ventral cervical PY. Aggressive thoracic actinomycosis compli-
and upper thoracic spinal epidural abscess. J Neu- cated by vertebral osteomyelitis and epidural
rosurg Spine 2010;13(2):229–233 PubMed abscess leading to spinal cord compression. Spine
23. Przybylski GJ, Sharan AD. Single-stage autogenous 2000;25(6):745–748 PubMed
bone grafting and internal fixation in the surgical 39. E ftekhar B, Ketabchi E, Ghodsi M, Ahmadi A. Cer-
management of pyogenic discitis and vertebral vical epidural actinomycosis. Case report. J Neu-
osteomyelitis. J Neurosurg 2001;94(1, Suppl): rosurg 2001;95(1, Suppl):132–134 PubMed
1–7 PubMed 40. P ina MA, Modrego PJ, Uroz JJ, Cobeta JC, Lerin FJ,
24. R
uf M, Stoltze D, Merk HR, Ames M, Harms J. Treat- Baiges JJ. Brucellar spinal epidural abscess of cervi-
ment of vertebral osteomyelitis by radical de- cal location: report of four cases. Eur Neurol 2001;
bridement and stabilization using titanium mesh 45(4):249–253 PubMed
cages. Spine 2007;32(9):E275–E280 PubMed 41. Ugarriza LF, Porras LF, Lorenzana LM, Rodríguez-
25. Carragee E, Iezza A. Does acute placement of Sánchez JA, García-Yagüe LM, Cabezudo JM. Bru-
instrumentation in the treatment of vertebral cellar spinal epidural abscesses. Analysis of eleven
osteomyelitis predispose to recurrent infection: cases. Br J Neurosurg 2005;19(3):235–240 PubMed
long-term follow-up in immune-suppressed pa- 42. Gerberding JL, Romero JM, Ferraro MJ. Case records
tients. Spine 2008;33(19):2089–2093 PubMed of the Massachusetts General Hospital. Case 34-
26. Robinson Y, Tschoeke SK, Kayser R, Boehm H, 2008. A 58-year-old woman with neck pain and fe-
Heyde CE. Reconstruction of large defects in ver- ver. N Engl J Med 2008;359(18):1942–1949 PubMed
tebral osteomyelitis with expandable titanium 43. R ezai AR, Lee M, Cooper PR, Errico TJ, Koslow
cages. Int Orthop 2009;33(3):745–749 PubMed M. Modern management of spinal tuberculo-
27. Lyu RK, Chen CJ, Tang LM, Chen ST. Spinal epi- sis. Neurosurgery 1995;36(1):87–97, discussion
dural abscess successfully treated with percu- 97–98 PubMed
taneous, computed tomography-guided, needle 44. Lindahl S, Nyman RS, Brismar J, Hugosson C,
aspiration and parenteral antibiotic therapy: case Lundstedt C. Imaging of tuberculosis. IV. Spi-
report and review of the literature. Neurosurgery nal manifestations in 63 patients. Acta Radiol
2002;51(2):509–512, discussion 512 PubMed 1996;37(4):506–511 PubMed
28. Perez-Toro MR, Burton AW, Hamid B, Koyyalagun- 45. M
etta H, Corti M, Redini L, Yampolsky C, Schtirbu
ta D. Two-Tuohy needle and catheter technique R. Spinal epidural abscess due to Mycobacterium
for fluoroscopically guided percutaneous drain- tuberculosis in a patient with AIDS: case report
age of spinal epidural abscess: a case report. Pain and review of the literature. Braz J Infect Dis 2006;
Med 2009;10(3):501–505 PubMed 10(2):146–148 PubMed
29. Grieve JP, Ashwood N, O’Neill KS, Moore AJ. A 46. M
uzii VF, Mariottini A, Zalaffi A, Carangelo BR,
retrospective study of surgical and conserva- Palma L. Cervical spine epidural abscess: experi-
tive treatment for spinal extradural abscess. Eur ence with microsurgical treatment in eight cases.
Spine J 2000;9(1):67–71 PubMed J Neurosurg Spine 2006;5(5):392–397 PubMed
30. Katonis P, Souvatzis X, Tsavalas N, Alpantaki K. 47. M
athew J, Tripathy P, Grewal S. Epidural tubercu-
Reversal of tetraplegia in a patient with hae- losis involving the entire spine. Neurol Neurochir
matogenous cervical epidural abscess. Acta Or- Pol 2009;43(5):470–474 PubMed
thop Belg 2011;77(4):543–547 PubMed 48. C
hia SL, Tan BH, Tan CT, Tan SB. Candida spondyl-
31. Jensen AG, Espersen F, Skinhøj P, Frimodt-Møller odiscitis and epidural abscess: management with
N. Bacteremic Staphylococcus aureus spondylitis. shorter courses of anti-fungal therapy in combi-
Arch Intern Med 1998;158(5):509–517 PubMed nation with surgical debridement. J Infect 2005;
32. Roblot F, Besnier JM, Juhel L, et al. Optimal du- 51(1):17–23 PubMed
ration of antibiotic therapy in vertebral osteo-
180
49. Metcalfe S, Morgan-Hough C. Cervical epidural 67. L ownie SP, Ferguson GG. Spinal subdural empy-
abscess and vertebral osteomyelitis following ema complicating cervical discography. Spine
non-traumatic oesophageal rupture: a case re- 1989;14(12):1415–1417 PubMed
port and discussion. Eur Spine J 2009;18(Suppl 2): 68. L evy ML, Wieder BH, Schneider J, Zee CS, Weiss
224–227 PubMed MH. Subdural empyema of the cervical spine:
50. Herron LD, Kissel P, Smilovitz D. Treatment of coc- clinicopathological correlates and magnetic reso-
cidioidal spinal infection: experience in 16 cases. nance imaging. Report of three cases. J Neurosurg
J Spinal Disord 1997;10(3):215–222 PubMed 1993;79(6):929–935 PubMed
51. Kakarla UK, Kalani MY, Sharma GK, Sonntag VK, 69. P ark SW, Yoon SH, Cho KH, Shin YS, Ahn YH. In-
Theodore N. Surgical management of coccidioi- fantile lumbosacral spinal subdural abscess with
domycosis of the spine: clinical article. J Neuro- sacral dermal sinus tract. Spine 2007;32(1):
surg Spine 2011;15(4):441–446 PubMed E52–E55 PubMed
52. Dubbeld P, van Oostenbrugge RJ, Twinjstra A, 70. N adkarni T, Shah A, Kansal R, Goel A. An intradu-
Schouten HC. Spinal epidural abscess due to As- ral-extramedullary gas-forming spinal abscess in
pergillus infection of the vertebrae: report of 3 a patient with diabetes mellitus. J Clin Neurosci
cases. Neth J Med 1996;48(1):18–23 PubMed 2010;17(2):263–265 PubMed
53. Tew CW, Han FC, Jureen R, Tey BH. Aspergillus 71. B artels RH, de Jong TR, Grotenhuis JA. Spinal
vertebral osteomyelitis and epidural abscess. Sin- subdural abscess. Case report. J Neurosurg 1992;
gapore Med J 2009;50(4):e151–e154 PubMed 76(2):307–311 PubMed
54. H ardjasudarma M, Willis B, Black-Payne C, Ed- 72. K im SH, Lee JK, Jang JW, Seo BR, Kim TS, Kim
wards R. Pediatric spinal blastomycosis: case re- SH. Laminotomy with continuous irrigation in
port. Neurosurgery 1995;37(3):534–536 PubMed patients with pyogenic spondylitis in thoracic
55. Karadereler S, Orakdögen M, Kiliç K, Ozdogan C. and lumbar spine. J Korean Neurosurg Soc 2011;
Primary spinal extradural hydatid cyst in a child: 50(4):332–340 PubMed
case report and review of the literature. Eur Spine 73. H ershkowitz S, Link R, Ravden M, Lipow K. Spinal
J 2002;11(5):500–503 PubMed empyema in Crohn’s disease. J Clin Gastroenterol
56. Ruberti RF, Saio M. Epidural Bilharzioma mansoni 1990;12(1):67–69 PubMed

compressing the spinal cord: case report. East Afr 74. A lessi G, Lemmerling M, Nathoo N. Combined
Med J 1999;76(7):414–416 PubMed spinal subdural tuberculous empyema and in-
57. Legmann P, Chiras J, Launay M, Philippon J, Bories tramedullary tuberculoma in an HIV-positive pa-
J. Epidural dracunculiasis: a rare cause of spinal tient. Eur Radiol 2003;13(8):1899–1901 PubMed
cord compression. Neuroradiology 1980;20(1): 75. B yrne RW, von Roenn KA, Whisler WW. Intra-
43–45 PubMed medullary abscess: a report of two cases and a re-
58. D elobel P, Signate A, El Guedj M, et al. Unusual view of the literature. Neurosurgery 1994;35(2):
form of neurocysticercosis associated with HIV 321–326, discussion 326 PubMed
infection. Eur J Neurol 2004;11(1):55–58 PubMed 76. David C, Brasme L, Peruzzi P, Bertault R, Vinsonneau
59. Richards BR, Emara KM. Delayed infections after M, Ingrand D. Intramedullary abscess of the spinal
posterior TSRH spinal instrumentation for idio- cord in a patient with a right-to-left shunt: case re-
pathic scoliosis: revisited. Spine 2001;26(18): port. Clin Infect Dis 1997;24(1):89–90 PubMed
1990–1996 PubMed 77. T ufan K, Cekinmez M, Sener L, Erdogan B. Infected
60. Connor PM, Darden BV II. Cervical discogra- lumbar dermoid cyst presenting with tetrapare-
phy complications and clinical efficacy. Spine sis secondary to holocord central lesion. J Child
1993;18(14):2035–2038 PubMed Neurol 2008;23(8):934–937 PubMed
61. Junila J, Niinimäki T, Tervonen O. Epidural abscess 78. C andon E, Frerebeau P. Bacterial abscesses of the
after lumbar discography. A case report. Spine spinal cord. Review of the literature (73 cases)
1997;22(18):2191–2193 PubMed [in French]. Rev Neurol (Paris) 1994;150(5):
62. Byers K, Axelrod P, Michael S, Rosen S. Infections 370–376 PubMed
complicating tunneled intraspinal catheter sys- 79. Chan CT, Gold WL. Intramedullary abscess of the
tems used to treat chronic pain. Clin Infect Dis spinal cord in the antibiotic era: clinical features, mi-
1995;21(2):403–408 PubMed crobial etiologies, trends in pathogenesis, and out-
63. Sillevis Smitt P, Tsafka A, van den Bent M, et al. comes. Clin Infect Dis 1998;27(3):619–626 PubMed
Spinal epidural abscess complicating chronic 80. C ondette-Auliac S, Lacour JC, Anxionnat R, et al.
epidural analgesia in 11 cancer patients: clinical MRI aspects of spinal cord abscesses. Report of 5
findings and magnetic resonance imaging. J Neu- cases and review of the literature [in French ]. J
rol 1999;246(9):815–820 PubMed Neuroradiol 1998;25(3):189–200 PubMed
64. Vats HS, McKiernan FE. Infected vertebroplas- 81. P fadenhauer K, Rossmanith T. Spinal manifesta-
ty: case report and review of literature. Spine tion of neurolisteriosis. J Neurol 1995;242(3):
2006;31(22):E859–E862 PubMed 153–156 PubMed
65. Cosar M, Sasani M, Oktenoglu T, et al. The major 82. M orandi X, Mercier P, Fournier HD, Brassier G.
complications of transpedicular vertebroplasty. J Dermal sinus and intramedullary spinal cord
Neurosurg Spine 2009;11(5):607–613 PubMed abscess. Report of two cases and review of the
66. Velissaris D, Aretha D, Fligou F, Filos KS. Spinal literature. Childs Nerv Syst 1999;15(4):202–206,
subdural Staphylococcus aureus abscess: case re- discussion 207–208 PubMed
port and review of the literature. World J Emerg 83. DiTullio MV Jr. Intramedullary spinal abscess: a case
Surg 2009;4:31 PubMed report with a review of 53 previously described
cases. Surg Neurol 1977;7(6):351–354 PubMed
181
IV
Neurosurgical Issues
14
Neurosurgical Antibiotic
Prophylaxis
Daraspreet Singh Kainth, Dino Terzic, and Stephen J. Haines
■■ G
eneral Principles of based on the level of evidence to support
Antibiotic Prophylaxis them. These recommendations are out-
lined in Tables 14.1 and 14.2.3 The CDC
Effective antibiotics for use in neurosurgical recommends that a prophylactic antibiotic
procedures provide adequate coverage of be administered intravenously at the ap-
the organisms commonly associated with propriate time before an incision is made
neurosurgical infections, such as staphylo- such that the bactericidal concentration of
cocci. An ideal antibiotic will have minimal the drug has been established when the
adverse effects and be low in cost.1 In ad- incision is made.3 Prophylactic antibiotics
dition, it should reach adequate concentra- should not be extended significantly into
tions in the tissues of the operative site, the postoperative period.
have the least potential for adverse side The administration of prophylactic an-
effects, have a half-life that permits single- tibiotics is not without risks. Before ad-
dose injections, and not interact with other ministration, the clinical history should be
drugs given perioperatively.2 examined to prevent the administration of
The Centers for Disease Control and Pre- antibiotics to which the patient may have
vention (CDC) has provided recommen- an allergic reaction. Other risks associ-
dations in regard to the administration of ated with antibiotic use include thrombo-
prophylactic antibiotics. The CDC recom- phlebitis and the suppression of natural
mendations are based on a thorough re- flora, which can lead to urinary or gastro-
view of the literature and are categorized intestinal infections.4 Allergic reactions to
Table 14.1 Classification of Centers for Disease Control and Prevention recommendations for the prevention
of surgical site infections3
Rankings Recommendations
Category 1A Strongly recommended for implementation and supported by well-designed

experimental, clinical, or epidemiologic studies
Category 1B Strongly recommended for implementation and supported by some experimen-

tal, clinical, or epidemiologic studies and strong theoretical rationale
Category II Suggested for implementation and supported by suggestive clinical or epide-

miologic studies or theoretical rationale
No recommendation; Practices for which insufficient evidence or no consensus regarding efficacy exists
unresolved issue
Table 14.2 Antimicrobial prophylaxis recommendations3
Category IA
• Select an antimicrobial agent with efficacy against expected pathogens. For neurosurgical patients, the
antibiotic regimen should cover gram-positive organisms such as Staphylococcus species.
• The intravenous route should be used to obtain adequate serum levels during the operation and for at
most a few hours after the incision is closed.
Category IB
• Vancomycin should not be routinely used for antimicrobial prophylaxis.
• Additional intraoperative doses of prophylactic antibiotics should be considered in cases in which opera-
tive length exceeds the half-life of the drug, in operations with significant blood loss, and in operations on
morbidly obese patients.
penicillin derivatives are quite common. ■■ C

linical Data Regarding
Cephalosporins cause fewer allergic reac-
Systemic Antimicrobial
tions; however, they demonstrate cross
reactivity in roughly 10% of patients with Prophylaxis in
penicillin allergy. 2 In addition, prophylactic Neurosurgical Procedures

antibiotics have been found to be associat-
ed with the risk for developing Clostridium The incidence of infection after clean neu-
difficile colitis, although C. difficile coloni- rosurgical procedures ranges from 1 to 3%.1
zation is more commonly associated with Although the incidence of infection is low,
prolonged antibiotic treatment.5,6 such infections carry the risk for potentially
Antibiotics for surgical prophylaxis devastating complications in neurosurgical
should be chosen to have as narrow a procedures. Currently, prophylactic anti-
spectrum as possible while still covering biotics in clean neurosurgical procedures
relevant pathogens. The widespread use are used routinely and have become the
of broad-spectrum antibiotics leads to standard of care.7 Randomized controlled
the development of resistant organisms.2 trials have demonstrated that the use of
For example, the increasing prevalence of prophylactic antibiotics reduces the inci-
methicillin-resistant Staphylococcus aureus dence of surgical site infections. Random-
(MRSA) is concerning.4 Antibiotics that are ized studies from the 1970s, 1980s, and
typically used to treat resistant organisms early 1990s have concluded that systemic
should not routinely be used for prophy- antibiotic prophylaxis is effective at reduc-
laxis unless no alternative is available.2 ing the infection rate in clean neurosurgi-
Even with the use of prophylactic anti- cal procedures.8–16
biotics, infections are not completely pre- In 1994, Barker conducted a meta-anal-
ventable. Inherent factors may exist that ysis of randomized studies published prior
increase the risk for developing a postop- to 1992, comparing antibiotics with pla-
erative infection, such as malnutrition, im- cebo in clean neurosurgical procedures.17
munosuppression, diabetes mellitus, and Pooled data from eight eligible random-
steroid use. Intraoperative conditions that ized studies showed 19 infections in 1,014
increase the risk for infection include lon- craniotomies with prophylactic antibiotics
ger duration of the operation, placement and 93 infections in 1,061 craniotomies
of drains in the wound, blood transfusions, without prophylactic antibiotics. The dif-
cerebrospinal fluid (CSF) fistulas, and tis- ference was statistically significant, and the
sue injury.2 author estimated that the odds of infection
186
without the use of antibiotics are 4.2 times onstrate different degrees of effectiveness
higher than the odds of infection with the for different antibiotics is constrained by
use of antibiotic prophylaxis. Over all, the the sample sizes required for definitive
estimated incidence of infection was 2% studies. When the clean neurosurgical pro-
with antibiotics and 8% without antibiot- cedure infection rate with the use of anti-
ics (p < 0.001).17 These results confirmed biotic prophylaxis approximates 1%, trials
that systemic antibiotic prophylaxis is ef- with an 80% chance of demonstrating an
fective in reducing the infection rate after infection rate decrease to 0.5% need to have
clean neurosurgical procedures. After the approximately 2,000 patients. Decisions
establishment that systemic antibiotic pro- regarding the appropriate prophylactic an-
phylaxis is superior to placebo, subsequent tibiotic to administer will depend on local
trials have focused on comparing different microorganism sensitivity profiles and ex-
antibiotic regimens. ternal factors, such as cost.
When the blood–CSF barrier is intact, In 2001, Zhu et al conducted a prospec-
the cephalosporins commonly used for tive randomized trial comparing the use of
prophylaxis in neurosurgical procedures do prophylactic ceftriaxone and ampicillin-
14 Neurosurgical Antibiotic Prophylaxis

not penetrate the CSF.18–20 In 1979, Friedrich sulbactam in clean neurosurgical opera-
et al demonstrated that cephacetril, a first- tions. Surgical site infections occurred in
generation cephalosporin, is not detectable 3.3% of patients in the ceftriaxone group
in the CSF when the blood–CSF barrier is and 2.3% of patients in the ampicillin-
intact.19 Similarly, Knoop et al demon- sulbactam group. There was no statisti-
strated that cefotiam, a second-generation cally significant difference in the infection
cephalosporin, does not penetrate the CSF rates.1 However, because the trial was not
during surgery.20 On the other hand, cepha- designed as an equivalence trial, the ab-
losporins do demonstrate good penetration sence of a significant difference must be
of the CSF when the blood–brain barrier is interpreted with caution. We cannot reli-
disrupted, as in the case of meningeal in- ably conclude whether differences actually
flammation. For example, Cherubin et al in exist in various antibiotic regimens unless
1989 and Cadoz et al in 1981 described the such trials are designed as equivalence tri-
excellent penetration of ceftriaxone into als or unless they are adequately powered
the CSF and the quick clearance of bacteria to detect differences in infection rates.
in children with meningitis.21,22 Case se- Similarly, Whitby et al29 compared infec-
ries and randomized controlled trials have tion rates in neurosurgical procedures that
shown that ceftriaxone used as prophylaxis used either cefotaxime or trimethoprim-
in neurosurgical procedures is effective at sulfamethoxazole as systemic antibiotic pro-
reducing surgical site infections.14,23,24 phylaxis. The infection rate in the cefotaxime
Even though cephalosporins do not ef- group was 2.5%, and the infection rate was
fectively penetrate the CSF in the absence 2.3% in the trimethoprim-sulfamethoxazole
of meningeal inflammation, they are able group. The authors concluded that both
to reach effective concentrations in the regimens are equally effective at controlling
tissue to prevent surgical site infections.25 neurosurgical infection rates.29 The sample
However, after a neurosurgical procedure, size was calculated to achieve a power of 0.8
damage may occur to the blood–brain bar- or greater, assuming an infection rate of 4%
rier that enables the CSF penetration of an- in the absence of prophylaxis and a reduc-
tibiotics.26,27 Other prophylactic systemic tion in the rate to 2% with prophylaxis.
antibiotic regimens that have been used The neurosurgical literature discussing
in neurosurgical procedures include piper- the use of prophylactic antibiotics in clean–
acillin, vancomycin, vancomycin with gen- contaminated procedures is limited. Clean–
tamicin, cloxacillin, and oxacillin.9–12,14–16,28 contaminated procedures are defined by
At present, no regimen has been shown entry into the respiratory, gastrointestinal,
to be superior to others in terms of reduc- or genitourinary tract under controlled
ing the infection rate. The attempt to dem- conditions. This circumstance is encoun-
187
tered during transnasal trans-sphenoidal monitored the infection rate in 2,847 pa-
approaches, transoral approaches, or other tients undergoing elective clean or clean–
complex cranial base approaches. The gen- contaminated surgical procedures. The
eral surgery literature has demonstrated patients were divided into four groups ac-
the beneficial role of prophylactic antibiot- cording to the time of prophylactic antibi-
ics in this group, such as in cases in which otic administration. The groups included
the bowel or biliary tract is entered.30,31 patients who received antibiotics between
Dirty and contaminated wounds are fre- 24 and 2 hours before incision time (early),
quently encountered in the trauma setting. within 2 hours before incision (preopera-
The use of antibiotics in this situation is of tive), within 3 hours after incision (periop-
therapeutic value and no longer prophylac- erative), and between 3 and 24 hours after
tic. Factors such as the level of contamina- incision (postoperative). The patients who
tion, the patient’s immune status, violation received the antibiotic within 2 hours be-
of the dura mater, and the extent of dé- fore incision had the lowest infection rate
bridement required will play a role in de- (0.6%), which suggested that appropriate
termining the administration of antibiotics. timing of administration should fall within
this window.
In terms of the duration of prophylactic
■■ T
iming and Duration antibiotic, there is no evidence to support
of Prophylaxis multiple-dose versus single-dose admin-
istration. No neurosurgical trials exist on
Early animal model experiments by Burke this topic, although it has been examined
and by Miles et al established the impor- in the surgery literature. DiPiro et al have
tance of the timing of antibiotic adminis- reported on eight studies that compared
tration in preventing incision infections.32,33 a single-dose prophylactic regimen ver-
Burke established that systemic antibiotics sus multiple-dose regimens of the same
have no effect on primary staphylococcal drug. In all of these studies, no difference
infections if the bacteria have been present in the infection rates was witnessed.36 Such
in the tissue longer than 3 hours before the results fit with pioneering experimental
administration of antibiotics. In order for animal data, which showed that antimi-
the antibiotic to suppress an infection, the crobials administered as soon as within 3
antibiotic has to be present before the bac- hours after bacterial contamination of the
teria have time to gain access to the tissue. wound do not influence the size of the skin
With regard to the timing of the admin- lesion measured at 24 hours.32,33,36
istration of prophylactic antibiotics, the an- Similarly, in a prospective randomized
tibiotic should be given at the appropriate trial by Nooyen et al, no statistically signifi-
time before the operation begins such that cant difference in infection rates was seen
the bactericidal concentration of the drug in patients undergoing coronary artery
has been established when the incision is bypass grafting who were randomized to
made.3 The exact timing will depend on receive either a single dose of cefuroxime
the pharmacokinetics of the drug. In gen- at the induction of anesthesia or the same
eral, prophylactic antibiotics are suggested dose for an additional 3 days consecutive-
to be given within 1 hour before the inci- ly.37 A total of 844 patients were random-
sion is made.2 A study by Galandiuk et al ized, and the sternal site infection rate was
showed that the infection rate is higher in 14% in the single-dose group compared
general surgery patients who receive pro- with 13% in the 3-day-course group.
phylactic antibiotics more than 1 hour be- These trials demonstrate that there
fore the incision is made.34 is no significant benefit to extending the
Similarly, Classen et al35 showed that the administration of prophylactic antibiot-
timing of prophylactic antibiotic admin- ics. Given the risks and complications that
istration has an impact on the rate of de- can occur with antibiotic administration,
veloping an infection. They prospectively without any definitive evidence for ex-
188
tended use, such a practice is not recom- whose ventricular catheter was changed
mended. However, antibiotics may need at 5-day intervals to calculate the power
to be redosed in lengthy operations and for the study. The finding of a difference of
in cases in which there is significant blood almost 50% in the infection rates raises the
loss.2 question of whether the use of the histori-
cal infection rates led to this study being
underpowered.
■■ A
ntimicrobial Prophylaxis in Advances in technology have led to the
availability of antibiotic-impregnated ven-
Special Circumstances tricular catheters. Catheters can be im-
pregnated with more than one antibiotic
External Cerebrospinal Fluid Drains
to prevent the development of antibiotic
The rate of infection with placement of resistance. In vitro studies have shown that
an external ventricular drain varies in the impregnated catheters can decrease colo-
literature based on the criteria and meth- nization by Staphylococcus epidermidis for
odology used to determine the presence at least 1 year and prevent the spread of

of infection. External ventricular drain in- bacteria along the catheter surface. Studies
fection rates have been reported to range demonstrate that antibiotic-impregnated
from 4% to more than 20% per procedure catheters decrease the incidence of cathe-
per patient.38–42 ter-related infections.44,45 Rivero-Garvía et
Reported risk factors for infection include al reported a decrease in the catheter in-
longer duration of catheter placement,41 fection rate from 17% to 2.4% with the use
CSF leakage,38 presence of intraventricular of antibiotic-impregnated catheters.45 In
blood, and trauma.39 The most common a prospective randomized trial by Wong
pathogens involved in external ventricu- et al, it was demonstrated that antibiotic-
lar drain infections are gram-positive mi- impregnated catheters were as effective
croorganisms of the skin flora, most often as systemic antibiotics in preventing CSF
coagulase-negative staphylococci.39,41 infections. Patients were randomized to
A study by Mayhall et al in 1984 sug- receive an antibiotic-impregnated cath-
gested that ventricular catheters be eter with no systemic antibiotics versus
changed and inserted in a different site systemic antibiotics without an antibiot-
if monitoring is required more than 5 ic-impregnated catheter. The difference
days to reduce the risk for ventriculos- between the infection rates, 1% versus 3%,
tomy-related infections.42 This remains a was not statistically significant.46
debated topic. In 2002, Wong et al pub- Higher infection rates have been ob-
lished a randomized prospective trial served when the catheter has been tun-
that was powered to detect a statistically neled in the subcutaneous tissue for a
significant difference between the infec- distance of less than 5 cm. Sandalcioglu et
tion rates of patients randomized to ex- al found that the ventricular catheter was
ternal ventricular drainage with the drain tunneled less than 5 cm in 83% of their pa-
changed at 5-day intervals and the infec- tients with CSF infections.47 The authors
tion rates of those randomized to external hypothesize that this disproportion was
ventricular drainage with the drain not related to the observation that CSF leak-
changed. This study demonstrated that age was more common when the catheter
there was no statistically significant dif- was not tunneled an adequate distance,
ference between the infection rates of the increasing the chance for colonization and
two groups: 7.8% versus 3.8% (p = 0.50).43 infection.
However, when designing this study, the The use of antibiotic treatment during
authors used a historical infection rate of external ventricular drainage remains an
30% in patients whose ventricular cath- issue of debate.40,48,49 The practice of us-
eter remained unchanged after 5 days ing prophylactic antibiotics is variable. In a
versus an infection rate of 8% in patients survey of the members of the Neurocritical
189
Care Society, of whom 77% (599 individuals) drains similarly can lead to the develop-
were neurosurgeons, 56% recommended ment of CSF infections. The risks for infec-
the use of antibiotics while the catheter was tion increase with drain leakage or blockage,
in place.49 In 1985, Blomstedt conducted a hemorrhagic CSF, and the length of time the
prospective randomized trial in which one drain remains in place.53 In a cohort study
group of patients was randomized to be giv- by Schade et al in 2005, the authors com-
en trimethoprim-sulfamethoxazole as pro- pared the rates of infection in ventricular
phylaxis during ventricular drainage and a and lumbar drainage. After correcting for
second group to be given no antibiotic pro- duration of drainage, they did not find a
phylaxis. The study contained 52 patients significant difference between the infection
and did not show a difference in the infec- rates for these two drainage techniques.52
tion rates, but the study was not powered
adequately. A retrospective study by Alleyne
Cerebrospinal Fluid Shunts and
et al in 2000 did not show a difference be-
Other Foreign Bodies
tween the rates of ventriculitis in patients
who received continued antibiotics while The placement of CSF shunts is one the
their ventricular drain remained in place most frequent neurosurgical procedures
and the rates of those who did not receive performed. Other neurosurgical proce-
continued antibiotics.48 Currently, practices dures that require the implantation of a
vary based on limited evidence. However, foreign body include synthetic cranioplas-
the routine use of antibiotics is not without ties, placement of intrathecal catheters for
risks and has the potential to lead to the de- drug delivery, and implantation of deep
velopment of drug-resistant organisms and brain and epidural spinal cord electrodes.
C. difficile colitis.49,51 We would benefit from Shunt infection can complicate the place-
a prospective randomized trial of adequate ment of a CSF shunt, and the infection rate
power to answer this question. ranges from 5 to 10%.54 The common or-
In patients who received antibiotics ganisms responsible for shunt infections
through the duration of ventricular drain- include those that are part of the skin flora:
age, Wong et al in 2006 reported that a S. epidermidis, S. aureus, and Propionibacte-
single broad-spectrum antibiotic such as rium acnes. The clustering of 70% of shunt
cefepime was as effective in preventing infections within 2 months after shunt
ventriculitis as alternative regimens that placement suggests that initial coloniza-
contained dual antibiotics, such as ampicil- tion during shunt placement contributes
lin-sulbactam with aztreonam. In this pro- significantly to resulting shunt infections.53
spective randomized controlled trial, the Many studies have examined the role that
infection rate was 6.6% in the single-anti- prophylactic systemic antibiotics can play
biotic group and 2.3% in the dual-antibiotic in reducing the shunt infection rate.
group (p = 0.17).52 Before the meta-analysis performed
Protocols for the placement of ventricu- by Haines and Walters in 1994, attempts
lar drains, surveillance, and treatment of to confirm the efficacy of antibiotic pro-
catheter-related infections vary between phylaxis for CSF shunt operations had
institutions. Over all, recommendations yielded inconclusive results.55–58 Haines
for the placement of an external ventricu- and Walters combined the results of seven
lar drain include antibiotic prophylaxis at high-quality controlled trials into a meta-
the time of catheter insertion, placement analysis. A reduction of approximately 50%
of an antibiotic-impregnated catheter un- (p = 0.001) in infection risk was demon-
der sterile conditions, catheter exchange in strated when antibiotic prophylaxis was
the event of positive CSF culture demon- used. The infection rate in the prophylactic
strating CSF infection, and minimization of antibiotic group was 7%, compared with
catheter manipulation. 13% in the control group (p = 0.003). The
Similar principles apply to the insertion study also showed a correlation between
and maintenance of lumbar drains. Lumbar the efficacy of prophylactic antibiotics in
190
reducing the infection rate and the base- could be reduced at their hospital, where
line infection rate. Through the use of a MRSA was prevalent, with the use of peri-
regression equation, it was demonstrated operative vancomycin instead of cefazo-
that once the baseline infection rate fell be- lin.28 They categorized their institution as
low 5.5%, the efficacy of prophylactic anti- having a high prevalence of MRSA based on
biotics on the infection rate was negligible. published consensus guidelines suggesting
It is interesting to note that prophylactic that a high rate of MRSA transmission is in-
antibiotics have been found to reduce the dicated by a threshold of 0.5 new nosoco-
infection rate in clean neurosurgical pro- mial cases of MRSA per 100 admissions in a
cedures even with baseline infection rates hospital that has more than 500 beds.62 The
as low as 3%.58 The difference may relate to shunt infection rate was 4% in the patients
the ability of foreign body implants to har- treated with vancomycin, compared with
bor microorganisms and provide an envi- 14% in the patients who received cefazolin
ronment that makes the microorganisms (p = 0.03).28
less accessible to the antibiotic effect.58,59 In regard to the efficacy of prophylac-
Similarly, Langley et al performed a tic antibiotics in the implantation of other

meta-analysis of 12 randomized controlled foreign bodies in neurosurgical procedures
trials in patients who had undergone CSF (e.g., synthetic cranioplasties, intrathecal
shunt placement with random allocation catheters for drug delivery, deep brain and
either to perioperative systemic antibiot- epidural spinal cord electrodes), a paucity
ics or to no perioperative antibiotics. One of trials exists. Here, we can extrapolate
study achieved statistical significance on the principles gleaned from studies on an-
its own, and the other 11 studies had rela- tibiotic prophylaxis in CSF shunting and
tive risks in the same direction as the com- make the argument that theoretically, an-
bined analysis. In total, 1,359 patients had tibiotic prophylaxis under these circum-
been randomized, and the pooled results stances should also play a role in reducing
demonstrated a 50% (p = 0.0002) reduction infection rates.
in risk for subsequent CSF shunt infections
with the use of perioperative systemic an-
tibiotics.59 In the groups treated with pro- ■■ Spinal Neurosurgery
phylactic antibiotics, the shunt infection
rate averaged 6.8% (range, 1.9 to 17%).60 The vast majority of spinal neurosurgical
Ratilal et al also performed a meta- operations are clean elective operations.
analysis that included 17 trials and a total Patients in this group have the lowest in-
number of 2,134 patients.61 Their results trinsic rate of infection to begin with, and
confirmed that the use of systemic antibi- some have suggested that the balance be-
otic prophylaxis decreased the shunt infec- tween risk and benefit of antibiotic pro-
tion rate by approximately 50%. The results phylaxis may be swayed toward its harmful
of these studies show that antibiotic pro- and costly side effects. The available data
phylaxis is useful in reducing shunt infec- do not support this concern.
tion rates; however, the impact appears to Infection of the operated spine can un-
be marginal in conditions in which a low dermine its mechanical stability and ex-
baseline infection rate exists. tend to involve neural structures, leading
In terms of choosing the appropriate to debilitating deformity and compromise
perioperative prophylactic antibiotic, lo- of neurologic function. The potential of
cal resistance rates should guide decision such devastating consequences has se-
making. For example, the current preva- cured widespread acceptance of antibiotic
lence of MRSA among S. aureus isolates is prophylaxis before spinal surgeries in the
roughly 20 to 25%, but this varies among past three decades. Multiple studies have
institutions and communities.62 A ran- examined this question, but all have sig-
domized controlled trial by Tacconelli et nificant shortcomings. Taken together, they
al demonstrated the shunt infection rate indicate a trend toward a benefit of anti-
191
biotic prophylaxis for clean spine surgery. or against prophylactic antibiotics in such
The evidence supporting this policy is re- cases, as well as in cases of traumatic or
viewed below. spontaneous CSF leakage, is slim. When
Among the most important of the stud- Brodie conducted a meta-analysis of trials,
ies is that of Pavel et al,63 who demonstrated each individually failing to show a benefit
reduced infection rates after preoperative of antibiotic prophylaxis in posttraumatic
antibiotics for a variety of orthopedic pro- CSF fistulas, the results suggested a signifi-
cedures. The spinal surgery subgroup was cant reduction in infection from 2.5 to 10%
too small for the difference to reach statis- (p = 0.006).67 This study, however, included
tical significance. nonrandomized case series, and 73% of the
Rubinstein et al reported a double- blind patients received antibiotic prophylaxis.
randomized controlled trial comparing ce- Villalobos et al conducted a meta-analysis
fazolin with placebo in 141 patients under- in 1998, examining antibiotic prophylaxis
going clean spine surgery.64 They showed a in the setting of basilar skull fractures, and
12.7% infection rate in the placebo group concluded that there was no benefit to an-
versus 4.3% in the cefazolin group. tibiotic prophylaxis against meningitis.68
The strongest evidence has been derived Following those studies, several ran-
from a meta-analysis of multiple trials that domized controlled trials were conducted.
individually failed to show benefit.65 The A Cochrane review by Ratilal et al analyzed
results of six randomized controlled trials the utility of antibiotics in preventing men-
with 843 patients were pooled. There was a ingitis following basilar skull fractures. His
2.2% infection rate if antibiotics were given group was able to combine four random-
(10/451) and 5.9% (23/392) without prophy- ized controlled trials with a total of 208
laxis (p < 0.01). Barker’s review also showed patients, 109 in the treatment group and
that additional coverage of gram-negative 99 in the control group, but not all of them
organisms, as well as multiple dosing, did had a CSF leak. Given the data at hand, they
not show superiority over a single agent. were unable to demonstrate a benefit of
The specific antibiotic, repetitive dos- prophylactic antibiotics in patients with
ing, instrumented versus noninstrument- basilar skull fractures. Nevertheless, they
ed surgery, and the effect of additional risk concluded that there is insufficient evi-
factors have not been sufficiently studied to dence to support or refute such practice.69
allow firm conclusions to be drawn. Wat-
ters et al summarized the current evidence Topical Antibiotic Prophylaxis
in 2009 and put forward recommendations
regarding prophylaxis in spine surgery66: A Topical antiseptic prophylaxis is a well-
single dose of a broad-spectrum antibiotic, accepted procedure. The application of
covering gram-positive organisms and tak- alcohol and turpentine to wounds, in an
ing into account the spectrum of infectious attempt to prevent wound infections, was
agents at the local institution, given before described by 1700 bc in the Edwin-Smith
incision in time sufficient to reach ade- Papyrus. Antiseptic preparation of the skin
quate serum concentration, is the accepted before incision is a standard practice in
practice for this type of surgery. modern surgery.
After the advent of antibiotics in the
second half of the previous century, the
Cerebrospinal Fluid Fistulas
practice of powdering or spraying them
The role of antibiotics in preventing men- into wounds developed. It was Malis, how-
ingitis due to open communication be- ever, who by 1979 established the practice
tween the CSF and the nonsterile world of continuous antibiotic solution irrigation
remains a controversial subject. Leakage together with parenteral administration.70
of CSF following neurosurgical procedures He proceeded to demonstrate the benefit of
has long been recognized as a risk factor that practice but never separated the anal-
for postsurgical infection. The evidence for ysis of topical and parenteral approaches.
192
Although it has become a widely ac- References
cepted practice since then, it remains poorly 1. Zhu XL, Wong WK, Yeung WM, et al. A random-
studied, and solid evidence supporting or ized, double-blind comparison of ampicillin/
refuting it is lacking. Miller et al performed sulbactam and ceftriaxone in the prevention of
surgical-site infections after neurosurgery. Clin
a retrospective analysis demonstrating a Ther 2001;23(8):1281–1291 PubMed
reduction of stereotactic and functional 2. Gyssens IC. Preventing postoperative infections:
hardware infections after the injection of current treatment recommendations. Drugs
antibiotics into wounds before closure, in 1999;57(2):175–185 PubMed
3. Mangram AJ, Horan TC, Pearson ML, Silver LC, Jar-
addition to systemic prophylaxis and local vis WR; Centers for Disease Control and Prevention
irrigation.71 Alves and Godoy72 performed (CDC) Hospital Infection Control Practices Advisory
a review of the literature on this subject in Committee. Guideline for Prevention of Surgical Site
Infection, 1999. Am J Infect Control 1999;27(2):97–
2010, updating that of Haines,73 and summa-
132, quiz 133–134, discussion 96 PubMed
rized the few studies looking at this practice 4. Tadiparthi S. Prophylactic antibiotics for clean,
in neurosurgery, concluding that they are non-implant plastic surgery: what is the evi-
lacking strength in numbers and design. dence? J Wound Care 2008;17(9):392–394,
396–398 PubMed
Nevertheless, the simplicity, relative

5. Spencer RC. The role of antimicrobial agents in the
lack of toxicity, and superficial reasonable- aetiology of Clostridium difficile-associated dis-
ness of the practice make it a common one ease. J Antimicrob Chemother 1998;41(Suppl C):
in modern neurosurgery. When coupled 21–27 PubMed
6. Mukhtar S, Shaker H, Basarab A, Byrne JP. Prophy-
with implant material, such as CSF shunts lactic antibiotics and Clostridium difficile infec-
and other catheters, as well as deep brain tion. J Hosp Infect 2006;64(1):93–94 PubMed
stimulation electrodes and batteries, topi- 7. Malis LI, Ruberti RF, Kaufman AB, et al. Intra-
operative antibiotic prophylaxis. Surg Neurol
cal antibiosis is almost a universal practice. 1997;47(5):481–483 PubMed
Several general principles, extrapolated 8. Savitz MH, Malis LI. Prophylactic clindamycin
from theory and studies applied in other for neurosurgical patients. NY State J Med 1976;
surgical specialties, should be followed. 76(1):64–67 PubMed
9. Bullock R, van Dellen JR, Ketelbey W, Reinach SG. A
The antibiotic solution should be bacteri- double-blind placebo-controlled trial of periopera-
cidal against the flora present at the insti- tive prophylactic antibiotics for elective neurosur-
tution where it is applied, and antibiotics gery. J Neurosurg 1988;69(5):687–691 PubMed
10. B lomstedt GC, Kyttä J. Results of a randomized
with minimal potential for toxicity should
trial of vancomycin prophylaxis in craniotomy. J
be chosen. Penicillins should be avoided Neurosurg 1988;69(2):216–220 PubMed
when the cerebrum is exposed because 11. G eraghty J, Feely M. Antibiotic prophylaxis in
of their epileptogenic potential. Bacitracin neurosurgery. A randomized controlled trial. J
Neurosurg 1984;60(4):724–726 PubMed
and metronidazole, conversely, have been 12. S hapiro M, Wald U, Simchen E, et al. Randomized
shown to be the least likely to produce epi- clinical trial of intra-operative antimicrobial pro-
leptiform activity. phylaxis of infection after neurosurgical proce-
dures. J Hosp Infect 1986;8(3):283–295 PubMed
13. v an Ek B, Dijkmans BA, van Dulken H, van Furth
R. Antibiotic prophylaxis in craniotomy: a pro-
■■ Conclusion spective double-blind placebo-controlled study.
Scand J Infect Dis 1988;20(6):633–639 PubMed
14. Winkler D, Rehn H, Freckmann N, Nowak G, Her-
Antibiotic prophylaxis before surgery has rmann HD. Clinical efficacy of perioperative
been demonstrated to play a major role in antimicrobial prophylaxis in neurosurgery—a pro-
the avoidance of operative site infections spective randomized study involving 159 patients.
Chemotherapy 1989;35(4):304–312 PubMed
and has become the standard of practice.
15. Young RF, Lawner PM. Perioperative antibiotic
Because the rate of postoperative infections prophylaxis for prevention of postoperative neu-
in most neurosurgical procedures is low, rosurgical infections. A randomized clinical trial.
there is a paucity of evidence regarding J Neurosurg 1987;66(5):701–705 PubMed
16. Djindjian M, Lepresle E, Homs JB. Antibiotic prophy-
several aspects of perioperative antibiotic laxis during prolonged clean neurosurgery. Results
prophylaxis, including the ideal prophylac- of a randomized double-blind study using oxacillin.
tic antibiotic regimen and certain aspects J Neurosurg 1990;73(3):383–386 PubMed
of the timing of administration. 17. Barker FG II. Efficacy of prophylactic antibiotics
for craniotomy: a meta-analysis. Neurosurgery
1994;35(3):484–490, discussion 491–492 PubMed 193
18. Walstad RA, Hellum KB, Blika S, et al. Pharmaco- 33. M iles AA, Miles EM, Burke J. The value and dura-
kinetics and tissue penetration of ceftazidime: tion of defence reactions of the skin to the primary
studies on lymph, aqueous humour, skin blister, lodgement of bacteria. Br J Exp Pathol 1957;38(1):
cerebrospinal and pleural fluid. J Antimicrob Che- 79–96 PubMed
mother 1983;12(Suppl A):275–282 PubMed 34. G alandiuk S, Polk HC Jr, Jagelman DG, Fazio VW.
19. Friedrich H, Pelz K, Hänsel-Friedrich G. Lack of Re-emphasis of priorities in surgical antibiotic
penetration of cephacetril into the cerebro-spinal prophylaxis. Surg Gynecol Obstet 1989;169(3):
fluid of patients without meningitis. Infection 219–222 PubMed
1979;7(1):41–44 PubMed 35. Classen DC, Evans RS, Pestotnik SL, Horn SD,
20. Knoop M, Schütze M, Piek J, Drewelow B, Mund- Menlove RL, Burke JP. The timing of prophylactic
kowski R. Antibiotic prophylaxis in cerebrospinal administration of antibiotics and the risk of sur-
fluid shunting: reassessment of Cefotiam penetra- gical-wound infection. N Engl J Med 1992;326(5):
tion into human CSF. Zentralbl Neurochir 2007; 281–286 PubMed
68(1):14–18 PubMed 36. D iPiro JT, Cheung RP, Bowden TA Jr, Mansberger
21. Cherubin CE, Eng RH, Norrby R, Modai J, Hum- JA. Single dose systemic antibiotic prophylaxis of
bert G, Overturf G. Penetration of newer cepha- surgical wound infections. Am J Surg 1986;152(5):
losporins into cerebrospinal fluid. Rev Infect Dis 552–559 PubMed
1989;11(4):526–548 PubMed 37. N ooyen SM, Overbeek BP, Brutel de la Rivière A,
22. C adoz M, Denis F, Félix H, Diop Mar I. Treatment of Storm AJ, Langemeyer JJ. Prospective randomised
purulent meningitis with a new cephalosporin— comparison of single-dose versus multiple-dose
Rocephin (Ro 13-9904). Clinical, bacteriological cefuroxime for prophylaxis in coronary artery
and pharmacological observations in 24 cases. bypass grafting. Eur J Clin Microbiol Infect Dis
Chemotherapy 1981;27(Suppl 1):57–61 PubMed 1994;13(12):1033–1037 PubMed
23. Rehn H, Winkler D, Freckmann N, Nowak G, Her- 38. Korinek AM, Reina M, Boch AL, Rivera AO, De Bels
rmann H. Perioperative prophylaxis in neurosur- D, Puybasset L. Prevention of external ventricular
gery with ceftriaxone. Chemioterapia 1987;6(2, drain–related ventriculitis. Acta Neurochir (Wien)
Suppl):566–568 PubMed 2005;147(1):39–45, discussion 45–46 PubMed
24. Zhao JZ, Wang S, Li JS, et al. The perioperative use 39. S cheithauer S, Bürgel U, Ryang YM, et al. Prospec-
of ceftriaxone as infection prophylaxis in neu- tive surveillance of drain associated meningitis/

rosurgery. Clin Neurol Neurosurg 1995;97(4): ventriculitis in a neurosurgery and neurological
285–289 PubMed intensive care unit. J Neurol Neurosurg Psychia-
25. White RR IV, Pitzer KD, Fader RC, Rajab MH, Song try 2009;80(12):1381–1385 PubMed
J. Pharmacokinetics of topical and intravenous ce- 40. A ucoin PJ, Kotilainen HR, Gantz NM, Davidson R,
fazolin in patients with clean surgical wounds. Plast Kellogg P, Stone B. Intracranial pressure monitors.
Reconstr Surg 2008;122(6):1773–1779 PubMed Epidemiologic study of risk factors and infec-
26. Wang Q, Shi Z, Wang J, Shi G, Wang S, Zhou J. Postop- tions. Am J Med 1986;80(3):369–376 PubMed
eratively administered vancomycin reaches thera- 41. C amacho EF, Boszczowski I, Basso M, et al. In-
peutic concentration in the cerebral spinal fluid of fection rate and risk factors associated with in-
neurosurgical patients. Surg Neurol 2008;69(2): fections related to external ventricular drain.
126–129, discussion 129 PubMed Infection 2011;39(1):47–51 PubMed
27. Wang JF, Wang Q, Zhao LH, Shi GZ, Zhou JX. 42. M ayhall CG, Archer NH, Lamb VA, et al. Ven-
Blood-brain barrier penetration of cefepime after triculostomy-related infections. A prospective
neurosurgery. Chin Med J (Engl) 2007;120(13): epidemiologic study. N Engl J Med 1984;310(9):
1176–1178 PubMed 553–559 PubMed
28. Tacconelli E, Cataldo MA, Albanese A, et al. Van- 43. Wong GK, Poon WS, Wai S, Yu LM, Lyon D, Lam
comycin versus cefazolin prophylaxis for cerebro- JM. Failure of regular external ventricular drain
spinal shunt placement in a hospital with a high exchange to reduce cerebrospinal fluid infection:
prevalence of methicillin-resistant Staphylococcus result of a randomised controlled trial. J Neurol Neu-
aureus. J Hosp Infect 2008;69(4):337–344 PubMed rosurg Psychiatry 2002;73(6):759–761 PubMed
29. Whitby M, Johnson BC, Atkinson RL, Stuart G; 44. M uttaiyah S, Ritchie S, John S, Mee E, Roberts
Brisbane Neurosurgical Infection Group. The S. Efficacy of antibiotic-impregnated exter-
comparative efficacy of intravenous cefotaxime nal ventricular drain catheters. J Clin Neurosci
and trimethoprim/sulfamethoxazole in prevent- 2010;17(3):296–298 PubMed
ing infection after neurosurgery: a prospective, 45. R ivero-Garvía M, Márquez-Rivas J, Jiménez-Me-
randomized study. Br J Neurosurg 2000;14(1): jías ME, Neth O, Rueda-Torres AB. Reduction in
13–18 PubMed external ventricular drain infection rate. Impact
30. Stone HH, Hooper CA, Kolb LD, Geheber CE, of a minimal handling protocol and antibiotic-
Dawkins EJ. Antibiotic prophylaxis in gastric, bili- impregnated catheters. Acta Neurochir (Wien)
ary and colonic surgery. Ann Surg 1976;184(4): 2011;153(3):647–651 PubMed
443–452 PubMed 46. W ong GK, Ip M, Poon WS, Mak CW, Ng RY. Anti-
31. Polk HC Jr, Lopez-Mayor JF. Postoperative wound biotics-impregnated ventricular catheter versus
infection: a prospective study of determinant systemic antibiotics for prevention of nosocomial
factors and prevention. Surgery 1969;66(1): CSF and non-CSF infections: a prospective ran-
97–103 PubMed domised clinical trial. J Neurol Neurosurg Psy-
32. Burke JF. The effective period of preventive anti- chiatry 2010;81(10):1064–1067 PubMed
biotic action in experimental incisions and der- 47. Sandalcioglu IE, Stolke D. Failure of regular external
194 mal lesions. Surgery 1961;50:161–168 PubMed ventricular drain exchange to reduce CSF infection.
J Neurol Neurosurg Psychiatry 2003;74(11):1598– 60. R atial B, Costa J, Sampaio C. Antibiotic prophy-
1599, author reply 1599 PubMed laxis for surgical introduction of intracranial ven-
48. Alleyne CH Jr, Hassan M, Zabramski JM. The effi- tricular shunts. Cochrane Database Syst Rev 2006
cacy and cost of prophylactic and perioprocedural July 19;(3):CD005365
antibiotics in patients with external ventricular 61. L angley JM, LeBlanc JC, Drake J, Milner R. Efficacy
drains. Neurosurgery 2000;47(5):1124–1127, of antimicrobial prophylaxis in placement of ce-
discussion 1127–1129 PubMed rebrospinal fluid shunts: meta-analysis. Clin In-
49. McCarthy PJ, Patil S, Conrad SA, Scott LK. In- fect Dis 1993;17(1):98–103 PubMed
ternational and specialty trends in the use of 62. W enzel RP, Reagan DR, Bertino JS Jr, Baron EJ,
prophylactic antibiotics to prevent infectious Arias K. Methicillin-resistant Staphylococcus au-
complications after insertion of external ventric- reus outbreak: a consensus panel’s definition
ular drainage devices. Neurocrit Care 2010;12(2): and management guidelines. Am J Infect Control
220–224 PubMed 1998;26(2):102–110 PubMed
50. Blomstedt GC. Results of trimethoprimsulfa- 63. P avel A, Smith RL, Ballard A, Larson IJ. Prophy-
methoxazole prophylaxis in ventriculostomy and lactic antibiotics in elective orthopedic surgery:
shunting procedures. A double-blind randomized a prospective study of 1,591 cases. South Med J
trial. J Neurosurg 1985;62(5):694–697 1977;70(Suppl 1):50–55 PubMed
51. Ortiz R, Lee K. Nosocomial infections in neuro- 64. Rubenstein E, Findler G, Amit P, Shaked I. Periop-
critical care. Curr Neurol Neurosci Rep 2006;6(6): erative prophylactic cephazolin in spinal surgery. A
525–530 PubMed double-blind placebo-controlled trial. J Bone Joint

52. Wong GK, Poon WS, Lyon D, Wai S. Cefepime vs. Surg Br 1994;76(1):99–102
ampicillin/sulbactam and aztreonam as antibi- 65. Barker FG II. Efficacy of prophylactic antibiotic ther-
otic prophylaxis in neurosurgical patients with apy in spinal surgery: a meta-analysis. Neurosurgery
external ventricular drain: result of a prospective 2002;51(2):391–400, discussion 400–401 PubMed
randomized controlled clinical trial. J Clin Pharm 66. Watters WC III, Baisden J, Bono CM, et al; North
Ther 2006;31(3):231–235 PubMed American Spine Society. Antibiotic prophylaxis in
53. Schade RP, Schinkel J, Visser LG, Van Dijk JM, Voor- spine surgery: an evidence-based clinical guide-
molen JH, Kuijper EJ. Bacterial meningitis caused line for the use of prophylactic antibiotics in spine
by the use of ventricular or lumbar cerebrospi- surgery. Spine J 2009;9(2):142–146 PubMed
nal fluid catheters. J Neurosurg 2005;102(2): 67. Brodie HA. Prophylactic antibiotics for post-
229–234 PubMed traumatic cerebrospinal fluid fistulae. A meta-
54. Gardner P, Leipzig TJ, Sadigh M. Infections of me- analysis. Arch Otolaryngol Head Neck Surg
chanical cerebrospinal fluid shunts. Curr Clin Top 1997;123(7):749–752 PubMed
Infect Dis 1988;9:185–214 PubMed 68. V illalobos T, Arango C, Kubilis P, Rathore M. An-
55. Zentner J, Gilsbach J, Felder T. Antibiotic prophy- tibiotic prophylaxis after basilar skull fractures:
laxis in cerebrospinal fluid shunting: a prospec- a meta-analysis. Clin Infect Dis 1998;27(2):
tive randomized trial in 129 patients. Neurosurg 364–369 PubMed
Rev 1995;18(3):169–172 PubMed 69. R atilal B, Costa J, Sampaio C. Antibiotic prophy-
56. Schmidt K, Gjerris F, Osgaard O, et al. Antibiotic laxis for preventing meningitis in patients with
prophylaxis in cerebrospinal fluid shunting: a pro- basilar skull fractures. Cochrane Database Syst
spective randomized trial in 152 hydrocephalic Rev 2006;(1):CD004884 PubMed
patients. Neurosurgery 1985;17(1):1–5 PubMed 70. M alis LI. Prevention of neurosurgical infection
57. Wang EE, Prober CG, Hendrick BE, Hoffman HJ, Hum- by intraoperative antibiotics. Neurosurgery
phreys RP. Prophylactic sulfamethoxazole and trim- 1979;5(3):339–343 PubMed
ethoprim in ventriculoperitoneal shunt surgery. A 71. Miller JP, Acar F, Burchiel KJ. Significant reduction in
double-blind, randomized, placebo-controlled trial. stereotactic and functional neurosurgical hardware
JAMA 1984;251(9):1174–1177 PubMed infection after local neomycin/polymyxin applica-
58. Haines SJ, Walters BC. Antibiotic prophylaxis for tion. J Neurosurg 2009;110(2):247–250 PubMed
cerebrospinal fluid shunts: a metanalysis. Neuro- 72. A lves RV, Godoy R. Topical antibiotics and neu-
surgery 1994;34(1):87–92 PubMed rosurgery: have we forgotten to study it? Surg
59. Borges LF. Cerebrospinal fluid shunts interfere Neurol Int 2010;1(1):22
with host defenses. Neurosurgery 1982;10(1): 73. Haines SJ. Topical antibiotic prophylaxis in neurosur-
55–60 PubMed gery. Neurosurgery 1982;11(2):250–253 PubMed
195
15
Postoperative Intracranial Infections
Arya Nabavi, Frederike Knerlich-Lukoschus, and Andreas M. Stark
Postoperative infections in cranial neu- Besides open questions in epidemiol-

rosurgery are reported within a range of ogy, the rarity of postoperative infections
0.5 to 6.6%.1–3 An analysis of predisposing combined with the irregularities encoun-
conditions and risk factors, in addition to tered in reporting represents a challenge
sufficient preventative measures, should in evaluating and a still greater challenge
provide a solid basis for further evaluation in comparing prevention techniques with
of this problem. However, closer scrutiny sufficient statistical power.
of the literature before 19924–6 and the To obtain such information, examina-
contemporary literature, which provides tion of the literature for other surgical
the basis for this chapter, raises concern. specialties is useful.1,15–18 The Centers for
The rarity of this complication demands Disease Control and Prevention (CDC) has
high case numbers to permit conclusive anal- provided a working definition of surgical
ysis beyond anecdotal case reports. As such, wound infections, more precisely labeled
some studies combine the results of spinal as surgical site infections (SSIs), as a basis
and cranial (burr holes and open cranioto- for structured reporting.1,15,19,20 Risk factors
mies) cases to generate a single neurosurgi- for infection have been corroborated in
cal infection rate.3,7,8 When these subdivisions various series.1–3,7,8,10,17,21–24
are accounted for, only a few contemporary Only a few neurosurgical reports that
studies remain with sufficient case numbers address wound infections are structured
for a meaningful analysis of cranial postop- accordingly.2,7 Most publications report
erative infections. As a consequence, McClel- infection rates indiscriminately, preclud-
land could find only two recent neurosurgical ing further analysis, or consider only those
studies to include in a meta-analysis.9 Fur- complications that required reoperation,12,13
thermore, basic inconsistencies in adherence obscuring the true dimension of the prob-
to an antibiotic prophylaxis protocol (e.g., lem. Information with regard to risk factors,
incorrect timing, wrong or no prophylaxis, follow-up, and true infection rate remains
continuation at the surgeon’s discretion, vague. Larger studies that enable a more
regionally adapted unconventional combi- thorough investigation are infrequent.
nations8,10,11) and in reporting of infections McClelland and Hall3 analyzed 1,587
(wound or general infections,11 only infec- elective cranial cases performed by the
tions that were reoperated,12,13 classification senior author as a “single-surgeon” series.
of wound infections) prevent comparison. In For the 562 elective craniotomies, five in-
addition to these issues, potential detection fections were reported, resulting in an
error,14 referral bias, and unrecorded treat- infection rate of 0.89%. Korinek et al2 re-
ment at different institutions 12 may result in ported an overall infection rate of 6.6% in
miscalculation of the “true” infection rate. a single-center, “multiple-surgeon” study
with 4,578 craniotomies (emergency and hypotheses on decreased wound healing
elective). While the former study shows and a defective immune system have been
how under the best possible circumstances discussed. However, Kaye et al23 showed
infection rates can be lowered and almost that longitudinally, the risk for SSI increas-
eradicated, the latter most likely reflects es up to the age of 65, after which there is a
the challenge that confronts most neuro- decrease in a linear fashion at a rate of 1.1%
surgical units.2 per year.17,23
In this chapter, we review the contempo- Various patient-related characteristics
rary literature with respect to risk factors, can reasonably be identified as risk fac-
the classification of postoperative wound tors. Careful reevaluation may provide new
infections (SSIs), and potential methods for insights17 that will enable us to influence
future analysis. The specific postoperative preoperative states to reduce the hazard of
infections in cranial neurosurgery are dis- infections.
cussed within this framework.
Procedure-Related Risk Factors
15 Postoperative Intracranial Infections

Procedure-related risk factors can be
■■ R
isk Factors for Surgical
broadly categorized as local (related to the
Site Infections surgical site) or general (related to systemic
issues).18,25 Most of the local factors pertain
A multitude of factors have been identified
to site preparation: lack of preoperative
that result in SSI. Although information
cleansing (antiseptic shower); hair re-
remains contradictory on their respective
moval26–28 (type and timing, improper skin
validity, risk factors can be categorized as
preparation); and surgical techniques25 (ex-
patient- or procedure-related.17
cessive tissue damage, intraoperative place-
ment of chemotherapeutic wafers22,29).
Patient-Related Risk Factors
General issues include inappropriate an-
Patient-related risk factors include vul- tibiotic prophylaxis with regard to timing,
nerability due to metabolic states21 (e.g., reapplication, and choice2; hypothermia
diabetes mellitus); unbalanced nutritional and hypoxia; perioperative blood trans-
states (obesity, malnutrition manifested by fusion; and postoperative anemia.17 Spe-
weight loss and a low preoperative albumin cial risks in the neurosurgical population
level); tobacco use; specific exposure risks are implantation of foreign material (i.e.,
(infection at another site at the time of sur- ventriculoperitoneal shunts, dural substi-
gery, prolonged preoperative hospital stay, tutes); local radiation (causing subsequent
colonization with Staphylococcus aureus); decreased vascularity of the skin) and che-
reduced defensive capacity (impaired im- motherapy (prior treatment24 or intracavi-
mune response, corticosteroid use, irradia- tary wafers22); and early reoperation. 2
tion to the surgical field); and age. The single most important procedure-
Although these factors may be interre- related risk factor for a postoperative in-
lated and thus not valid as independent risk fection in neurosurgery is cerebrospinal
factors, they warrant heightened attention. fluid (CSF) leakage.2,7,8,13,30–33 A multicenter
Furthermore, a closer investigation of these study by Korinek et al10 identified emer-
risk factors may yield potential approaches gency surgery, clean–contaminated class
to reduce or prevent their impact.17 For in- of surgery, length of surgery of more than
stance, diabetes is not in itself a risk factor3 4 hours, and reoperation as additional risk
for infection in the absence of preoperative factors for infection. In the subsequent
hyperglycemia.17 Therefore, metabolic cor- single-center study,2 CSF leakage remained
rection to normoglycemia reduces the in- the most important risk factor (odds ratio,
fection risk in every patient, irrespective of 11.48), whereas neither emergency sur-
the underlying disorder. Advanced age has gery nor contamination class was found to
also been considered a risk factor. Various be statistically significant. However, surgi-
197
cal diagnosis, surgeon, early reoperation, than those for other cranial procedures. To
and surgery lasting more than 4 hours were account for this discrepancy, the cases in
identified as independent risk factors. Me- the clean subdivision have been separated
ningiomas (76/729, or 10%) and metastases into those with and those without foreign
(29/183, or 15%) accounted for 34.7% of 303 body implantation.34 Although the ques-
infections in 4,578 surgeries, making the tion remains of how much material con-
surgical diagnosis an independent risk fac- stitutes the difference between clean and
tor. The reason for the high incidence of in- clean with foreign body, this seems like a
fection in metastases remains unclear, but reasonable subdivision, in particular with
it has been attributed to altered immune regard to shunt procedures, cranioplasty,
defenses. Although in meningiomas2,13 the and surgeries involving dural substitutes.34
individual circumstances are not specified, The term clean–contaminated describes
the most likely explanation is the potential procedures in which the respiratory or
for CSF leakage after dural reconstruction. alimentary membranes are entered under
Because surgery is the required event controlled conditions, as in trans-sphe-
for SSI, it is not surprising that the sur- noidal or endoscopic approaches30,33 to the
geon plays an important role. Although it skull base. With proper attention to an-
is misleading to describe the surgeon as tiseptic techniques, these cases can have
a general risk factor,2 there are interest- similar infection rates (1.8%),33 as can clean
ing implications. In the available reports, elective craniotomies. Contaminated and
single-surgeon studies3 provide the lower dirty procedures are rarely performed in
end of the infection range, and multicenter neurosurgery and are mostly associated
studies2 determine the upper end. Cushing with emergency situations, which in them-
(1915) pointed out the surgeon’s pivotal selves represent a risk factor.
role in postoperative infections: “Certainly
infections cannot be attributed to the inter-
vention of the devil but must be laid at the ■■ Shaving of the Surgical Site
surgeon’s door.” It is important to interpret
this statement properly; it is neither accu- Hair has previously been considered a risk
satory nor placing blame, but rather repre- factor for wound infections. However, evi-
sents a challenge to the individual surgeon dence exists that shaving itself poses a risk.
to live up to this essential obligation. A clear association between the manner of
Two other aspects of the surgical site hair removal and SSI has been found in that
that warrant a more elaborate discussion the use of a razor results in a higher risk for
are classification of the wound and shaving SSI than do clippers or a depilation cream.26
of the operative field. A razor produces microscopic abrasions of
the skin, which are subsequently colonized
by bacteria. Shaving the surgical site the
■■ Wound Categories evening before surgery poses the greatest
risk for SSI because of the extended pe-
The National Academy of Sciences has riod in which bacterial colonization can
proposed the widely accepted classifica- occur, and this practice has largely been
tion of the contamination status of sites abandoned.
of surgery as clean, clean–contaminated, A comprehensive article by Winston26
contaminated, and dirty.15 With the correct offers an enjoyable analysis of this issue of
administration of antibiotic prophylaxis hair removal. Hair can be rendered void of
and appropriate aseptic technique, the infecting organisms by using proper local
infection rates are lowered in all catego- preparation and surgical scrubbing. The in-
ries.1,15,20,21 In neurosurgery, most cases are fecting flora is found in the deeper layers of
considered clean; however, reported infec- the skin, which are not affected by shaving.
tion rates for shunt implantations, which There is no increase in infection rates if the
are considered clean surgeries, are higher hair is not removed. Subsequently, various
198
groups have published their data on sur- ■■ S
urgical Site Infections in
gery without shaving.26–28 A prerequisite to Postoperative Cranial Surgery
prevent infection is thorough preparation
of the site before surgery with shampoo- To distinguish general postoperative from
ing and antiseptic cleansing. Furthermore, wound infections, the latter are appropri-
in closing the wound, the surgeon must ately termed SSIs. 19 The neurosurgical site
ensure that no hair remains in the wound, is divided into extra- and intradural parts.
thus making the final part of the procedure Extradural infections involve every level
more involved. Staples and interrupted from the skin to the dura mater, including
sutures26–28 are used to close the skin. The the bone flap. Intradural infections can be
studies were carefully designed and should localized to the subdural space (empyema)
be read attentively before a “no-shave” pol- or to an intracerebral location (abscess),
icy is adopted. Bekar et al27 administered or they can be generalized (meningitis
antibiotics for 3 days after surgery. This and ventriculitis). To allow a more thor-
practice may have resulted in a skewed rep- ough analysis of SSIs, the CDC introduced
resentation of the true infection risk posed a classification19 that differentiates be-

by not shaving. Tokimura et al28 adminis- tween incisional (superficial and deep) and
tered antibiotics for 24 hours and had the organ-related SSIs. In neurosurgery, inci-
patients’ hair washed on the second, fourth, sional SSIs represent extradural infections.
and sixth postoperative days. Accordingly, Organ-related SSIs include every intradural
all studies that pertain to “no-shaving” rou- infection (subdural empyema, intracere-
tines instituted additional safety measures. bral abscess, meningitis, and ventriculitis).
Thus, “not shaving” poses no additional risk In the CDC definition, organ SSIs are speci-
for infection if proper precautions are taken. fied as “all infections . . . [which] . . . involve
any part of the anatomy other than the in-
cision opened or manipulated during the
■■ E
stimating the Risk for operative procedure,”19 which includes the
Surgical Site Infection: cranial opening. Thus, epidural abscess and
NNIS Risk Index bone flap infection are considered deep
wound infections, whereas osteomyelitis
In an effort to identify patients with a sus- as a CDC organ/space SSI refers to orthope-
ceptibility to postoperative infection, the dic surgery.
CDC (National Nosocomial Infections Sur- Although this clear categorization of
veillance [NNIS] system) developed a risk location can facilitate appropriate report-
index, which has been validated and found ing, a gray zone exists for potential under-
to correlate well with infection rates.15 The reporting. In the neurosurgical literature,
risk index is based on an ASA (American a particularly pragmatic approach is taken
Society of Anesthesiologists) preoperative whereby only those SSIs that required reop-
assessment, the wound category, and the eration are considered. This practice covers
duration of surgery (75th percentile of the only those complications with immediate
NNIS data for craniotomies rounded to the serious consequences, whereas “near-com-
nearest whole number of hours: 4 hours). plications” such as superficial SSIs treated
The index is divided into four categories (0 on the ward (e.g., additional stitches, lum-
to 3), which correlate with increasing risk bar drainage for CSF collections without
for postoperative wound infections. The leakage) may be incompletely reported.
categories are calculated by adding one However, these near-complications or inci-
point for each of the following when pres- dents allow us to understand and address
ent: an ASA score of 3, 4, or 5; contami- the issue of SSI more comprehensively. In
nated or dirty wounds; and a duration of risk management and prevention, special
surgery exceeding 4 hours. This NNIS risk emphasis is given to near-incidents, which
score allows an estimate of the risk for de- are more frequent than actual events and
veloping an SSI.1,10,20 therefore represent a larger database. This 199
more extensive pool of information facili- pronounced ring enhancement. To plan
tates the analysis of potential risk factors the surgical procedure, the extent of the
and the assessment of surgical and preven- infection must be defined. The increased
tive techniques. availability of magnetic resonance (MR)
Additional concern exists that SSIs may imaging provides further structural and
be underreported because of cases that are pathophysiologic (perfusion) information.
not detected by the surgeon,14 as well as Most often, the offending organisms
infections that occur after discharge7,10,16,35 are gram-positive skin flora (i.e., coagu-
and are handled either on an outpatient lase-negative staphylococci, S. aureus, and
basis or at other institutions. This is par- Propionibacterium acnes). Various reports
ticularly relevant for infection of the bone on rare and resistant bacterial strains em-
flap, which may manifest months after phasize the importance of adhering to the
surgery.6 With shorter hospital stays and general principles of antibiotic prophylaxis
increased patient transfer to specialized and of coordinating treatment closely with
centers,12 referral and admission patterns microbiologists. Fungal SSIs are rare but
may indeed result in problems with ac- should not be disregarded.
curately reporting SSIs. Patient transfer, Although incisional and organ SSIs mani-
which is less developed in Europe, has to be fest at different time intervals after surgery,
considered when infection rates9 are com- the range is too wide to provide a solid ba-
pared by countries or continents. sis for differential diagnosis. In a population
The CDC criteria for wound infection of 2,944 patients in a multicenter study,10
include “purulent discharge” and the “sur- scalp infections (5 ± 9 days; median, 13
geon’s impression” of the wound as key days) and meningitis/ventriculitis (10 ± 8

features. Infections present mostly with days; median, 7 days) occurred earlier than
local signs of inflammation. Fever is an intradural infections (empyema and ab-
explicit symptom, but in milder courses scess, 25 ± 31 days; median, 15 days), with
of infection, temperature elevation can be the longest latency seen for bone flap in-
either absent or slight. Neurologic symp- fection (42 ± 56 days; median, 27 days). In
toms in intracranial infections range from a single-institution2 follow-up study with
headaches to altered mental status and fo- a larger population of 4,578 patients, the
cal deficits. authors corroborated the order with time
Currently, the most useful postopera- to manifestation—with, however, an even
tive laboratory parameter is the C-reactive larger range (mean time between surgery
protein (CRP) level.36–38 Although elevated and onset of infection in days: meningitis,
levels are not surprising after surgery (cor- 12 ± 14; scalp infection, 23 ± 51; brain ab-
relating with tissue damage), sustained el- scess or empyema, 25 ± 27; bone flap, 118 ±
evation beyond the fourth day or renewed 157), reemphasizing the long latency period
elevation after normalization should raise for bone flap infection.
suspicion for infection. In the presence of
neurologic symptoms, imaging is indicated
to assess for the presence of intracranial ■■ Incisional Surgical Site
suppuration. Computed tomography (CT)
is the most readily available imaging mo-
Infections
dality. Contrast-enhanced CT provides a Incisional SSIs are subdivided into superfi-
firm basis for the diagnosis of intracranial cial and deep infections.19
and epidural infectious complications. Al-
though nonspecific contrast enhancement Superficial Incisional Surgical Site
may appear a few days postoperatively,
Infections
when considered together with clinical
suspicion and laboratory findings, the re- The CDC defines superficial incisional wound
sults rarely remain ambiguous. Generally, infections as “. . . infection . . . [which] . . .
infections present as fluid collections with occurs within 30 days after the operative
200
procedure and involves only skin and subcu- identified 77 of 4,578 patients (1.68%) as
taneous tissue of the incision and at least one having bone flap infection. Dashti et al12 re-
. . . [of the following] . . .: purulent discharge operated on 22 patients for this diagnosis
from the superficial incision/organisms iso- among 16,540 craniotomies over 10 years.
lated/signs of infection/diagnosis by the sur- Considering that bone flaps are devascu-
geon or attending physician. (Stitch abscess larized and that 50% of flaps lifted for cra-
is not an SSI).” Korinek et al2 reported 191 niotomy are contaminated29 (albeit with
scalp infections in 4,578 patients. Because few colony-forming units), this low rate is
multiple infection sites per patient could be remarkable.
recorded, it remains unclear how many scalp The clinical symptoms are limited, usu-
infections were isolated or associated with ally without headache and neurologic
deeper infections. Generally, if not associ- signs; local symptoms of wound infection
ated with deeper infections, incisional SSIs are often present. An epidural abscess can
can be managed by local measures. Aware- develop local mass effect, causing focal
ness, prevention, and immediate treatment neurologic deficit. Fever can occur but is
of these infections can prevent progression. not obligatory for the diagnosis. Manifesta-

Most patients with an epidural abscess had tion of bone flap infection can be delayed.
a previous superficial wound infection.5,39,40 The reported mean presentation time lies
Although bacteriologic samples are manda- beyond 30 to 40 days and up to 180 days
tory, these usually represent noncausative after surgery.2,5,6,29,40,42
skin flora. Surgical débridement with removal of
foreign material is mandatory, as is ob-
Deep Incisional Surgical Site Infections taining a specimen for microbiological
analysis. Subsequently, antibiotic irriga-
Deep incisional wound infections are “. . . tion and a “ball pen” ultrasonic aspirator
infections within 30 days after the opera- (personal experience) are employed to
tive procedure if no implant is left in place clean the surgical site. Intradural inspec-
or within 1 year, if implant is in place and tion should be avoided unless the dura ap-
infection involves the deep soft tissue and pears tense. 6 With prior surgery, however,
one of the following: purulent discharge/ deeper extension of the epidural infection
spontaneously dehisces or opened because should be suspected. Preoperative MR im-
of fever, local pain, or tenderness/patholog- aging is helpful in planning the extent of
ical, radiological, or intraoperative proof/ the operation. Postoperatively, antibiot-
diagnosis by physician.” ics are administered according to culture
Deep incisional infections should be results. In the setting of bone infection, a
inspected in the operating room with protracted course of antibiotics is usually
cleaning, débridement, local antiseptic administered in accordance with general
techniques, and readaptation. In our prac- and local guidelines.
tice, we apply a specially constructed ball With the surgical evacuation of pus, the
tip ultrasonic aspirator for wound débride- standard recommendation is to remove
ment and local antibacterial effect through the contaminated bone.5,6,39,40 Cranioplasty
the cavitation (unpublished data). usually is planned 6 months after removal.
Efforts to salvage the bone in posi-
tion have recently yielded encouraging
■■ B
one Flap Infection with results. It is evident that antibiotic treat-
Epidural Abscess ment alone is insufficient, and various
surgical methods have been tested. Thor-
Bone flap infections and epidural abscesses ough surgical débridement resulted in
are deep incisional infections. Hlavin et al the long-term resolution of infection in
reported on 23 patients over a period of 11 11 of 13 uncomplicated cases.43 In more
years with postoperative epidural abscess complex cases, a “wash-in, wash-out in-
and bone flap infection.39,41 Korinek et al2 dwelling antibiotic irrigation system” was
201
employed, resulting in complete resolu- ■■ Subdural Empyema
tion in 11 of 12 patients.44 However, if the
bone flap cannot be salvaged, immediate Subdural empyema is infrequently en-
reconstruction with titanium mesh may countered after surgery. In the largest se-
be an alternative. After extensive surgical ries of subdural empyema, only 4 of 699
débridement, this approach was success- cases occurred postoperatively.45 Hlavin
ful in 10 of 12 patients.42 Although these et al identified 11 patients with postop-
measures may present good alternatives erative suppuration involving the subdu-
after individual careful consideration, ral space over 11 years (3 purely subdural
the numbers are too small to permit their empyemas; 1 combined with an intrace-
general endorsement in the treatment of rebral abscess; 7 patients with subdural
bone flap infections. empyema and epidural abscess that were
regarded as continuous from the epidur-
al to the subdural space).39 Dashti et al12
■■ O
rgan/Space Surgical Site found 7 patients with subdural empyema.
However, because multiple sites were af-
Infections fected in their 50 patients with intracranial
The CDC defines organ/space SSI as follows: infections (among a total of 16,540 cases),
“An organ/space SSI involves any part of the those were not isolated infections.
anatomy other than the incision, opened or Spontaneous subdural empyema (Fig.
manipulated during the operative proce- 15.1) generally follows a prodromal infec-
dure, with infection within 30 days, if no tion, most often of the adjacent air-filled
implant is left in place and . . . [one of the

following] . . .: purulent discharge/organ-
isms cultured/an abscess or other evidence
of infection on direct reexamination by the
surgeon.”
The microbiological spectrum of these
infections encompasses the most frequent
offenders: coagulase-negative staphylococ-
ci, S. aureus, and P. acnes. However, gram-
negative and atypical bacteria (documented
by a plethora of case reports) are also im-
portant. Postoperative subdural suppura-
tion should raise concern with regard to
unsuspected sources of bacteremia or com-
munication with air-filled sinuses.5,6,39–41
These infections encompass localized
subdural empyema and intracerebral ab-
scesses within the resection cavity, as well
as generalized infections (i.e., meningitis
and ventriculitis). Because the subdural
space and post-resection cavity may be in-
terconnected, concomitant empyema and
abscess may result.39 Thus, subdural em-
pyema and intracerebral abscess are often
discussed together.2 However, some stud- Fig. 15.1 Contrast-enhanced axial T1-weighted
ies differentiate between the two clinical magnetic resonance image demonstrates a subdural
empyema located over the left hemisphere in a pa-
entities, permitting a rough estimate39 of
tient with fever and chronic sinusitis. (Figure courtesy
their respective incidence. of Walter A. Hall, MD, MBA.)
202
sinuses. Subsequent spread into the subdu- Fortunately, when it occurs as a post-
ral compartment with the rapid accumu- operative complication, the progress and
lation of pus in preformed spaces leads to presentation of this entity are often less
rapid neurologic deterioration, mandating aggressive.39 This is attributed to the post-
urgent diagnosis and subsequent surgery. operative formation of membranes that
Septa can compartmentalize the subdu- protect the cortex and limit the extension
ral space, making the surgical treatment of the empyema.41 The main symptoms are
challenging (Fig. 15.2). Therefore, a com- local pain and tenderness at the surgical
mon recommendation in these entities is site. Recurrent seizures and mild neuro-
to remove the pus through a craniotomy logic deficits should draw attention to this
because burr holes do not provide access possible complication and warrant imag-
for sufficient drainage.40,46 Subdural em- ing. Hlavin et al found 30% of their CT scans
pyema represents a surgical emergency, inconclusive. However, this statement per-
with a high rate of morbidity (10 to 20% tains to scans acquired before 1994; more-
of patients develop purulent meningitis, over, 50% of those imaging studies were
and 10 to 25% have an associated intrapa- done without contrast.39,41 Contemporary

renchymal abscess) and mortality. Early CT with contrast should provide enough
recognition and treatment are the main information for the diagnosis. Additionally,
factors necessary for a good clinical out- MR imaging provides structural as well as
come.5,39,41,46 Thrombosis of cortical vessels perfusional information.
with subsequent venous infarction may ac- Treatment is immediate surgical evacu-
celerate the already rapid clinical decline.41 ation by repeat craniotomy. Antibiotics
alone are ineffective. One should be pre-
pared to enlarge the cranial opening to
reach all potential “pockets” of purulence
if imaging suggests a wider extension of
the empyema. Where the arachnoid is
breached, a resection, which would endan-
ger the underlying cortex and vessels,39,41
should be avoided. As much pus as is acces-
sible should be removed. Gross total evac-
uation of the empyema is a prerequisite
for successful antibiotic treatment. After
treatment is begun with a broad spectrum
of antibiotics, targeted treatment should
be initiated subsequent to microbiological
differentiation.
■■ Intracerebral Abscess
Postoperative intracerebral abscesses are
rare (percentage of abscesses among total
number of craniotomies: 0.53% (3/556) 3;
0.17% (31/18,600) 47; and 0.05% (8/16,540).12
This complication occurs primarily in the
Fig. 15.2 Axial contrast-enhanced computed tomo- immediate postoperative period and pres-
graphic scan of the brain shows a septated subdural ents with nonspecific symptoms of men-
empyema over the right frontal lobe. There is also pu- ingitis and clinical deterioration. A new
rulence in the interhemispheric fissure. (Figure cour- neurologic deficit, normal or elevated tem-
tesy of Walter A. Hall, MD, MBA.)
203
perature, and progressively impaired levels cur. The CRP level rises sharply. Cerebral
of consciousness warrant imaging to obtain imaging should be obtained to rule out local
a diagnosis. In postoperative abscesses, the causative SSI as well as postoperative mass
frequency of gram-negative and polymi- lesions. After contraindications have been
crobial etiologies complicates subsequent excluded, lumbar puncture should be per-
antibiotic therapy.40,47 formed to acquire material for bacteriology.
The treatment of postoperative abscesses, A broad-spectrum antibiotic combination
unlike that of spontaneous cases, requires should then be initiated and subsequently
open surgical reexploration of the surgi- changed according to the microbiology cul-
cal site5,12,13,40,47 to obtain viable specimens, ture results.5,49 If aseptic meningitis is diag-
drain the abscess, and inspect and clean nosed, antibiotics should be discontinued.
the resection cavity. Leaving a drain inside In this condition, corticosteroids relieve the
the cavity is not recommended. Antibiotic meningeal inflammatory response.49
treatment should be initiated as a broad- The most common risk factor for bacte-
spectrum combination and continued ac- rial meningitis (organ SSI) is persistent CSF
cording to microbiological differentiation. leakage.2,7,31 CSF cushions without leakage
An additional noninfectious differential are mostly treated successfully by conser-
diagnosis for ring-enhancing lesions with- vative means. However, fistulas should be
in the operative cavity has occurred with addressed surgically when diagnosed to
more aggressive treatment for gliomas. prevent any form of SSI. Under special cir-
So-called pseudo-progression, with new cumstances, after careful assessment of the
contrast-enhancing tissue due to concomi- intraoperative conditions and an evalua-
tant radiation and chemotherapy, may be tion of the extent of CSF leakage, a short-
distinguished by its delayed time course, term conservative treatment with lumbar
silent clinical presentation, and patchy ap- puncture or drain may be attempted to
pearance on imaging. avoid reopening the surgical site. However,
Chemotherapy wafer implantation may lumbar or ventricular drains are risk fac-
lead to an enlarging resection cavity that tors by themselves.49,50 In these cases, close
presents with neurologic changes due to clinical and laboratory observation is nec-
the mass lesion.48 On imaging, homoge- essary.50 There is no consensus with regard
neous ring enhancement with perifocal to prophylactic antibiotics.
edema may meet the criteria for the diag- Definitive surgical closure of the CSF leak
nosis of an abscess. However, the smooth is preferable in most cases. With persistent
and linear-appearing contrast ring should CSF leakage, the surrounding inflammation
raise suspicion that this might be a nor- will increase, complicating subsequent
mal reaction after local chemotherapy. In wound closure. Foreign material should be
this case, symptoms resolve with a short removed during revision surgery. Prepara-
course of high-dose dexamethasone. Sub- tions should be made to harvest fascia lata
sequently, the enhancement decreases and and umbilical fat for dural reconstruction.
the cavity contracts over the course of sev-
eral weeks. Occasionally, puncture of the
pseudocyst and rarely implantation of a ■■ Summary and Conclusion
reservoir are needed.
Postoperative infections in cranial neu-
rosurgery are rare. They encompass bone
■■ Meningitis flap infection, epidural and intracerebral
abscesses, subdural empyema, and men-
Postoperative meningitis may be either ingitis. Meningitis can generally be treated
aseptic or bacterial in origin.49 This infec- with antibiotics, but the other SSIs require
tion manifests within a few days after sur- surgical treatment.
gery. Classic signs, such as nuchal rigidity, The single most important risk factor for
alteration of consciousness, and fever, oc- the development of SSI is CSF leakage.2,7,8,13
204
Further procedural risk factors are the fol- 2. Korinek AM, Golmard JL, Elcheick A, et al. Risk
factors for neurosurgical site infections after cra-
lowing: absent or inadequate antibiotic
niotomy: a critical reappraisal of antibiotic pro-
prophylaxis, longer duration of surgery, phylaxis on 4,578 patients. Br J Neurosurg 2005;
implantation of foreign materials, early re- 19(2):155–162 PubMed
operation, and irradiated skin.2,3,7,8,13 Hair 3. McClelland S III, Hall WA. Postoperative central
nervous system infection: incidence and associ-
removal does not show advantages over ated factors in 2111 neurosurgical procedures.
unshaven surgical sites.26 Clean and clean– Clin Infect Dis 2007;45(1):55–59 PubMed
contaminated wound categories do not 4. Blomstedt GC. Craniotomy infections. Neurosurg
have any impact if the surgical site is prop- Clin N Am 1992;3(2):375–385 PubMed
5. Hall WA. Cerebral infectious processes. In: Loftus
erly prepared.2,30,33 CM, ed. Neurosurgical Emergencies. Vol 1. Park
General adherence to CDC wound and Ridge, IL: American Association of Neurological
SSI definitions15,19 provides a basis for the Surgeons; 1994:165–182
6. Olsen JJ, Bingaman KD. Cranial bone flap infec-
structured reporting of postoperative tions and osteomyelitis of the skull. In: Osenbach
wound infections. Still, because of their RK, Zeidman SM, eds. Infections in Neurological
scarcity, gathering comprehensive infor- Surgery. Philadelphia, PA: Lippincott–Raven Pub-
mation on the occurrence, causes, and pre- lishers; 1999:65–83

7. Lietard C, Thébaud V, Besson G, Lejeune B.
vention of SSIs remains challenging. Risk factors for neurosurgical site infections:
In neurosurgery, there is a considerable an 18-month prospective survey. J Neurosurg
variation in reported cranial postopera- 2008;109(4):729–734 PubMed
8. Valentini LG, Casali C, Chatenoud L, Chiaffarino F,
tive infection rates, increasing from single-
Uberti-Foppa C, Broggi G. Surgical site infections
surgeon series3 to series with only elective after elective neurosurgery: a survey of 1747 pa-
cases8 to less selective multiple-center10 tients. Neurosurgery 2008;62(1):88–95, discus-
and multiple-surgeon studies.2 However, a sion 95–96 PubMed
9. McClelland S III. Postoperative intracranial neu-
comparison of only these rates disregards rosurgery infection rates in North America versus
differences in data accumulation.9 Regard- Europe: a systematic analysis. Am J Infect Control
ing postoperative infections in cranial neu- 2008;36(8):570–573 PubMed
rosurgery, Bloomsted had already stated 10. Korinek AM; Service Epidémiologie Hygiène et
Prévention. Risk factors for neurosurgical site infec-
in 1992 that “… incidence rates should be tions after craniotomy: a prospective multicenter
read with skepticism.” Various reasons for study of 2944 patients. The French Study Group of
this cautious assessment have been high- Neurosurgical Infections, the SEHP, and the C-CLIN
Paris-Nord. Neurosurgery 1997;41(5):1073–1079,
lighted in this chapter. discussion 1079–1081 PubMed
For future reporting, adherence to the 11. Sharma MS, Vohra A, Thomas P, et al. Effect of risk-
locations summarized in this chapter stratified, protocol-based perioperative chemopro-
would enable a more comprehensive anal- phylaxis on nosocomial infection rates in a series
of 31,927 consecutive neurosurgical procedures
ysis of SSIs across studies in regard to their (1994-2006). Neurosurgery 2009;64(6):1123–
occurrence, respective risk factors, and 1130, discussion 1130–1131 PubMed
prevention. Presently, the surgeon remains 12. D ashti SR, Baharvahdat H, Spetzler RF, et al. Oper-
ative intracranial infection following craniotomy.
the most crucial element in preempting
Neurosurg Focus 2008;24(6):E10 PubMed
SSIs. Control of the general operating room 13. Lassen B, Helseth E, Rønning P, et al. Surgical mortali-
situation, careful case preparation, adher- ty at 30 days and complications leading to recranioto-
ence to antiseptic principles, minimiza- my in 2630 consecutive craniotomies for intracranial
tumors. Neurosurgery 2011;68(5):1259–1268, dis-
tion of tissue damage, operating in a timely cussion 1268–1269 PubMed
fashion, and meticulous wound closure are 14. H eipel D, Ober JF, Edmond MB, Bearman GM. Sur-
all within the surgeon’s dominion. gical site infection surveillance for neurosurgical
procedures: a comparison of passive surveil-
lance by surgeons to active surveillance by in-
References fection control professionals. Am J Infect Control
1. G
aynes RP, Culver DH, Horan TC, Edwards JR, Rich- 2007;35(3):200–202 PubMed
ards C, Tolson JS. Surgical site infection (SSI) rates 15. C ulver DH, Horan TC, Gaynes RP, et al; National
in the United States, 1992-1998: the National Nosocomial Infections Surveillance System. Sur-
Nosocomial Infections Surveillance System basic gical wound infection rates by wound class, op-
SSI risk index. Clin Infect Dis 2001;33(Suppl 2): erative procedure, and patient risk index. Am J
S69–S77 PubMed Med 1991;91(3B):152S–157S PubMed
205
16. Kasatpibal N, Jamulitrat S, Chongsuvivatwong 32. D ubey A, Sung WS, Shaya M, et al. Complications
V. Standardized incidence rates of surgical site of posterior cranial fossa surgery—an institu-
infection: a multicenter study in Thailand. Am J tional experience of 500 patients. Surg Neurol
Infect Control 2005;33(10):587–594 PubMed 2009;72(4):369–375 PubMed
17. Talbot TR, Schaffner W. Relationship between age 33. K ono Y, Prevedello DM, Snyderman CH, et al.
and the risk of surgical site infection: a contem- One thousand endoscopic skull base surgical
porary reexamination of a classic risk factor. J In- procedures demystifying the infection potential:
fect Dis 2005;191(7):1032–1035 PubMed incidence and description of postoperative men-
18. Owens CD, Stoessel K. Surgical site infections: ep- ingitis and brain abscesses. Infect Control Hosp
idemiology, microbiology and prevention. J Hosp Epidemiol 2011;32(1):77–83 PubMed
Infect 2008;70(Suppl 2):3–10 PubMed 34. Narotam PK, van Dellen JR, du Trevou MD, Gouws
19. Horan TC, Gaynes RP, Martone WJ, Jarvis WR, E. Operative sepsis in neurosurgery: a meth-
Emori TG. CDC definitions of nosocomial surgical od of classifying surgical cases. Neurosurgery
site infections, 1992: a modification of CDC defi- 1994;34(3):409–415, discussion 415–416 PubMed
nitions of surgical wound infections. Am J Infect 35. S ands K, Vineyard G, Platt R. Surgical site infec-
Control 1992;20(5):271–274 PubMed tions occurring after hospital discharge. J Infect
20. Mangram AJ, Horan TC, Pearson ML, Silver LC, Jar- Dis 1996;173(4):963–970 PubMed
vis WR; Centers for Disease Control and Prevention 36. B engzon J, Grubb A, Bune A, Hellström K, Lind-
(CDC) Hospital Infection Control Practices Advisory ström V, Brandt L. C-reactive protein levels fol-
Committee. Guideline for prevention of surgical site lowing standard neurosurgical procedures. Acta
infection, 1999. Am J Infect Control 1999;27(2):97– Neurochir (Wien) 2003;145(8):667–670, discus-
132, quiz 133–134, discussion 96 PubMed sion 670–671 PubMed
21. M alone DL, Genuit T, Tracy JK, Gannon C, Napoli- 37. M irzayan MJ, Gharabaghi A, Samii M, Tatagiba
tano LM. Surgical site infections: reanalysis of risk M, Krauss JK, Rosahl SK. Response of C-reac-
factors. J Surg Res 2002;103(1):89–95 PubMed tive protein after craniotomy for microsurgery
22. M cGovern PC, Lautenbach E, Brennan PJ, Lustig RA, of intracranial tumors. Neurosurgery 2007;
Fishman NO. Risk factors for postcraniotomy sur- 60(4):621–625, discussion 625 PubMed
gical site infection after 1,3-bis (2-chloroethyl)- 38. A l-Jabi Y, El-Shawarby A. Value of C-reactive pro-
1-nitrosourea (Gliadel) wafer placement. Clin tein after neurosurgery: a prospective study. Br J
Infect Dis 2003;36(6):759–765 PubMed Neurosurg 2010;24(6):653–659 PubMed
23. Kaye KS, Schmit K, Pieper C, et al. The effect of in- 39. H lavin ML, Kaminski HJ, Fenstermaker RA, White
creasing age on the risk of surgical site infection. RJ. Intracranial suppuration: a modern decade of
J Infect Dis 2005;191(7):1056–1062 PubMed postoperative subdural empyema and epidural
24. Clark AJ, Butowski NA, Chang SM, et al. Im- abscess. Neurosurgery 1994;34(6):974–980, dis-
pact of bevacizumab chemotherapy on crani- cussion 980–981 PubMed
otomy wound healing. J Neurosurg 2011;114(6): 40. H all WA, Truwit CL. The surgical management of
1609–1616 PubMed infections involving the cerebrum. Neurosurgery
25. McHugh SM, Hill AD, Humphreys H. Intraopera- 2008;62(Suppl 2):519–530, discussion 530–
tive technique as a factor in the prevention of 531 PubMed
surgical site infection. J Hosp Infect 2011;78(1): 41. H lavin ML, Ratcheson RA. Subdural empyema. In:
1–4 PubMed Kaye AH, Black PM, eds. Operative Neurosurgery.
26. Winston KR. Hair and neurosurgery. Neurosur- Vol 2. London, England: Churchill Livingstone;
gery 1992;31(2):320–329 PubMed 2000:1667–1678
27. Bekar A, Korfali E, Doğan S, Yilmazlar S, Başkan 42. K shettry VR, Hardy S, Weil RJ, Angelov L, Bar-
Z, Aksoy K. The effect of hair on infection af- nett GH. Immediate titanium cranioplasty after
ter cranial surgery. Acta Neurochir (Wien) debridement and craniectomy for post-craniot-
2001;143(6):533–536, discussion 537 PubMed omy surgical site infection. Neurosurgery 2011;
28. Tokimura H, Tajitsu K, Tsuchiya M, et al. Cranial (Jul):29 PubMed
surgery without head shaving. J Craniomaxillofac 43. B ruce JN, Bruce SS. Preservation of bone flaps in
Surg 2009;37(8):477–480 PubMed patients with postcraniotomy infections. J Neuro-
29. Chiang HY, Steelman VM, Pottinger JM, et al. Clin- surg 2003;98(6):1203–1207 PubMed
ical significance of positive cranial bone flap cul- 44. A uguste KI, McDermott MW. Salvage of infected
tures and associated risk of surgical site infection craniotomy bone flaps with the wash-in, wash-
after craniotomies or craniectomies. J Neurosurg out indwelling antibiotic irrigation system.
2011;114(6):1746–1754 PubMed Technical note and case series of 12 patients. J
30. Harvey RJ, Smith JE, Wise SK, Patel SJ, Frankel BM, Neurosurg 2006;105(4):640–644 PubMed
Schlosser RJ. Intracranial complications before 45. N athoo N, Nadvi SS, van Dellen JR, Gouws E.
and after endoscopic skull base reconstruction. Intracranial subdural empyemas in the era of
Am J Rhinol 2008;22(5):516–521 PubMed computed tomography: a review of 699 cases.
31. Korinek AM, Baugnon T, Golmard JL, van Effen- Neurosurgery 1999;44(3):529–535, discussion
terre R, Coriat P, Puybasset L. Risk factors for 535–536 PubMed
adult nosocomial meningitis after craniotomy: 46. Nathoo N, Nadvi SS, Gouws E, van Dellen JR. Crani-
role of antibiotic prophylaxis. Neurosurgery otomy improves outcomes for cranial subdural em-
2008;62(Suppl 2):532–539 PubMed pyemas: computed tomography-era experience
206
with 699 patients. Neurosurgery 2001;49(4):872– 49. Infection in Neurosurgery Working Party of the
877, discussion 877–878 PubMed British Society for Antimicrobial Chemotherapy.
47. Yang KY, Chang WN, Ho JT, Wang HC, Lu CH. Post- The management of neurosurgical patients with
neurosurgical nosocomial bacterial brain abscess postoperative bacterial or aseptic meningitis or
in adults. Infection 2006;34(5):247–251 PubMed external ventricular drain-associated ventriculi-
48. Dörner L, Ulmer S, Rohr A, Mehdorn HM, Nabavi tis. Br J Neurosurg 2000;14(1):7–12 PubMed
A. Space-occupying cyst development in the 50. S cheithauer S, Bürgel U, Bickenbach J, et al. Exter-
resection cavity of malignant gliomas follow- nal ventricular and lumbar drainage-associated
ing Gliadel® implantation: incidence, thera- meningoventriculitis: prospective analysis of
peutic strategies, and outcome. J Clin Neurosci time-dependent infection rates and risk factor
2011;18(3):347–351 PubMed analysis. Infection 2010;38(3):205–209 PubMed
207
16
Implanted Devices and
Central Nervous System Infection
Ramesh Grandhi, Gillian Harrison, and Elizabeth Tyler-Kabara
The use of implanted devices is common- carotid ligation, high morbidity and fail-
place in most neurosurgical practices. ure rates have forced these methods to be
Because of the tendency of implanted abandoned. The development of endosco-
hardware to harbor microorganisms, the py has increased the use of third ventricu-
rate of postsurgical infections is generally lostomy, but a cerebrospinal fluid (CSF)
higher, and the treatment of such infec- shunt is the current mainstay of treatment
tions often necessitates surgical removal for hydrocephalus.5
of the involved hardware. In this chapter, CSF shunts have three main compo-
we review the diagnosis, microbiology, and nents—a proximal ventricular catheter,
treatment of these challenging infections a unidirectional valve, and a distal cath-
by category. We also review current strat- eter—that function by diverting fluid from
egies for prevention, which are discussed the ventricles to other body cavities, most
from other viewpoints in other chapters of commonly the peritoneum and rarely the
this volume. right atrium or pleural space. The first
shunts were used in the 1950s,6 and they
currently account for nearly 70,000 hos-
■■ Shunt Infections pital discharges and 36,000 surgical pro-
cedures in the United States, costing over
Hydrocephalus, estimated to affect nearly $100 million annually.2,7 Although some
1 in every 500 children,1 is one of the most studies suggest that the incidence of hy-
common pediatric pathologies requiring drocephalus and corresponding shunt in-
neurosurgical intervention. This disorder sertion is decreasing,8,9 others have found
may coexist with a variety of congenital or that the prevalence has increased because
acquired brain disorders, most commonly of the improved survival of premature in-
myelomeningocele2 or intraventricular fants and older children with hydrocepha-
hemorrhage,3 followed by aqueductal ste- lus.10 Despite nearly 60 years of experience
nosis, tumor, prior central nervous system with CSF shunts, their placement remains
(CNS) infection, and head injury. In con- fraught with complications, and overall
trast, common forms of hydrocephalus in failure rates remain high, at nearly 40% in
adults include idiopathic normal-pressure the first year.11,12 Malfunction due to me-
hydrocephalus and obstructive hydro- chanical obstruction or disconnection re-
cephalus; it is also caused by cysts, tumors, mains the most common complication, but
hemorrhage, head injury, and meningitis.4 infection is arguably the most dangerous,
Although a variety of other treatments resulting in serious patient morbidity and
have been utilized, such as choroid plex- mortality, long hospital stays, and costly
ectomy, choroid plexus cauterization, and interventions.5
Epidemiology and Risk Factors tient factors found to increase the risk for
infection include prior CSF leak, shunt re-
The incidence of shunt infection varies vision, and infection.3,4,21,28,29 Demographic
greatly, with most modern studies re- factors such as race, insurance type, and
porting rates ranging from 2.1 to 12% per chronic medical conditions were found to
procedure4,9,13–27 and from 6.3 to 18% per be significant risk factors in one study15;
patient.15,23,25 Following surgery, the me- however, these results were not widely
dian time to infection ranges from 10 to 72 reproduced. Studies have shown mixed re-
16 Implanted Devices and Central Nervous System Infection

days,4,14,21,26 with approximately 60% pre- sults for the etiology of hydrocephalus as a
senting within the first month17 and nearly risk factor for infection. Some suggest that
90% presenting in the first 6 months.28 In- etiologies such as intraventricular hemor-
vestigators have attempted to identify fac- rhage or prior shunt infection15,28 increase
tors predicting the length of time to the risk; however, others have not found any
development of infection, such as type of difference between etiologies.4,30 General
bacteria28 and whether the shunt is prima- risk factors for infection, such as prolonged
ry insertion or a revision14; however, most hospitalization, prolonged steroid treat-
studies have not identified such a correla- ment, immunosuppressive states, and
tion. Although it is difficult to establish poor skin condition, may also play a role.
significant differences between infection Several surgeon and operative factors have
rates in ventriculoperitoneal (VP), ventric- also been reported to affect the incidence
uloatrial (VA), and ventriculopleural shunts of infection, such as surgeon experience or
because of small sample sizes of the latter case volume,9,19 time of day and length of
two, it has been suggested that the infec- surgery,4,31 use of a neuroendoscope,21 and
tion incidence is lowest for VP shunts.9 the number of times the shunt is handled
There is a clear association between during surgery.24
age and the incidence of infection, with
the highest incidence noted in children.
Pathogenesis and Microbiology
Tulipan and Cleves documented a rate of
15.7% in patients younger than 11.3 years The bacteria most often responsible for
of age, statistically higher than the rate of shunt infection are commensal, low-vir-
6.7% in adults, with the highest incidence ulence, slowly replicating organisms. By
of 23% in infants less than 1 month old.16 far the most commonly observed patho-
These results have been corroborated in gens (up to 71.8%)32 are coagulase-negative
multiple studies,20,27 with a demonstrable staphylococci, with Staphylococcus epider-
inverse relationship between age and the midis the most often reported causative or-
incidence of infection.21 Most investiga- ganism (Table 16.1). Other gram-positive
tors note the highest infection rates in pathogens observed to cause infection in-
children younger than 1 year of age, many clude Staphylococcus aureus, particularly in
citing early gestational age, preterm birth, patients with concomitant skin infections,4
hydrocephalus etiology of intraventricular and less frequently viridans-group strep-
hemorrhage, or younger age at the time tococci, pneumococci, Enterococcus, Propi-
of shunt placement as independent risk onibacterium acnes, and Corynebacterium.
factors for infection.15,24,25,28 Although the Gram-negative bacteria (e.g., Escherichia
basis for this trend remains unclear, pos- coli, which accounts for more than 50%26
sible reasons include a relative immuno- of cases, Klebsiella, Proteus, and Pseudomo-
deficient response to bacterial infection in nas) account for a lower percentage of in-
the first 6 months of life, higher bacterial fections than gram-positive organisms and
density on the skin, longer hospital stays, are usually associated with corresponding
and prior exposure to antibiotics. A mul- abdominal pathology. Although generally
titude of patient, surgeon, and operative considered uncommon, polymicrobial in-
factors have been examined to identify risk fections account for up to 20% of infections
factors for infection. In addition to age, pa- and are often associated with an abdomi-
209
Table 16.1 Incidence of specific pathogens in shunt dehiscence over the shunt tract, hematog-
infection enous spread, and bowel perforation by the
Pathogen Incidence, % distal catheter tip, resulting in an ascending
infection.29 Although VA shunts are more
Gram-positive bacteria prone to infection through bacteremia, VP
shunts are more susceptible to distal infec-
Coagulase-negative 24–71.84,16,17,29,32,37,38
staphylococci
tion by intestinal pathogens.
(Staphylococcus Once contamination occurs, bacteria
epidermidis) colonize the shunt lumen, which is an
immune-protected space, and exposure
Staphylococcus aureus 9.3–333,16,21,22,29,32,37,38 to CSF aids bacterial adherence to the tub-
Other < 1–21.83,21,22,29,32 ing.34 The prevalence of infection with
(Propionibacterium acnes, coagulase-negative staphylococci is par-
Corynebacterium, ticularly important in the pathogenesis of
viridans-group streptococci, shunt infection because these organisms
Streptococcus pneumoniae, are able to form an extracellular matrix
Enterococcus)
made of glycoproteins, called a biofilm,
Gram-negative bacteria 6–4917,22,29 that further facilitates adhesion and pro-
(Escherichia coli, tects the bacteria from the immune system
Pseudomonas, and antibiotics.28 Formation of the biofilm
Klebsiella, Proteus) and peritoneal inflammation that walls
off the distal end of the shunt catheter by
Polymicrobial 11–204,20,32
forming a pseudocyst are two major con-

tributors to the association between shunt
infection and malfunction.35
nal origin or contaminated head wounds.20 Diagnosis

Fungal infections, most commonly involv-
Clinical Presentation
ing Candida, are seen infrequently, usually
in premature infants or immunocompro- The presentation of a shunt infection may
mised patients.28 be insidious and nonspecific, with variable
Given the frequency with which infec- clinical features that depend on the site of
tion occurs soon after shunt surgery and the the infection. The most common manifes-
predominance of common skin flora as the tation of infection is fever with signs and
causative organisms, it is logical to hypoth- symptoms indicative of shunt malfunction,
esize that the majority of infections are the such as headache, irritability, nausea and
result of contamination at the time of sur- vomiting, and lethargy.28 Wounds with lo-
gery; indeed, Conen et al associated 72% of calized signs and symptoms, such as ery-
shunt infections with intraoperative sourc- thema, pain, swelling, CSF accumulation
es. 29 Although Bayston and Lari reported along the shunt track, and with progression
wound contamination in 58% of cases at purulent discharge, particularly in children
incision closure,33 the origin of the such or- with poor skin quality, may provide a visible
ganisms was unclear. In a study comparing source of infection, with at least one of these
skin cultures with infection culture results, signs observed in up to half of cases.29 Less
Shapiro et al noted that 22% of patients commonly, patients may present with neck
were infected with organisms identical to stiffness or frank meningismus and, more
their skin flora, 22% had infections associat- rarely, seizures20 or glomerulonephritis.36 In
ed with other identifiable causes, and 55% the case of the VP shunt, abdominal symp-
were infected with typical skin flora that toms mimicking common viral syndromes
were different from the patients’ isolates.27 may confound the diagnosis, with signs of
In addition to intraoperative contamina- intra-abdominal infection being pain, vom-
210 tion, other sources of infection include skin iting, food intolerance, and peritonitis.
Diagnostic Course (MR) imaging should be used to examine
the size of the ventricles, which may be en-
In patients presenting with nonspecific
larged with concurrent shunt malfunction.
signs and symptoms, particularly those
CT may show signs of infection in approxi-
with recent shunt surgery, a high level
mately 10% of cases, manifested mainly as
of suspicion for shunt infection should
meningeal enhancement or the presence
be maintained; however, it is always im-
of a brain abscess.29 For suspected cases
portant, particularly with children, to
of distal infection, older studies have sug-

complete a full history and physical exami-
gested the use of ultrasound35; however, CT
nation to exclude other common infectious
has since been found to be more reliable
sources. Routine blood tests often show a
than ultrasound, demonstrating signs of
peripheral leukocytosis22; positive blood
infection such as inflammation of the fat or
culture in the setting of VP shunt infection
muscle around the shunt, thickened intes-
is infrequent. Elevated C-reactive protein
tinal wall, abscess, shunt tip dislocation, or
(CRP) levels may also be observed in nearly
pseudocyst in three-fourths of episodes, in
three-fourths of cases.37 Additionally, any
contrast to only half of episodes in which
apparent sites of infection, such as open
ultrasound was used.29 In summary, the
wounds, should be cultured.
most important method of diagnosis is a
The most definitive way to diagnose a
high level of clinical suspicion at the time
shunt infection is through the direct sam-
of presentation, supported by CSF studies
pling of CSF from the shunt, known as a
and imaging.
shunt tap, with the observation of organ-
isms on either Gram stain or culture.39 Cul-
Management
ture positivity is highest when sampling is
done directly from the valve or reservoir Once the diagnosis of a shunt infection is
(> 90%) rather than from a lumbar punc- made, the mainstay of treatment includes
ture, which yields a positive culture in few- antibiotics with or without surgical man-
er than half of cases.29 CSF cultures should agement. Immediate clinical decisions
be held for a minimum of 7 to 10 days to include the choice of antibiotics, route of
ensure growth of fastidious organisms.36,40 administration (systemic with or without
Although positive cultures provide a defin- intraventricular administration), and the
itive diagnosis, studies have reported neg- fate of the shunt. Review of the literature
ative CSF cultures in infections confirmed reveals three general approaches to the
by later culture of the shunt tip anywhere management of an infected shunt38:
from 8%21 to 55.8%16 of the time, indicating
that a negative culture does not rule out in- 1. A two-stage surgical procedure with
fection but may be due to several factors, removal of the entire shunt and ex-
such as prior antibiotic use. CSF findings ternal drainage of the CSF, either by
supporting infection include leukocytosis an external ventricular drain or by
with a predominance of neutrophils, eo- periodic tapping of the ventricles,
sinophilia,22 elevated protein, decreased with antibiotics administered sys-
glucose, and elevated lactate. Although all temically, intraventricularly, or both
of these criteria may not be met, CSF analy- ways, followed by replacement of
sis is completely normal in fewer than 3% the shunt when the CSF is sterile
of patients,29 and the combination of fever 2. A one-stage procedure with removal
and ventricular neutrophils above 10% has of the entire shunt and immediate
a reported specificity of 99% and a positive replacement, with antibiotics ad-
predictive value of 93% for infection.22 ministered systemically, intraven-
Imaging in the diagnosis of shunt infec- tricularly, or both ways
tion may include a shunt series to establish 3. Antibiotic therapy alone, adminis-
continuity of the shunt hardware. Comput- tered systemically, intraventricular-
ed tomography (CT) or magnetic resonance ly, or both ways
211
Additional surgical options in combina- ventricular administration allows maximal
tion with antibiotics may include distal ex- drug concentration at the site of infection,
ternalization of the peritoneal catheter in with higher peak concentrations and bet-
cases with a mild suspicion for infection or ter maintenance of therapeutic levels, as
isolated abdominal infection and malfunc- opposed to the observed ratios of CSF con-
tion,35,36 complete removal of the shunt centrations to blood concentrations after
without replacement, and complete re- systemic antibiotic administration, which
moval with the later performance of a third can range from 0 to 30%.41 Reported com-
ventriculostomy.23 The majority of patients plications with intraventricular antibiotic
will continue to require management of administration are infrequent, with the
their intracranial pressure through CSF most serious being focal motor seizure.42
drainage, making the latter two options vi- The appropriate duration of therapy is
able in only a small subset of patients. not well defined in the literature and is
predominately based on the observation
Antibiotics of clinical improvement combined with
sterilization of the CSF. The reported mean
The choice of antibiotics is highly depen- duration of antibiotics ranges from 9 to 18
dent on the presumed etiology of the in- days.14,29,38,39 Arnell et al reported that clini-
fection, patterns of susceptibility, and cal improvement paralleled CSF steriliza-
penetration of the blood–brain barrier tion and suggested performing repeat CSF
(BBB). Typical empiric, broad-spectrum an- culture 2 to 3 days after diagnosis, then if
tibiotics initiated before culture and sen- the cultures are negative, completing a total
sitivity results are obtained may include
of 5 to 10 days of antibiotics, and if they are

vancomycin, a third-generation cephalo- positive, continuing daily CSF cultures.40
sporin, and a third agent to cover anaer- Anderson and Yogev reported cost and
obes.36 First-generation cephalosporins health benefits for shorter periods of anti-
should be avoided because of their poor biotics and recommended as few as 3 days
BBB penetration.39 Because of high rates of of therapy for the mildest infections and 10
resistance to methicillin (> 60%38), oxacil- days for persistent cases.39 The definition of
lin, and penicillin (33%20), vancomycin is infection “cure” varies; it may be limited to
the drug of choice against staphylococci. clinical improvement and CSF sterilization
Oral or intravenous rifampin may be added or include an extended period of infection-
in combination with vancomycin because free follow-up. After cure of the immediate
it is able to penetrate the biofilm and at- infection, if it has been surgically managed
tain bactericidal levels at the shunt sur- with shunt removal and later replacement,
face38; however, it should not be used alone antibiotics are typically discontinued on
because of the development of resistance. the day of shunt replacement.
CSF Gram stain may be of early assistance
in choosing an antibiotic regimen, and CSF
Medical Management
culture and sensitivity results will allow
antibiotic coverage to be tailored to spe- Treatment with antibiotics alone has the
cific pathogens. benefit of avoiding surgery and its associ-
All patients should receive systemic ated morbidity, especially in patients with
antibiotics. Whether or not to add intra- multiple retained catheters. Simon et al
ventricular antibiotics to the regimen is a managed 13.3% of patients with antibiotics
point of contention. The logical rationale alone with a statistically significant shorter
behind the use of intraventricular antibiot- length of hospital stay, but they also iden-
ics is to overcome the poor BBB penetration tified a trend toward higher reinfection
achieved with intravenous administra- rates.14 In contrast to most reported cure
tion, especially in shunt infections caused rates with antibiotics alone,40 Brown et al
by low-virulence bacteria associated with achieved a cure rate of 84% over all and in
minimal meningeal inflammation. Intra- 93% of patients with S. epidermidis infec-
212
tion.38 Importantly, this study excluded pa- surgical approaches, all patients receiving
tients with S. aureus infection because of a both systemic and intraventricular anti-
high early failure rate, as well as patients biotics.43 This study reported a cure rate
with shunt malfunction, redundant shunts, of 100% with a two-stage approach, 90%
brain abscess or subdural empyema, exter- with a one-stage approach, and 30% with
nal infection, fungal infection, or local ab- antibiotics alone. The antibiotic group also
dominal infection, thus making the study exhibited a higher mortality rate (20% ver-
population quite specific. Additionally, all sus 0% in other groups) and longer hospital

patients received intraventricular antibiot- stays (45, 33, and 24 days for antibiotics,
ics through a ventricular catheter, which one-stage procedures, and two-stage pro-
was placed if the patient did not have one cedures, respectively). Although this trial
before presentation. Although likely not was limited by the small sample size,
the best choice for a majority of patients, modern reviews of published studies have
this study suggests that antibiotic therapy corroborated the results. In 1985, Yogev
alone may be efficacious for a carefully se- reviewed 18 studies and documented cure
lected group of patients. rates of 96%, 65%, and 36% for two-stage
procedures, one-stage procedures, and an-
Surgical Management tibiotics alone, respectively.44 Similarly, in
2002, Schreffler et al performed a decision
Despite the potential complications associ- analysis and reviewed 17 studies with cor-
ated with undergoing a surgical procedure roborating cure rates of 87.7%, 64.4%, and
in view of the adherence of bacteria to shunt 33.5% for each approach. 45
material, removal of the hardware is the de- With respect to morbidity and mor-
finitive method of eliminating persistent tality, historical studies have shown that
contamination that could cause recurrent morbidity, measured as average number
infection.36 Two primary surgical approach- of subsequent hospital admissions and av-
es dominate the treatment of shunt infec- erage number of days in the hospital for
tion: a two-stage and a one-stage procedure. each infection, is lowest for surgical treat-
Most institutions report surgical treatment ment, as is mortality.23 In a more recent
as the standard of care,3,14,29,39,40 with a ma- study of treatment approaches, a trend
jority employing the two-stage method. toward lower mortality was documented
In the case of a two-stage treatment with for a two-stage approach,37 and reviews
placement of an external ventricular drain, have documented 5.7%, 11.1%, and 20.4%
the average length of external ventricular mortality rates for two-stage procedures,
drain placement is approximately 1 week; one-stage procedures, and antibiotic treat-
however, reinternalization should not be ments, respectively.45 The decision analysis
unnecessarily delayed because reinfection for this same study assigned utility values
rates correlate with the duration of exter- to each approach based on cure, morbid-
nal ventricular drain placement.39 Kestle3 ity, and mortality and concluded that the
reported a mean time to replacement of two-stage approach has the highest utility.
13 days after CSF sterilization; however, Although the two-stage approach is not
in a study of more “aggressive” treatment, without complications, it has been estab-
James and Bradley reported similar success lished as the current standard of care by re-
rates with shunt replacement after antibiot- sulting in the highest cure rate with lowest
ic treatment for less than 12 days and after morbidity and mortality rates.
CSF cultures were negative for 24 compared
with 48 hours.42
Outcomes
The choice of optimal treatment of
shunt infection is hampered by the lack Long-term outcomes after shunt infection
of prospective, randomized clinical trials. have serious implications for the health
An older published trial compared an- and well-being of patients. After an initial
tibiotics alone with one- and two-stage infection, the risk for reinfection is higher,
213
with 16 to 25% of patients admitted with ing older adults in the United States will
reinfection within 12 months.3,14 Although continue to increase, and it is estimated that
infections are usually insidious, nearly 20% there will be 87 million Americans past the
of patients are admitted to neurosurgical age of 65 by the year 2050, representing
intensive care units.29 Infection can lead more than 20% of the total population.51 In
to the development of multiloculate hy- turn, the growing number of older Ameri-
drocephalus, with an increased need for cans with spinal pathology requiring op-
repeat surgery and lifelong shunt depen- erative intervention will lead to an increase
dence,36 an increased risk for seizures and in the number of fusion procedures per-
decreased intellectual performance and formed. This trend in spinal surgery has al-
cognitive function, and a twofold higher ready begun, and based on recent estimates,
increase in long-term mortality rate.23,46,47 over 460,000 spinal fusions were performed
in 2010, with a total cost of upward of $43
Prevention billion. In comparison, in 1997, roughly
130,000 spinal fusions were performed in
Although preoperative antibiotics are the United States, with an estimated aggre-
widely employed,18 many studies suggest gate charge of slightly over $3 billion.52
that the common use of cephalosporins,
such as cefazolin, may not decrease the
risk for infection,4,34 especially as first- and Definitions
second-generation antibiotics do not have
The Centers for Disease Control and Pre-
good BBB penetration. Intravenous vanco-
vention (CDC) classify surgical wound
mycin has been shown to be more effective
infections as either incisional site infec-

(14% versus 4% infection rate) than cepha-
tions or organ/space infections, with fur-
losporins, with lower mortality rates and
ther stratification of incisional surgical
shorter lengths of stay18 in hospitals that
site infections (SSIs) based on the tissue
have a high prevalence of methicillin-resis-
compartment involved (Table 16.2).53 A
tant S. aureus (MRSA). The intraoperative
superficial incisional SSI involves the skin
use of intraventricular antibiotics, specifi-
and/or subcutaneous tissues, whereas
cally vancomycin and gentamicin, resulted
a deep incisional SSI involves the fascial
in one study in a decrease in the infection
and subfascial layers. In the lumbar spine
rate from 6.5% to 0.412% with no adverse
(Fig. 16.1), deep infections occur sub-
effects.17 Meticulous operative technique
jacent to the lumbodorsal fascia with a
and control of the operative theater are
posterior lumbar wound and below the
thought to be the best prevention,1,48 with
anterior abdominal fascia with an ante-
the inclusion of double gloving into stan-
rior approach. The ligamentum nuchae
dard surgical practice.16 The introduc-
and fascial layer serve as the anatomic
tion of antibiotic-impregnated ventricular
landmarks to delineate the deep layers
catheters has provided some evidence for
of the posterior cervical tissue, whereas
the prevention of infection13; however, re-
deep wound infections after anterior cer-
sults have been mixed.49,50
vical surgery are located deep to the pla-
tysma.54 Of note, postoperative infections
may also involve the intervertebral disks,
■■ Spinal Instrumentation– the vertebral bodies, and/or the epidural
Associated Infections space, resulting in diskitis, osteomyelitis,
or epidural phlegmon/abscess.
The multiple indications for spinal fusions
include treatment of scoliosis, stenosis,
Epidemiology
spondylosis, spondylolisthesis, trauma, tu-
mor, and instability. Because of the advanc- The development of an infection is a
ing age of the baby boomer generation, the known complication following surgery
percentage of the total population compris- and is a common cause of patient morbid-
214
Table 16.2 Criteria for defining a surgical site infection
Superficial incisional SSI
Infection occurs within 30 days after the operation and involves only skin or subcutaneous tissue of the inci-
sion and at least one of the following:
1. Purulent drainage, with or without laboratory confirmation, from the superficial incision.

2. Organisms isolated from an aseptically obtained culture of fluid or tissue from the superficial incision.
3. At least one of the following signs or symptoms of infection: pain or tenderness, localized swelling, red-
ness, or heat, and superficial incision is deliberately opened by the surgeon, unless incision is culture-
negative.
4. Diagnosis of superficial incisional SSI by the surgeon or attending physician.
Deep incisional SSI
Infection occurs within 30 days after the operation if no implant is left in place or within 1 year if implant is
in place and the infection appears to be related to the operation and involves deep soft tissues (e.g., fascial
and muscle layers) of the incision and at least one of the following:
1. Purulent drainage from the deep incision but not from the organ/space component of the surgical site.
2. A deep incision spontaneously dehisces or is deliberately opened by a surgeon when the patient has at
least one of the following signs or symptoms: fever (> 38°C), localized pain, or tenderness, unless site is
culture-negative.
3. An abscess or other evidence of infection involving the deep incision is found on direct examination, dur-
ing reoperation, or by histopathologic or radiologic examination.
4. Diagnosis of a deep incisional SSI by a surgeon or attending physician.
Abbreviation: SSI, surgical site infection

Source: Adapted from Mangram AJ, Horan TC, Pearson ML, et al; Hospital Infection Control Practices Advisory Committee
(HICPAC) and Centers for Disease Control and Prevention (CDC). Guidelines for prevention of surgical site infection. Infect
Control Hosp Epidemiol 1999;24(4):247–278.
ity in the postoperative period. Wound

infections, particularly deep wound infec-
tions of the spine, have significant con-
sequences for patients and for the health
care system at large. Postoperative spinal
wound infections generally lead to longer
in-hospital lengths of stay, higher costs,
and the potential for reoperation. More-
over, these complications are known to
increase patient morbidity and mortal-
ity.55–59 Achieving a decrement in the rate
of postoperative wound infections has
been the premise behind many centers’
adopting various guidelines for periopera-
tive patient care; however, the prevention
of wound infections involves consideration
of pre-procedural, intra-procedural, and
Fig. 16.1 T2-weighted sagittal magnetic resonance post-procedural sources of microbial colo-
image of a lumbar wound infection depicts hyperin- nization and thus requires a multifaceted
tensity within the soft tissues. approach to patient management. 215
Patient-specific risk factors, such as ad- with deep wound infections after under-
vanced age, a history of drug and alcohol going anterior cervical diskectomy and fu-
abuse, smoking, diabetes, obesity, malnutri- sion, the clinician must have a high index of
tion, and immunologic compromise,60 reduce suspicion for esophageal injury, which car-
the patient’s ability to mount an adequate ries significant morbidity and mortality.88
inflammatory response against pathogens.61 Understanding surgery-specific risk fac-
Smoking and diabetes, specifically, are be- tors, adhering meticulously to aseptic tech-
lieved to lead to microvascular damage and nique, and employing measures to decrease
tissue ischemia, which in turn increase the the potential for microbial colonization are
risk for SSI development.62–66 In terms of pre- crucial to minimizing the potential for de-
procedural care, advocating for measures veloping subsequent deep wound infec-
such as smoking cessation and improved pre- tions, as highlighted by recommendations
operative diabetic control and nutritional sta- published by the CDC for SSI prevention.53
tus should be employed to optimize patient As previously noted, measures to re-
risk factors. In addition, surgeries performed duce the risk for developing a postopera-
for patients with traumatic spinal injuries or tive wound infection are not relegated to
neoplastic processes are associated with an the preoperative and immediate periop-
increased incidence of SSIs.61 erative periods. As such, the postoperative
As surgeries become more complex, management of patients is also important
with an increasingly wide variety of pain preventing surgical site complications.
thologies treated and instrumentation Open and effective communication be-
used, the likelihood of infectious compli- tween the patient, nursing staff, and phy-
cations increases.67,68 Studies have esti- sicians is integral to optimizing patient

mated that the incidence of deep wound outcomes. Protecting the surgical wound
infections following instrumented lum- with a sterile dressing for 24 to 48 hours
bar fusion surgery ranges between 1 and postoperatively, washing hands before and
14%.55–58,67,69–79 Repeat surgery, a greater after dressing changes and when any con-
number of levels fused, a posterior ap- tact with the surgical site is anticipated,
proach, longer operative times, blood and using sterile technique are recom-
transfusions, and increased intraoperative mended.53 Administration of antibiotics
blood loss are all associated with postop- is discouraged beyond 24 hours as there
erative SSI.60,68,80–82 Another risk factor that is scant evidence to support this practice.
has been identified is the presence of more Additionally, prolonged administration of
people in the operating theater, a finding antibiotics has been shown to result in the
especially germane to spinal instrumenta- selection of antibiotic-resistant bacterial
tion surgeries, in which the surgeon, as- species.89 Although closed suction drainage
sistants, anesthesia team, circulators, and has traditionally been employed because
equipment representatives all share the of its potential to promote wound healing
operating room, increasing traffic and add- and also prevent bacterial colonization and
ing potential sources of infection.83 growth within the surgical bed, there is
Minimally invasive approaches have little evidence to support its use.90 The re-
been shown to compare favorably with sults of recently published works illustrate
traditional, open surgical approaches with that drains may not lead to any reduction in
respect to the incidence of wound infec- wound infections,90,91 and with prolonged
tions.84,85 Fewer postoperative deep wound use, they are an independent risk factor for
infections are seen after instrumented cer- subsequent development of an SSI.92
vical fusion surgery; however, as recent re-
ports demonstrate, patients who undergo
Microbiology
operative fixation and arthrodesis via an
isolated posterior approach have a higher Most commonly, S. aureus is responsible
rate of wound infection than those treated for SSI development. Recent reviews have
anteriorly.86,87 In patients who manifest shown that the incidence of MRSA isolates
216
in patients manifesting with SSI is upward followed a more predictable kinetic profile
of 34%.83 S. epidermidis, Enterococcus fae- compared with the ESR, which demon-
calis, Pseudomonas species, Enterobacter strated increased variability and typically
cloacae, and Proteus mirabilis are other, peaked later in the postoperative period,
less commonly isolated bacterial patho- and they showed that a second rise in CRP
gens. Patients with traumatic injuries to levels or their failure to decrease had good
the spine and those with urosepsis are par- specificity and negative predictive value
ticularly vulnerable to infection by gram- for postoperative deep wound infection.93

negative organisms.61 MR imaging with administration of in-
travenous gadolinium is the optimal im-
Presentation and Diagnostic Work-Up aging modality for evaluating patients
for deep postsurgical infections. In cases
Patients with postoperative deep wound of deep wound infections, T2-weighted
infections can present in a variety of ways. sequences will demonstrate hyperinten-
Increasing pain is often experienced and sity within the involved tissues. Diskitis
represents a subjective complaint that is and osteomyelitis manifest on MR imag-
important to take in context with the pa- ing with decreased signal on T1-weighted
tient’s general postoperative course. To sequences and increased signal on T2-
avoid delays in diagnosis, one must con- weighted images within the disk space
sider how much time has passed since and vertebral bodies, respectively, with
surgery and note whether the increased contrast enhancement after gadolinium
pain is disproportionate to the amount of administration. Epidural abscesses are
discomfort that the patient has previously isointense with the spinal cord on T1-
experienced during his or her recovery.67 weighted imaging and appear hyperin-
Patients typically present with signs and tense on T2-weighted sequences. Contrast
symptoms of infection between 2 and 4 enhancement is also typically present54
weeks after surgery63,92 and will frequently (Fig. 16.2). Given their ability to detail bony
manifest with incisional drainage.63,78 As
noted by Beiner et al, systemic signs such
as fever are often absent; however, local
signs such as peri-incisional erythema and
other manifestations of wound inflamma-
tion are frequently present.67
Laboratory studies of the white blood
cell count, erythrocyte sedimentation rate
(ESR), and C-reactive protein (CRP) level
are performed as part of the diagnostic
work-up of patients presenting with sus-
pected postoperative SSI. All three acute
phase reactants become elevated in states
of systemic inflammation and are nonspe-
cific markers of infection because their
levels rise in association with other dis-
ease processes. Various publications have
highlighted the utility of CRP level testing
in cases of spinal SSIs.93,94 Noting that the
white blood cell count is an unreliable in-
fectious biomarker,95 Mok et al found that
in their patient cohort, the CRP level was
more reliable and applicable as a test for Fig. 16.2 Sagittal T1-weighted magnetic resonance
infection compared with ESR. The authors image of a cervical epidural abscess depicts avid con-
demonstrated that postoperative CRP levels trast enhancement after administration of gadolinium.
217
anatomy, CT scans are useful in the workin patients with spinal instrumentation.
up of patients with infections. In the set- Given the added concern that arthrodesis
ting of diskitis and osteomyelitis, CT scans will not have occurred, there is additional
often reveal narrowing of the disk spaces debate as to whether hardware removal is
and erosion of the adjacent end plates. The warranted in patients who present with
presence of haloing around screws is in- deep SSI in the early postoperative period.
dicative of hardware failure, which may be Some authors state that hardware must
due to concomitant infection. be removed to clear the infection.100 A
study by Collins et al showed that among
patients who presented with early post-
Treatment
operative deep SSIs, 40% of those who un-
The treatment of deep SSIs requires iden- derwent repeat wound debridements and
tification of the particular tissue(s) or washouts with concomitant administra-
compartment(s) involved and the clinical tion of intravenous antibiotics had active
state of the patient. Once these have been infection at the time of eventual hardware
identified, quick and definitive treatment removal.101 However, the efficacy of serial
is compulsory to maximize the patient’s operations for wound debridement and
chances of normal recovery and to mini- washout without removal of instrumenta-
mize long-term sequelae of the infection. tion has been documented.55,71,78
As mentioned previously, patients with The use of the vacuum-assisted closure
deep wound infections have increased of postoperative spinal wounds has gained
morbidity and mortality55–59; however, de- popularity. This involves placing a sponge
spite the development of this complication, into the wound, covering it with an occlusive
such patients can still derive benefit from dressing, and then connecting the sponge to
their initial surgery and experience a sig- a suction device. By introducing negative
nificant improvement over their preopera- pressure to the wound, the vacuum-assist-
tive health-related quality of life.96,97 ed closure device (V.A.C. Dynamic Wound
The nonoperative management of Therapy; KCI Medical, San Antonio, Texas)
postoperative deep SSI is rarely indicated has been shown to promote the formation
because of the fact that such infections typ- of granulation tissue while also optimizing
ically cannot be cleared with the adminis- tissue perfusion and decreasing interstitial
tration of intravenous antibiotics alone.61,67 edema, thus facilitating bacterial removal
At our center, unless the patient appears from the wound.102 The specific manner in
clinically ill with systemic signs of sepsis, which the vacuum-assisted device has been
administration of intravenous antibiotics used among patients with deep SSI follow-
is withheld until after intraoperative tis- ing spinal hardware implantation varies in
sue cultures are obtained. Surgery involves the literature; some authors have used a vac-
opening the incision and obtaining wound uum-assisted closure device after an initial
cultures, followed by aggressive removal irrigation and debridement procedure and
of the necrotic tissue and bone graft with allowed the wound to heal via secondary
wound debridement and thorough lavage intention,103 whereas others have utilized
of the wound with antibiotic irrigation. Be- the device until granulation tissue forms
cause of a high diagnostic yield in the set- over the retained hardware, at which time
ting of infection, tissue specimens should definitive wound closure is undertaken.104,105
be sent for microbiological analysis and At our institution, the treatment paradigm
culture.98 In cases in which the wound can requires that patients presenting with post-
be closed, some authors recommend plac- operative deep SSI undergo serial wound
ing surgical drains before closure.55,99 washout and debridement procedures; in-
No consensus exists in the literature re- traoperative wound cultures are taken with
garding the utility of serial wound debride- each procedure, and a vacuum-assisted clo-
ments and washouts and the necessity of sure dressing is left in place attached to con-
wound closure in the setting of deep SSI tinuous suction. Plastic surgeons, infectious
218
disease specialists, and clinical nutritionists Patients must be carefully assessed for the
are consulted, and after sterile cultures have presence of active infections, and surgery
been obtained from the wound and the pa- should be delayed if they are found. The
tient has been nutritionally optimized, pri- appropriate use and timing of presurgical
mary closure is undertaken. antibiotic prophylaxis are necessary. Close
After the surgical treatment and inpa- attention to sterile operative technique is
tient management of patients with deep particularly important, and sterile prepara-
SSI, the multidisciplinary team approach tion of the surgical site can be challenging

must be continued on an outpatient basis. because of the lateral positioning of the pa-
The CRP level has been demonstrated to tient. At Children’s Hospital of Pittsburgh of
be of utility in measuring the response to UPMC, pledgets soaked with Betadine are
antibiotics of patients with wound infec- stapled to the wound edges immediately
tions after spinal surgery.106 Patients are after incision to reduce the risk for contam-
often kept on long-term oral suppressive ination. The surgical site is also irrigated
antibiotic therapy at the recommendation with a total of 1 L of saline and Betadine
of the infectious disease specialists. From solution before closure. Meticulous atten-
the standpoint of the spine surgeon, close tion to wound closure is also of key impor-
monitoring with serial imaging studies is tance, as is the avoidance of tension on the
also important to monitor for progression wound, which may result from the bulk of
of instability or pseudoarthrosis.107 the pump in what is often a malnourished
patient. Subfascial placement of the pump
may help reduce wound tension.
■■ Intrathecal Pump Infections Infection of the intrathecal pump most
often necessitates removal of the device.
Implantable pumps are now commonly Systemic antibiotics may be used to sup-
used to treat spasticity, dystonia, and intrac- press an infection while a drug delivered
table pain. These devices present a unique at high doses is withdrawn. Infection may
subset of challenges in terms of infection occasionally be treated with antibiotics
prevention and the treatment of infections alone112,113; however, in the authors’ expe-
when they do occur. The rate of infection rience, treatment with antibiotics alone
after pump implantation has been estimat- does not typically eradicate an infection.
ed to be from 4.0 to more than 10%.108–111 In Attempts to treat pump infections without
addition to the issues associated with other an interruption in intrathecal drug delivery
implantable devices, these devices are of- have included washout without removal of
ten implanted in patients with numerous the device,114 removal with replacement in
comorbidities, such as immunosuppression the same setting, and intrathecal co-infu-
in patients with intractable cancer pain sion of antibiotics.115,116 In cancer patients
and pressure ulcers, gastrostomy tubes, with limited life expectancy who are re-
and indwelling catheters in patients being ceiving intrathecal opioids, palliative sup-
treated for spasticity. These patients have pression of the infection without removal
often previously been exposed to multiple of the device should be considered.
antibiotics; therefore, they are at increased
risk for harboring resistant strains of bac-
teria and may have developed allergies to ■■ D
eep Brain Stimulator
antibiotics commonly used in prophylaxis. Hardware Infections
Gastrostomy tubes, pediatric age, and in-
continence have been associated with a Over the last quarter of a century, deep
higher risk for infection.109 brain stimulation (DBS) has evolved from
Many techniques to prevent infection an experimental therapy to a well-accepted
of intrathecal pumps have been described. treatment for a wide variety of medical con-
Before surgery, the nutritional status of the ditions. Most commonly, DBS is used to treat
patient should be assessed and optimized. movement disorders, such as Parkinson
219
disease,117–122 essential tremor,117,120–122 dys- hemorrhage, stroke, and even death, are rare,
tonia,117,120–122 and Tourette syndrome119,123; with reported rates ranging from 1 to 2%.133,134
psychological disorders, such as obsessive- In contrast, hardware-related complications
compulsive disorder124; and other neuro- are extremely common, occurring in up to
logic and pain disorders.118,119,121,122,124,125 25% of patients124 and in 17% of procedures.128
A DBS system consists of a multicontact They are of particular importance because
intracranial electrode, extension leads or they usually require surgical correction or re-
wires with a connector, and an internal moval of the system with an associated loss of
pulse generator. Surgical implantation of therapeutic benefit, need for hospitalization,
the electrode generally involves the use of and significant economic burden.119 The most
a stereotactic frame126 to target a prede- common hardware-related complications
termined region after appropriate imaging include electrode migration, lead fracture,
and physiologic mapping with the patient infections, erosions, and internal pulse gener-
under minimal, if any, anesthesia.122 Inter- ator malfunction.119,121,122,128,133 Although hard-
nal pulse generator implantation is most ware failure may require costly replacement,
commonly subclavicular and may occur at infection remains one of the most significant
the same time as electrode implantation potential complications, and the risk for infec-
(single procedure)126 or in a second proce- tion persists long after the immediate periop-
dure following a period of temporary lead erative period, making it the most common
externalization and continuous test stimu- late complication of DBS therapy.125,135
lation (staged procedure).127
DBS is a reversible procedure, with its
Epidemiology and Risk Factors
effect based on electric modulation of the

nervous system,118 resulting in a functional The reported incidence of DBS hardware-
rather than a structural lesion. In contrast related infection varies with study de-
to the ablative procedures (thalamotomy, sign, definition of infection, and length
pallidotomy) that may be used as alternative of follow-up. Individual studies have de-
therapy for movement disorders, DBS offers scribed infection rates ranging from 0
the ability to adjust stimulation parameters to 15% of patients,117,122,126,133,136–140 with
noninvasively and tailor treatment to the most reporting rates of approximately 5
patient’s individual needs without creating to 10% of patients and 3 to 7% of devic-
an irreversible lesion,119 but it precludes the es.120,121,124,126,128,132,134,141–146 In a recent meta-
use of potential neurorestorative therapies analysis of more than 3,000 patients, Bhatia
that may become available in the future.127 et al calculated an average infection rate of
Given these benefits and the low risk for 4.7%147; similarly, in an earlier review, the
permanent neurologic deficit associated authors reported rates of 3.3% of electrodes
with the procedure, the number of patients and 3.8% of patients, with a decline in the
undergoing DBS has increased dramatically incidence after implantation.141 Addition-
in recent years, and the number of those ally, Baizabal Carvallo et al noted that the
undergoing ablative therapy has propor- overall incidence has declined in recent
tionally decreased. However, treatment is years, with reported rates after 2010 rang-
lifelong, based on implantation of foreign ing from 0.62 to 9.3%.119
material, and thus is subject to the inherent Risk factors for infection following DBS
risk for complication.128 are poorly understood. There are conflict-
Complications associated with DBS can be ing data about age as a predisposing fac-
classified as operation-, stimulation-, or hard- tor,120,125,127 with some authors identifying
ware-related.119,129,130 Overall complication younger age as a risk factor,138,144 but the
rates reported in the literature vary widely, majority of studies fail to associate age
ranging from 3.8 to 37% of patients,119,131–133 with an increased incidence of infec-
4.3 to 19% of implants,128,133,134 and 3.2 to 8.4% tion.117,124 General patient characteristics
per electrode-year.121,125,133 Serious operation- and comorbidities traditionally identified
related complications, such as intracranial as neurosurgical risk factors, particularly
220
those that may impair wound healing the implanted device119; accordingly, bac-
(e.g., smoking, excessive alcohol consump- terial inoculation may occur directly at the
tion, systemic illness, diabetes mellitus, time of surgery, via hematogenous spread,
hypertension, and obesity) have not been or secondary to skin breakdown.118 Dis-
demonstrated to increase risk in most stud- tal inoculation at the connection site be-
ies of DBS outcomes.119–121,124,125,127,139,144,146 tween electrodes and extension cables or
Furthermore, operative factors, such as at the internal pulse generator pocket is
duration of surgery, unilateral versus bi- the most common route of hardware in-

lateral lead placement, type of operating fection.124,126,128,133,136,148 Most investigators
room (conventional versus MR imaging report that a majority of infections pres-
suite), number of personnel in the operat- ent as suppurative cellulitis at the internal
ing room, surgeon experience, and method pulse generator pocket in association with
of hair removal, have not been found to skin erosion or less commonly trauma,
convey a significant increase in infection with rapid spread to incisional sites in the
risk.120,121,124,138,139,144,146 Importantly, DBS in retroauricular or scalp regions.124,125,128,138
which a staged implantation is used, with Although the vast majority of infections
externalization and continuous stimu- occur in the distal system components,
lation of leads, has not been found to reinfection at the burr hole incision is not
sult in higher infection rates, even with uncommon and often secondary to, or
longer time between surgeries; Piacen- coexistent with, distal hardware infec-
tino et al reported that no infections oc- tion.120,125 Intracranial infection of elec-
curred in wounds that were reopened trodes is rarely observed.143 Reviews of the
and resutured during the second-stage literature have identified just a handful of
procedure.120,124,127,138 Specific devices, in- cases of intracranial infection,133,139,143,149
cluding brand or one dual-channel versus with one particular case study describing
two small single-channel internal pulse an early diagnosis of Enterobacter abscess
generators, are not associated with in- on postoperative day 10.150
fection risk.117,124,138 One operative factor Given the natural history of hardware
found to convey an increased risk for infec- infections associated with skin erosion,127
tion is the use of a straight incision directly the average time to diagnosis of infec-
over burr holes rather than a curvilinear tion tends to extend into the months fol-
incision; Constantoyannis et al reported an lowing implantation. Reports of mean
increase in incidence from 2 to 12.5% in pa- time to infection range from 1 to 4
tients with a straight incision (p = 0.03).121 months,120,126,134,138,139 with varied identi-
Perhaps the most commonly noted risk fication of highest rate of infection in the
factor for infection, particularly in long- first 3 months compared with the 3- to
term follow-up and often reported undis- 6-month period after surgery.121,124,140,141 In-
tinguished from frank infection, is skin terestingly, in studies of pediatric patients,
erosion over hardware sites.125 Although all infections were diagnosed at the inter-
rates of infection decrease in the months nal pulse generator site and within 4 to 6
to years postoperatively, of those who do weeks after implantation, leading authors
experience complications, more than half to postulate that pulse generators, origi-
have associated skin erosions,121,126–128,134,138 nally designed for the larger subclavicular
and as noted by Oh et al, it may be difficult areas of adults, may cause undue tension
to distinguish the temporal relationship beat the chest wall and thus lead to an in-
tween erosion and infection because both creased risk for infection.137 Although diag-
complications present concomitantly.125 nosis can rarely occur within the first week
postoperatively, time to infection may also
be months to years121,125,126,128,134,139; studies
Pathogenesis and Microbiology
of long-term complications of DBS have
Infection of DBS hardware can initially af- noted that infections may occur at more
fect any part of the system and spread to than 1 year in 40%126 and more than 2 years
221
adjacent tissue by following the track of in 25% of patients following DBS,128 thus
underscoring the need for close long-term tion, with purulence visualized through
follow-up. the subcutaneous level and in contact with
Constantoyannis et al classify DBS hard- portions of the hardware system.124,126,138,144
ware infections and bacterial etiologies Cultures obtained from exposed device
into two categories: external infections, components, wound drainage, or intraop-
which may begin as erythema or heal- erative specimens may be used to confirm
ing problems at the surgical site and are the diagnosis of infection and identify
usually caused by skin flora, and internal pathogens to guide therapy117,124,138; howev-
infections, which are secondary to the he- er, a significant percentage of cultures may
matogenous spread of bacteria and may not provide positive results. In one case se-
result in meningismus or intracranial ab- ries, no organisms were identified by blood
scess.122 Gram-positive cocci are the most culture, but 10 of 12 surgical swabs pro-
common organisms responsible for infec- vided positive cultures127; other series have
tion, with S. aureus identified in 40 to 100% described positive cultures in only half of
of culture-positive cases,117,125,126,129,137,138,144 clinically diagnosed infections.121 Systemic
in addition to S. epidermidis,126,136,143 other signs and symptoms of infection are un-
coagulase-negative staphylococci,138,143,145 common in DBS hardware–related infec-
and less commonly other skin flora, such as tion; Fily et al reported mild fever in only
P. acnes and Micrococcus.126,137,138 Additional one-quarter of patients and change in men-
pathogens routinely identified, although tal status in only one patient.126 Although
with much lower frequency, include En- uncommon, intracranial infection may be
terobacter,121,126,144 Serratia,141 Klebsiella,144 apparent on CT or MR imaging of the head.
and Pseudomonas,142,143 which may reflect In patients presenting with local infection
the potential for patients to contract noso- near the external portion of the electrode
comial infections. Polymicrobial infections and new neurologic symptoms, imaging
have not been routinely described in the may demonstrate abscess or edema around
literature; fungal infections do account for the electrodes, signified by signal change on
a small percentage of pathogens, with Can- T2-weighted MR images or hypodensity on
dida117,141,144 most frequently isolated. CT scans.126,143,150,151
In addition to a thorough history and
physical examination, one suggested algo-
Diagnosis
rithm for work-up includes CT of the head
The definitions of hardware-related infec- with contrast, complete blood count, ESR,
tion vary quite widely in the literature. CRP level, electrolyte levels, and urinalysis.
Some definitions include patients with Certain institutions may advocate the use
only superficial inflammatory changes at of technetium-99m sulesomab immunos-
incisional sites and/or skin erosion, where- cintigraphy to evaluate for the presence and
as other, stricter definitions are based on extent of infection and thus aid in surgical
specimen cultures.119 In contrast to what planning.152 If the examination or imaging is
is observed with other types of implanted concerning for intracranial infection, a neu-
hardware, temporal proximity to surgery is rosurgical consult should be obtained.122
of less importance because skin dehiscence Because of the variability of culture results,
may occur at any time and is highly corre- particularly because cultures are often ob-
lated with infection risk. tained after surgical treatment is under-
Most authors use the presence of clini- taken, thereby somewhat negating their
cal or microbiological criteria to diagnose diagnostic value, and because of the subtle-
infection. Clinical evidence of infection ty or lack of systemic symptoms at presen-
may include superficial signs, such as in- tation, a high level of clinical suspicion and
duration, erythema, pain, warmth, and a low threshold for the initiation of therapy
purulence at an incision over a hardware are important for patients with potential
component,117,142 or signs of deep infec- hardware-related infections.
222
Management early surgical hardware removal, others
opt for an initial attempt at conservative
In patients presenting with likely DBS medical therapy.119 A small percentage of
hardware infection, wide-spectrum em- patients may successfully be managed con-
piric antibiotics may be started early.117 servatively; in one series, 25% of patients
Importantly, antibiotic therapy must target with cranial wound infections initially
S. aureus and P. acnes,123 but they can then treated with antibiotics and wound de-
be altered to address the subsequent final bridement avoided surgical intervention.117

culture results and sensitivities. Reported Similarly, in a pooled analysis of a large
success rates of management with antibi- study sample, 20% of infections were suc-
otics alone range from 4 to 75%.122,144 Oral cessfully treated with antibiotics alone.148
and topical antibiotics may be tried as pri- Factors associated with an increased risk
mary therapy for patients with mild super- for antibiotic failure include deep, purulent
ficial skin infection without purulence or infections and the isolation of S. aureus.141
signs of inflammation along the hardware Partial removal of distal hardware com-
tract119; for those with more prominent lo- ponents is frequently attempted in cases
cal infections, successful therapy with 10 of infection localized to the internal pulse
to 14 days of intravenous antibiotics fol- generator or extracranial lead extend-
lowed by 7 to 14 days of oral antibiotics ers.124,133,138,142 In cases of infection over the
has also been described.139 In one series, internal pulse generator secondary to skin
patients adequately treated with antibiot- erosion, surgical removal is nearly always
ics alone presented earlier after the onset necessary; however, some success has
of symptoms compared with those requir- been reported with removal of the genera-
ing surgical therapy; on average, the eradi- tor, sterilization, and immediate reimplan-
cation of infection was achieved following tation in the contralateral subclavicular
3.5 weeks of antibiotics.117 region.118,133 Failure of partial removal, ne-
The majority of hardware-related infec- cessitating complete removal, can occur in
tions require surgical intervention, either patients managed in this manner126 and has
as the initial management or following a been associated with deep, purulent infec-
failed trial of antibiotics with or without tions, positive S. aureus cultures, extensive
wound debridement.125,126,141,142 Surgical cellulitis, and wound dehiscence.133 Some
management ranges from minimal re- investigators have noted that if infection of
moval of one component of a DBS system a cranial incision, which can easily spread
to complete removal of the internal pulse to electrodes, or evidence of intracranial
generator, lead extender, and intracra- involvement is present, complete removal
nial electrodes. Rates of complete removal is likely necessary for effective therapy.
range from 11 to 73%.124,141,142 If infection is This is compared with infection limited to
located around the internal pulse genera- the internal pulse generator site, in which
tor or extension wires, however, removal of case partial removal with prolonged anti-
these distal parts of the system may be at- biotic therapy is highly successful.126
tempted with preservation of the intracra- Surgical removal of hardware is com-
nial electrodes. Salvage rates of 21 to 89% bined with extended courses of antibi-
have been reported for partial hardware otic therapy for complete eradication of
removal of just the internal pulse genera- device-related infection. The reported
tor or the internal pulse generator and lead duration of antibiotic therapy follow-
extenders,126,141,142 although conversion to ing hardware removal varies, as does the
full removal may be necessary in up to mode of administration. Nearly all stud-
one-third of cases.138 ies report using intravenous antibiotics in
Continued controversy exists regarding the immediate postoperative period, with
initial management of DBS hardware infec- the majority of courses ranging from 3 to
tions; while some groups tend to utilize 6 weeks124,126,133,143,144; subsequently, it is
223
possible to switch to oral medication in with associated sequelae may lead patients
patients without clinical or radiographic to refuse replacement of the hardware or
evidence of intracranial involvement.126,144 choose to undergo ablative therapy, even
After completion of antibiotics and an as- though such methods have largely been
ymptomatic period, hardware replacement abandoned.135
is generally possible, with reported time
to reimplantation ranging from 3 to 11 Prevention
months.124,126,137
Although consensus regarding the early The prevention of DBS hardware-related in-
management of DBS device-related infec- fection largely centers on the careful mod-
tions has proved difficult, review of the ulation of perioperative factors. Clinicians
literature supports an initial attempt at routinely use a preoperative antibiotic,
management with antibiotics in selected most commonly cefazolin or vancomycin
cases, followed by hardware removal if (for those allergic to penicillin), to pre-
the infection persists.121 Antibiotics alone vent postoperative infection.117,119,124,125 Al-
may be sufficient to treat superficial, local- though some physicians prefer to prescribe
ized infections at the distal system com- a course of antibiotics after implantation,
ponents121,143; however, if deep infection little evidence exists to suggest that post-
with clear involvement of the internal operative antibiotics prevent infection,117
pulse generator or external lead extenders nor does the use of intraoperatively pouch-
is present, partial hardware removal with installed antibiotics or the completion of
preservation of the intracranial leads is ap- implantation in one procedure rather than
a staged procedure.147 The use of a self-ad-
propriate.143 Additionally, in these cases,

unaffected contralateral hardware may be ministered 70% ethyl alcohol wash above
left in place.121,139 Patients who have diffuse the waist on the evening and morning be-
infection of the system with extensive cel- fore surgery has been found to decrease the
lulitis or multiple purulent sites along the risk for infection significantly.142 One series
tract and those who have involvement of noted that shaving the head before surgery
intracranial components will likely require did not reduce the infection rate; therefore,
early removal of the entire system for ef- the authors modified their clinical practice
fective treatment.121,138,143 to eliminate head shaving.140 Intraopera-
tively, the injection of a dilute povidone-io-
dine irrigation, which is superior to saline
Outcomes
and is bactericidal against MRSA, has been
Although most patients with infection re- successfully utilized.153,154 Alternatively, ir-
quiring hardware removal eventually are rigation with a solution of 40 mg of neomy-
able to undergo replacement, this man- cin and 200,000 U of polymyxin B sulfate
agement is not without serious reper- just after fascial closure but before skin clo-
cussions. After removal, patients are left sure has been shown to reduce the risk for
for an extended period of time (up to 11 infection in patients receiving neurosurgi-
months in some series) without treat- cal hardware.137 Additionally, the use of ce-
ment, and if they are unfortunate enough ment containing erythromycin and colistin
to develop an abscess, they may be unable for fixation of the intracerebral electrode
ever to undergo replacement.126 In addi- has been advocated.139 Depending on the
tion to losing the benefits of stimulation, type of hardware available, some surgeons
patients are subjected to further lengthy may choose to drill troughs into the skull
stereotactic procedures,137 during which above the mastoid to lower the profile of
the risk for permanent neurologic deficit, the connector and reduce the risk for scalp
although small, does exist; they are also erosion135; however, with the advent of
subjected to additional hospitalizations, low-profile connection cables, skin erosion
the long-term use of antibiotics, and ad- and the risk for infection at this site have
ditional cost.125 Lastly, repeated infection been greatly reduced.128
224
References cerebrospinal fluid shunt infection. J Neurosurg
2006;104(1, Suppl):5–8 PubMed
1. S impkins CJ. Ventriculoperitoneal shunt infec- 17. R agel BT, Browd SR, Schmidt RH. Surgical shunt
tions in patients with hydrocephalus. Pediatr infection: significant reduction when using in-
Nurs 2005;31(6):457–462 PubMed traventricular and systemic antibiotic agents. J
2. Kestle JR. Pediatric hydrocephalus: current Neurosurg 2006;105(2):242–247 PubMed
management. Neurol Clin 2003;21(4):883–895, 18. T acconelli E, Cataldo MA, Albanese A, et al.
vii PubMed Vancomycin versus cefazolin prophylaxis for
3. Kestle JRW, Garton HJL, Whitehead WE, et al. cerebrospinal shunt placement in a hospital
Management of shunt infections: a multicenter with a high prevalence of methicillin-resistant

pilot study. J Neurosurg 2006;105(3, Suppl): Staphylococcus aureus. J Hosp Infect 2008;69(4):
4. Korinek A-M, Fulla-Oller L, Boch A-L, Golmard 19. Cochrane DD, Kestle JRW. The influence of surgical
J-L, Hadiji B, Puybasset L. Morbidity of ventricu- operative experience on the duration of first ven-
lar cerebrospinal fluid shunt surgery in adults: triculoperitoneal shunt function and infection.
an 8-year study. Neurosurgery 2011;68(4):985– Pediatr Neurosurg 2003;38(6):295–301 PubMed
994, discussion 994–995 PubMed 20. W ang K-W, Chang W-N, Shih T-Y, et al. Infection
5. Boaz JC. Central nervous system infectious dis- of cerebrospinal fluid shunts: causative patho-
eases and therapy. In: Roos KL, ed. Neurologi- gens, clinical features, and outcomes. Jpn J Infect
cal Disease and Therapy. New York, NY: Marcel Dis 2004;57(2):44–48 PubMed
Dekker; 1997:519–544 21. M cGirt MJ, Zaas A, Fuchs HE, George TM, Kaye
6. Nulsen FE, Spitz EB. Treatment of hydrocephalus K, Sexton DJ. Risk factors for pediatric ven-
by direct shunt from ventricle to jugular vain. triculoperitoneal shunt infection and predic-
Surg Forum 1951;399–403 PubMed tors of infectious pathogens. Clin Infect Dis
7. Bondurant CP, Jimenez DF. Epidemiology of ce- 2003;36(7):858–862 PubMed
rebrospinal fluid shunting. Pediatr Neurosurg 22. M cClinton D, Carraccio C, Englander R. Predic-
1995;23(5):254–258, discussion 259 PubMed tors of ventriculoperitoneal shunt pathology.
8. Massimi L, Paternoster G, Fasano T, Di Rocco C. Pediatr Infect Dis J 2001;20(6):593–597 PubMed
On the changing epidemiology of hydrocephalus. 23. W alters BC, Hoffman HJ, Hendrick EB, Hum-
Childs Nerv Syst 2009;25(7):795–800 PubMed phreys RP. Cerebrospinal fluid shunt infec-
9. Cochrane DD, Kestle J. Ventricular shunting for tion. Influences on initial management and
hydrocephalus in children: patients, procedures, subsequent outcome. J Neurosurg 1984;60(5):
surgeons and institutions in English Canada, 1014–1021 PubMed
1989-2001. Eur J Pediatr Surg 2002;12(Suppl 1): 24. K ulkarni AV, Drake JM, Lamberti-Pasculli M. Ce-
S6–S11 PubMed rebrospinal fluid shunt infection: a prospective
10. Fernell E, Hagberg G, Hagberg B. Infantile hy- study of risk factors. J Neurosurg 2001;94(2):
drocephalus—the impact of enhanced preterm 195–201 PubMed
survival. Acta Paediatr Scand 1990;79(11): 25. F ilka J, Huttova M, Tuharsky J, Sagat T, Kralinsky
1080–1086 PubMed K, Krcmery V Jr. Nosocomial meningitis in chil-
11. Drake JM, Kestle JR, Milner R, et al. Randomized trial dren after ventriculoperitoneal shunt insertion.
of cerebrospinal fluid shunt valve design in pediat- Acta Paediatr 1999;88(5):576–578 PubMed
ric hydrocephalus. Neurosurgery 1998;43(2):294– 26. Stamos JK, Kaufman BA, Yogev R. Ventriculoperi-
303, discussion 303–305 PubMed toneal shunt infections with gram-negative bac-
12. Kestle JRW, Drake JM, Cochrane DD, et al; Endo- teria. Neurosurgery 1993;33(5):858–862 PubMed
scopic Shunt Insertion Trial participants. Lack 27. Shapiro S, Boaz J, Kleiman M, Kalsbeck J, Mealey J.
of benefit of endoscopic ventriculoperitoneal Origin of organisms infecting ventricular shunts.
shunt insertion: a multicenter randomized trial. Neurosurgery 1988;22(5):868–872 PubMed
J Neurosurg 2003;98(2):284–290 PubMed 28. P russeit J, Simon M, von der Brelie C, et al. Epi-
13. Steinbok P, Milner R, Agrawal D, et al. A mul- demiology, prevention and management of ven-
ticenter multinational registry for assess- triculoperitoneal shunt infections in children.
ing ventriculoperitoneal shunt infections for Pediatr Neurosurg 2009;45(5):325–336 PubMed
hydrocephalus. Neurosurgery 2010;67(5): 29. C onen A, Walti LN, Merlo A, Fluckiger U, Bat-
1303–1310 PubMed tegay M, Trampuz A. Characteristics and
14. Simon TD, Hall M, Dean JM, Kestle JRW, Riva- treatment outcome of cerebrospinal fluid shunt-
Cambrin J. Reinfection following initial cerebro- associated infections in adults: a retrospective
spinal fluid shunt infection. J Neurosurg Pediatr analysis over an 11-year period. Clin Infect Dis
2010;6(3):277–285 PubMed 2008;47(1):73–82 PubMed
15. Simon TD, Hall M, Riva-Cambrin J, et al; Hydro- 30. L und-Johansen MSF, Svendsen F, Wester K. Shunt
cephalus Clinical Research Network. Infection failures and complications in adults as related to
rates following initial cerebrospinal fluid shunt shunt type, diagnosis, and the experience of the
placement across pediatric hospitals in the Unit- surgeon. Neurosurgery 1994;35(5):839–844,
ed States. Clinical article. J Neurosurg Pediatr discussion 844 PubMed
2009;4(2):156–165 PubMed 31. K
ontny U, Höfling B, Gutjahr P, Voth D, Schwarz
16. Tulipan N, Cleves MA. Effect of an intraopera- M, Schmitt HJ. CSF shunt infections in children.
tive double-gloving strategy on the incidence of Infection 1993;21(2):89–92 PubMed
225
32. anaclocha V, Sáiz-Sapena N, Leiva J. Shunt mal-
V 49. K an PKJ, Kestle J. Lack of efficacy of antibiotic-im-
function in relation to shunt infection. Acta Neu- pregnated shunt systems in preventing shunt in-
rochir (Wien) 1996;138(7):829–834 PubMed fections in children. Childs Nerv Syst 2007;23(7):
33. Bayston RLJ, Lari J. A study of the sources of in- 773–777 PubMed
fection in colonised shunts. Dev Med Child Neu- 50. R itz RRF, Roser F, Morgalla M, Dietz K, Tatagiba
rol 1974;16(6, Suppl 32):16–22 PubMed M, Will BE. Do antibiotic-impregnated shunts in
34. Bayston R, Ashraf W, Bhundia C. Mode of ac- hydrocephalus therapy reduce the risk of infec-
tion of an antimicrobial biomaterial for use in tion? An observational study in 258 patients.
hydrocephalus shunts. J Antimicrob Chemother BMC Infect Dis 2007;7(5):38 PubMed
2004;53(5):778–782 PubMed 51. H e W, Sengupta M, Velkoff VA, et al. 65+ in the
35. McLaurin RL, Frame PT. Treatment of infections United States: 2005. In: Current Population Re-
of cerebrospinal fluid shunts. Rev Infect Dis ports. Washington, DC: US Government Print-
1987;9(3):595–603 PubMed ing Office; 2005:23–209. www.census.gov/
36. D uhaime AC. Evaluation and management of prod/2006pubs/p23-209.pdf. Accessed Decem-
shunt infections in children with hydrocephalus. ber 22, 2012
Clin Pediatr (Phila) 2006;45(8):705–713 PubMed 52. N ationwide Inpatient Sample (NIS). Healthcare
37. Wong GKC, Wong SM, Poon WS. Ventriculoperi- Cost and Utilization Project (HCUP). 2007–2009.
toneal shunt infection: intravenous antibiotics, Rockville, MD: Agency for Healthcare Research
shunt removal and more aggressive treatment? and Quality. www.hcup-us.ahrq.gov/nisover-
ANZ J Surg 2011;81(4):307 PubMed view.jsp. Accessed December 22, 2012
38. B rown EM, Edwards RJ, Pople IK. Conservative 53. M angram AJ, Horan TC, Pearson ML, et al. Hos-
management of patients with cerebrospinal pital Infection Control Practices Advisory Com-
fluid shunt infections. Neurosurgery 2006;58(4): mittee (HICPAC) and Centers for Disease Control
657–665 PubMed and Prevention (CDC). Guidelines for prevention
39. Anderson EJ, Yogev R. A rational approach to the of surgical site infection. Infect Control Hosp
management of ventricular shunt infections. Pe- Epidemiol 1999;24:247–278
diatr Infect Dis J 2005;24(6):557–558 PubMed 54. C haudhary SB, Vives MJ, Basra SK, Reiter MF.
40. Arnell K, Enblad P, Wester T, Sjölin J. Treat-
Postoperative spinal wound infections and post-
ment of cerebrospinal fluid shunt infections in procedural diskitis. J Spinal Cord Med 2007;
children using systemic and intraventricular 30(5):441–451 PubMed
antibiotic therapy in combination with exter- 55. Levi AD, Dickman CA, Sonntag VK. Management of
nalization of the ventricular catheter: efficacy in postoperative infections after spinal instrumenta-
34 consecutively treated infections. J Neurosurg tion. J Neurosurg 1997;86(6):975–980 PubMed
2007;107(3, Suppl):213–219 PubMed 56. R
echtine GR, Bono PL, Cahill D, Bolesta MJ, Chrin
41. Lutsar IMG, McCracken GH Jr, Friedland IR. Anti- AM. Postoperative wound infection after instru-
biotic pharmacodynamics in cerebrospinal fluid. mentation of thoracic and lumbar fractures. J
Clin Infect Dis 1998;27(5):1117–1127, quiz Orthop Trauma 2001;15(8):566–569 PubMed
1128–1129 PubMed 57. R
ihn JA, Lee JY, Ward WT. Infection after the sur-
42. James HE, Bradley JS. Aggressive management gical treatment of adolescent idiopathic scolio-
of shunt infection: combined intravenous and sis: evaluation of the diagnosis, treatment, and
intraventricular antibiotic therapy for twelve impact on clinical outcomes. Spine (Phila Pa
or less days. Pediatr Neurosurg 2008;44(2): 1976) 2008;33(3):289–294 PubMed
104–111 PubMed 58. V
eeravagu A, Patil CG, Lad SP, Boakye M. Risk
43. James HE, Walsh JW, Wilson HD, Connor JD,
factors for postoperative spinal wound infec-
Bean JR, Tibbs PA. Prospective randomized study tions after spinal decompression and fusion
of therapy in cerebrospinal fluid shunt infection. surgeries. Spine (Phila Pa 1976) 2009;34(17):
Neurosurgery 1980;7(5):459–463 PubMed 1869–1872 PubMed
44. Yogev R. Cerebrospinal fluid shunt infections: 59. M
ok JM, Guillaume TJ, Talu U, et al. Clinical
a personal view. Pediatr Infect Dis 1985;4(2): outcome of deep wound infection after instru-
113–118 PubMed mented posterior spinal fusion: a matched co-
45. Schreffler RT, Schreffler AJ, Wittler RR. Treat- hort analysis. Spine (Phila Pa 1976) 2009;34(6):
ment of cerebrospinal fluid shunt infections: a 578–583 PubMed
decision analysis. Pediatr Infect Dis J 2002;21(7): 60. W
atanabe M, Sakai D, Matsuyama D, Yamamoto
632–636 PubMed Y, Sato M, Mochida J. Risk factors for surgical site
46. Hunt GMHA, Holmes AE. Factors relating to in- infection following spine surgery: efficacy of in-
telligence in treated cases of spina bifida cystica. traoperative saline irrigation. J Neurosurg Spine
Am J Dis Child 1976;130(8):823–827 PubMed 2010;12(5):540–546 PubMed
47. Chadduck WAJ, Adametz J. Incidence of seizures in 61. M
eredith DS, Kepler CK, Huang RC, Brause BD,
patients with myelomeningocele: a multifactorial Boachie-Adjei O. Postoperative infections of the
analysis. Surg Neurol 1988;30(4):281–285 PubMed lumbar spine: presentation and management.
48. Bayston R, Ashraf W, Fisher L. Prevention of
Int Orthop 2012;36(2):439–444 PubMed
infection in neurosurgery: role of “antimicro- 62. O
lsen MA, Mayfield J, Lauryssen C, et al. Risk fac-
bial” catheters. J Hosp Infect 2007;65(Suppl 2): tors for surgical site infection in spinal surgery. J
39–42 PubMed Neurosurg 2003;98(2, Suppl):149–155 PubMed
226
63. ull ter Gunne AF, Cohen DB. Incidence, preva-
P 2,391 consecutive index procedures. J Spinal
lence, and analysis of risk factors for surgical site Disord 2000;13(5):422–426 PubMed
infection following adult spinal surgery. Spine 79. W
immer C, Gluch H, Franzreb M, Ogon M. Pre-
(Phila Pa 1976) 2009;34(13):1422–1428 PubMed disposing factors for infection in spine surgery: a
64. Friedman ND, Sexton DJ, Connelly SM, Kaye KS. survey of 850 spinal procedures. J Spinal Disord
Risk factors for surgical site infection complicat- 1998;11(2):124–128 PubMed
ing laminectomy. Infect Control Hosp Epidemiol 80. T
helander U, Larsson S. Quantitation of C-re-
2007;28(9):1060–1065 PubMed active protein levels and erythrocyte sedimen-
65. Capen DA, Calderone RR, Green A. Periopera- tation rate after spinal surgery. Spine (Phila Pa
tive risk factors for wound infections after lower 1976) 1992;17(4):400–404 PubMed

back fusions. Orthop Clin North Am 1996;27(1): 81. A
bdul-Jabbar A, Takemoto S, Weber MH, et al.
83–86 PubMed Surgical site infection in spinal surgery: descrip-
66. Goodson WH III, Hung TK. Studies of wound
tion of surgical and patient-based risk factors
healing in experimental diabetes mellitus. J Surg for postoperative infection using administra-
Res 1977;22(3):221–227 PubMed tive claims data. Spine (Phila Pa 1976) 2012;
67. Beiner JM, Grauer J, Kwon BK, Vaccaro AR. Post- 37(15):1340–1345 PubMed
operative wound infections of the spine. Neuro- 82. S
chwarzkopf R, Chung C, Park JJ, Walsh M, Spi-
surg Focus 2003;15(3):E14 PubMed vak JM, Steiger D. Effects of perioperative blood
68. Schimmel JJ, Horsting PP, de Kleuver M, Wonders product use on surgical site infection following
G, van Limbeek J. Risk factors for deep surgical thoracic and lumbar spinal surgery. Spine (Phila
site infections after spinal fusion. Eur Spine J Pa 1976) 2010;35(3):340–346 PubMed
2010;19(10):1711–1719 PubMed 83. Koutsoumbelis S, Hughes AP, Girardi FP, et al. Risk
69. Cho KJ, Suk SI, Park SR, et al. Complications in factors for postoperative infection following pos-
posterior fusion and instrumentation for degen- terior lumbar instrumented arthrodesis. J Bone
erative lumbar scoliosis. Spine (Phila Pa 1976) Joint Surg Am 2011;93(17):1627–1633 PubMed
2007;32(20):2232–2237 PubMed 84. P
arker SL, Adogwa O, Witham TF, Aaronson OS,
70. Fang A, Hu SS, Endres N, Bradford DS. Risk factors Cheng J, McGirt MJ. Post-operative infection af-
for infection after spinal surgery. Spine (Phila ter minimally invasive versus open transforami-
Pa 1976) 2005;30(12):1460–1465 PubMed nal lumbar interbody fusion (TLIF): literature
71. Glassman SD, Dimar JR, Puno RM, Johnson JR. review and cost analysis. Minim Invasive Neuro-
Salvage of instrumental lumbar fusions compli- surg 2011;54(1):33–37 PubMed
cated by surgical wound infection. Spine (Phila 85. M
cGirt MJ, Parker SL, Lerner J, Engelhart L, Knight
Pa 1976) 1996;21(18):2163–2169 PubMed T, Wang MY. Comparative analysis of periop-
72. Kornberg M, Rechtine GR, Herndon WA, Rein- erative surgical site infection after minimally
ert CM, Dupuy TE. Surgical stabilization of invasive versus open posterior/transforaminal
thoracic and lumbar spine fractures: a retro- lumbar interbody fusion: analysis of hospital
spective study in a military population. J Trauma billing and discharge data from 5170 patients. J
1984;24(2):140–146 PubMed Neurosurg Spine 2011;14(6):771–778 PubMed
73. Olsen MA, Nepple JJ, Riew KD, et al. Risk fac- 86. C
ampbell PG, Yadla S, Malone J, et al. Early com-
tors for surgical site infection following ortho- plications related to approach in cervical spine
paedic spinal operations. J Bone Joint Surg Am surgery: single-center prospective study. World
2008;90(1):62–69 PubMed Neurosurg 2010;74(2-3):363–368 PubMed
74. Sasso RC, Garrido BJ. Postoperative spinal
87. F
ehlings MG, Smith JS, Kopjar B, et al. Periop-
wound infections. J Am Acad Orthop Surg 2008; erative and delayed complications associated
16(6):330–337 PubMed with the surgical treatment of cervical spon-
75. Sierra-Hoffman M, Jinadatha C, Carpenter JL, dylotic myelopathy based on 302 patients from
Rahm M. Postoperative instrumented spine in- the AOSpine North America Cervical Spondy-
fections: a retrospective review. South Med J lotic Myelopathy Study. J Neurosurg Spine 2012;
2010;103(1):25–30 PubMed 16(5):425–432 PubMed
76. Smith JS, Shaffrey CI, Sansur CA, et al; Scoliosis 88. F
ountas KN, Kapsalaki EZ, Nikolakakos LG, et
Research Society Morbidity and Mortality Com- al. Anterior cervical discectomy and fusion as-
mittee. Rates of infection after spine surgery sociated complications. Spine (Phila Pa 1976)
based on 108,419 procedures: a report from 2007;32(21):2310–2317 PubMed
the Scoliosis Research Society Morbidity and 89. K
anayama M, Hashimoto T, Shigenobu K, Oha F,
Mortality Committee. Spine (Phila Pa 1976) Togawa D. Effective prevention of surgical site
2011;36(7):556–563 PubMed infection using a Centers for Disease Control and
77. Sponseller PD, LaPorte DM, Hungerford MW,
Prevention guideline-based antimicrobial pro-
Eck K, Bridwell KH, Lenke LG. Deep wound in- phylaxis in lumbar spine surgery. J Neurosurg
fections after neuromuscular scoliosis surgery: Spine 2007;6(4):327–329 PubMed
a multicenter study of risk factors and treat- 90. S
cuderi GJ, Brusovanik GV, Fitzhenry LN, Vac-
ment outcomes. Spine (Phila Pa 1976) 2000; caro AR. Is wound drainage necessary after
25(19):2461–2466 PubMed lumbar spinal fusion surgery? Med Sci Monit
78. Weinstein MA, McCabe JP, Cammisa FP Jr. Post- 2005;11(2):CR64–CR66 PubMed
operative spinal wound infection: a review of 91. D
iab M, Smucny M, Dormans JP, et al. Use and
outcomes of wound drain in spinal fusion for
227
adolescent idiopathic scoliosis. Spine (Phila Pa 106. K han MH, Smith PN, Rao N, Donaldson WF. Se-
1976) 2012;37(11):966–973 PubMed rum C-reactive protein levels correlate with clin-
92. Rao SB, Vasquez G, Harrop J, et al. Risk factors for ical response in patients treated with antibiotics
surgical site infections following spinal fusion for wound infections after spinal surgery. Spine J
procedures: a case-control study. Clin Infect Dis 2006;6(3):311–315 PubMed
2011;53(7):686–692 PubMed 107. Weiss LE, Vaccaro AR, Scuderi G, McGuire M,
93. Mok JM, Pekmezci M, Piper SL, et al. Use of C-reac- Garfin SR. Pseudarthrosis after postoperative
tive protein after spinal surgery: comparison with wound infection in the lumbar spine. J Spinal
erythrocyte sedimentation rate as predictor of ear- Disord 1997;10(6):482–487 PubMed
ly postoperative infectious complications. Spine 108. Borowski A, Littleton AG, Borkhuu B, et al.
(Phila Pa 1976) 2008;33(4):415–421 PubMed Complications of intrathecal baclofen pump
94. Kang BU, Lee SH, Ahn Y, Choi WC, Choi YG. Sur- therapy in pediatric patients. J Pediatr Orthop
gical site infection in spinal surgery: detection 2010;30(1):76–81 PubMed
and management based on serial C-reactive 109. Fjelstad AB, Hommelstad J, Sorteberg A. Infec-
protein measurements. J Neurosurg Spine tions related to intrathecal baclofen therapy in
2010;13(2):158–164 PubMed children and adults: frequency and risk factors. J
95. Takahashi J, Ebara S, Kamimura M, et al. Early- Neurosurg Pediatr 2009;4(5):487–493 PubMed
phase enhanced inflammatory reaction after 110. Motta F, Buonaguro V, Stignani C. The use of in-
spinal instrumentation surgery. Spine (Phila Pa trathecal baclofen pump implants in children
1976) 2001;26(15):1698–1704 PubMed and adolescents: safety and complications in
96. Falavigna A, Righesso O, Traynelis VC, Teles AR, 200 consecutive cases. J Neurosurg 2007;107(1,
da Silva PG. Effect of deep wound infection fol- Suppl):32–35 PubMed
lowing lumbar arthrodesis for degenerative 111. Njee TB, Irthum B, Roussel P, Peragut JC. Intrathe-
disc disease on long-term outcome: a prospec- cal morphine infusion for chronic non-malignant
tive study: clinical article. J Neurosurg Spine pain: a multiple center retrospective survey.
2011;15(4):399–403 PubMed Neuromodulation 2004;7(4):249–259. doi: 10
97. Petilon JM, Glassman SD, Dimar JR, Carreon LY. .1111/j.1094-7159.2004.04210.x PubMed
Clinical outcomes after lumbar fusion compli- 112. Kallweit U, Harzheim M, Marklein G, Welt T,
cated by deep wound infection: a case-control Pöhlau D. Successful treatment of methicillin-

study. Spine (Phila Pa 1976) 2012;37(16): resistant Staphylococcus aureus meningitis using
1370–1374 PubMed linezolid without removal of intrathecal infusion
98. El-Gindi S, Aref S, Salama M, Andrew J. Infection pump. Case report. J Neurosurg 2007;107(3):
of intervertebral discs after operation. J Bone 651–653 PubMed
Joint Surg Br 1976;58(1):114–116 PubMed 113. Boviatsis EJ, Kouyialis AT, Boutsikakis I, Korfias S,
99. Bassewitz HL, Fishgrund JS, Herkowitz HN. Post- Sakas DE. Infected CNS infusion pumps. Is there
operative spine infections. Semin Spine Surg a chance for treatment without removal? Acta
2000;12:203–211 Neurochir (Wien) 2004;146(5):463–467 PubMed
100. Richards BS. Delayed infections following pos- 114. Hester SM, Fisher JF, Lee MR, Macomson S,
terior spinal instrumentation for the treatment Vender JR. Evaluation of salvage techniques
of idiopathic scoliosis. J Bone Joint Surg Am for infected baclofen pumps in pediatric pa-
1995;77(4):524–529 PubMed tients with cerebral palsy. J Neurosurg Pediatr
101. Collins I, Wilson-MacDonald J, Chami G, et al. 2012;10(6):548–554 PubMed
The diagnosis and management of infection fol- 115. Zed PJ, Stiver HG, Devonshire V, Jewesson PJ,
lowing instrumented spinal fusion. Eur Spine J Marra F. Continuous intrathecal pump infusion
2008;17(3):445–450 PubMed of baclofen with antibiotic drugs for treatment
102. Venturi ML, Attinger CE, Mesbahi AN, Hess CL,
of pump-associated meningitis. Case report. J
Graw KS. Mechanisms and clinical applications of Neurosurg 2000;92(2):347–349 PubMed
the vacuum-assisted closure (VAC) Device: a review. 116. Galloway A, Falope FZ. Pseudomonas aeruginosa in-
Am J Clin Dermatol 2005;6(3):185–194 PubMed fection in an intrathecal baclofen pump: successful
103. van Rhee MA, de Klerk LW, Verhaar JA. Vacuum- treatment with adjunct intra-reservoir gentamicin.
assisted wound closure of deep infections after Spinal Cord 2000;38(2):126–128 PubMed
instrumented spinal fusion in six children with 117. Fenoy AJ, Simpson RK Jr. Management of device-
neuromuscular scoliosis. Spine J 2007;7(5): related wound complications in deep brain
596–600 PubMed stimulation surgery. J Neurosurg 2012;116(6):
104. Vicario C, de Juan J, Esclarin A, Alcobendas M. 1324–1332 PubMed
Treatment of deep wound infections after spi- 118. Themistocleous MS, Boviatsis EJ, Stathis P,
nal fusion with a vacuum-assisted device in pa- Stavrinou LC, Sakas DE. Infected internal pulse
tients with spinal cord injury. Acta Orthop Belg generator: treatment without removal. Surg
2007;73(1):102–106 PubMed Neurol Int 2011;2:33 PubMed
105. Mehbod AA, Ogilvie JW, Pinto MR, et al. Post- 119. Baizabal Carvallo JF, Simpson R, Jankovic J. Di-
operative deep wound infections in adults after agnosis and treatment of complications related
spinal fusion: management with vacuum-assist- to deep brain stimulation hardware. Mov Disord
ed wound closure. J Spinal Disord Tech 2005; 2011;26(8):1398–1406 PubMed
18(1):14–17 PubMed
228
120. Voges J, Waerzeggers Y, Maarouf M, et al. 134. G oodman RR, Kim B, McClelland S III, et al. Op-
Deep-brain stimulation: long-term analysis of erative techniques and morbidity with subtha-
complications caused by hardware and surgery— lamic nucleus deep brain stimulation in 100
experiences from a single centre. J Neurol Neuro- consecutive patients with advanced Parkin-
surg Psychiatry 2006;77(7):868–872 PubMed son’s disease. J Neurol Neurosurg Psychiatry
121. Constantoyannis C, Berk C, Honey CR, Mendez 2006;77(1):12–17 PubMed
I, Brownstone RM. Reducing hardware-related 135. Bronstein JM, Tagliati M, Alterman RL, et al. Deep
complications of deep brain stimulation. Can J brain stimulation for Parkinson disease: an ex-
Neurol Sci 2005;32(2):194–200 PubMed pert consensus and review of key issues. Arch
122. Resnick AS, Foote KD, Rodriguez RL, et al. The Neurol 2011;68(2):165 PubMed

number and nature of emergency department 136. Haridas A, Tagliati M, Osborn I, et al. Pallidal
encounters in patients with deep brain stimula- deep brain stimulation for primary dystonia in
tors. J Neurol 2010;257(1):122–131 PubMed children. Neurosurgery 2011;68(3):738–743,
123. Müller-Vahl KR, Cath DC, Cavanna AE, et al; ESSTS discussion 743 PubMed
Guidelines Group. European clinical guidelines 137. Miller JP, Acar F, Burchiel KJ. Significant reduc-
for Tourette syndrome and other tic disorders. tion in stereotactic and functional neurosurgical
Part IV: deep brain stimulation. Eur Child Ado- hardware infection after local neomycin/poly-
lesc Psychiatry 2011;20(4):209–217 PubMed myxin application. J Neurosurg 2009;110(2):
124. Piacentino M, Pilleri M, Bartolomei L. Hardware- 247–250 PubMed
related infections after deep brain stimulation 138. Sillay KA, Larson PS, Starr PA. Deep brain stimu-
surgery: review of incidence, severity and man- lator hardware-related infections: incidence and
agement in 212 single-center procedures in the management in a large series. Neurosurgery
first year after implantation. Acta Neurochir 2008;62(2):360–366, discussion 366–367 PubMed
(Wien) 2011;153(12):2337–2341 PubMed 139. Temel Y, Ackermans L, Celik H, et al. Manage-
125. Oh MY, Abosch A, Kim SH, Lang AE, Lozano AM. ment of hardware infections following deep
Long-term hardware-related complications of brain stimulation. Acta Neurochir (Wien)
deep brain stimulation. Neurosurgery 2002;50(6): 2004;146(4):355–361, discussion 361 PubMed
1268–1274, discussion 1274–1276 PubMed 140. Umemura A, Jaggi JL, Hurtig HI, et al. Deep brain
126. Fily F, Haegelen C, Tattevin P, et al. Deep brain stimulation for movement disorders: morbid-
stimulation hardware-related infections: a re- ity and mortality in 109 patients. J Neurosurg
port of 12 cases and review of the literature. Clin 2003;98(4):779–784 PubMed
Infect Dis 2011;52(8):1020–1023 PubMed 141. Bhatia S, Zhang K, Oh M, Angle C, Whiting D. In-
127. Sixel-Döring F, Trenkwalder C, Kappus C, Hell- fections and hardware salvage after deep brain
wig D. Skin complications in deep brain stimu- stimulation surgery: a single-center study and
lation for Parkinson’s disease: frequency, time review of the literature. Stereotact Funct Neuro-
course, and risk factors. Acta Neurochir (Wien) surg 2010;88(3):147–155 PubMed
2010;152(2):195–200 PubMed 142. Halpern CH, Mitchell GW, Paul A, et al. Self-
128. Blomstedt P, Hariz MI. Hardware-related compli- administered preoperative antiseptic wash
cations of deep brain stimulation: a ten year ex- to prevent postoperative infection after deep
perience. Acta Neurochir (Wien) 2005;147(10): brain stimulation. Am J Infect Control 2012;
1061–1064, discussion 1064 PubMed 40(5):431–433 PubMed
129. Chan DTM, Zhu XL, Yeung JHM, et al. Complica- 143. Vergani F, Landi A, Pirillo D, Cilia R, Antonini
tions of deep brain stimulation: a collective re- A, Sganzerla EP. Surgical, medical, and hard-
view. Asian J Surg 2009;32(4):258–263 PubMed ware adverse events in a series of 141 patients
130. Benabid A, Koudsie A, Benazzouz A. Subthalamic undergoing subthalamic deep brain stimula-
nucleus deep brain stimulation. In: Lozano A, ed. tion for Parkinson disease. World Neurosurg
Movement Disorders Surgery. Progress in Neu- 2010;73(4):338–344 PubMed
rological Surgery. Basel, Switzerland: Karger; 144. Gorgulho A, Juillard C, Uslan DZ, et al. Infection
2000:196–226 following deep brain stimulator implantation
131. Seijo FJ, Alvarez-Vega MA, Gutierrez JC, Fdez- performed in the conventional versus magnetic
Glez F, Lozano B. Complications in subthalamic resonance imaging-equipped operating room. J
nucleus stimulation surgery for treatment of Neurosurg 2009;110(2):239–246 PubMed
Parkinson’s disease. Review of 272 procedures. 145. Kenney C, Simpson R, Hunter C, et al. Short-term
Acta Neurochir (Wien) 2007;149(9):867–875, and long-term safety of deep brain stimulation
discussion 876 PubMed in the treatment of movement disorders. J Neu-
132. Paluzzi A, Belli A, Bain P, Liu X, Aziz TM. Opera- rosurg 2007;106(4):621–625 PubMed
tive and hardware complications of deep brain 146. Voges J, Hilker R, Bötzel K, et al. Thirty days
stimulation for movement disorders. Br J Neuro- complication rate following surgery per-
surg 2006;20(5):290–295 PubMed formed for deep-brain-stimulation. Mov Disord
133. Boviatsis EJ, Stavrinou LC, Themistocleous M, 2007;22(10):1486–1489 PubMed
Kouyialis AT, Sakas DE. Surgical and hardware 147. Bhatia R, Dalton A, Richards M, Hopkins C, Aziz T,
complications of deep brain stimulation. A Nandi D. The incidence of deep brain stimulator
seven-year experience and review of the lit- hardware infection: the effect of change in antibi-
erature. Acta Neurochir (Wien) 2010;152(12): otic prophylaxis regimen and review of the litera-
2053–2062 PubMed ture. Br J Neurosurg 2011;25(5):625–631 PubMed
229
148. H amani C, Lozano AM. Hardware-related com- 152. R eal R, Linhares P, Fernandes H, et al. Role of
plications of deep brain stimulation: a review of Tc-Sulesomab immunoscintigraphy in the man-
the published literature. Stereotact Funct Neuro- agement of infection following deep brain stimu-
surg 2006;84(5-6):248–251 PubMed lation surgery. Neurology Research International
149. Merello M, Cammarota A, Leiguarda R, Pikielny R. 2011;2011:817-951. doi: 10.1155/2011/817951
Delayed intracerebral electrode infection after bilat- 153. Cheng MT, Chang MC, Wang ST, Yu WK, Liu CL,
eral STN implantation for Parkinson’s disease. Case Chen TH. Efficacy of dilute betadine solution ir-
report. Mov Disord 2001;16(1):168–170 PubMed rigation in the prevention of postoperative in-
150. Vanderhorst VG, Papavassiliou E, Tarsy D, fection of spinal surgery. Spine (Phila Pa 1976)
Shih L. Early brain abscess: a rare complica- 2005;30(15):1689–1693 PubMed
tion of deep brain stimulation. Mov Disord 154. Chundamala J, Wright JG. The efficacy and risks
2009;24(9):1395–1397 PubMed of using povidone-iodine irrigation to prevent
151. Deligny C, Drapier S, Verin M, Lajat Y, Raoul S, Dam- surgical site infection: an evidence-based re-
ier P. Bilateral subthalamotomy through DBS elec- view. Can J Surg 2007;50(6):473–481 PubMed
trodes: a rescue option for device-related infection.
Neurology 2009;73(15):1243–1244 PubMed
230
V
Special Populations
17
Pediatric Central Nervous
System Infections
Ian Mutchnick and Thomas M. Moriarty
This chapter focuses on two of the most tion focuses on the diagnostic challenges
common pediatric infectious conditions that may influence the decision to operate
requiring neurosurgical intervention: in- and the treatment options available to the
tracranial focal suppurative infections and neurosurgeon, with an emphasis on the
cerebrospinal fluid (CSF) ventricular shunt information required to choose the correct
infections. Limited space and the intended management pathway for the patient.
audience have directed content decisions.
This chapter is targeted at the neurosur- Clinical Context
geon, who will be managing the surgical
issues within the context of a team of pe- A recent review of large inpatient databas-
diatric specialists representing infectious es found that the rate of admission for all
disease, neuroradiology, intensive care, identifiable intracranial focal suppurative
and inpatient hospitalist services, who infections secondary to sinusitis or otitis
will provide depth in topics not covered (including epidural abscesses, subdural
in this chapter. Therefore, we have empha- empyemas, and brain abscesses) was 2.74
sized content more germane to the neu- to 4.38 per million children in the United
rosurgeon—detailed clinical information States.1 A busy neurosurgical service in the
required to bring clarity to the decision- developed world with two pediatric neuro-
making process and an explicit review of surgeons can therefore expect to see two
the literature on management. to four of these patients in a given year.1,2
Several key events have shaped our current
approach to these lesions. The introduc-
tion of antibiotics to patient care reduced
■■ Focal Intracranial reported mortality from between 60 and
Infectious Lesions 80% to between 20 and 40%.3 This rate has
been further reduced to between 0 and 10%
An abscess of the brain was one of in modern series both by the availability of
those cases which occurred but once computed tomography (CT) and magnetic
in the course of a lifetime. resonance (MR) imaging and by improve-
—Macewen, 1893 ments in antibiotic therapy.1,2,4,5
Extra-axial abscesses have a bimodal dis-
This section covers focal intracranial sup- tribution based on patient age. This finding
purative lesions: cranial epidural abscess, is consistent throughout the literature and
subdural empyema, and intraparenchymal was recently reiterated in a review of 70
abscess. Because specialists of the pediatric patients treated for extra-axial abscesses at
neurosurgical service usually see patients The Hospital for Sick Children in Toronto,
with these entities as consults, the sec- Canada, between 1995 and 2009.2 Fifty
percent of these children were older than low yield, though, because of their ease of
11 years of age, and 21% were below 1 year collection, they should be obtained on the
of age. In children younger than 5 years of slight chance of assisting in the microbial
age, the extra-axial abscess was most of- identification. CSF analysis for these le-
ten the consequence of meningitis or otitis sions is neither sensitive nor specific, and
media. All patients with post-meningitis results will often be normal.8
extra-axial abscesses were younger than 1 The identification of most extra-axial
year of age. All patients with post-sinusitis abscesses on CT and MR imaging is straight-
abscesses were older than 7 years of age forward. On CT scans, the extra-axial ab-
because the frontal sinus is not pneuma- scess will show a hypodense collection of
tized in younger children. Central nervous pus with enhancement along both the cor-
system (CNS) infection complicates 3 to tical and the dural border. T1-weighted MR
4% of hospital-admitted cases of sinusitis.6 imaging will show the pus collection to be
Valveless mucosal veins penetrate the in- iso- to hypointense, and on T2-weighted
ner lamina of this sinus and allow com- imaging it will be hyper- to isointense.10
munication with both the diploë and the On post-contrast MR imaging, there is usu-
dura mater.7 Unlike other etiologies, post- ally enhancement of the outer border on
operative extra-axial abscesses were seen the medial, lateral, or both margins. Infants
to span these age groups. can pose a radiographic challenge in dif-
Infants who develop a post-meningitic ferentiating a post-meningitic subdural
abscess (often subdural) have signs and empyema from a sterile reactive subdural
symptoms of meningitis that include a effusion. Although reactive subdural effu-
bulging fontanelle, and their condition of- sions can occur in 33% of infantile patients
ten fails to improve despite adequate an- with meningitis and usually do not require
tibiotic therapy for their meningitis.8 In intervention, subdural empyemas occur in
the older child, Pott puffy tumor is a com- only 1%.11 On ultrasound, the reactive sub-
mon finding in patients who have devel- dural effusion is usually anechoic, with the
oped an intracranial extra-axial abscess; thickened hyperechoic inner membranes
in the Toronto series, this was found in 16 and echogenic cerebral sulci characteris-
of 38 (42.1%) patients with post-sinusitis tic of meningitis. Chen et al were able to
abscesses.2,9 In the absence of a Pott puffy use ultrasound to correctly distinguish
tumor, the clinical presentation does not subdural empyema from reactive subdu-
follow a consistent pattern; although ral effusion in 15 of 16 lesions. They found
headache, fever, emesis, and meningismus that subdural empyema tends to be an-
are often present, the specificity of these echoic with prominent traversing fibrinous
findings is far too low to be used for ef- strands in the early stages and hyperechoic
fective decision making.8 However, the in its entirety with frequent loculi as it ma-
clinical presentation, in conjunction with tures.12 CT scans of a subdural empyema
a high degree of suspicion, often prompts can vary widely and lack high specificity or
imaging studies by the admitting and sub- sensitivity, although some authors in the
sequently the consult-seeking service, developing world have used CT as the sole
whereupon intracranial mass lesions are radiographic modality because of its acces-
revealed if present. Routine blood work is sibility and low cost.10,13,14 MR imaging is
rarely useful in diagnosing these infectious probably the best modality to differentiate
lesions. Neither a leukocytosis nor a left these entities. Wong et al reported on 10
shift is always present. The erythrocyte patients with a total of 12 lesions. Of the
sedimentation rate (ESR) and C-reactive 12 lesions, 10 were subdural empyemas
protein (CRP) level can be useful for moni- and 2 were reactive subdural effusions;
toring response to therapy for established MR images of 9 of the patients with sub-
lesions but lack the positive or negative dural empyemas revealed restricted diffu-
predictive value needed to be helpful in sion, while one image demonstrated mixed
diagnosis.8 Blood cultures are similarly of signal on diffusion-weighted imaging.
234
Both patients with reactive subdural effu- tous region with mass effect in the cereb-
sions demonstrated low signal intensity ritis stage or a ring-enhancing lesion with
on diffusion-weighted imaging.15 In older a hypodense interior in the later stages.
children, imaging is more straightforward, Early abscesses can have a radiographic
with CT the nearly universal modality used appearance similar to that of an ischemic
to evaluate children with a suspected ex- stroke on CT without contrast; therefore,
tra-axial suppurative process. MR imaging the index of clinical suspicion should guide
is often used to clarify anatomic detail or to the need for repeat CT with contrast or en-
characterize the abscess better in cases in hanced MR imaging.19 Characteristics that
which it will be followed with conservative distinguish mature abscess from tumor
treatment. In the previously cited Toronto are gas within the center of the lesion, a
series, MR imaging was used in only 12 of rim of less than 5 mm (which tends to be
38 patients with sinusitis-related extra-ax- thinner than that of a brain tumor), and
17 Pediatric Central Nervous System Infections

ial abscess; this may be related to the fact ependymal enhancement that can be as-
that the vast majority of these cases (64 sociated with ventriculitis or ventricular
of 70 patients) were managed operatively, rupture. Diffusion-weighted images show
necessitating only CT localization rather restriction (hyperintensity) in the interior
than the subtle definition of improvement of the abscess, with a dark absolute diffu-
with medical therapy.2 sion coefficient (ADC).18 If needed, further
Abscesses of the brain parenchyma tend differentiation from a tumor can be made
to have two main causes. Hematogenous with perfusion MR imaging, which dem-
spread occurs in children with congenital onstrates hypovascularity in an abscess
cyanotic heart disease and a left-to-right capsule and hypervascularity in a tumor
shunt, which bypasses the reticuloendo- capsule.8 A radioactively labeled leukocyte
thelium of the lung, or an infectious focus scan can also be used to diagnose an in-
elsewhere in the body. Contiguous spread fectious process in uncertain situations.20
can occur, as with extra-axial abscesses, In infants with an open fontanelle, ultra-
from sinus or middle ear disease. Cases sound can be used to diagnose and follow
arising from trauma or as a postsurgical intraparenchymal abscesses.21
complication are less common, while ab-
scess in the context of immunosuppression
is an increasingly frequent clinical situa-
tion.8 Some 10 to 37% of intraparenchymal
■■ Management Issues
abscesses are idiopathic.16 The clinical pre- Medical Management
sentation of an intraparenchymal abscess
lacks both sensitivity and positive predic- Although clear parameters for medical
tive value for the disease. The classic triad management of intracranial abscesses (epi-
of headache, fever, and neurologic deficit is dural, subdural, and intraparenchymal) are
present in only 17 to 30% of cases.8,17 As with still not defined, the method of treatment
extra-axial abscesses, the clinical blood has been under investigation since 1970.4
count (CBC), ESR, CRP level, and CSF evalu- The widespread availability of both po-
ations are seldom helpful beyond tracking tent antibiotics and improved intracranial
the effect of therapy in patients with a di- imaging has expanded the role of medical
agnosis. An exception to this rule is in the management. In most cases, intracranial
patient in whom the abscess has ruptured abscesses that are less than 2.5 cm can be
into the ventricle, who will usually have a managed medically if they present in oth-
positive CSF evaluation. Blood cultures re- erwise healthy patients without focal defi-
turn relevant results approximately 30% of cits, altered sensorium, or the imminent
the time and should be obtained if there is threat of either. In sick, high-risk patients
suspicion of this diagnosis.18 or in patients with deep-seated abscesses,
CT or MR imaging should be obtained neurologic deficits may be unavoidable
with contrast and reveal either an edema- and can worsen with surgery.
235
Few specifics exist for the medical man- treated surgically.26,27 Similar to Heran et al,
agement of epidural abscesses. Nathoo et Leys found that minor deterioration in neu-
al first reported on this strategy in 1999, rologic status within 24 to 48 hours of the
managing six patients without fever with start of medical treatment often resolved
antibiotic therapy and serial imaging. No without the need for surgical interven-
information is available on lesion size or tion. A few modern series have made ref-
whether there was associated sinus disease erence to medically managed empyemas,
that was treated by the otolaryngologic ser- but they do not include the details of these
vice.22,23 Heran et al contributed to the lit- patients.2,28 Salunke et al did describe one
erature on this topic in 2003, treating four patient treated successfully with antibiot-
patients who had isolated epidural abscess- ics alone who had a thin subtentorial em-
es with sinus drainage and antibiotics with- pyema.28 At our institution, we have even
out intracranial intervention. There was had success treating subdural empyemas
no evidence of bony erosion, which would of the posterior fossa with antibiotic ther-
have allowed spontaneous drainage of the apy. Recently, we successfully treated an
intracranial component into the extracra- 8-day-old infant with Currarino triad; she
nial space. None of these patients had focal had multiple infratentorial subdural empy-
neurologic deficits or an altered sensorium, emas that measured 1 and 0.6 cm, and at
and the average size of the abscesses was no time did she demonstrate a neurologic
2.9 × 2.6 × 1.4 cm, with a maximum size 3.5 deficit. After 6 weeks of intravenous antibi-
× 3.5 × 1.2 cm in one that was infratento- otics, all empyemas had resolved, and she
rial.24 At our institution, we routinely treat remained without neurologic deficit (Fig.
epidural abscesses as a medical disease to 17.1).
great effect and rarely operate unless there Decisions regarding the medical man-
is a decreased level of consciousness or fo- agement of intraparenchymal abscesses
cal neurologic deficits attributable to the are similar to those for other intracranial
lesion. Decisions regarding the treatment of abscesses and include abscess size, neuro-
primary sinus disease are left to the discre- logic status of the patient, general medi-
tion of the otolaryngologists. cal condition of the patient, and the need
The medical management of subdural for organism identification. In addition to
empyema was first explored in an article these factors, the location of the intrapa-
from 1979 by Rossaza et al, in which a renchymal abscess must be considered be-
child with an interhemispheric empyema cause the indications for operating within
and foot weakness was cured clinically and eloquent brain must be justified. No spe-
radiographically with antibiotics alone.25 cific criteria for the appropriate size of
Steroids were used in this case to amelio- an intraparenchymal abscess have been
rate the foot weakness. Leys et al provided established that will result in its success-
more support for medical management ful medical treatment. A comprehensive
in the 1980s, finding that individuals as review of the literature has provided a
young as 2 years of age with empyemas thoughtful, well-supported approach to
up to 44 mm thick in the supratentorial patients with intraparenchymal abscess.29
space, with an average Glasgow Coma Scale Patients with intraparenchymal abscesses
score of 11 (range, 7 to 13) and even with smaller than 2.5 cm in maximum diameter
a severe neurologic deficit, could be medi- are the best candidates for medical man-
cally treated with a good clinical outcome. agement, especially where their overall
Although the length of stay was shorter neurologic condition is good and micro-
and the infectious organism was more of- biological speciation has been determined
ten identified in both the aspiration and from another source. Although well sup-
craniotomy groups of patients, medically ported in the literature, the size of 2.5 cm
treated patients had the same mortality or less may be an unduly conservative re-
rates and a lower probability of persistent quirement for medical management. In a
neurologic deficits and seizures than those review of reports of the medical treatment
236
a b c

d e f
Fig. 17.1a–f (a–c) Post-contrast magnetic resonance (MR) imaging of the brain on day 18 of life of a girl who
had Currarino triad with meningitis complicated by multiple subdural empyemas of the posterior fossa. At no
point was there focal or global deficit. This patient was observed closely in the pediatric intensive care unit and
received intravenous vancomycin and meropenem. (d–f) At day 48 of life, repeat MR imaging showed resolution
of the empyemas with residual meningeal enhancement that resolved over the next month.
of intraparenchymal abscesses, Bamberger Surgical Management

found that 100% of 113 brain abscesses less
than 5 cm in maximum diameter and 74% Although the indications for medical man-
of 30 intraparenchymal abscesses 5 cm or agement of intracranial focal infections have
more in diameter were successfully treated expanded, the large majority of these lesions
medically.30 At our institution, we routine- are handled operatively. In their large review
ly treat intraparenchymal abscesses more of 70 patients with extra-axial abscesses,
than 2.5 cm in maximum diameter medi- Gupta et al operated on all but six patients.2
cally, with only a rare conversion to opera- Similarly, most modern series reporting on
tive management. Multiple abscesses can extra-axial abscesses indicate that surgery
also be treated medically, with surgical ex- is overwhelmingly the first choice of treat-
cision of intraparenchymal abscesses larg- ment.14,28,31,32 The main cause for concern
er than 2.5 cm or of smaller ones causing in approaching an extra-axial abscess op-
symptomatic mass effect. When a patient eratively is the extent of exposure. Although
is being treated medically, surgery should it is clear that extra-axial abscesses can be
be reconsidered if the patient’s condition treated with either burr hole drainage or
deteriorates clinically or if clinical or ra- limited craniotomy, the rate of recurrence—
diographic improvement is not observed requiring reoperation to clear the infec-
within 1 to 2 weeks. tion—is potentially higher after burr hole
237
drainage in larger extra-axial abscesses and not comment on the degree of osteomyeli-
in those with evidence of loculi.5,16,22,31,33–37 tis present in the flaps.39,40 Unfortunately,
Parafalcine or paratentorial empyemas may there are no clear data on the possibility
pose a higher risk for recurrence after burr of immediate reimplantation of a bone flap
hole drainage than after craniotomy.28 In affected with frank osteomyelitis, and the
contrast, a series of post-meningitis empy- risks and benefits of aggressive débride-
emas demonstrated that these lesions might ment and immediate replacement of the
preferentially be treated safely with burr osteomyelitis flap must be left to the sur-
hole drainage rather than with craniotomy.31 geon. Of note, in the report by Gupta et al
Certainly, in a decision to use a surgical ap- on 12 patients receiving a craniectomy for
proach to an infection, the clinical context osteomyelitis, six did not require a cranio-
must be considered. Those patients with plasty because in situ bone growth with a
significant focal or global neurologic deficits good cosmetic result was present. No ages
should be considered candidates for craniot- were provided for these patients.2
omy, with craniectomy more appropriate for Although abundant literature is avail-
those at risk for postoperative hemispheric able on the management of intraparenchy-
swelling. For the significant number of pa- mal abscesses, it lacks patient stratification,
tients who have an associated sinusitis or clear management protocols, and consistent
mastoiditis, an otorhinologic consult should outcome measures, decreasing the useful-
be obtained. If possible, definitive intracra- ness of this body of information. In a review
nial management should occur at the same from Italy, the authors made several useful
time as otorhinologic treatment because conclusions regarding intraparenchymal
several authors have reported lower rates abscesses.29 First, the choice of a surgical
of intracranial recurrence with concurrent approach that includes either a burr hole or
management.2,7,22 a craniotomy did not appear to impact out-
Issues regarding management of the come. Instead, the patient’s initial neuro-
bone flap arise in these cases, with most logic condition and the rapidity with which
authors advocating immediate replace- therapeutic intervention is initiated are far
ment of the bone flap unless frank, ex- more important prognostic factors. Those
tensive osteomyelitis is present. A report determinants of operation type are influ-
addressed the issue of devascularized bone enced by the preference and abilities of the
flaps in the context of extra-axial abscesses surgeon and whether the patient will be
without osteomyelitis.38 In this series of able to tolerate the proposed procedure. It
14 patients, all had successful immediate might be more reasonable to aspirate those
reimplantation of the bone flap follow- intraparenchymal abscesses that are locat-
ing craniotomy for an extra-axial abscess. ed deep within eloquent areas of the brain
One of these patients had tetralogy of Fal- or that are small or multiple, even if they
lot, and two had undergone chemotherapy are recurrent. Those intraparenchymal ab-
and radiation therapy following resection scesses that are superficial, are located in
of brain tumors. In each case, the surgeons the posterior fossa, or result from posttrau-
removed all soft tissue from the bone flap, matic or postoperative complications might
scrubbed the flap for 3 to 5 minutes in io- better be treated by a craniotomy than by
dophor or bacitracin solution, then soaked burr holes. It is not clear whether the size
the flap in an iodine or bacitracin solution of the abscess and the neurologic status of
until reimplantation. In addition, the sur- the patient are independent determinants
gical bed was scrubbed abrasively with of what type of management is required.
surgical sponges, and the bone edges were We recently encountered a 9-month-old
débrided, with care taken not to injure the girl with a 3-week history of progressive
exposed brain. Two other reports used an lethargy and decreased appetite. On her
implanted irrigation–drainage system to evaluation in the emergency department,
salvage devascularized bone flaps in the she was fussy but consolable and had a
context of postsurgical infection but did bulging fontanelle. MR imaging revealed
238
multiple abscesses occupying nearly the are of great importance to all neurosur-
entire left hemisphere. Each abscess was geons, especially those who specialize in
aspirated through a separate burr hole with pediatrics.41 The risk for a shunt infection
a ventricular catheter and a syringe that is estimated to be 10%, and the number of
had a Luer connector. A catheter was left admissions to U.S. hospitals in 2003 for the
overnight in the largest abscess, and that treatment of shunt infections was approxi-
abscess was reaspirated the next day. The mately 2,300, or 6% of all hydrocephalus-re-
patient was then treated with antibiotics lated hospital admissions.42,43 The impact on
and had a good clinical outcome (Fig. 17.2). children struck by infection is considerable:
treatment requires multiple-day hospital
Cerebrospinal Fluid Ventricular stays with limited mobility and long-term
Shunt Infections effects include lower IQ, seizures, and fu-
ture shunt failure.44 At an approximate cost

Infections of the central nervous sys-
tem in shunted hydrocephalic patients of $49,000 per infection (making infection
are the neurosurgeon’s nightmare. the most costly per-case complication of
—Walters, Hoffman, Hendrick, and shunt systems), the estimated cost to the
Humphreys, 1984 U.S. health care system in 2003 caused by
infected shunts was $112,700,000.44 It is
Infection is the most serious complication therefore imperative for neurosurgeons to
of a ventricular CSF shunt, so that the treat- be well versed in the management of ven-
ment and prevention of shunt infections tricular shunt infections.
a b
c d
Fig. 17.2a–d (a) T2-weighted axial magnetic resonance (MR) imaging of the brain of a 9-month-old girl with
lethargy and decreased oral intake showing large, multiple, left-sided brain abscesses taking up virtually the
entire left hemisphere. (b) Intraoperative MR imaging–guided drainage of both abscesses on day 1. (c) Drainage
on day 2. (d) Follow-up MR imaging 9 months after the MR imaging in (a). After a lengthy intravenous antibiotic
course, the patient has continued to do well. 239
Clinical Context Second, the time from the last shunt
manipulation to infection can be useful
The pediatric patient with a ventricular both in understanding the clinical picture
shunt infection does not have a stereotypic and in predicting the possible infectious
presentation because the possible infec- agent. Some 80% of all shunt infections oc-
tious and neurologic signs and symptoms cur within the first 3 months after place-
are numerous, highly variable, and non- ment, with the earliest infections occurring
specific. For example, fever is common, but within 8 to 15 days.45 Arnell et al found that
approximately 25% of patients with a con- of 25 patients presenting after revision or
firmed case of ventricular shunt infection initial placement within 20 weeks, 21 were
have no fever.45 Equally challenging are the infected with coagulase-negative staphylo-
many shunt infections that present as me- cocci (15 patients) or Staphylococcus aureus
chanical malfunctions without overt infec- (6 patients).48 All patients presenting with
tious signs or symptoms. Walters et al noted a visible wound infection had coagulase-
that in their series of ventricular shunt in- negative staphylococci or S. aureus infec-
fection, shunt malfunction was diagnosed tion, with a mean time to infection of 3.5
as infection in only half of the cases, result- weeks (range, 1.5 to 6 weeks after opera-
ing in delayed treatment.41,42 Because the tion). Similarly, coagulase-negative staphy-
number of shunt malfunctions without in- lococci or S. aureus was the infectious agent
fection is much larger than the number of in 8 of 9 initial shunt placements (mean
malfunctions with occult infection, it would time to infection, 3 weeks) and in 7 of 8
be counterproductive to obtain cultures proximal revisions (mean time to infection,
from all patients with a ventricular shunt 1 week). A single patient with Enterococcus
malfunction. The overall clinical picture infection had an inguinal hernia repaired
can be helpful in guiding the management at the time of shunt placement, and a sec-
of patients with ventricular shunt infection. ond patient grew Propionibacterium acnes
First, infections in the different compo- after a proximal revision in which the valve
nents of the shunt system can present with was punctured. Although one easily pre-
localizable clinical findings. Patients with sumes that contamination with skin flora
proximal catheter infections are more likely at the time of surgery explains early infec-
to present with neurologic findings that in- tion, several studies have found that fewer
clude nausea, mental status changes, sei- than 50% of the microorganisms cultured
zures, and meningeal symptoms. Abdominal from the wound or infected shunt could
pain, gastrointestinal symptoms, and a pos- be traced directly to the patient.49 A pro-
sible pseudocyst may be present if a distal spective study by Thompson et al carefully
peritoneal catheter is involved. Patients with sampled the flora of the skin covering the
distal atrial catheter infections can present operative site of a shunt placement, and
with bacteremia and evidence of systemic the isolated bacteria matched a preopera-
infections. Nearly all patients with infected tive swab specimen in only 1 of the 7 pa-
ventriculoatrial shunts present with fevers tients who went on to develop ventricular
because of the vascular position of the distal shunt infection.50 Although the timing of
catheter.41,46 In addition, these patients can postoperative ventricular shunt infection
develop shunt nephritis, presenting with strongly suggests a perioperative etiology,
hepatosplenomegaly, anemia, and cerebral these consistent findings suggest that the
manifestations.47 This condition is relatively method of contamination and subsequent
rare and arises from the deposition of im- infection may be more complex than simple
munoglobulin M and immunoglobulin G intraoperative wound seeding. As the time
antigen–antibody complexes in the renal from shunt surgery becomes longer than
glomeruli secondary to persistent stimula- 20 weeks, infection with gram-negative
tion of the immune system due to chronic rods and fungi becomes more likely as ven-
infection. Renal disease usually resolves triculoperitoneal shunts are seeded hema-
with treatment of the shunt infection. togenously or via retrograde infection from
240
the abdomen.49 Fungal infections are rare with a serum CRP level below 7 mg/L was
in this population but should be more seri- only 2.7%.52
ously considered with patients on antibi- Perhaps the most important and contro-
otic therapy, with immunocompromise, on versial diagnostic maneuver for the patient
steroids, or receiving hyperalimentation.49 with suspected ventricular shunt infec-
In patients who present with the pos- tion is a tap of the shunt for the purpos-
sibility of ventricular shunt infection, the es of obtaining CSF and evaluating shunt
evaluation can be as difficult as the presen- function. Although a lumbar puncture is
tation. As previously stated, the absence also possible, CSF obtained this way is of-
of fever does not rule out an infection, nor ten sterile, even in patients who are later
does a benign CBC or negative blood cul- proven to have a ventricular shunt infec-
ture unless the patient has a ventriculoatri- tion.49 Only one paper exists regarding the
al shunt.42,51 Even CSF protein, glucose, cell complication rate of a shunt tap, published

count, and Gram stain are imperfectly in 1984 by Noetzel et al.54 In this study, a
sensitive to the presence of infection.52 “neurosurgeon experienced in dealing
Patients with coagulase-negative staphy- with shunts” soak-scrubbed the area to be
lococcal infections may not have CSF pleo- tapped, shaved the area for 2 inches in all
cytosis, and conversely, an increased CSF directions, triple-washed the area with an
cell count may be seen in patients within alcohol and betadine solution, and then fi-
approximately 14 days of intracranial pro- nally covered the area with a Steri-Drape
cedures as well as in patients without any so as to expose only the small area to be
CNS infectious process.45 Neuroimaging tapped. The authors had no mechanical
and shunt series are of limited use unless or medical complications, and of the 53
there is suspicion of shunt failure or there patients whose shunts were tapped and
is evidence of meningitis or encephalitis. whose cultures revealed no infection, two
Several laboratory parameters have been later became infected at 15 and 20 months
described that have diagnostic power, but after the tap, both with Haemophilus influ-
clarity is required to prevent their misuse. enzae. The diagnostic yield was high; in 12
CSF eosinophilia comprising more than of 13 patients with infection proven in the
5% of white blood cells has been shown to end, infection was correctly diagnosed via
have a positive predictive value for infec- shunt tap. It should be kept in mind that
tion in the 90th percentile range but may the administration of antibiotics before the
also arise as an allergic reaction to latex, tap decreases the positive culture rate from
shunt materials, or even the ethylene oxide 96 to 53%.51 Despite these findings, shunt
used to sterilize shunts. The absence of CSF taps remain a maneuver of debated impor-
eosinophilia is of no diagnostic value.45,53 Of tance, and many investigators, including
greater diagnostic value is the combination those at our institution, feel that nearly all
of fever and CSF neutrophilia comprising diagnostic challenges involving shunts can
more than 10% of white blood cells, as de- be safely addressed without performing a
scribed by McClinton et al.53 This combina- shunt tap.55–57
tion had a 99% specificity, a 93% positive
predictive value, a 95% negative predictive
Management Issues
value, and a posttest probability of 92%.
Recently, serum CRP levels have shown The neurosurgical literature concerning
promise in helping to determine if patients ventricular shunt infection is divided into
have an infected shunt. Schuhmann et al two main categories: procedural tech-
found that patients with a serum CRP level niques to avoid ventricular shunt infection
above 7 mg/L had a posttest probability of during shunt placement and strategies for
ventricular shunt infection of 72.3% (an managing ventricular shunt infection with
increase of 73% from a pretest probability minimal morbidity and mortality. Many
of 41.7%), and the probability of missing preventive strategies for lowering ventricu-
ventricular shunt infection in an individual lar shunt infection rates have been gener-
241
ated over the years and include, but are not the shunt, and 8 of the 10 grew coagulase-
limited to, perioperative antibiotic prophy- negative staphylococci.70 Tulipan and Clev-
laxis, limiting traffic through the operating es made a more direct connection between
room, not using a scrub nurse, no-touch op- wearing double gloves and ventricular
erative technique, iodine solution irrigation, shunt infection in 2006; they reported a
preoperative hair washes, and short opera- decrease in the ventricular shunt infection
tive times.58–64 A multicenter study by Kestle rate from 15.2 to 6.7% when the operating
et al has provided strong empiric evidence room staff changed to a shunt insertion
that procedural rigor can reduce the risk for protocol that required double gloving.71
ventricular shunt infection.65 These authors Evidence has also clarified the role of
found that the average rate of ventricular prophylactic antibiotics in the prevention
shunt infection in four separate institutions of ventricular shunt infection. In a 2009 Co-
dropped from 8.5 to 5.7% (p = 0.0028) after a chrane review, Ratilal et al found in a meta-
standard operative protocol for shunt inser- analysis of 17 trials with 2,134 participants
tion had been adopted. Brushless preopera- that the use of systemic antibiotic prophy-
tive hand preparation by any member of the laxis perioperatively and for 24 hours post-
operative team was associated with a higher operatively was associated with a decrease
ventricular shunt infection rate than tradi- in the ventricular shunt infection rate (odds
tional brush scrub (p = 0.025). In addition, ratio [OR], 0.52; 95% confidence interval
antibiotic-impregnated sutures for wound [CI], 0.36 to 0.74).72 This same review also
closure (p = 0.026), preoperative chlorhexa- found a decrease in the ventricular shunt
dine hair wash (p = 0.004), and double glov- infection rate (OR, 0.21; 95% CI, 0.08 to
ing by all operating room personnel (p = 0.55) with the use of antibiotic-impregnat-
0.043) were all associated with lower ven- ed shunts. In a separate review from 2011,
tricular shunt infection rates. Parker et al73 conducted a meta-analysis of
Double gloving is an easy measure to 12 studies that included 5,613 shunt proce-
institute that has multiple sources of sup- dures (2,664 antibiotic-impregnated shunts
port in the literature. The Food and Drug versus 2,949 non–antibiotic-impregnated
Administration (FDA), which regulates the shunts). Antibiotic-impregnated shunts
manufacture of sterile surgical gloves, has were associated with a reduction in the
set the Acceptable Quality Level at 2.5 mi- shunt infection rate from 7.2 to 3.3% (p <
croperforations per sterile pair. Multiple 0.0001). In a meta-analysis of 9 studies
studies have shown that the rate of tears that included only pediatric patients and
in surgical gloves during surgery is any- compared 854 procedures with antibiotic-
where from 10 to 60%.66,67 Double gloving impregnated shunts and 795 procedures
protects both the surgeon and the patient without antibiotic-impregnated shunts, the
from manufacturing defects and frequent ventricular shunt infection rates fell from
intraoperative glove damage. The litera- 11.2 to 5.0% (p < 0.0001). Although it is clear
ture suggests that gloves should be con- that many procedural interventions can
sidered only temporarily sterile during a reduce the rate of ventricular shunt infec-
procedure, even if strict sterile protocol is tion, further study must be done to deter-
maintained. In 2005, Al-Maiyah et al found mine the most cost-effective measures to
that frequent glove changes reduce the risk institute.
for contamination during hip arthroplasty Despite nearly 60 years of experience,
procedures.68 Bukhari et al found not only the optimal treatment strategy for ventric-
that gloved fingertips become contami- ular shunt infection is still a topic of great
nated in 52% of operations but also that debate. In a large retrospective multicenter
bacterial counts increase through the dura- analysis from 2010, Simon et al reviewed
tion of surgery.69 Sørensen found that all 10 collected data on 675 children who under-
pairs of the surgeon’s gloves in a ventricu- went an uncomplicated ventricular shunt
lar shunt implantation case grew P. acnes placement, had 24 months of follow-up,
by the time it was appropriate to implant and developed a ventricular shunt infec-
242
tion.74 Of these children, 111 developed a studies yielded similar results, with cure
second ventricular shunt infection within rates of 96%, 65%, and 36%, respectively, for
12 months after treatment; however, no the same three strategies. Although these
patient, hospital, or surgeon factors were results plus those of Simon et al strongly
identified that correlated significantly imply that any cure for ventricular shunt
with a risk for reinfection. Of the 675 chil- infection must include some form of sur-
dren, 483 had retrospectively identifiable gical intervention, a few organisms have
treatment details that allowed an analysis been identified for which only systemic
of infection risk according to treatment antibiotics are required to achieve eradi-
strategy. All 675 children received anti- cation successfully; these include Strepto-
biotics. The surgical strategies for these coccus pneumoniae, Neisseria meningitidis,
483 patients were as follows: 286 (59.2%) and H. influenzae, the bacteria most com-
had the shunt removed with placement monly associated with community-ac-

of an external ventricular drain followed quired meningitis.77–81
by placement of a new shunt once the CSF The striking difference between the
was cleared of infection; 59 (12.2%) had rates of reinfection following nonoperative
shunt externalization and placement of a treatment of ventricular shunt infection in
new shunt once the CSF was cleared; 64 the studies of Yogev and of Schreffler et al
(13.3%) received nonsurgical management and the empiric reinfection rate of 23.4% in
(antibiotic only); and 74 (15.3%) had the the study of Simon et al is somewhat puz-
shunt removed without being replaced. Of zling but may be due to modifications in
these treatment strategies, nonoperative nonoperative management. An example of
management had a significantly (p = 0.03) how this treatment modality has changed
higher risk for reinfection, with 15 (23%) of in recent years is provided by Brown et al,
the 64 patients becoming reinfected. As a who in 2006 reported an 84% cure rate in
measure of internal consistency, no patient 43 patients who were treated with system-
who had a shunt removed permanently ex- ic and intraventricular antibiotics. In 36 pa-
perienced reinfection. Although there was tients without S. aureus infection, the cure
a trend (p = 0.19) toward a greater risk for rate was 92%. Conservative management of
infection in patients whose shunts were S. aureus infection was discontinued when
externalized, this was not a statistically an early cure rate of only 50% was found.
significant finding; 12 of 59 patients with There was no increased risk for mechanical
externalized shunts experienced reinfec- shunt failure in follow-up lasting 6 to 128
tion, and 44 of 286 patients who had shunt months when the infecting agents were
removal with external ventricular drain coagulase-negative staphylococci (28/30
replacement experienced reinfection. Even cured), Enterococcus species (3/3 cured),
an extensive study such as this failed to de- P. acnes (2/2 cured), Streptococcus sanguis
termine the best treatment for ventricular (1/1 cured), and Pseudomonas aeruginosa
shunt infection. (0/1 cured). There are a few important
Two meta-analyses in the literature, one methodologic aspects of this study. First, ri-
by Yogev and the other by Schreffler et al, fampin was included in the treatment regi-
have been influential in guiding operative men because this agent has been shown to
treatment.75,76 Schreffler et al constructed have good penetration into the biofilm cre-
a decision tree based on the information ated by coagulase-negative staphylococcal
from 17 published studies and concluded species. Second, intraventricular antibiotics
that the cure rates were 88% for a two- were administered via a ventricular access
stage strategy (shunt removal with exter- device, which was already present in 33 of
nal ventricular drain placement followed the patients but had to be implanted in 10.
by shunt replacement), 64% for one-stage Although the requirement for a ventricu-
treatment (shunt removal and immediate lar access device may limit the usefulness
replacement), and 34% for nonoperative of this technique, this paper does estab-
management. Yogev’s assessment of 18 lish the possibility of clearing ventricular
243
shunt infection without the removal of 6. G lickstein JS, Chandra RK, Thompson JW. Intracra-
nial complications of pediatric sinusitis. Otolaryn-
shunt hardware. The strategy may be opti-
gol Head Neck Surg 2006;134(5):733–736 PubMed
mal for patients with a complex CSF diver- 7. Cochrane DD, Price AV, Dobson S. Intracranial
sion system or with retained hardware, in epidural and subdural infections. In: Albright AL,
whom the risk of ventricular access device Adelson PD, Pollack IF, eds. Principles and Prac-
tice of Pediatric Neurosurgery. 2nd ed. New York,
implantation to clear a ventricular shunt NY: Thieme; 2007:1148–1155
infection may be warranted. 8. Yogev R. Focal suppurative infections of the central
Shunt externalization was also the sub- nervous system. In: Long SS, Pickering LK, Prober
ject of a study by Arnell et al in 2007, in CG, eds. Principles and Practice of Pediatric Infec-
tious Diseases. 3rd ed. Philadelphia, PA: Saun-
which 34 consecutive ventricular shunt ders; 2009. http://www.mdconsult.com/books/
infections were treated with ventricular p age. d o ? e i d = 4 - u 1 . 0 - B 9 7 8 - 0 - 7 0 2 0 - 3 4 6 8 -
catheter externalization followed by sys- 8.50054-7&isbn=978-0-7020-3468-8&type=
bookPage&from=content&uniqId=290678879-2.
temic and intraventricular antibiotics. After Accessed December 23, 2012
a negative CSF culture had been obtained, 9. Bambakidis NC, Cohen AR. Intracranial complica-
the ventricular catheter was replaced, and tions of frontal sinusitis in children: Pott’s puffy
a new subcutaneous route for the valve and tumor revisited. Pediatr Neurosurg 2001;35(2):
82–89 PubMed
distal catheter was used. Infecting organ- 10. K irmi O, Sheerin F, Patel N. Imaging of the menin-
isms included coagulase-negative staphy- ges and the extra-axial spaces. Semin Ultrasound
lococci, S. aureus, P. acnes, Enterococcus CT MR 2009;30(6):565–593 PubMed
11. Yikilmaz A, Taylor GA. Sonographic findings in
species, Escherichia coli and other gram-
bacterial meningitis in neonates and young in-
negative rods, and β-hemolytic streptococ- fants. Pediatr Radiol 2008;38(2):129–137 PubMed
ci; cure was obtained in all cases. Although 12. C hen CY, Huang CC, Chang YC, Chow NH, Chio
technically a two-stage procedure, the CC, Zimmerman RA. Subdural empyema in 10
infants: US characteristics and clinical correlates.

single ventricular catheter replacement Radiology 1998;207(3):609–617 PubMed
with use of the same burr hole may be of 13. B anerjee AD, Pandey P, Devi BI, Sampath S, Chan-
less risk to the CNS and can also reduce the dramouli BA. Pediatric supratentorial subdural
number of operated sites in patients with empyemas: a retrospective analysis of 65 cases.
Pediatr Neurosurg 2009;45(1):11–18 PubMed
shunts. Although individual investigators 14. Venkatesh MS, Pandey P, Devi BI, et al. Pediatric in-
continue to pursue the optimal treatment fratentorial subdural empyema: analysis of 14 cases.
of ventricular shunt infection, it may turn J Neurosurg 2006;105(5, Suppl):370–377 PubMed
15. W ong AM, Zimmerman RA, Simon EM, Pollock
out that no one single treatment is best and AN, Bilaniuk LT. Diffusion-weighted MR imaging
that applying valid options to an individual of subdural empyemas in children. AJNR Am J
patient’s specific circumstances may yield Neuroradiol 2004;25(6):1016–1021 PubMed
the best results. 16. H all WA, Truwit CL. The surgical management
of infections involving the cerebrum. Neuro-
surgery 2008;62(Suppl 2):519–530, discussion
References 530–531 PubMed
17. T seng J-H, Tseng M-Y. Brain abscess in 142 pa-
1. P iatt JH Jr. Intracranial suppuration complicat-
tients: factors influencing outcome and mortal-
ing sinusitis among children: an epidemiological
ity. Surg Neurol 2006;65(6):557–562, discussion
and clinical study. J Neurosurg Pediatr 2011;7(6):
562 PubMed
567–574 PubMed
18. Bernardini GL. Diagnosis and management of
2. Gupta S, Vachhrajani S, Kulkarni AV, et al. Neu-
brain abscess and subdural empyema. Curr Neu-
rosurgical management of extraaxial central ner-
rol Neurosci Rep 2004;4(6):448–456 PubMed
vous system infections in children. J Neurosurg
19. F itzpatrick MO, Gan P. Lesson of the week: con-
Pediatr 2011;7(5):441–451 PubMed
trast enhanced computed tomography in the
3. Morgan H, Wood MW, Murphey F. Experience
early diagnosis of cerebral abscess. BMJ 1999;
with 88 consecutive cases of brain abscess. J Neu-
319(7204):239–240 PubMed
rosurg 1973;38(6):698–704 PubMed
20. F razier JL, Ahn ES, Jallo GI. Management of brain
4. Heineman HS, Braude AI, Osterholm JL. Intracra-
abscesses in children. Neurosurg Focus 2008;
nial suppurative disease. Early presumptive diag-
24(6):E8 PubMed
nosis and successful treatment without surgery.
21. M oorthy RK, Rajshekhar V. Management of brain
JAMA 1971;218(10):1542–1547 PubMed
abscess: an overview. Neurosurg Focus 2008;
5. Madhugiri VS, Sastri BVS, Srikantha U, et al. Focal
24(6):E3 PubMed
intradural brain infections in children: an analy-
22. N athoo N, Nadvi SS, van Dellen JR, Gouws E.
sis of management and outcome. Pediatr Neuro-
Intracranial subdural empyemas in the era of
surg 2011;47(2):113–124 PubMed
computed tomography: a review of 699 cases.
244
Neurosurgery 1999;44(3):529–535, discussion 40. D elgado-López PD, Martín-Velasco V, Castilla-Díez
535–536 PubMed JM, Galacho-Harriero AM, Rodríguez-Salazar A.
23. Nathoo N, van Dellen JR, Nadvi SS. Conserva- Preservation of bone flap after craniotomy infection.
tive neurological management of intracranial Neurocirugia (Astur) 2009;20(2):124–131 PubMed
epidural abscesses in children. Neurosurgery 41. Walters BC, Hoffman HJ, Hendrick EB, Humphreys
2004;55(1):263–264, author reply 264 PubMed RP. Cerebrospinal fluid shunt infection. Influences
24. Heran NS, Steinbok P, Cochrane DD. Conserva-
on initial management and subsequent outcome.
tive neurosurgical management of intracranial J Neurosurg 1984;60(5):1014–1021 PubMed
epidural abscesses in children. Neurosurgery 42. Campbell J. Shunt infections. In: Albright AL,
2003;53(4):893–897, discussion 897–898 PubMed Adelson PD, Pollack IF, eds. Principles and Prac-
25. Rosazza A, de Tribolet N, Deonna T. Nonsurgical
tice of Pediatric Neurosurgery. 2nd ed. New York,
treatment of interhemispheric subdural empyemas. NY: Thieme; 2007:1141–1147
Helv Paediatr Acta 1979;34(6):577–581 PubMed 43. S imon TD, Hall M, Riva-Cambrin J, et al; Hydro-
26. Leys D, Christiaens JL, Derambure P, et al. Manage- cephalus Clinical Research Network. Infection
ment of focal intracranial infections: is medical rates following initial cerebrospinal fluid shunt
treatment better than surgery? J Neurol Neuro- placement across pediatric hospitals in the Unit-

surg Psychiatry 1990;53(6):472–475 PubMed ed States. Clinical article. J Neurosurg Pediatr
27. Leys D, Destee A, Petit H, Warot P. Management 2009;4(2):156–165 PubMed
of subdural intracranial empyemas should not 44. A ttenello FJ, Garces-Ambrossi GL, Zaidi HA, Sci-
always require surgery. J Neurol Neurosurg Psy- ubba DM, Jallo GI. Hospital costs associated with
chiatry 1986;49(6):635–639 PubMed shunt infections in patients receiving antibiotic-
28. Salunke PS, Malik V, Kovai P, Mukherjee KK. Fal- impregnated shunt catheters versus standard
cotentorial subdural empyema: analysis of 10 shunt catheters. Neurosurgery 2010;66(2):284–
cases. Acta Neurochir (Wien) 2011;153(1):164– 289, discussion 289 PubMed
169, discussion 170 PubMed 45. P russeit J, Simon M, von der Brelie C, et al. Epi-
29. Arlotti M, Grossi P, Pea F, et al; GISIG (Gruppo demiology, prevention and management of ven-
Italiano di Studio sulle Infezioni Gravi) Working triculoperitoneal shunt infections in children.
Group on Brain Abscesses. Consensus document Pediatr Neurosurg 2009;45(5):325–336 PubMed
on controversial issues for the treatment of in- 46. K ontny U, Höfling B, Gutjahr P, Voth D, Schwarz
fections of the central nervous system: bacterial M, Schmitt HJ. CSF shunt infections in children.
brain abscesses. Int J Infect Dis 2010;14(Suppl 4): Infection 1993;21(2):89–92 PubMed
S79–S92 PubMed 47. H affner D, Schindera F, Aschoff A, Matthias S, Wald-
30. Bamberger DM. Outcome of medical treatment herr R, Schärer K. The clinical spectrum of shunt
of bacterial abscesses without therapeutic drain- nephritis. Nephrol Dial Transplant 1997;12(6):
age: review of cases reported in the literature. 1143–1148 PubMed
Clin Infect Dis 1996;23(3):592–603 PubMed 48. Arnell K, Cesarini K, Lagerqvist-Widh A, Wester
31. Liu Z-H, Chen N-Y, Tu P-H, Lee S-T, Wu C-T. The T, Sjölin J. Cerebrospinal fluid shunt infections in
treatment and outcome of postmeningitic sub- children over a 13-year period: anaerobic cultures
dural empyema in infants. J Neurosurg Pediatr and comparison of clinical signs of infection with
2010;6(1):38–42 PubMed Propionibacterium acnes and with other bacteria.
32. Yilmaz N, Kiymaz N, Yilmaz C, et al. Surgical treat- J Neurosurg Pediatr 2008;1(5):366–372 PubMed
ment outcome of subdural empyema: a clinical study. 49. Tunkel AR, Drake JM. Cerebrospinal fluid shunt in-
Pediatr Neurosurg 2006;42(5):293–298 PubMed fections. In: Mandell GL, Bennett JE, Dolin R, eds.
33. Ak HE, Ozkan U, Devecioglu C, Kemaloglu MS; Mandell, Douglas, and Bennett’s Principles and Prac-
AK HE. Treatment of subdural empyema by burr tice of Infectious Diseases. 7th ed. Philadelphia, PA:
hole. Isr J Med Sci 1996;32(7):542–544 PubMed Churchill Livingstone/Elsevier; 2010:1231–1236
34. Bok AP, Peter JC. Subdural empyema: burr holes 50. T hompson DNP, Hartley JC, Hayward RD. Shunt
or craniotomy? A retrospective computerized to- infection: is there a near-miss scenario? J Neuro-
mography-era analysis of treatment in 90 cases. J surg 2007;106(1, Suppl):15–19 PubMed
Neurosurg 1993;78(4):574–578 PubMed 51. A nderson EJ, Yogev R. A rational approach to the
35. Druhan SM, Shiels WE II, Kang DR, Elton SW, Ko- management of ventricular shunt infections. Pe-
ranyi K. Successful sonographically guided drain- diatr Infect Dis J 2005;24(6):557–558 PubMed
age of epidural abscess. AJR Am J Roentgenol 52. S chuhmann MU, Ostrowski KR, Draper EJ, et al.
2006;187(5):W512–W514 PubMed The value of C-reactive protein in the manage-
36. Eviatar E, Lavi R, Fridental I, Gavriel H. Endonasal ment of shunt infections. J Neurosurg 2005;
endoscopic drainage of frontal lobe epidural ab- 103(3, Suppl):223–230 PubMed
scess. Isr Med Assoc J 2008;10(3):239–240 PubMed 53. M cClinton D, Carraccio C, Englander R. Predictors
37. Tummala R, Chu R, Hall W. Subdural empyema in of ventriculoperitoneal shunt pathology. Pediatr
children. Neurosurg Q 2004;14(4):257–265 Infect Dis J 2001;20(6):593–597 PubMed
38. Widdel L, Winston KR. Pus and free bone flaps. J 54. N oetzel MJ, Baker RP. Shunt fluid examination:
Neurosurg Pediatr 2009;4(4):378–382 PubMed risks and benefits in the evaluation of shunt
39. Auguste KI, McDermott MW. Salvage of infected malfunction and infection. J Neurosurg 1984;
craniotomy bone flaps with the wash-in, wash- 61(2):328–332 PubMed
out indwelling antibiotic irrigation system. 55. M iller JP, Fulop SC, Dashti SR, Robinson S, Co-
Technical note and case series of 12 patients. J hen AR. Rethinking the indications for the ven-
Neurosurg 2006;105(4):640–644 PubMed triculoperitoneal shunt tap. J Neurosurg Pediatr
2008;1(6):435–438 PubMed 245
56. Oakes WJ. Ventriculoperitoneal shunt tap. J Neu- 69. B ukhari SS, Harrison RA, Sanderson PJ. Con-
rosurg Pediatr 2008;1(6):433, 433–434 PubMed tamination of surgeons’ glove fingertips during
57. Rocque BG, Lapsiwala S, Iskandar BJ. Ventricular surgical operations. J Hosp Infect 1993;24(2):
shunt tap as a predictor of proximal shunt mal- 117–121 PubMed
function in children: a prospective study. J Neu- 70. S ørensen P, Ejlertsen T, Aaen D, Poulsen K. Bacteri-
rosurg Pediatr 2008;1(6):439–443 PubMed al contamination of surgeons’ gloves during shunt
58. Choi S, McComb JG, Levy ML, Gonzalez-Gomez I, insertion: a pilot study. Br J Neurosurg 2008;
Bayston R. Use of elemental iodine for shunt in- 22(5):675–677 PubMed
fection prophylaxis. Neurosurgery 2003;52(4): 71. T ulipan N, Cleves MA. Effect of an intraopera-
908–912, discussion 912–913 PubMed tive double-gloving strategy on the incidence of
59. Choux M, Genitori L, Lang D, Lena G. Shunt im- cerebrospinal fluid shunt infection. J Neurosurg
plantation: reducing the incidence of shunt infec- 2006;104(1, Suppl):5–8 PubMed
tion. J Neurosurg 1992;77(6):875–880 PubMed 72. R atilal BO, Costa J, Sampaio C. Antibiotic pro-
60. Haines SJ, Walters BC. Antibiotic prophylaxis for phylaxis for surgical introduction of intracranial
cerebrospinal fluid shunts: a meta-analysis. Neu- ventricular shunts. Cochrane Database Syst Rev
rosurgery 1994;34(1):87–92 PubMed 2006;19(3):CD005365. http://onlinelibrary.wiley
61. Kanev PM, Sheehan JM. Reflections on shunt .com/doi/10.1002/14651858.CD005365.pub2/
infection. Pediatr Neurosurg 2003;39(6): abstract. Accessed December 23, 2012 PubMed
285–290 PubMed 73. P arker SL, Anderson WN, Lilienfield S, et al. Ce-
62. Langley JM, LeBlanc JC, Drake J, Milner R. Efficacy rebrospinal shunt infection in patients receiving
of antimicrobial prophylaxis in placement of ce- antibiotic-impregnated versus standard shunts. J
rebrospinal fluid shunts: meta-analysis. Clin In- Neurosurg Pediatr 2011;8(3):859–865
fect Dis 1993;17(1):98–103 PubMed 74. S imon TD, Hall M, Dean JM, Kestle JRW, Riva-
63. Rotim K, Miklic P, Paladino J, Melada A, Marcikic M, Cambrin J. Reinfection following initial cerebro-
Scap M. Reducing the incidence of infection in pe- spinal fluid shunt infection. J Neurosurg Pediatr
diatric cerebrospinal fluid shunt operations. Childs 2010;6(3):277–285 PubMed
Nerv Syst 1997;13(11-12):584–587 PubMed 75. S chreffler RT, Schreffler AJ, Wittler RR. Treat-
64. Moriarty T, Angelini M, Carpenter J, et al. Rigid ment of cerebrospinal fluid shunt infections: a
standardization of technique to affect outcome: decision analysis. Pediatr Infect Dis J 2002;21(7):
ventricular shunt infection rate. J Neurosurg Pe- 632–636 PubMed

diatr. 2008;1(4):A356 76. Y ogev R. Cerebrospinal fluid shunt infections:
65. K estle JRW, Riva-Cambrin J, Wellons JC III, et al; a personal view. Pediatr Infect Dis 1985;4(2):
Hydrocephalus Clinical Research Network. A stan- 113–118 PubMed
dardized protocol to reduce cerebrospinal fluid 77. D rake J, Sainte-Rose C. Cerebrospinal fluid shunt
shunt infection: the Hydrocephalus Clinical Re- complications. In: Drake J, Sainte-Rose C, eds. The
search Network Quality Improvement Initiative. J Shunt Book. Cambridge, MA: Blackwell Science;
Neurosurg Pediatr 2011;8(1):22–29 PubMed 1995:69–121
66. Palmer JD, Rickett JW. The mechanisms and 78. K lein D, Scott R. Shunt infections. In: Hydroceph-
risks of surgical glove perforation. J Hosp Infect alus: Concepts in Neurosurgery. Baltimore, MD:
1992;22(4):279–286 PubMed Williams & Wilkins; 1990:88
67. Laine T, Aarnio P. How often does glove perfo- 79. Leggiadro RJ, Atluru VL, Katz SP. Meningococcal men-
ration occur in surgery? Comparison between ingitis associated with cerebrospinal fluid shunts.
single gloves and a double-gloving system. Am J Pediatr Infect Dis 1984;3(5):489–490 PubMed
Surg 2001;181(6):564–566 PubMed 80. L erman SJ. Haemophilus influenzae infections of
68. Al-Maiyah M, Bajwa A, Mackenney P, et al. Glove cerebrospinal fluid shunts. Report of two cases. J
perforation and contamination in primary to- Neurosurg 1981;54(2):261–263 PubMed
tal hip arthroplasty. J Bone Joint Surg Br 2005; 81. Patriarca PA, Lauer BA. Ventriculoperitoneal shunt-
87(4):556–559 PubMed associated infection due to Haemophilus influen-
zae. Pediatrics 1980;65(5):1007–1009 PubMed
246
18
Central Nervous System Infections
in Immunocompromised Hosts
Ouzi Nissim, Gahl Greenberg, Zvi R. Cohen, and Roberto Spiegelmann
The pool of patients with underlying con- In secondary immunodeficiency states,

ditions associated with immune compro- a primary illness or the treatment of an ill-
mise is continuously expanding. Improved ness results in immunosuppression. This
medical management of malignancies and category includes human immunodeficien-
chronic illnesses and the extensive use of cy virus (HIV) infection, cancer, and the use
immunosuppressive medications has led of corticosteroids or immunosuppressive
to a dramatic increase in the need to treat medications to treat patients with condi-
this patient population. tions like collagen vascular diseases and
Immune dysfunction is characterized by the recipients of organ transplants. Again,
the emergence of infections with opportu- the mechanism of immunosuppressive
nistic microorganisms that under normal action of these drugs will affect the type
conditions are less virulent and that ex- of infections that can arise.1 In the grow-
ploit this breach in immunocompetence. ing group of patients with malignancies,
The unique characteristics of dysfunc- there is usually interplay between several
tion in a specific arm of this multi-compo- factors: the effects of the primary disease,
nent immune system generates a unique myelosuppression from chemotherapy,
pattern of susceptibility to a specific class and at times corticosteroid-induced im-
of pathogens. Patients with defects in an- mune dysfunction, each of them contribut-
tibody or complement function more often ing to the overall immune dysfunction.
have infections with pyogenic encapsulated Central nervous system (CNS) infections
bacteria, whereas those with deficient cell– in immunocompromised patients cause
mediated immune deficiency are more sus- considerable morbidity and mortality. The
ceptible to fungal, viral, mycobacterial, and CNS resides in a unique environment that
protozoal infections. This principle is clear- affects the pathogenesis of infections. The
ly illustrated in primary immunodeficiency brain is protected from infection by the
states that stem from genetic abnormalities calvaria and meninges, which serve as a
selectively affecting specific arms of the im- mechanical barrier, and also by the chemi-
mune system. For example, in chronic gran- cal and mechanical filtering capabilities
ulomatous disease and in Chédiak-Higashi of the blood–brain barrier. However, the
syndrome, there is a selective abnormal- composition of the CSF makes it an excel-
ity of phagocytosis. The infectious agents lent culture medium. In addition, the brain
affecting these patients differ from those and subarachnoid space are considered im-
seen in patients with another genetic dis- munologically sequestered because of the
order, severe combined immunodeficiency absence of lymphatics.2
(SCID), in which T-lymphocyte abnormali- The clinical manifestations of CNS in-
ties damage both the humoral and cell-me- fections in the immunocompromised host
diated arms of the immune system. can reflect cerebral parenchymal and/or
leptomeningeal involvement. With local- Stereotactic or image-guided needle bi-
ized involvement in the form of solid mass opsy is a minimally invasive method of es-
lesions (abscesses, granulomas, or cysts) tablishing a definite diagnosis and allows
or more localized encephalitis, a clinical the institution of appropriate treatment.
picture of focal neurologic deficits is ex- This surgical technique is especially well
pected to predominate. Brain abscesses suited for deep-seated lesions, such as those
in immunocompromised patients (as opin the brainstem or hypothalamus. An open
posed to those in the general population) surgical excision is an appropriate option
are caused more frequently by nonpyogenic for large, accessible lesions with multiple
microorganisms, such as fungi, protozoa, loculi that cause brain herniation and also
and mycobacteria. Meningeal or ependy- for those that do not respond to aspiration.
mal involvement will induce more general- This chapter focuses on CNS infections
ized neurologic dysfunction, manifested by in immunocompromised patients from a
headache, photophobia, seizures, reduced neurosurgical perspective. First, the caus-
level of consciousness, or other signs of el- ative fungal, protozoal, bacterial, and viral
evated intracranial pressure (papilledema, microorganisms causing intraparenchy-
sixth cranial nerve palsy).3 In addition to mal masses or cerebritis are reviewed. A
the characteristic infectious profile that patient-oriented perspective follows, in
emerges, immunosuppression can alter the which issues relevant to specific underlying
host response to the offending agents, thus causes of immunodeficiency (HIV infection
obscuring diagnostic clues. Investigation for and organ transplant) are addressed.
the presence of infection should therefore
be diligently pursued in the appropriate set-
ting of progressive neurologic dysfunction.4 ■■ Fungal Infections

Fungi are ubiquitous in the environment
■■ Principles of Treatment and exist as yeast, molds, and dimorphic
forms. Fungal exposure occurs mostly
As patterns of infection are relatively de- through inhalation, ingestion, or direct con-
fined in many subgroups of the immuno- tact. Although invasive fungal infections
compromised population, prophylactic do occur in immunocompetent patients
measures play a major role in disease pre- (primary mycoses, mostly in endemic re-
vention. The treatment of invasive infec- gions and by trauma-induced inoculations),
tions in immunocompromised hosts is they are far more prevalent and consider-
primarily pharmacologic. Definitive cul- ably more life-threatening in immuno-
ture is ideal, but this can be time- and compromised patients, and they occur
resource-consuming. Considering the high predominantly when the underlying cause
morbidity and mortality rates in immu- of immunodeficiency is cell-mediated im-
nocompromised patients with infectious mune dysfunction. Fungi can reach the
diseases and the dire consequences of de- CNS by hematogenous dissemination from
laying therapy, empiric treatment is fre- the primary site of inoculation or by direct
quently considered the standard of care. spread from a contiguous site of infection
With CNS involvement, the manage- (nasal sinusitis, osteomyelitis, after surgi-
ment of discrete CNS space-occupying le- cal procedures, and following the intro-
sions is directed by several principles: duction of foreign bodies like indwelling
catheters). Clinical syndromes associated
1. The need to obtain tissue samples for with CNS fungal infections depend on the
prompt and definite diagnosis pathologic reaction elicited by the fungus.
2. Reduction of the size of the lesion to The three cardinal manifestations of fun-
enhance treatment efficacy gal infection are meningitis, the formation
3. When needed, alleviation of mass of mass lesions (abscesses or granulomas)
effect in the brain, and brain infarction. Meningi-
248
tis has been reported in almost two-thirds Aerosolized spores usually gain entry to
of subjects with CNS fungal infections and the CNS through the sinopulmonary system.
is caused mostly by small yeastlike forms Invasive aspergillosis develops mostly in
(Candida and Cryptococcus). These organ- hosts with neutrophil- or T-cell–mediated
18 Central Nervous System Infections in Immunocompromised Hosts

isms reach the arterioles and capillaries dysfunction, including bone marrow, stem
to produce subpial ischemic lesions. From cell, or solid organ transplant recipients;
there, spread to the subarachnoid space oc- those treated with high-dose corticoste-
curs, causing meningitis. In this setting, in roids; and those with hematologic malig-
addition to the signs of meningeal irritation, nancies, liver disease, or sarcoid.9 Patients
increased intracranial pressure can develop. with HIV-associated aspergillosis typi-
Space-occupying lesions are predominantly cally have CD4+ cell counts below 100/µL
caused by molds (filamentous fungi). When and a history of other acquired immunode-
brain abscesses are formed, signs and symp- ficiency syndrome (AIDS)–defining oppor-
toms of focal neurologic dysfunction will tunistic infections, and they typically are
predominate. Rarely, fungal infections can not receiving highly active antiretroviral
lead to granuloma formation.5 Large hyphal therapy (HAART).
forms, such as Aspergillus and Zygomycetes, Aspergillus is an angioinvasive mold, and
can invade and obstruct large and interme- CNS seeding typically occurs after hema-
diate-size arteries to cause brain infarction togenous dissemination from a pulmonary
and strokelike symptoms.6,7 The incidence site. Additionally, direct spread from the
of CNS fungal infections seems to be un- primary site of infection may occur: from
derestimated because of their nonspecific the nasal sinuses to the adjacent frontal
clinical presentations and the insufficient and temporal lobes, by extension of an ear
diagnostic work-up that these patients infection, or by invasion of the thoracic
sometimes undergo.8 vertebrae and eventually the spinal epi-
dural space. CNS involvement is diagnosed
Treatment in 10 to 20% of patients with systemic dis-
semination; however, it is discovered at
The treatment of invasive fungal infections autopsy in as many as 44 to 94% of cases.10
is primarily pharmacologic. The extensive Cerebral aspergillosis frequently causes
use of antifungal medications, either for single or multiple brain abscesses and rare-
treatment or for prophylaxis, has resulted ly granulomas. Aspergillus granulomas are
in the emergence of new, previously less characterized by abundant fibrosis, an ill-
encountered causative agents. The resis- defined epithelioid granuloma, and many
tance of these pathogens to conventional foreign body and Langhans-type giant
treatment poses new challenges. Thus, cells. Uncommonly, basal meningitis, dural
diagnosis by culture with identification of abscesses, mycotic aneurysms, and mul-
susceptibility patterns should be accom- tifocal cerebritis can occur. Carotid artery
plished whenever possible.9 The approach invasion can cause cerebral ischemia or
to any space-occupying lesion is directed hemorrhagic infarction. Pulmonary infec-
by the aforementioned principles of care. tions extending to thoracic vertebrae and
the epidural space are capable of causing
spinal cord compression and myelitis.
■■ Aspergillosis The clinical presentation of Aspergillus
infection is nonspecific. This type of infec-
Aspergillus, a mold with septate hyphae, tion should be suspected with the develop-
is clinically the most important fungal ment of facial pain, fever, headache, altered
pathogen. Of the more than 100 Aspergillus mental status, seizures, or focal neurologic
species that are known, the most virulent deficits, but severely immunocompro-
pathogen is A. fumigatus, although infec- mised patients are less likely to develop
tions occur also with A. niger, A. flavus, and symptoms. Orbital infiltration is suspected
A. terreus. with periorbital pain, proptosis, blurred vi-
249
sion, or diplopia. Strokelike syndromes can Epidemiology and Clinical
develop, especially if the internal carotid Manifestations
artery is involved.6 With case-fatality rates
in CNS aspergillosis reported to be as high Mucormycosis is the second most common
as 88%, the prompt diagnosis of invasive as- mycosis caused by molds and is especially
pergillosis is crucial, but difficult.11 known to infect patients with poorly con-
The radiologic appearance of cerebral trolled diabetes mellitus, although another
aspergillosis is variable, showing regions population at high risk comprises patients
of edema, hemorrhage, infarction (which with hematologic malignancies.16,17 Ad-
can be poorly defined with minimal mass ditionally, recipients of bone marrow
effect), or focal reticular or ring-enhancing transplants, patients with prolonged neu-
mass lesions.12 Standard CSF analysis is tropenia or renal disease, and those receiv-
generally nondiagnostic and cultures are ing corticosteroid therapy are susceptible
almost always negative, but recently de- to infection. High glucose levels in patients
veloped serologic methods hold promise with poorly controlled diabetes reduce
for early diagnosis. These tests rely on the the binding of iron to transferrin. The in-
detection of cell wall components, galacto- creased levels of free iron promote an ac-
mannan, and 1,3-β-d-glucan in serum or celerated growth of the fungus.
CSF. Galactomannan has an overall report- The major mode of infection is by inha-
ed sensitivity of 71% and specificity of 89% lation. Mucor organisms then lodge in the
for Aspergillus infections. Additionally, the lungs or sinuses to establish the primary
usefulness of a variety of molecular poly- site of infection. Among intravenous drug
merase chain reaction (PCR) tests is being users, hematogenous transmission can
investigated.13 occur. The clinical spectrum of CNS in-

volvement can be part of a fulminant, dis-
seminated disease or occur as an isolated
Pharmacologic Treatment
cerebral or rhinocerebral mucormycosis.
The recommended treatment for invasive Rhinocerebral mucormycosis most often
aspergillosis in patients without HIV in- develops by direct spread from the para-
fection is voriconazole. Amphotericin B nasal sinuses to adjacent structures, which
deoxycholate and lipid-formulation am- include the palate, face, and orbit. Cerebral
photericin B are alternatives.9 Unfortunate- infection often occurs after direct exten-
ly, with the increasing use of voriconazole sion from the ethmoid sinus through the
for prophylaxis, the empiric, preemptive, meninges or via a perineural route. Mucor-
and targeted treatment of invasive as- mycosis, like aspergillosis, has a tendency
pergillosis has resulted in an increase in to invade blood vessels and cause tissue
the incidence of voriconazole-resistant necrosis or serve as a vehicle for further
zygomycosis. More recently, a combina- propagation of the infection.18
tion of therapeutic approaches has been Patients with rhinocerebral mucormy-
explored.14,15 cosis present with headache or facial pain
that is often localized to the frontal or ret-
ro-orbital regions. A dark sinus discharge
■■ Zygomycosis occurs, and necrotic tissue can be seen as a
black eschar. Intracranial involvement can
Zygomycetes are filamentous fungi with lead to cranial nerve palsies, acute motor
nonseptate branching hyphae. These mi- or sensory deficits from infarction caused
croorganisms are ubiquitous saprophytes by major arterial thrombosis, lethargy and
found in soil, plants, and decaying food. seizures.19 Orbital cellulitis, together with
The three orders in this category are Mu- proptosis, ophthalmoplegia, and visual
corales (including the genera Mucor, Rhi- impairment, signifies intraorbital or cav-
zopus, and Rhizomucor), Cunninghamella, ernous sinus involvement and represents a
and Absidia.6 medical emergency.6
250
Diagnosis is the most common presentation, brain ab-
scesses and granulomas can appear, causing
CSF analysis results are usually nonspecif-
mass effect and localized signs.6,9
ic. The growth of Zygomycetes organisms

in blood cultures or tissue exudate is rare.
Core tissue samples are preferable but non-
diagnostic in 40% of the cases. Computed ■■ Coccidioidomycosis
tomography (CT) and especially magnetic
There are two species of the dimorphic
resonance (MR) imaging of the brain are
fungus Coccidioides. C. immitis is endemic
quite sensitive for the diagnosis of mucor-
in California, and C. posadasii is endemic
mycosis. The MR signal intensity of Mucor
in northern Mexico, the southwestern
species lesions tends to be isointense or
United States (California and Arizona),
hypointense on all sequences. After the
Central America, and South America. The
administration of gadolinium, the lesions
two species cause clinically indistinguish-
have variable enhancement patterns rang-
able disease. They are abundant in soil, and
ing from homogeneous to heterogeneous
primary pulmonary infection results pri-
or have no enhancement. MR imaging can
marily after outdoor exposure. In immu-
also clearly demonstrate cavernous sinus
nocompetent hosts, the infection can be
and dural involvement.20,21
clinically silent. When it is evident, signs
MR spectroscopy shows markedly el-
and symptoms suggest mild respiratory
evated lactate, depleted N-acetyl aspartate,
involvement. On the other hand, in im-
and metabolite resonance attributable to
munocompromised patients with deficient
succinate and acetate, which is essentially
cellular immunity, the rate of disseminated
the same as that of pyogenic bacterial ab-
disease is as high as 22%.
scess without the commonly seen eleva-
Disseminated disease mostly involves
tions of amino acids valine, leucine, and
the skin, joints, bones, and spleen, but
isoleucine.22
approximately 50% of patients will have
meningeal involvement. In some cases,
Treatment
subclinical, chronic meningitis will devel-
Disseminated mucormycosis with CNS in- op, only to become manifest clinically after
volvement has a 98% mortality rate. For a delayed period of weeks to months.
localized cerebral or rhinocerebral disease, With meningitis, headache, fever, nau-
the mortality can reach 62%. Appropriate sea and vomiting, nuchal rigidity, seizures,
drug therapy together with aggressive sur- and papilledema can be present. Hydro-
gical débridement of tissue and treatment cephalus will develop in approximately
of underlying risk factors provides the best 50% of patients. CNS infection can progress
chance for a good outcome.16,17 infrequently to the development of a com-
pressive space-occupying lesion, such as
brain abscess or granuloma.
■■ Primary (Endemic) Mycoses
Diagnosis and Treatment
These fungi are endemic in certain geo-
graphic locations and affect primarily im- Although CSF analysis will show nonspe-
munocompetent individuals. In individuals cific biochemical changes compatible with
with immunosuppression, the disease has a meningitis and lymphocytic pleocytosis,
very high probability of becoming dissemi- the presence of eosinophilia is highly sug-
nated from the primary site, which is usu- gestive of Coccidioides infection. Cultures
ally the respiratory system, to reach the CNS will be positive in approximately 50% of
and cause severe debilitation. Additionally, cases. The diagnosis can be made by exam-
under these conditions, clinically evident ining skin biopsies or by serologic tests. In
disease can reflect reactivation of a dormant the past, intrathecal amphotericin B was
past infection. Aside from meningitis, which used. Amphotericin B has been replaced
251
by fluconazole as the drug of choice. Those CNS involvement. In immunocompromised
responding to therapy remain on lifelong patients, the risk for CNS spread is consider-
treatment because of the high relapse rate.9 ably higher. CNS seeding can result in either
meningitis or brain mass lesions (includ-
ing abscesses). Additionally, spinal epidural
■■ Histoplasmosis abscesses can develop by direct extension
from infected vertebrae.
Histoplasma capsulatum, a dimorphic fun-
gus, is the only species of the genus His- Diagnosis and Treatment
toplasma. H. capsulatum var. capsulatum
Serology is usually noninformative, but the
is associated with North American histo-
fungus can be isolated directly from infect-
plasmosis. The organism is found in bird
ed tissue specimens or from CSF samples if
droppings and bat guano, and in the United
a lesion is based in the dura. Amphotericin
States it is endemic in the states border-
B is the drug of choice for treatment.9 Effec-
ing the Ohio and lower Mississippi River
tive surgical resection has been reported in
valleys. Primary infection involves the re-
small series.
spiratory system. Although disseminated
histoplasmosis is rare, it develops after in-
fection in as many as 80% of immunocom-
promised patients. Most reports are from ■■ Candidiasis
patients with HIV infection and lympho-
ma. CNS involvement occurs in 5 to 20% of Candida species (primarily C. albicans)
those with disseminated disease but can are opportunistic yeasts. They are a major
occur in isolation. The clinical spectrum of cause of bloodstream infections, especially

disease is chronic meningitis with the de- in surgical and critical care hospital set-
velopment of hydrocephalus, or less com- tings. Immunodeficiency, especially phago-
monly focal parenchymal mass lesions or cyte dysfunction, predisposes patients to
strokes due to emboli. both systemic candidiasis and CNS involve-
ment.16 Candida CNS infections are report-
ed in 18 to 25% of those with disseminated
Diagnosis and Treatment
disease and are likely underdiagnosed. In-
With the exception of patients with HIV infection can develop in patients with diabe-
fection, serologic antibody tests in immu- tes or cancer, organ transplant recipients,
nocompromised patients are of little value. those receiving cytotoxic or prolonged
The diagnosis can be made by detecting the corticosteroid therapies, and patients who
antigen in serum, urine, or CSF samples. Ad- have undergone invasive procedures. From
ditionally, the fungus can be cultured from an immunologic perspective, patients with
sputum or blood. The treatment of choice HIV infection are not at higher risk for in-
for CNS histoplasmosis is amphotericin B.9 fection because their defective cellular im-
munity is due to T-lymphocyte dysfunction.
CNS involvement usually manifests as
■■ Blastomycosis multiple microabscesses measuring less
than 1 mm in diameter. These occur pri-
The dimorphic fungus Blastomyces is en- marily within the supratentorial cortex
demic in the southeastern and central and less often in the basal ganglia and
southern United States, the Great Lakes white matter.23 Less commonly, meningitis
region of Canada and the bordering Mid- (> 20%) and rarely macroabscesses can de-
western states, and an area along the Saint velop.24 Vascular complications (infarction,
Lawrence River in New York and Canada. mycotic aneurysms, and subarachnoid
The lungs are the primary site from which hemorrhage) have also been documented.
disseminated disease can evolve. In 6 to 35% Microabscess formation usually presents
of those with disseminated disease, there is as a diffuse, vague encephalopathy. These
252
lesions are below CT resolution but can HIV patients can benefit from the adminis-
be visualized on MR imaging.25 Meningitis tration of trimethoprim-sulfamethoxazole
usually presents with a subacute onset of prophylaxis against Pneumocystis jiroveci
headache and fever, confusion, and altered pneumonia, which is also effective against

sensorium but can be fulminant and re- Nocardia infections.28,29 Because of the en-
sult in hydrocephalus. Macroabscesses will larging pool of susceptible patients, the in-
present with localizing signs and seizures. cidence of nocardiosis is increasing, so that
nocardiosis is now viewed as an emerging
Diagnosis infectious disease.30
The most common site of primary in-
Because CSF serology and cultures are un- fection is pulmonary (approximately 40%
reliable, the diagnosis is often made indi- of patients), but nocardiosis can be trans-
rectly, by funduscopic examination, blood mitted transcutaneously via penetrating
cultures, and infrequently by samples from trauma, animal scratches, or bites and can
other tissues. CSF 1,3-β-d-glucan has bet- also be spread iatrogenically. Nocardia fre-
ter sensitivity than serum assays, ranging quently erodes into blood vessels and thus
from 70 to 90%. PCR tests are being intro- has the potential for hematogenous spread.
duced but are of limited use because of a Although any organ can be involved, the
lack of availability and clinical validation incidence of CNS nocardiosis is dispropor-
and their high cost.15 tionately high during dissemination (44%)
or as an isolated primary site of infection
(38%). The hallmark of CNS involvement is
■■ Nocardiosis brain abscess formation without a predi-
lection for any specific cerebral region (Fig.
Nocardia, an aerobic actinomyces, is a 18.1). Although constitutional symptoms
gram-positive branching rod found in soil, can be found, the presentation can be sole-
decaying vegetables, and aquatic media. N. ly that of a space-occupying lesion causing
asteroides, which causes human disease, mass effect. A clinical presentation of sub-
has been redefined to include a complex of acute or chronic meningitis is infrequent.
four members: N. asteroides sensu stricto,
N. farcinica, N. nova, and N. transvalensis. Diagnosis
Of those, N. nova and N. farcinica are the
most virulent. Nocardia does not normally CNS nocardiosis should be suspected in
colonize human tissue and is considered an any immunocompromised patient whose
opportunistic microorganism, particularly clinical and radiologic presentation is com-
in patients with cell-mediated immune patible with a brain mass and concurrent
dysfunction. Nocardia has the capacity to pulmonary involvement. Additionally, a
evade clearance by the immune system by proven cutaneous or pulmonary nocardio-
several mechanisms that disrupt phagocyt- sis infection in an immunocompromised
ic activity, and about one-third of infected patient, even without the suspicion of CNS
individuals have an intact immune sys- involvement, warrants brain MR imaging
tem.26 Organ transplant recipients consti- to rule out occult CNS disease. The defini-
tute around 20% of patients with Nocardia tive diagnosis of nocardiosis requires iden-
infection, with an incidence of 0.1 to 3.5%. tification of the pathogen in a collected
Steroid-sparing regimens have reduced the specimen. Delay in diagnosis is common
risk in this population.27 The prevalence of because of the nonspecific clinical pre-
nocardiosis in HIV-positive patients is low sentation and difficulties in obtaining ad-
(0.2 to 2.0%), and nocardiosis appears most- equate specimens. Growing the bacteria is
ly in severely immunocompromised (CD4+ difficult, and blood cultures are rarely di-
cell count < 35/µL) patients. However, in agnostic. PCR provides rapid results and is
cases of invasive nocardiosis, patients with highly sensitive and specific, but its avail-
HIV infection comprise a major risk group. ability is limited and its cost is high.
253
a b
c d
Fig. 18.1 Magnetic resonance (MR) imaging. Nocardia abscess in a 74-year-old man on corticosteroid treat-
ment for chronic obstructive pulmonary disease. T2-weighted MR image demonstrates a hypointense lesion in
the occipital region with surrounding edema (b). Coronal and axial T1-weighted MR images with gadolinium
show a ring-enhancing lesion (a,c). The lesion shows restriction on diffusion-weighted sequence (d).
Treatment munocompromised patients.32 In addition,

some parasites, such as Strongyloides sterco-
Because the sensitivity of isolated strains
ralis, can rarely cause CNS infection in immu-
to antibiotics is highly variable, defining
nocompromised hosts. We discuss the more
patterns of susceptibility is mandatory in
common opportunistic pathogens that selec-
each case. While these results are awaited,
tively affect immunocompromised patients.
combination therapy is frequently used
for the empiric treatment of nocardiosis.
Toxoplasmosis
Trimethoprim-sulfamethoxazole and cef-
triaxone are used primarily,27 often with Toxoplasma gondii is an obligatory intra-
great success. The treatment of brain ab- cellular protozoan. This parasite is able to
scesses generally follows the guidelines develop in a variety of vertebrate hosts, but
set before for the treatment of infectious its definitive host is the house cat and oth-
space-occupying lesions.31 er members of the family Felidae. Infection
in humans occurs after the ingestion of
cysts contained in uncooked meat or after
■■ Parasitic Infections exposure to oocytes shed in cat feces. Sero-
logic markers reveal a variable geographic
Many parasitic infections, including malaria, prevalence of toxoplasmosis. In Europe, 50
schistosomiasis, microsporidiosis, leish- to 90% of the healthy adult population is
maniasis, and trypanosomiasis, can involve seropositive, whereas the rate is estimated
the CNS in both immunocompetent and im- to be 15 to 35% in the United States.33
254
In immunocompetent adults and chil- Diagnosis
dren past the neonatal period, the infec-
The diagnosis is based on the demon-
tion is usually asymptomatic. In a small
stration of the pathogen (tachyzoites or
percentage of patients, the clinical picture

cysts) in tissue sections or by CSF stain-
resembles that of infectious mononucleo-
ing. MR imaging typically shows multiple
sis. Hematogenous spread from the intes-
ring-enhancing or smaller nodular lesions
tine can seed any nucleated cell but most
surrounded by cerebral edema. Less com-
commonly affects the lungs, lymphoid sys-
monly, MR imaging demonstrates signs of
tem, heart, and CNS. Multiplication of the
meningoencephalitis. Although these MR
parasite within invaded cells leads to cel-
imaging findings are nonspecific, the extent
lular disruption and death. Focal areas of
of CNS involvement is well demonstrated.
necrosis and cyst formation result.32
A small eccentric nodule (eccentric target
Most cases of clinically apparent toxo-
sign) in the enhancing ring is suggestive
plasmosis in immunocompromised pa-
of toxoplasmosis, although the sensitivity
tients are the result of reactivation of a
of this finding is less than 30%. Rarely, the
previously acquired latent infection. The
lesions can be hemorrhagic (Fig. 18.2). In
vast majority of cases of cerebral toxo-
immunosuppressed patients without HIV
plasmosis have been documented in AIDS
infection, the degree of perilesional en-
patients, in whom it is the most frequent
hancement has been found to be inversely
opportunistic brain infection, occurring
related to the extent of immunosuppres-
in approximately 20 to 30% of individu-
sion. The radiologic differential diagnosis
als.34 Toxoplasmosis is the leading cause
for toxoplasmosis in the CNS includes CNS
of a mass lesion in AIDS patients. How-
lymphoma (typically subependymal le-
ever, patients with malignancies may
sions that lack the eccentric target sign),
also develop cerebral toxoplasmosis, in
metastatic disease, and other nonpyogenic
particular those who undergo an alloge-
infections.3
neic stem cell transplant (SCT) or a T-cell–
The definitive diagnosis of toxoplas-
depleting treatment regimen containing
mosis can be established by identifying
alemtuzumab or fludarabine. In addition
tachyzoites in tissue samples. Serologic
to fungal infection, cerebral toxoplasmo-
investigations of the CSF may be use-
sis has become one of the leading causes
ful, particularly for immunoglobulin G
of cerebral abscesses in patients after al-
by enzyme-linked immunosorbent assay
logeneic SCT.35,36 In solid organ transplant
(ELISA). Immunoglobulin M antibody de-
recipients, a primary infection can devel-
tection has a negligible value in the diag-
op if a donor organ containing encysted T.
nosis of neurotoxoplasmosis because most
gondii is transplanted into a seronegative
cases are not newly acquired. The detection
recipient. Seronegative patients receiv-
of specific DNA by PCR in the CSF, claimed
ing cardiac or renal allografts from sero-
to have high sensitivity and specificity, has
positive donors are at the highest risk for
produced inconsistent results and thus
toxoplasmosis.37,38
cannot be relied on for making the diagno-
In the CNS, toxoplasmosis produces
sis. The presence of multiple ring-enhanc-
multiple necrotic brain abscesses that
ing lesions in the basal ganglia or cerebrum
develop at the corticomedullary junction
on neuroimaging, in the presence of anti-
and in the basal ganglia. These lesions
Toxoplasma immunoglobulin G antibodies,
manifest clinically as seizures and local-
is suggestive of CNS toxoplasmosis and is
ized signs of a mass lesion, such as focal
sufficient to start empiric pharmacologic
neurologic deficits and cranial nerve pal-
treatment.32
sies. Lesions are solitary in approximately
30% of patients. Systemic manifestations
include hepatosplenomegaly, pneumoni- Treatment
tis, myositis, myocarditis, and skin rash. See later section on HIV coinfections.
255
a b
c d
Fig. 18.2 Magnetic resonance (MR) imaging. Toxoplasmosis in a 29-year-old patient with acute lymphoblastic
leukemia. Diffusion-weighted (b), T2-weighted (a), and fluid-attenuated inversion recovery (FLAIR) (d) sequenc-
es demonstrate multiple scattered bilateral lesions in the globus pallidus, left thalamus, and right subcortical
white matter. Lesions are nonenhancing on T1-weighted MR imaging with gadolinium (c).
Neurocysticercosis of neurocysticercosis in transplant recipi-

ents have been published.
Neurocysticercosis is caused by the larvae Patients who have HIV infection present
of Taenia solium. This is the most common most frequently with a clinical picture re-
helminthic infection of the CNS and the sulting from multiple parenchymal lesions
primary cause of acquired epilepsy in the that represent enhancing or nonenhancing
world. Cysticercosis is endemic in most cysts. Uncommonly, solitary lesions, giant
areas of the developing world where pigs cysts, and mixed forms (parenchymal, sub-
are raised, including Latin America, most arachnoidal, and ventricular) of intracranial
of Asia, sub-Saharan Africa, and parts of involvement are seen. An intracystic scolex
Oceania, but its frequency has increased in can sometimes be visualized. Patients may
developed countries owing to emigration exhibit findings compatible with those of
from these areas. Humans are infected by other, concomitant CNS infections.
the accidental ingestion of Taenia eggs dur- A clinical manifestation of neurocysti-
ing fecal–oral contamination.32 Considering cercosis has been recognized in the context
the high prevalence of neurocysticercosis, of an immune reconstitution syndrome
reports of this disease in immunocompro- that develops in HIV patients under HAART.
mised patients are surprisingly scarce, and A paradoxical clinical deterioration, initi-
it occurs generally as a coinfection in pa- ated by an intense inflammatory response
tients infected with HIV. Only a few cases to various subclinical or previously rec-
256
ognized infectious agents, can develop in stercoralis hyperinfection was considered
these patients.39 The current consensus is an opportunistic AIDS-defining illness, but
that HIV does not increase the tendency the rarity of its occurrence despite the vast
to develop neurocysticercosis, and that numbers of people who are likely coin-

because of its high prevalence, neurocys- fected suggests that HIV patients are not
ticercosis is merely a coincidental finding. exceptionally predisposed.41–43
Still, neurocysticercosis is a condition that
should be included in the differential diag- American Trypanosomiasis
nosis of CNS involvement and cystic lesions
in an immunocompromised patient. American trypanosomiasis, or Chagas
disease, is a zoonotic disease caused by
Trypanosoma cruzi, a hemoflagellate pro-
Strongyloidiasis
tozoan. T. cruzi develops successfully in
Strongyloides stercoralis is a human in- several insects, but the domesticated re-
testinal nematode with an estimated duviid bugs, also known as cone nose
prevalence of tens of millions worldwide. bugs or triatomids, are the only vectors
Although most individuals are asymptom- of importance. Dogs and cats are impor-
atic, Strongyloides is capable of causing tant reservoirs in Brazil. In regions where
fulminant disease under conditions associ- the disease is endemic, from the southern
ated with compromised host immunity. United States to the south of Argentina and
Strongyloidiasis is often considered a Chile, its impact has been staggering. With
disease of tropical and subtropical regions urbanization, population migration, and
in Asia and Africa, but foci of endemicity frequent traveling, the population at risk is
are also seen in temperate regions of South growing, and nonzoonotic forms of trans-
America and the southeastern United mission are emerging. In Latin America,
States. Additionally, infection with human the disease affects approximately 25% of
T-lymphotropic virus type 1 (HTLV-1) is the population, with 8 to 11 million people
associated with an increased prevalence of infected. Beyond the acute stage and after
S. stercoralis infection. The common mode a variable latency period that can last 20
of transmission is by transcutaneous pen- years, a chronic form of the disease appears
etration. The infective filariform larvae in approximately 30% of those primarily af-
then migrate to the small intestine, enter fected.32 In distinction to the cardiac and
the bloodstream, reach the lungs, and as- intestinal manifestations in immunocom-
cend the tracheobronchial tree to enter petent individuals, the primary expression
the gastrointestinal tract. Thus, a subclini- of disease in patients with immunodefi-
cal cycle can be established that allows ciency is CNS involvement. Most reports
the disease to persist in the host indefi- focus on HIV patients, in whom the disease
nitely. CNS involvement can appear when is considered to represent reactivation.44
chronic strongyloidiasis transforms to a The neurologic presentation in these cases
state of hyperinfection, with an increased is that of a space-occupying lesion (usually
larval load and possible dissemination at- evident in the subcortical or central white
tributed to accelerated autoinfection. Im- matter), encephalitis, or meningoencepha-
munocompromised patients, especially litis. Toxoplasmosis can coexist with Cha-
those treated with corticosteroids for their gas disease in HIV-positive individuals.
underlying illness, are more prone to de- Although the two lesions have similar ra-
velop this syndrome.40 The predominant diologic features, toxoplasmosis on MR im-
manifestation of CNS involvement is men- aging is more likely to demonstrate lesions
ingitis. Rarely, the occurrence of discrete of the cortex or basal ganglia. Two epide-
mass lesions has been reported in HIV pa- miologic criteria are useful for suspecting
tients, in those requiring autologous STCs, chagasic encephalitis at the time of initial
and in the recipients of kidney transplants presentation in patients with HIV infection
before the cyclosporine era. In the past, S. and space-occupying lesions: a history of
257
travel from an area where Chagas disease miasis is potentially a public health risk to
is endemic and a history of blood transfu- those traveling to areas within Africa and
sions or intravenous drug abuse.45 Asia where it is endemic.46,50
Because of a smaller egg size, the Asian
Leishmaniasis schistosome S. japonicum causes 60% of all
schistosomal brain infections. S. haema-
Leishmaniasis is an obligate intracellular tobium can infect either the brain or the
protozoan infection introduced by the bite spinal cord, whereas the larger egg size of
of a female sand fly. Besides this natural S. mansoni usually limits infection to the
vector, infection can be transmitted by sy- spinal cord. CNS infection is thought to oc-
ringe sharing in drug users. Leishmaniasis cur either through egg embolization or in
is endemic in 88 countries, and nearly 2 situ egg deposition following the aberrant
million people become infected each year. migration of adult worms to the brain or
Most infections are due to species of the spinal cord. The encephalopathy that en-
Leishmania donovani group, specifically sues typically presents with focal or gener-
Leishmania infantum. In regions where alized tonic-clonic epilepsy. The presence
leishmaniasis is endemic, such as India, of numerous eggs can induce granuloma
Nepal, Bangladesh, and Sudan, disseminat- formation in the cortex, subcortex, basal
ed infection is more common in immuno- ganglia, or internal capsule. These granulo-
suppressed hosts. In HIV-infected people, mas eventually become exudative and ne-
symptomatic leishmaniasis may represent crotic, create mass effect, and present with
reactivation of latent infection rather than focal neurologic deficits and cranial nerve
primary infection. The most common neu- abnormalities.51
rologic manifestation of leishmaniasis is a

peripheral neuropathy. CNS leishmaniasis
is uncommon regardless of host immune
status and usually occurs via the exten- ■■ H
uman Immunodeficiency
sion of contiguous infection, most often Virus Coinfections
in the paranasal sinuses.46 Leishmaniasis
has been reported in immunosuppressed Despite the availability of HAART and the
patients, usually in conjunction with dis- application of prophylactic antimicrobial
seminated infection. Dysfunctions of the regimens, opportunistic infections con-
optic and other cranial nerves and menin- tinue to be a leading cause of morbidity in
gitis have been reported.47,48 HIV patients. At least 10% of patients with
AIDS present with neurologic involvement,
Schistosomiasis (Bilharziasis) and more than one-third will develop neu-
rologic complications during the course
Schistosoma is a blood fluke. Infection fol- of the disease.52 Apart from the adverse
lows contact with freshwater in which in- clinical impact of these secondary infec-
fected snails have liberated cercariae that tions, treating them effectively is impor-
penetrate the skin. Schistosomiasis is, after tant because opportunistic infections can
malaria, the second most prevalent tropi- enhance HIV activity, as evidenced by an
cal disease. Immunosuppression appears increased viral load.
to have little effect on the natural history of The selective loss of CD4+ cells during
schistosomiasis, but transmission by organ HIV infection results in clinical manifesta-
transplant has been described.49 Neurolog- tions that often differ from those seen in
ic complications are the most severe clini- other immunocompromised hosts. The
cal consequence of Schistosoma infection. majority of opportunistic CNS infections
Three Schistosoma species are capable of are due to T. gondii, Epstein-Barr virus
causing CNS infection: S. mansoni, S. hae- (which also may cause primary CNS lym-
matobium (African form), and S. japonicum. phoma), JC virus (progressive multifocal
Although only a minority of patients (< 5%) leukoencephalopathy [PML]), and Cryp-
258 will develop CNS involvement, schistoso- tococcus neoformans. Parasitic infections
aside from toxoplasmosis and tuberculosis Cryptococcosis
(TB) are most commonly found in HIV-in-
fected people from developing countries, C. neoformans (serotypes A, D, and the hy-
but they are becoming increasingly com- brid AD) is a yeastlike fungus ubiquitous

mon in developed nations as the result of in soil and bird excreta that is responsible
international travel and immigration.34 for most infections worldwide. In Australia,
The risk for CNS infection usually varies Cryptococcus gattii is found in the vicinity
with the CD4+ cell count. With the excep- of eucalyptus trees and is also a source of
tion of TB and JC viral infections, CNS infec- infection, mostly in immunocompetent in-
tion increases substantially with CD4+ cell dividuals. Cryptococcus is transmitted by
counts of less than 200/mm3. In addition to inhalation into the respiratory system.6
infectious causes, the differential diagno- Usually, cryptococcal pulmonary in-
sis of focal neurologic disease in patients volvement develops unnoticed, and the
with AIDS should include central CNS first clinical expression of infection is iso-
lymphoma.53 Because of the attenuated lated meningitis. Other organs at risk for
cellular immune response in severely im- infection are the skin, prostate, and eyes.
munocompromised HIV patients, findings Cryptococcal meningitis is the most com-
on neuroimaging usually differ from those mon fungal infection in patients with re-
seen in other immunocompromised hosts duced cellular immunity. In HIV patients
or in HIV hosts whose immune system has with CD4+ cell counts below 100 to 200/
been reconstituted under HAART. mL, it is the most frequent fungal infec-
tion (prevalence of 1 to 8%) and ranks third
Toxoplasmosis (after HIV encephalitis and toxoplasmosis)
as a cause of CNS disease.32 Cryptococco-
Patients with primary HIV infection and sis of the CNS occurs in 2.6 to 8% of organ
toxoplasmosis are almost uniformly sero- transplant recipients. Infections involving
positive for anti-Toxoplasma immunoglob- the CNS are associated with higher mortal-
ulin G antibodies. Clinical disease is rare ity rates, which reach 40%.9,56 In addition
among patients with CD4+ cell counts above to meningitis, CNS involvement includes
200/mL. The greatest risk for infection oc- discrete parenchymal or intraventricular
curs among patients with a CD4+ cell count lesions (abscesses or granulomas), pseudo-
below 50/mL.34,54 Prophylactic therapy has cysts of the basal ganglia and thalami, and
been effective in reducing the incidence of infarction. The latter are a complication
the disease. The majority of clinicians rely of basal meningitis and arteritis of pen-
initially on an empiric diagnosis, which can etrating vessels. Cryptococcal meningitis
be established as an objective response on reportedly causes hydrocephalus in up to
the basis of clinical and radiographic re- two-thirds of patients.57 Cryptococcomas
sponses to specific anti–T. gondii therapy are mass lesions that contain mucinous
in the absence of a likely alternative diag- material, inflammatory cells, and the mi-
nosis. Brain biopsy is reserved for patients croorganism. They develop with blood–
who fail to respond to specific therapy. The brain barrier disruption and extension of
initial therapy of choice for toxoplasmosis the fungus from the perivascular spaces
is pharmacologic and consists of the combi- into the parenchyma.5,58
nation of pyrimethamine, sulfadiazine, and
leucovorin.34,55 A brain biopsy, if not previ- Diagnosis
ously performed, should be strongly con-
sidered for patients who fail to respond to In the setting of AIDS, CSF biochemical or
initial therapy for toxoplasmosis, as defined cellular markers of inflammation are mildly
by clinical or radiologic deterioration dur- elevated (suppressed), but CSF cryptococcal
ing the first week despite adequate therapy, antigen is detected in more than 90%. With
or lack of clinical improvement within 2 India ink staining of the CSF, the fungus can
weeks. be seen surrounded by a halo created by its
259
inert capsule. The rate of a positive India ink to 0.5%).34,59,60 In these settings, the rate
test ranges from very low (immunocompe- of dissemination and the development of
tent patients) to 91%. A definitive diagnosis CNS disease is also higher than in the gen-
can be reached by CSF cultures. However, it eral population. About 20 to 36% of HIV pa-
is suggested that PCR has a higher sensitiv- tients develop neurotuberculosis, mostly
ity, of more than 90%. Radiologic features meningitis, usually in the context of a dis-
include meningeal enhancement, hydro- seminated disease.
cephalus, and the demonstration of discrete Contrary to what is observed in other
lesions (cryptococcomas or abscesses), all coinfections, the incidence of active TB
of which are nonspecific. does not depend on the CD4+ cell count,
The MR imaging features of cryptococ- but the severity of the disease does, with
cal mass lesions are variable. They are usu- a higher probability of extrapulmonary
ally hypointense on T1-weighted imaging involvement occurring with lower CD4+
and hyperintense on T2-weighted imag- cell counts. Without profound immunode-
ing sequences, with peripheral edema and ficiency (CD4+ cell count > 350 /mL), HIV-
nodular or ring-shaped enhancement after related TB clinically resembles the TB seen
gadolinium injection. Enhancement is seen among non-HIV patients, and the majority
more frequently in patients with an intact of patients have disease limited to the lungs.
immune response. More suggestive of the In the setting of severe immunodeficiency,
diagnosis are pseudocysts of the basal gan- extrapulmonary TB, including lymphadeni-
glia and thalami, which appear as punctate tis, pleuritis, pericarditis, and meningitis,
hyperintensities on T2 sequences. At times, may develop with or without pulmonary
these lesions can enhance with gadolinium. involvement. Extrapulmonary involve-
Intraventricular cystic lesions can develop, ment is detected in the majority of TB pa-
although uncommonly. The differential di- tients with CD4+ cell counts below 200/mL.
agnosis includes tumors and bacterial and Such patients may have severe systemic
protozoan mass lesions. From a neurosur- disease, rapid progression, and sepsis, but
gical perspective, these patients come to they also may be only mildly affected or as-
attention when a ventricular catheter or a ymptomatic. After the initiation of HAART,
permanent shunt is installed to treat hy- immunologic recovery can unveil subclini-
drocephalus, or when surgical resection is cal TB, resulting in pronounced inflamma-
needed for a lesion causing mass effect.6 tory reactions at the sites of infection. In
solid organ transplant recipients, infection
generally occurs within the first year. Espe-
Tuberculosis
cially susceptible to TB infection are kidney
TB is acquired predominantly by the inha- and lung transplant patients. CNS involve-
lation of mycobacteria-containing drop- ment manifests primarily as meningitis.
lets. In immunocompetent individuals, Space-occupying lesions, tuberculomas
this primary infection is of short duration, (more common) or abscesses, develop in
although latent infection remains. HIV pa- 10 to 25% of patients. In intravenous drug
tients are predisposed to the development users, cerebral TB mass lesions are much
of TB; new infection is responsible for ap- more frequent (the second most common
proximately one-third of TB cases in HIV cause of cerebral lesions after cerebral
patients, whereas the transformation of toxoplasmosis).61 The type of lesion that
latent disease accounts for the remainder. develops depends on the degree of immu-
The rate of reactivation of latent TB is 3 to nodeficiency. Patients with relatively intact
12 times higher in HIV patients than in in- immune function typically have granulo-
dividuals without HIV infection; the rate is matous inflammation. With progressive
estimated to be 35 to 160 cases per 1,000 immunodeficiency, granulomas become
patient-years. Solid organ transplant re- poorly formed or can be completely absent.
cipients are also at much higher risk (0.2 Tuberculous brain abscesses contain encap-
260
sulated pus with viable bacilli. The more JC Virus Infection and Progressive
common tuberculomas (granulomas) are Multifocal Leukoencephalopathy
usually small and contain caseous debris.
Mycobacterial infections can emerge in Classically, PML is a highly fatal and rapidly

approximately 40% of HIV patients who de- progressive demyelinating disease. It was
velop an immune reconstitution inflamma- described first in hematologic malignancies,
tory syndrome (IRIS) after the initiation of and the later association of PML with the JC
HAART. A vigorous granulomatous reaction polyoma virus was made 44 years ago. The
can occur, with caseation or with suppu- incidence of PML rose exponentially with
ration and necrotizing inflammation. This the HIV epidemic. Although the introduc-
syndrome can manifest as early as 2 weeks tion of HAART has lowered its occurrence
after the start of HAART, with neurologic and improved the prognosis, PML still mani-
manifestations occurring in more than 12% fests clinically in 1 to 5% of the HIV-positive
of TB cases with IRIS.62,63 Tuberculous brain population (in approximately 10% in patho-
abscesses are usually supratentorial. Mul- logic studies), and HIV infection accounts for
tiple lesions are found in one-third of cases. approximately 80 to 90% of all PML cases.32,68
The radiologic features of TB brain abscess- Other groups at risk for PML are patients
es are indistinguishable from those of other with hematologic malignancies, transplant
bacterial pyogenic abscesses. Tuberculomas recipients, those receiving chemotherapy
have a variable appearance on T2-weighted (notably fludarabine), and a recently growing
sequences, depending on their composi- new group of patients treated with immuno-
tion. When central (caseating) necrosis is modulatory antibodies for various autoim-
present, tuberculomas are hypointense to mune disorders, such as multiple sclerosis,
brain parenchyma on T2-weighted images rheumatoid arthritis, systemic lupus erythe-
with post-contrast ring enhancement. matosus, Crohn disease, and psoriasis.69,70 JC
A helpful clue leading to the diagnosis virus is ubiquitous. Among young adults in
of TB is the presence of associated lesions, developed countries, 50 to 91% of the urban
such as basal meningitis, multiple granulo- population is seropositive. No distinct clinical
mas, and deep cerebral infarcts.64 The eval- syndrome or mode of transmission has been
uation of suspected cases of CNS TB should defined for the initial infection. The patho-
include MR imaging of the spine. MR spec- genesis of PML in immunocompromised
troscopy can aid in the correct diagnosis by hosts results predominantly from activation
showing the absence of the 0.9-ppm amino of this previously acquired infectious state.
acid peak present in pyogenic abscesses Virulence is postulated to require the rear-
not caused by mycobacteria.65 rangement of the viral genome from the old
“archetypical” form to produce a neurotropic
strain. Several factors have been proposed
Treatment
to explain the exceptional rate at which HIV
Experience with the treatment of TB brain patients develop PML. These include1 facili-
abscesses is limited. Complete recovery tated entry of infected B lymphocytes into
with pharmacologic treatment has been the brain by HIV-induced disruption of the
described, but in most reported cases, early blood–brain barrier or by the creation of vas-
surgical drainage and chemotherapy are cular endothelium adhesion molecules,2 and
considered appropriate.66,67 Stereotactic transactivation of JC virus by HIV proteins
or image-guided needle aspiration can be or by chemokines elaborated by microg-
therapeutic as well as diagnostic. Early tri- lia in response to HIV.71 Unlike some of the
ple chemotherapy must be considered in all other CNS opportunistic infections, which
cases of suspected TB abscess, even before are almost wholly prevented when CD4+ cell
surgery, to reduce the risk for postoperative counts are maintained above100 to 200/mL,
meningitis. PML can still appear in such patients and in
261
those on HAART. Moreover, PML can develop scalloped outer margin (Fig. 18.3). Contrast
in the setting of initiating HAART and im- enhancement or edema is the exception (6
mune reconstitution.72,73 to 10% of patients), although the presence
of faint enhancement at the periphery of
Clinical Manifestations the lesion is not uncommon. In the context
of IRIS, enhancement, edema, and even
PML manifests as focal neurologic deficits,
mass effect can develop.74 The introduc-
usually with a slow onset but accelerating
tion of HAART has significantly decreased
progression that lasts weeks or months.
the incidence and improved the prognosis
Any region of the CNS can be involved,
of this disease. Whereas PML was once an
but the subcortical occipital lobes (result-
almost uniformly fatal disease, with death
ing in hemianopsia), the frontal and pari-
occurring within 6 months after diagno-
etal lobes (hemiparesis and hemisensory
sis, patients now have a median survival
deficits), and the cerebellar peduncles and
of more than 2 years. Outcome correlates
deep white matter (dysmetria and ataxia)
with the ability to reduce the JC viral load
are affected most often. Spinal cord in-
and improve immune function (CD4+ cell
volvement is rare. Although the lesions are
counts). Patients with contrast-enhancing
multifocal, often one lesion predominates
lesions on MR imaging may also have a
clinically. Rarely, pyramidal cell disease
relatively favorable outcome, probably be-
with encephalopathy and dementia or a
cause abnormal enhancement reflects an
cerebellar syndrome (secondary to granu-
improved immune response (“inflamma-
lar cell involvement) can develop. Even
tory PML”).75
though PML is a white matter disease, sei-
zures can appear in 20% of cases.74
Diagnosis
■■ Infections in Transplant
Recipients
The progression of disease over several
weeks often provides a clue to the diagno- Although clinically evident CNS infections
sis, as the other major opportunistic focal occur in 1.3 to 6% of transplant recipients,
brain disorders (cerebral toxoplasmosis the autopsy-proven prevalence of CNS in-
and primary CNS lymphoma) characteris- volvement can reach 15%. The timing of
tically progress more rapidly, over hours the appearance and the nature of the of-
or a few days. A definitive diagnosis can be fending pathogens affecting hematopoietic
made by demonstrating the presence of JC and solid organ transplant recipients have
virus in a specimen collected by brain bi- some distinguishing features. The risk for
opsy. New CSF PCR methods have become acquiring infections after either a solid or-
reliable, less invasive means, with 90 to gan transplant or a hematopoietic stem cell
100% specificity. Sensitivity, though, is up transplant (HSCT) and the specific micro-
to 80%, and a PCR test can be negative at the organisms involved follow a relatively pre-
first stages of the disease, necessitating ad- dictable pattern. The type of infection that
ditional samples. PCR results coupled with develops is determined mainly by the organ
characteristic MR imaging findings in the transplanted, patient factors (age, comor-
appropriate clinical setting are diagnostic. bid state, previous infections), exposure
T2-weighted MR imaging and fluid-attenu- to environmental hazards, and additional
ated inversion recovery (FLAIR) sequences medical interventions. The introduction of
reveal bilateral, asymmetric focal areas of new immunosuppressive protocols, organ
high signal intensity, which become larger screening, the use of prophylactic medi-
and confluent over time and lack any sig- cations, and longer recipient survival are
nificant associated cerebral edema or mass changing the patterns of infection.76 Still,
effect. The disorder tends to involve the pe- as a diagnostic framework, a time line can
ripheral white matter, giving the lesions a be plotted to reflect a patient’s chrono-
262
a b
c d
Fig. 18.3 Magnetic resonance (MR) imaging. Progressive multifocal leukoencephalopathy in a 39-year-old pa-
tient with human immunodeficiency virus (HIV) infection presenting with left hemiparesis. Diffuse white matter
involvement is seen on T2-weighted MR (a) and fluid-attenuated inversion recovery (FLAIR) (b,c) sequences. On
T1-weighted MR image with gadolinium (d), faint enhancement is seen in a small right periventricular region.
logic “net immunosuppression” status and pecially CMV) infections can increase the
susceptibility to specific infections. Con- patient’s vulnerability to other infections,
ventionally, the emergence of infections either by their adverse immunomodulato-
is divided into three periods: the early or ry effect or by precipitating graft rejection,
perioperative period, up to 1 month after which necessitates more intense pharma-
transplant; the intermediate period, lasting cologic immunosuppression. After this pe-
1 to 6 months after transplant; and the late riod, as the level of immunosuppression is
period, starting at 6 months after trans- usually reduced, the risk becomes lower
plant. Because immunosuppression has unless aggressive immunosuppression is
not fully taken effect, opportunistic infec- reinstituted to treat graft-versus-host dis-
tions are usually not observed during the ease. Fungi, Toxoplasma, Nocardia, rarely
first month after transplant. From month TB mycobacteria, and other bacteria cause
1 to month 6, immunosuppression is most nearly all space-occupying lesions.77,78 In
pronounced. CNS infection during this pe- the differential diagnosis of focal CNS le-
riod is most often due to herpesviruses, sions in transplant recipients, one should
especially cytomegalovirus (CMV) and include EBV-induced CNS lymphoma (post-
Epstein-Barr virus (EBV), fungi, and atypi- transplant lymphoproliferative disorder).
cal bacteria or parasites. Herpesvirus (es- The incidence of B-cell lymphoma in pa-
263
tients with an HSCT is 2.0 to 7.7%, and 1 to the patients are neutropenic, and the major
6% of these will exhibit CNS involvement. risk is for the acquisition of fungal (Candida,
Additionally, as a result of exposure to Aspergillus) or bacterial infections (mostly
high-dose radiation, HSCT patients can de- iatrogenic) and the reactivation of latent vi-
velop other, secondary malignant tumors ral infections.
that include gliomas and meningiomas. At a later stage (beyond 1 month), de-
Space-occupying tumefacient demyelinat- fective cellular immunity exposes the
ing lesions can also develop in the chronic patients mostly to viral, fungal, and pro-
phase after HSCT. Finally, immunosuppres- tozoal infections. Infections with invasive
sive drug–induced lesions (tacrolimus) can molds (mostly Aspergillus species) have a
appear.79 high rate of CNS involvement (40 to 50%),
and these are the most frequent agents,
with an overall incidence of 3 to 4.5%.81
■■ H
ematopoietic Stem Cell Toxoplasma CNS infections occur in 0.3 to
3% of HSCT patients, depending on serop-
Transplant revalence; however, the incidence has de-
HSCT is employed to treat various hemato- creased because of the prophylactic use of
logic malignancies and hematopoietic and trimethoprim-sulfamethoxazole. T. gondii
autoimmune disorders. HSCT protocols vary infections, when they do occur in HSCT pa-
according to the source of stem cells and tients, can cause life-threatening complica-
the intensity of pretransplant myeloabla- tions, with an estimated mortality rate of
tion. In turn, these factors affect the pattern 60 to 90%.82,83
and susceptibility of HSCT recipients to in- Although aspergillosis can develop at
fections. Before HSCT, the recipient receives any stage, most HSCT patients exhibit a
chemotherapy or radiotherapy to eliminate bimodal susceptibility to Aspergillus in-
defective bone marrow or residual cancer fection—first in the early posttransplant
cells (conditioning). Then, blood- or bone neutropenic phase and later during the
marrow–derived hematopoietic progenitor post-engraftment period, when high levels
cells taken either from a human leukocyte of immunosuppression are maintained to
antigen (HLA)–matched donor (allogeneic) prevent graft-versus-host disease. Although
or from the patient (autologous) are im- they were initially thought to have lower
planted. The duration and degree of post- rates of invasive fungal infection, recipients
transplant myeloaplasia depend on the of nonmyeloablative allogeneic transplants
conditioning regimen. Immune reconstitu- are also reported to be at high risk.
tion takes at least 4 months, and complete
recovery is expected to happen after 1 year.
Graft-versus-host disease can appear acute- ■■ Solid Organ Transplant
ly (early) or several months after transplant
(chronic graft-versus-host disease). Ad- Solid organ transplants are increasing in
ditional immunosuppressive therapy for numbers. Patterns of infection under im-
acute or subacute graft-versus-host disease munosuppression are essentially similar to
can cause severe, life-threatening immuno- those in HSCT recipients. During the initial
suppression. After allogeneic HSCT, there is month after transplant, CNS infection is
the need for chronic immunosuppression infrequent. Infection is most often caused
to prevent graft-versus-host disease, which by common bacterial pathogens or oppor-
puts these patients at risk for opportunistic tunistic pathogens present in the environ-
infections. Cerebral infections occur in ap- ment or host (e.g., Candida and Aspergillus
proximately 0.3 to 4.5% of HSCT recipients.80 species or Mycobacterium tuberculosis). An
The most notable infections in HSCT pa- additional risk associated with solid organ
tients are due to viral, fungal, and protozoal transplant is that a latent, unrecognized
agents. In the initial posttransplant period, infectious agent can be inadvertently in-
264
troduced through the implanted organ References
and reactivated in the recipient. This set 1. Hayden RT, Carroll KC, Tang Y, Wolk DM, eds.
of events has been observed in regions Diagnostic Microbiology of the Immunocompro-
where Trypanosoma cruzi is endemic but mised Host. Washington, DC: ASM Press; 2009

2. Engelhardt B, Sorokin L. The blood-brain and the
has also been described for viral patho- blood-cerebrospinal fluid barriers: function and
gens. The majority of infections in solid or- dysfunction. Semin Immunopathol 2009;31(4):
gan transplant recipients occur more than 497–511 PubMed
90 days after transplant and are mostly of 3. Karampekios S, Hesselink J. Cerebral infections.
Eur Radiol 2005;15(3):485–493 PubMed
viral, fungal, or parasitic origin. Mass le- 4. Cunha BA. Central nervous system infections in the
sions are most often formed by invasive compromised host: a diagnostic approach. Infect
fungi. The highest incidence of invasive Dis Clin North Am 2001;15(2):567–590 PubMed
5. Dubey A, Patwardhan RV, Sampth S, Santosh V,
fungal infections is reported in recipients
Kolluri S, Nanda A. Intracranial fungal granu-
of small-bowel transplants (11.6%); this is loma: analysis of 40 patients and review of the
followed by 8.6% (especially aspergillosis) literature. Surg Neurol 2005;63(3):254–260,
in lung and heart–lung recipients, 4.7% in discussion 260 PubMed
6. Rauchway AC, Husain S, Selhorst JB. Neurologic
liver recipients, 4.0% in pancreas and kid- presentations of fungal infections. Neurol Clin
ney–pancreas recipients, and 3.4% in heart 2010;28(1):293–309 PubMed
transplant recipients. Kidney transplant 7. Scully EP, Baden LR, Katz JT. Fungal brain infections.
recipients have the lowest overall risk for Curr Opin Neurol 2008;21(3):347–352 PubMed
8. Bodey G, Bueltmann B, Duguid W, et al. Fungal infec-
infection of 1.3%. Most of these infections tions in cancer patients: an international autopsy
are caused by invasive Candida and Asper- survey. Eur J Clin Microbiol Infect Dis 1992;11(2):
gillus species. 99–109 PubMed
9. Black KE, Baden LR. Fungal infections of the CNS:
Importantly, a substantial number of treatment strategies for the immunocompromised
fungal infections (up to 25%), especially patient. CNS Drugs 2007;21(4):293–318 PubMed
cryptococcosis, mold infections other than 10. Kleinschmidt-DeMasters BK. Central nervous
aspergillosis, and endemic fungal infec- system aspergillosis: a 20-year retrospective se-
ries. Hum Pathol 2002;33(1):116–124 PubMed
tions can appear more than 3 years after 11. L in SJ, Schranz J, Teutsch SM. Aspergillosis case-
transplant.56 Nocardia infections have been fatality rate: systematic review of the literature.
reported in 0.1 to 3.5% of solid organ trans- Clin Infect Dis 2001;32(3):358–366 PubMed
12. Jain KK, Mittal SK, Kumar S, Gupta RK. Imaging
plant recipients, more often in lung trans-
features of central nervous system fungal infec-
plants and less often in kidney and liver tions. Neurol India 2007;55(3):241–250 PubMed
transplants. Although the rate of infection 13. P osteraro B, Torelli R, De Carolis E, Posteraro P,
has declined thanks to the prophylactic Sanguinetti M. Update on the laboratory diagno-
sis of invasive fungal infections. Mediterr J Hema-
use of trimethoprim-sulfamethoxazole, tol Infect Dis 2011;3(1):e2011002 PubMed
at increased risk for infection are patients 14. L ow CY, Rotstein C. Emerging fungal infections in
on high-dose steroids, those with recent immunocompromised patients. F1000 Med Rep
CMV infection, and those with high calci- 2011;3:14–21 PubMed
15. S ingh N, Pursell KJ. Combination therapeutic ap-
neurin inhibitor levels. The risk for infec- proaches for the management of invasive asper-
tion is highest during the first year after gillosis in organ transplant recipients. Mycoses
transplant—higher in lung (3.5%) and heart 2008;51(2):99–108 PubMed
16. M attiuzzi G, Giles FJ. Management of intracra-
(2.5%) transplants and lower in kidney nial fungal infections in patients with haemato-
and liver transplants (1 to 2%).27 Solid or- logical malignancies. Br J Haematol 2005;131(3):
gan transplant patients are also at greater 287–300 PubMed
risk for developing TB (0.2 to 0.5%). Infec- 17. R oden MM, Zaoutis TE, Buchanan WL, et al. Epi-
demiology and outcome of zygomycosis: a re-
tion generally occurs within the first year. view of 929 reported cases. Clin Infect Dis 2005;
Especially susceptible are kidney and lung 41(5):634–653 PubMed
transplant patients.34,59,60 18. T hajeb P, Thajeb T, Dai D. Fatal strokes in pa-
tients with rhino-orbito-cerebral mucormycosis
In this late posttransplant period, PML
and associated vasculopathy. Scand J Infect Dis
caused by infections with JC virus also 2004;36(9):643–648 PubMed
rarely appear. 19. P agano L, Offidani M, Fianchi L, et al; GIME-
MA (Gruppo Italiano Malattie EMatologiche
265
dell’Adulto) Infection Program. Mucormycosis Diseases Society of America. MMWR Recomm
in hematologic patients. Haematologica 2004; Rep 2009;58(RR-4):1–207, quiz CE1–CE4 PubMed
89(2):207–214 PubMed 35. D
enier C, Bourhis JH, Lacroix C, et al. Spectrum
20. Horger M, Hebart H, Schimmel H, et al. Dissemi- and prognosis of neurologic complications af-
nated mucormycosis in haematological patients: ter hematopoietic transplantation. Neurology
CT and MRI findings with pathological correla- 2006;67(11):1990–1997 PubMed
tion. Br J Radiol 2006;79(945):e88–e95 PubMed 36. S
chmidt-Hieber M, Zweigner J, Uharek L, Blau
21. Herrera DA, Dublin AB, Ormsby EL, Aminpour S, IW, Thiel E. Central nervous system infections
Howell LP. Imaging findings of rhinocerebral mucor- in immunocompromised patients: update on
mycosis. Skull Base 2009;19(2):117–125 PubMed diagnostics and therapy. Leuk Lymphoma 2009;
22. Luthra G, Parihar A, Nath K, et al. Comparative 50(1):24–36 PubMed
evaluation of fungal, tubercular, and pyogenic 37. G
ourishankar S, Doucette K, Fenton J, Purych D,
brain abscesses with conventional and diffusion Kowalewska-Grochowska K, Preiksaitis J. The use
MR imaging and proton MR spectroscopy. AJNR of donor and recipient screening for toxoplasma
Am J Neuroradiol 2007;28(7):1332–1338 PubMed in the era of universal trimethoprim sulfamethox-
23. Nakayama H, Shibuya K, Kimura M, Ueda M,
azole prophylaxis. Transplantation 2008;85(7):
Iwabuchi S. Histopathological study of candidal 980–985 PubMed
infection in the central nervous system. Nippon 38. M
artina MN, Cervera C, Esforzado N, et al. Toxo-
Ishinkin Gakkai Zasshi 2010;51(1):31–45 PubMed plasma gondii primary infection in renal trans-
24. Mendes V, Castro S, Linhares P, Ribeiro-Silva plant recipients. Two case reports and literature
ML. Tumoriform presentation of cerebral candi- review. Transpl Int 2011;24(1):e6–e12 PubMed
diasis in an HIV-infected patient. J Clin Neurosci 39. S
erpa JA, Moran A, Goodman JC, Giordano TP,
2009;16(4):587–588 PubMed White AC Jr. Neurocysticercosis in the HIV era:
25. Jain KK, Mittal SK, Kumar S, Gupta RK. Imaging a case report and review of the literature. Am J
features of central nervous system fungal infec- Trop Med Hyg 2007;77(1):113–117 PubMed
tions. Neurol India 2007;55(3):241–250 PubMed 40. K
eiser PB, Nutman TB. Strongyloides stercoralis in
26. Beaman BL, Beaman L. Nocardia species: host- the immunocompromised population. Clin Mi-
parasite relationships. Clin Microbiol Rev 1994; crobiol Rev 2004;17(1):208–217 PubMed
7(2):213–264 PubMed 41. Orlent H, Crawley C, Cwynarski K, Dina R, Ap-
27. Peleg AY, Husain S, Qureshi ZA, et al. Risk fac- perley J. Strongyloidiasis pre and post autologous
tors, clinical characteristics, and outcome of No- peripheral blood stem cell transplantation. Bone
cardia infection in organ transplant recipients: Marrow Transplant 2003;32(1):115–117 PubMed
a matched case-control study. Clin Infect Dis 42. M
orgello S, Soifer FM, Lin CS, Wolfe DE. Central
2007;44(10):1307–1314 PubMed nervous system Strongyloides stercoralis in ac-
28. Pintado V, Gómez-Mampaso E, Cobo J, et al. No- quired immunodeficiency syndrome: a report of
cardial infection in patients infected with the two cases and review of the literature. Acta Neu-
human immunodeficiency virus. Clin Microbiol ropathol 1993;86(3):285–288 PubMed
Infect 2003;9(7):716–720 PubMed 43. G
ompels MM, Todd J, Peters BS, Main J, Pinch-
29. Minero MV, Marín M, Cercenado E, Rabadán PM, ing AJ. Disseminated strongyloidiasis in AIDS:
Bouza E, Muñoz P. Nocardiosis at the turn of uncommon but important. AIDS 1991;5(3):
the century. Medicine (Baltimore) 2009;88(4): 329–332 PubMed
250–261 PubMed 44. C
ordova E, Boschi A, Ambrosioni J, Cudos C, Corti
30. Ambrosioni J, Lew D, Garbino J. Nocardiosis: up- M. Reactivation of Chagas disease with central
dated clinical review and experience at a tertiary nervous system involvement in HIV-infected pa-
center. Infection 2010;38(2):89–97 PubMed tients in Argentina, 1992-2007. Int J Infect Dis
31. Valarezo J, Cohen JE, Valarezo L, et al. Nocardial 2008;12(6):587–592 PubMed
cerebral abscess: report of three cases and review 45. D
iazgranados CA, Saavedra-Trujillo CH, Mantilla
of the current neurosurgical management. Neu- M, Valderrama SL, Alquichire C, Franco-Paredes
rol Res 2003;25(1):27–30 PubMed C. Chagasic encephalitis in HIV patients: com-
32. Walker M, Zunt JR. Parasitic central nervous sys- mon presentation of an evolving epidemiological
tem infections in immunocompromised hosts. and clinical association. Lancet Infect Dis 2009;
Clin Infect Dis 2005;40(7):1005–1015 PubMed 9(5):324–330 PubMed
33. Jones JL, Dargelas V, Roberts J, Press C, Remington 46. W
alker M, Kublin JG, Zunt JR. Parasitic central
JS, Montoya JG. Risk factors for Toxoplasma gon- nervous system infections in immunocompro-
dii infection in the United States. Clin Infect Dis mised hosts: malaria, microsporidiosis, leish-
2009;49(6):878–884 PubMed maniasis, and African trypanosomiasis. Clin
34. K
aplan JE, Benson C, Holmes KH, Brooks JT, Pau Infect Dis 2006;42(1):115–125 PubMed
A, Masur H; Centers for Disease Control and Pre- 47. Albrecht H, Sobottka I, Emminger C, et al. Visceral
vention (CDC); National Institutes of Health; HIV leishmaniasis emerging as an important opportu-
Medicine Association of the Infectious Diseases nistic infection in HIV-infected persons living in
Society of America. Guidelines for prevention and areas nonendemic for Leishmania donovani. Arch
treatment of opportunistic infections in HIV-in- Pathol Lab Med 1996;120(2):189–198 PubMed
fected adults and adolescents: recommendations 48. K
arak B, Garg RK, Misra S, Sharma AM. Neuro-
from CDC, the National Institutes of Health, and logical manifestations in a patient with visceral
the HIV Medicine Association of the Infectious
266
leishmaniasis. Postgrad Med J 1998;74(873): ciated immune reconstitution inflammatory syn-
423–425 PubMed drome: a case series. Clin Infect Dis 2009;48(11):
49. Kayler LK, Rudich SM, Merion RM. Orthotopic e96–e107 PubMed
liver transplantation from a donor with a his- 63. M arais S, Scholtz P, Pepper DJ, Meintjes G, Wilkin-
tory of schistosomiasis. Transplant Proc 2003; son RJ, Candy S. Neuroradiological features of the

35(8):2974–2976 PubMed tuberculosis-associated immune reconstitution
50. Li Y, Ross AG, Hou X, Lou Z, McManus DP. Orien- inflammatory syndrome. Int J Tuberc Lung Dis
tal schistosomiasis with neurological complica- 2010;14(2):188–196 PubMed
tions: case report. Ann Clin Microbiol Antimicrob 64. B ernaerts A, Vanhoenacker FM, Parizel PM, et al.
2011;10:5 PubMed Tuberculosis of the central nervous system: over-
51. Carod-Artal FJ. Neurological complications of view of neuroradiological findings. Eur Radiol
Schistosoma infection. Trans R Soc Trop Med Hyg 2003;13(8):1876–1890 PubMed
2008;102(2):107–116 PubMed 65. Luthra G, Parihar A, Nath K, et al. Comparative
52. Gray F, Chrétien F, Vallat-Decouvelaere AV, Scara- evaluation of fungal, tubercular, and pyogenic
villi F. The changing pattern of HIV neuropathol- brain abscesses with conventional and diffusion
ogy in the HAART era. J Neuropathol Exp Neurol MR imaging and proton MR spectroscopy. AJNR
2003;62(5):429–440 PubMed Am J Neuroradiol 2007;28(7):1332–1338 PubMed
53. Bayraktar S, Bayraktar UD, Ramos JC, Stefanovic 66. B ottieau E, Noë A, Florence E, Colebunders R.
A, Lossos IS. Primary CNS lymphoma in HIV posi- Multiple tuberculous brain abscesses in an
tive and negative patients: comparison of clinical HIV-infected patient successfully treated with
characteristics, outcome and prognostic factors. J HAART and antituberculous treatment. Infection
Neurooncol 2011;101(2):257–265 PubMed 2003;31(2):118–120 PubMed
54. Abgrall S, Rabaud C, Costagliola D; Clinical Epide- 67. Cárdenas G, Soto-Hernández JL, Orozco RV,
miology Group of the French Hospital Database Silva EG, Revuelta R, Amador JL. Tuberculous
on HIV. Incidence and risk factors for toxoplasmic brain abscesses in immunocompetent patients:
encephalitis in human immunodeficiency virus- management and outcome. Neurosurgery
infected patients before and during the highly 2010;67(4):1081–1087, discussion 1087 PubMed
active antiretroviral therapy era. Clin Infect Dis 68. d ’Arminio Monforte A, Cinque P, Mocroft A, et al;
2001;33(10):1747–1755 PubMed EuroSIDA Study Group. Changing incidence of
55. Dedicoat M, Livesley N. Management of toxoplas- central nervous system diseases in the EuroSIDA
mic encephalitis in HIV-infected adults (with an cohort. Ann Neurol 2004;55(3):320–328 PubMed
emphasis on resource-poor settings). Cochrane 69. A mend KL, Turnbull B, Foskett N, Napalkov P,
Database Syst Rev 2006;3(3):CD005420 PubMed Kurth T, Seeger J. Incidence of progressive mul-
56. Pappas PG, Alexander BD, Andes DR, et al. Inva- tifocal leukoencephalopathy in patients without
sive fungal infections among organ transplant HIV. Neurology 2010;75(15):1326–1332 PubMed
recipients: results of the Transplant-Associated 70. C arson KR, Focosi D, Major EO, et al. Monoclo-
Infection Surveillance Network (TRANSNET). Clin nal antibody-associated progressive multifocal
Infect Dis 2010;50(8):1101–1111 PubMed leucoencephalopathy in patients treated with
57. Singh N, Lortholary O, Dromer F, et al; Cryptococ- rituximab, natalizumab, and efalizumab: a Re-
cal Collaborative Transplant Study Group. Central view from the Research on Adverse Drug Events
nervous system cryptococcosis in solid organ and Reports (RADAR) Project. Lancet Oncol
transplant recipients: clinical relevance of abnor- 2009;10(8):816–824 PubMed
mal neuroimaging findings. Transplantation 2008; 71. K edar S, Berger JR. The changing landscape of
86(5):647–651 PubMed progressive multifocal leukoencephalopathy.
58. Li Q, You C, Liu Q, Liu Y. Central nervous system Curr Infect Dis Rep 2011;13(4):380–386 PubMed
cryptococcoma in immunocompetent patients: a 72. Tan K, Roda R, Ostrow L, McArthur J, Nath A.
short review illustrated by a new case. Acta Neu- PML-IRIS in patients with HIV infection: clini-
rochir (Wien) 2010;152(1):129–136 PubMed cal manifestations and treatment with steroids.
59. Nelson CA, Zunt JR. Tuberculosis of the central ner- Neurology 2009;72(17):1458–1464 PubMed
vous system in immunocompromised patients: 73. Sidhu N, McCutchan JA. Unmasking of PML by
HIV infection and solid organ transplant recipi- HAART: unusual clinical features and the role of IRIS.
ents. Clin Infect Dis 2011;53(9):915–926 PubMed J Neuroimmunol 2010;219(1-2):100–104 PubMed
60. Torre-Cisneros J, Doblas A, Aguado JM, et al; 74. T an CS, Koralnik IJ. Progressive multifocal leuko-
Spanish Network for Research in Infectious Dis- encephalopathy and other disorders caused by JC
eases. Tuberculosis after solid-organ transplant: virus: clinical features and pathogenesis. Lancet
incidence, risk factors, and clinical characteris- Neurol 2010;9(4):425–437 PubMed
tics in the RESITRA (Spanish Network of Infec- 75. H ernández B, Dronda F, Moreno S. Treatment
tion in Transplantation) cohort. Clin Infect Dis options for AIDS patients with progressive mul-
2009;48(12):1657–1665 PubMed tifocal leukoencephalopathy. Expert Opin Phar-
61. Bishburg E, Eng RHK, Slim J, Perez G, Johnson macother 2009;10(3):403–416 PubMed
E. Brain lesions in patients with acquired im- 76. L ow CY, Rotstein C. Emerging fungal infections in
munodeficiency syndrome. Arch Intern Med immunocompromised patients. F1000 Med Rep
1989;149(4):941–943 PubMed 2011;3:14–21 PubMed
62. Pepper DJ, Marais S, Maartens G, et al. Neurologic 77. F
ishman JA. Infection in solid-organ trans-
manifestations of paradoxical tuberculosis-asso- plant recipients. N Engl J Med 2007;357(25):
2601–2614 PubMed
267
78. Czartoski T. Central nervous system infections transplant recipients. Bone Marrow Transplant
in transplantation. Curr Treat Options Neurol 2003;31(3):191–196 PubMed
2006;8(3):193–201 PubMed 82. M
artino R, Bretagne S, Rovira M, et al. Toxoplas-
79. Nishiguchi T, Mochizuki K, Shakudo M, Takeshita mosis after hematopoietic stem cell transplanta-
T, Hino M, Inoue Y. CNS complications of hemato- tion. Report of a 5-year survey from the Infectious
poietic stem cell transplantation. AJR Am J Roent- Diseases Working Party of the European Group
genol 2009;192(4):1003–1011 PubMed for Blood and Marrow Transplantation. Bone
80. Bleggi-Torres LF, de Medeiros BC, Werner B, et al. Marrow Transplant 2000;25(10):1111–1114
Neuropathological findings after bone marrow PubMed
transplantation: an autopsy study of 180 cases. Bone 83. F
ricker-Hidalgo H, Bulabois CE, Brenier-Pinchart
Marrow Transplant 2000;25(3):301–307 PubMed MP, et al. Diagnosis of toxoplasmosis after allo-
81. Jantunen E, Volin L, Salonen O, et al. Central ner- geneic stem cell transplantation: results of DNA
vous system aspergillosis in allogeneic stem cell detection and serological techniques. Clin Infect
Dis 2009;48(2):e9–e15 PubMed
268
19
Systemic Infections in the
Neurologic Intensive Care Unit
Michael F. Regner, Christopher D. Baggott, Barry C. Fox, and
Joshua E. Medow
Evidence-based management guidelines neurologic patients probably benefit from

have been reported in recent years, with induced normothermia, which prevents
the hope of inspiring effective and cost- the hypermetabolic state of hyperthermia
efficient algorithms for the work-up and while avoiding the complications associ-
treatment of infectious diseases in the ated with hypothermia. Avoiding hypo-
critical care unit.1–7 Thoughtful application thermia requires the close monitoring of
of these guidelines in the neurologic inten- patient temperature and the establishment
sive care unit (ICU) is appropriate and im- of appropriate triggers to prompt an infec-
portant, given the impact of infection and tious work-up, appropriate systems-based
fever on patient outcomes. We intend to identification of infectious and noninfec-
present concise, guideline-based manage- tious sources, and measures to prevent hy-
ment principles for the critical care unit, pothermia or hyperthermia.
while addressing idiosyncrasies in the care
of neurologically injured patients. Monitoring
In order of preference, temperature moni-
toring should be achieved by intravascular,
■■ G
eneral Principles of esophageal, or bladder thermometry. If
Fever Management these methods are not available, measure-
ments can be collected at rectal, oral, or
Body Temperature and tympanic membrane sites. Axillary mea-
Neurologic Outcome surements, temporal artery estimates, and
chemical dot thermometers should not be
Hyperthermia and hypothermia are both
used.3
important clinical indicators that an infec-
tious process may be present in a critically
Triggers Prompting Infectious Work-up
ill patient. In units caring for neurological-
ly injured patients, body temperature has Although temperature is an important
a clear association with neurologic out- indicator of possible infectious status,
come.8 Hyperthermia within the first 24 automatic laboratory or radiologic investi-
hours has a negative impact on neurologic gations based on temperature alone should
outcome in stroke, probably because of in- be avoided. The new onset of a tempera-
creased metabolic demand in the ischemic ture of 38.3°C or higher or of 36.0°C or
pneumbra.9 Conversely, hypothermia is lower in the absence of a known cause of
associated with increased morbidity, par- pyrexia or hypothermia is an appropriate
ticularly in the context of infection, hy- trigger for clinical assessment.3 Careful
potension, and arrhythmias.10 Ultimately, clinical assessment drives decision mak-
ing. Routine “panculturing” should not be Suspected Bloodstream Infection
performed without a clinical assessment,
and microbiological specimens should be Bloodstream infections are a serious prob-
obtained at various time points for cul- lem, and any suspicion of this type of infec-
ture. The likelihood of infectious versus tion should be investigated thoroughly and
noninfectious processes arises from the adequately addressed. It is very important
clinical circumstance, and the site of infec- that the clinician and laboratory person-
tion may become apparent from the his- nel communicate effectively and regularly
tory and physical examination. Antibiotics regarding infection evaluation protocols to
should not be considered the antipyretics improve their diagnostic value and to re-
of choice3 (Table 19.1). duce technical errors as technology rapidly
Table 19.1 Overview of clinical work-up for infection3,11
Organ System Symptoms Signs
Central nervous system Headaches, vision changes, motor dis- Decreased arousal, cranial nerve
turbance, sensory disturbance, neck deficits, abnormal funduscopic
pain/stiffness, convulsions, changes examination, focal neurologic signs,
in mood/perception, psychiatric meningismus
symptoms
Cardiovascular Precordial pain; dyspnea (exertional, Murmurs, ectopic heart sounds,

positional, nocturnal); palpitations; rubs, hypertension, increased jugular
syncope; edema; cyanosis venous pressure, Janeway lesions,
splinter hemorrhages
Pulmonary Chest pain, shortness of breath, Decreased/adventitial sounds on

hemoptysis, wheezing, stridor, cough, auscultation (crackles, wheezes,
night sweats rhonchi, stridor, pleural rub);
secretions
Gastrointestinal Diarrhea, constipation, abnormal stools, Diarrhea, constipation, hematochezia/

appetite changes, nausea, vomiting, melena, emesis, hematemesis,
hematemesis, abdominal pain distention, rebound tenderness
Genitourinary Urgency, increased frequency, Erythema, genital discharge, foul

dysuria, hematuria, polyuria/oliguria, odor, epithelial changes, cutaneous
flank tenderness, genital discharge lesions
Skin/soft tissue Rash, itching, redness, pigmentation Erythema, induration, swelling,

changes, texture changes discharge, purulence
Bones/joints Pain, swelling, redness, decreased Erythema, swelling, discharge, puru-

range of motion, stiffness lence, sinus tracts, sensory deficits
Other/constitutional Weight loss, reduced sense of Weight loss, Homan sign, cutaneous
well-being, leg swelling, withdrawal stigmata, diaphoresis, palpitations,
symptoms, facial pain/sinus headache, pupillary size, Janeway lesions, heart
recent transfusion, recent travel murmurs, splinter hemorrhages,
history, recent surgery purulent nasal discharge, psychiatric
disturbance, many others
Abbreviations: ARDS, acute respiratory distress syndrome; BOOP, bronchiolitis obliterans–organizing pneumonia;
CVA, cerebrovascular accident; IBS, irritable bowel syndrome; SLE, systemic lupus erythematosus; UTI, urinary tract infection
270
evolves.12 Some important clinical triggers cially before the fever dissipates. However,
for obtaining a blood culture are listed in Ta- in the case of suspected endocarditis or the
ble 19.2. Standing orders should not be writ- more common intravascular device–related
ten for obtaining blood cultures; they should sepsis, blood cultures should be drawn as
be indicated either after clinical assessment soon as possible. When attempts have been
or in the presence of a known bloodstream made to achieve normothermia in a pa-
infection. Such test-of-cure cultures, when tient, blood cultures should be considered
indicated, may be discontinued after three for an elevation in the patient’s white blood
19 Systemic Infections in the Neurologic Intensive Care Unit

consecutive days of negative cultures.6 cell count. These blood cultures ideally are
Blood cultures are most useful if they drawn from two separate sites by percuta-
are drawn during a febrile episode, espe- neous venipuncture. Samples both by ve-
Table 19.1 (Continued) Overview of clinical work-up for infection3,11
Infectious Diseases Noninfectious Diseases
Meningitis; Posterior fossa syndrome, central fever, seizures,

encephalitis cerebral infarction, intracranial hemorrhage, CVA
(bacterial, viral, fungal, opportunistic); ventriculitis;
cerebritis/abscess
Central line infection, infected pacemaker, endo- Myocardial infarction, Dressler syndrome, vasculitis,
carditis, sternal osteomyelitis, viral pericarditis, balloon pump syndrome
myocardial/perivalvular abscess
Pneumonia, mediastinitis, tracheobronchitis, Pulmonary emboli, ARDS (fibroproliferative phase),

empyema atelectasis, BOOP, bronchogenic carcinoma, pneu-
monitis (SLE or others)
C. difficile colitis; intra-abdominal Pancreatitis, acalculous cholecystitis, bowel isch-

abscess; gastroenteritis (viral, bacterial); cholangitis; emia, bleeding, cirrhosis, ischemic colitis, IBS
cholecystitis; peritonitis
UTI, catheter-associated bacteriuria, pyelonephritis,

cystitis, sexually
transmitted infections
Decubitus ulcers, cellulitis, wound infection Drug rash/fever, autoimmune

processes (low-grade)
Osteomyelitis, septic arthritis Acute gout, heterotopic ossification
Bacteremia, sinusitis Adrenal insufficiency, phlebitis/thrombophlebitis,

neoplastic fever, alcohol/drug withdrawal, delirium
tremens, drug fever, fat emboli, deep venous
thrombosis, postoperative fever (48 hours), blood
product transfusion, cytokine storm, immune
reconstitution inflammatory syndrome, Jarisch-
Herxheimer reaction, thyroid storm, transplant
rejection, tumor lysis syndrome
271
Table 19.2 Triggers for blood culture catheter lumens is often involved in the
Fever and any one of the following:
pathogenesis of intravascular infections.13
If venous access is not an option, samples
• Rigors should be drawn from two separate vascu-
lar catheters and carefully labeled.6
• Mental status change
Blood cultures for bacteria and yeast
• Leukocytosis/unexplained leukopenia should consist of two samples in aerobic and
anaerobic bottles from each site. Current
• Oliguria blood culture media allow the detection of
• Hypoxia yeast without the need for special fungal
blood cultures. Quantitative blood cultures
• Tachypnea in which special isolator blood culture tubes
are used may be indicated for the diagnosis
• Metabolic acidosis
of bacteremia associated with cuffed Hick-
• Hypotension man or Broviac catheters or subcutaneous
central venous ports.6 The more common
• Significant change in white blood cell count method of diagnosis of catheter-related in-
Test of cure: fection is the differential time to positivity
of blood cultures taken from catheter and
• Endocarditis peripheral blood sites. When the differen-
tial time exceeds 2 hours between the cath-
• Staphylococcus aureus sepsis
eter culture and the peripheral culture, the
• Fungal sepsis inside of the catheter is usually considered
the source of bacteremia, and the catheter

• Continued signs/symptoms of sepsis
should be removed if possible.3
Table 19.3 summarizes some important
guidelines to be considered when blood
nipuncture and from an existing vascular cultures are obtained. Additional recom-
catheter are preferred only when vascular mendations are to avoid collecting from
access has exceeded 4 days. Inflammation more than two sites at a time, collecting
at the catheter exit site is not a reliable more than three cultures per day, and col-
predictor of intravascular catheter–related lecting more than four cultures per febrile
infection because the contamination of episode.
Table 19.3 Blood culture “do’s” and “don’ts”
Do: Don’t:
• Sample from two sites • Send < 5 mL to the laboratory
• Draw from venipuncture if possible • Send an anaerobic bottle without an aerobic

bottle
• Draw during a febrile episode unless suspected • Send adult specimens in pediatric bottles, or vice
endocarditis or intravascular-related sepsis versa
Avoid:
• Line-drawn specimens (± venipuncture) without a

simultaneous peripheral culture
• > 2 sites collected at a time
• > 3 cultures collected per day
• > 4 cultures per febrile episode

272
Diagnosing and treating the cause of a fe- sending the long line catheter tip than by
ver in a patient with catheters can be com- sending the intracutaneous segment.
plicated, but a standardized management
algorithm has been proposed in Fig. 19.1.
Suspected Noninfectious Fever
Treat resulting cultures per the Infectious
Diseases Society of America guidelines re- Noninfectious fevers can often be difficult
ported by Mermel et al for the catheters and to diagnose, necessitating a careful and
pathogenic species involved.6 Although the thorough history and physical examina-

tips of long intravascular catheters, such tion. All recent medication changes and
as percutaneously inserted central venous blood products received should be consid-
catheters, are often sent for culture, the ered in the febrile patient. Establishing a
preferred segment of the catheter to send temporal relationship between the initia-
to the laboratory is the “intracutaneous” tion or change of a suspected drug and the
segment. This is the catheter segment just fever can be helpful in establishing a causal
inside the blood vessel that is not contami- relationship. If a particular medication is
nated by the skin. The pathophysiology of suspected as the causative agent, it should
external (rather than intraluminal) coloni- be stopped, or a comparable substitution
zation and infection has a bacterial gradient should be made. Drug-induced fevers may
highest at the intracutaneous site and low- require several days to resolve, depending
est at the catheter tip. Hence, more false- on the drug pharmacokinetics and patient
negative results are likely to be obtained by profile. Phenytoin is notorious for causing
Positive laboratory
results
Action: treat
s pharmacologically,
ab remove any vascular
Illness is mild/ +L
lines and culture the Positive laboratory
moderate: no organ catheter tips results (≥ 15cfu)
failure or hypotension
Action: treat
Action: get two blood s pharmacologically
cultures, at least one ab
Negative laboratory +L for 5–7 days if
peripheral –L results/Gram stain, S. aureus
ab
s but continuing fever
Action: remove any
Patient has central vascular lines and
venous catheter (CVC) culture the catheter tips Negative laboratory
–L
or arterial catheter (AC) ab results/Gram stain,
s
AND but continuing fever
Fever Action: look for
another source
Action: perform clinical
Positive blood culture
assessment
laboratory results
d Action: treat
loo es
+ B ltur pharmacologically,
Illness is severe: sepsis cu remove/change any
Action: get two blood vascular lines
cultures, at least one
peripheral, change
vascular lines, culture
catheter tips, and start – Negative laboratory
antibiotics empirically cu Blo results/Gram stain,
lt od
– T ures but continuing fever
cu ip ,
ltu Action: look for
re another source
s
Positive catheter tip

– Blood cultures, culture laboratory
+ Tip cultures results (≥ 15cfu)
Action: treat
pharmacologically
for 5–7 days if
S. aureus
Fig. 19.1 Generalized algorithm for the diagnosis and management of fever in patients with central venous 273
catheters or arterial catheters.
drug fever and hepatitis in neurosurgical Assessment of a suspected CNS infection
patients. Some nonpharmacologic, nonin- must be rapid. The new onset of fever, un-
fectious causes of fevers are listed in the explained altered consciousness, or focal
last column of Table 19.1. neurologic signs should trigger a diagnos-
tic lumbar puncture unless there are con-
Suspected Postoperative Fever traindications.7 If the symptoms and signs
suggest a focal neurologic process proximal
A chest radiograph, urinalysis, and urine to the spinal cord, imaging studies are in-
culture are usually not necessary for fever dicated before a lumbar puncture is per-
during the first 72 postoperative hours if formed to prevent cerebral herniation. If a
the fever is observed as an isolated event.3 mass is found, a neurology or neurosurgery
Patients with an indwelling bladder cath- consultation should be considered to de-
eter and fever for longer than 72 hours post- termine the optimal diagnostic approach.
operatively should have a urinalysis, and a Febrile patients with an intracranial device
blood culture should be drawn.3 The careful should have a cerebrospinal fluid (CSF)
daily examination of surgical wounds is im- analysis conducted urgently. Patients with
portant in the setting of fever, and cultures a ventriculostomy who develop the signs
should be obtained if signs of symptoms of or symptoms listed in Table 19.4 and a CSF
infection exist. In any case of postoperative pleocytosis suggestive of possible micro-
fever, clinicians should be suspicious of deep biological infection should usually have
vein thrombosis, superficial thrombophle- their intracranial catheter removed and the
bitis, and pulmonary embolism.3 Suspicion catheter tip cultured.
for a thrombotic fever should be greater in CSF analysis should involve a cytocen-
sedentary patients, those with malignan- trifuged Gram stain and culture. The intra-
cies, those on oral contraceptives, or those cellular organisms on Gram stain should
with limb immobility.3 exclude for the clinician the likelihood of
Fever assessment in the neurologic ICU a contaminant. Urgent glucose quantifica-
must include a daily examination of the tion, protein quantification, and cell count
surgical site for signs of infection, such as with differential can be used as secondary
erythema, purulence, swelling, and tender- measures to help determine the presence
ness. Clinicians should maintain a moder- of infection. However, patients with recent
ate threshold for opening and culturing an
incision suspected of being infected and for
aspirating any deep fluid collections. Any
Table 19.4 Triggers of assessment for central
expressed purulence from within a deep
nervous system infection
incision consistent with a deep organ space
or surgical space infection should be sent Fever and at least one of the following:
for Gram stain and culture. Tissue biopsy
• Altered consciousness
and aspiration are recommended methods
to obtain infected material.3 In contrast, • Papilledema
superficial surgical site infections may be
adequately treated with incision, drainage, • Focal neurologic deficit
and local antiseptic care without systemic • Headache
antibiotic therapy. Superficial incision site
swabs are not recommended.3 • Nuchal rigidity
• New onset of seizure

Suspected Central Nervous System
Infection • Imaging findings (meningeal enhancement)
Assessment • Recent neurosurgical procedure
Some of the characteristics that should trigger • Basilar skull fracture

a clinical assessment for central nervous sys-
274 tem (CNS) infection are listed in Table 19.4.
• Cerebrospinal fluid leak
trauma, stroke (hemorrhagic or nonhem- Aseptic Meningitis
orrhagic), neoplasm, or surgery may have
derangements of the cell count and protein Aseptic meningitis is common after neu-
levels that are not related to infection, and rosurgical procedures, particularly those
therefore trends or spot checks with these involving the posterior fossa. There are
parameters alone may not be helpful. A CSF no clear clinical findings or laboratory
lactate determination may better assess for analyses that distinguish between bacte-
infection because an elevated lactate level rial meningitis and aseptic meningitis.20

may provide more specific and sensitive There is preliminary evidence that CSF
information on infection in the absence of lactate may be a sensitive and specific
the results of Gram stain and culture.14 Ad- indicator of bacterial meningitis, but this
ditional tests for infectious pathogens and requires further investigation.21 Empiric
neoplastic cells should be conducted as in- antimicrobial pharmacotherapy should be
dicated by the clinical situation. initiated in all patients with postoperative
meningitis; however, if the CSF culture re-
sults are negative, it is usually appropri-
Infectious Meningitis
ate to withdraw treatment after 48 to 72
If infectious meningitis is suspected, em- hours while monitoring closely for clinical
piric therapy should be initiated before signs and symptoms of infection.
confirmatory cultures are obtained. Such
therapy consists of dexamethasone and Ventriculitis
empiric antimicrobial pharmacotherapy,
such as ceftriaxone and vancomycin. Poten- The standardized management of intra-
tial nosocomial bacterial meningitis should ventricular catheters has been shown to
be treated with different antibiotic com- reduce the incidence of intraventricular
ponents, usually an agent active against catheter–related ventriculitis.22 The utility
methicillin-resistant Staphylococcus au- of routine CSF surveillance cultures has yet
reus (MRSA) and Pseudomonas aeruginosa. to be determined. Interestingly, patients
Clinicians should have a low threshold to who have catheters impregnated with
initiate acyclovir therapy to treat herpes antimicrobial agents have outcomes simi-
simplex virus infection empirically if the lar to those of patients who have nonim-
diagnosis is uncertain. pregnated catheters and receive systemic
Postoperative CNS infections most com- antimicrobial treatment.23 It remains to
monly include meningitis, subdural em- be seen whether antibiotic-impregnated
pyema, and brain abscess. The incidence of catheters have any advantage over non-
such sequelae after neurologic procedures impregnated catheters. Evidence from
has been reported in the literature to be randomized controlled trials suggests that
anywhere from 0.8 to 7%.15–18 Surgical pro- changing the ventricular catheter does
phylaxis is most important for S. aureus, not reduce the risk for CSF infection, and
Staphylococcus epidermidis, and Propionibac- there are no prospective randomized con-
terium acnes, usually with a cephalosporin trolled trials to demonstrate that prophy-
antibiotic. Patients known to be colonized lactic catheter exchange is efficacious.24–26
with MRSA generally should receive prophy- Despite evidence suggesting that the
laxis with vancomycin. Patients who have duration of ventricular or lumbar CSF
been hospitalized and who have received ex- drainage is an independent risk factor for
tended β-lactam antibiotics are at risk for in- infection,27 there is no evidence to support
fection with Staphylococcus species that are the practice of prophylactic ventricular
β-lactam–resistant and should be consid- catheter exchange.26,28 The subcutaneous
ered candidates for vancomycin prophylaxis. tunneling of catheters has also been de-
Prophylactic antimicrobial pharmacother- scribed for use in external ventricular
apy before craniotomy has been reported drains; however, not all studies support
to decrease the incidence of postoperative this practice. More research is needed to
meningitis by as much as 50%.19 make definitive recommendations. 275
Suspected Pulmonary Infection In the case of a high level of suspicion
for a pulmonary infection, a tracheal as-
Suspected pulmonary infections can be
pirate Gram strain can yield anywhere
categorized into four main types: (1) com-
from no organisms to numerous predomi-
munity-acquired pneumonia (CAP), (2) hos-
nant organisms. In the case of no or few
pital-acquired pneumonia (HAP), (3) health
organisms, a quantitative bronchoscopic
care–associated pneumonia (HCAP), and (4)
bronchoalveolar lavage (BAL) or respira-
ventilator-associated pneumonia (VAP).4,5
tory therapy “blind” mini-BAL may be
Table 19.5 defines the various types of pneu-
an important confirmatory evaluation. If
monia. Common pathogens and treatment
a moderate or large organism burden is
regimens differ according to the specific
demonstrated on the aspirate Gram stain,
type of pneumonia that is diagnosed, so that
a BAL can be considered but may not be
it is necessary to obtain a careful history and
necessary. Semiquantitative Gram stain
investigate the precise time line of the pa-
results are highly variable between micro-
tient’s clinical course. Aspiration pneumoni-
biology laboratories, so that a minimally
tis frequently masquerades as a pulmonary
invasive procedure may still be considered
infection31 and may require either no anti-
necessary. In either case, empiric treat-
biotic therapy or therapy that is limited to
ment should be initiated.4
72 hours because of a low bacterial burden.
In the case of a low level of suspicion for
Assessment a pulmonary infection, a tracheotomy aspi-
rate Gram stain with no or few organisms
Patients in the neurologic ICU with sus- has a high negative predictive value, argu-
pected nosocomial pulmonary infections ing against infection. A worsening clinical
should be assessed clinically and assigned a status in this scenario or a tracheotomy

clinical pulmonary infection score (CPIS) to aspirate Gram stain with moderate to nu-
guide their diagnostic and therapeutic man- merous organisms indicates that a quan-
agement.4 Table 19.6 describes the CPIS and titative bronchoscopic BAL or mini-BAL is
the clinical assessment criteria used to guide a reasonable diagnostic test to perform.4
diagnosis. If the CPIS is higher than 6 or an Contraindications to performing a mini-
infiltrate exists and more than one clinical BAL are listed in Table 19.7; if any of these
assessment criteria exist, then a high degree are present, a sputum Gram stain or cul-
of suspicion for infection is indicated. If the ture is the only suitable alternative diag-
CPIS is between 2 and 6 or an infiltrate exists nostic test. Empiric treatment is warranted
along with one clinical assessment criterion, if any of these tests demonstrates a signifi-
then a low degree of suspicion is warranted. cant infectious burden.4
Table 19.5 Types of pneumonia
Community-acquired Pneumonia in persons not satisfying the diagnostic criteria for HAP, HCAP, or
pneumonia (CAP) VAP
Hospital-acquired Pneumonia that occurs 48 hours or more after admission and was not present
pneumonia (HAP) on admission
Health care–associated Pneumonia that occurs in a nonhospitalized patient with health care contact or
pneumonia (HCAP) interaction, specifically with at least one of the following:
• Intravenous therapy, wound care, or intravenous chemotherapy within the
past 30 days
• Hospitalization in an acute care hospital for ≥ 2 days within the past 90 days
• Residence in a nursing home or long-term care facility
• Attendance at a hospital or hemodialysis clinic within the past 30 days
Ventilator-associated A subtype of HAP that develops > 48 hours after endotracheal intubation
pneumonia (VAP)
276
Table 19.6 Clinical pulmonary infection score Table 19.7 Contraindications to mini-BAL
Category Assessment Score Coagulopathy or bleeding disorder

(INR > 1.5 or platelet count ≤ 50,000/mm3)
Temperature (°C) > 36.5 and < 38.4 0
> 38.5 and < 38.9 1 Refractory hypoxemia (Sao2 < 90%)
> 39.0 or < 36.0 2
MyocardiaI infarction in last 6 weeks
WBC count (cells > 4,000 and < 11,000 0

per milliliter) < 4,000 or > 11,000 1 New onset of a significant cardiac arrhythmia
Tracheal Few 0 ICP > 20 cm H2O

secretions Moderate 1
Large 2 PEEP ≥ 15 cm H2O
Purulent +1
Endotracheal tube < 7.0 mm or tracheostomy <
Pao2/Fio2 > 240 or + ARDS 0 7.5 mm
< 240 and – ARDS 2
Abbreviations: BAL, bronchoalveolar lavage; ICP, intracranial
pressure; INR, International Normalized Ratio; PEEP, positive
Chest X-ray No infiltrate 0 end-expiratory pressure; Sao2, arterial oxygen saturation
Patchy or diffuse 1
infiltrate
Localized infiltrate 2
Table 19.8 Empiric treatment of pulmonary infection
Clinical assessment criteria if length of stay longer than 5 days or risk for multidrug
resistance
• Presence of new or progressive radiographic
infiltrate 1. Antipseudomonal penicillin, cephalosporin, or
• Fever > 38°C carbapenems
• Leukocytosis or leukopenia
AND
• Purulent pulmonary secretions
Abbreviations: ARDS, acute respiratory distress syndrome; 2. Aminoglycoside or fluoroquinolone

Fio2, fraction of inspired oxygen; Pao2, partial pressure of (renal impairment)
arterial oxygen; WBC, white blood cell
AND
3. Vancomycin or linezolid (if methicillin-resistant

Staphylococcus aureus suspected)
Treatment
Risk factors for multidrug resistance:
The standard empiric treatment of CAP
consists of ceftriaxone with ampicillin, sul- • Antimicrobial pharmacotherapy within last 90 days
bactam, and azithromycin, or moxifloxacin
• Current hospitalization > 4 days
in the case of a penicillin allergy. HAP de-
veloping less than 5 days after hospitaliza- • Community or hospital unit antimicrobial resistance
tion is still considered to be caused by the
same bacteria that cause CAP. If the length • Immunosuppression (disease-related or
therapeutic)
of stay is longer than 5 days or the risk for
multidrug resistance is present, treatment Risks for health care–associated pneumonia
as outlined in Table 19.8 is indicated.4
After empiric treatment has been initiated, • Hospitalization for > 1 day in the last 90 days
the patient should be monitored closely for • Resident of nursing home or extended-care
clinical improvement. If after 48 to 72 hours facility
there is evidence of clinical improvement and
culture results are negative or quantitative • Home infusion therapy
cultures are below the usual threshold for • Home wound care
clinical significance (usually 104 to 105 bacte-
ria per milliliter), antibiotic discontinuation • Close contact with multidrug-resistant pathogen
may be considered. If the culture results are
• Chronic dialysis in last 30 days 277
positive, antibiotics are adjusted to target the
causative agent, with continued treatment of UTI in the neurologically impaired pa-
for 7 to 8 days, and the patient is reassessed tient and the distinction from asymptomat-
after completing the course of antibiotic bacteriuria in the colonized patient with
ics. Note that all patients with endotracheal an indwelling catheter can be challenging.
tubes in place will be colonized with bacteria, Clinicians should be particularly suspi-
but not necessarily infected. In the case of P. cious of a possible UTI in patients with spinal
aeruginosa or Acinetobacter species, continu- cord injury, spasticity, upper motor neuron
ing antibiotics for more than 8 days may be disease, autonomic dysreflexia, or malaise
reasonable. If clinical deterioration or lack of and in elderly patients with delirium.
improvement is observed and the cultures
are positive, antibiotics are adjusted accord- Assessment
ing to the causative agent, and consideration
is given to repeating the respiratory micro- Because the clinical diagnosis of UTI in neu-
biological assessment while one continues rologically impaired patients is difficult,
to search for other pathogens, diseases, or laboratory investigation is usually indicated,
potential complications. If the culture results but it may still be difficult to differentiate
are negative in the setting of clinical deterio- UTI from catheter-acquired asymptomatic
ration or lack of clinical improvement, one bacteriuria. Some risk factors for UTI include
should consider stopping the pneumonia- kidney transplant, recent genitourinary sur-
targeted antibiotics if clinically appropriate.4 gery, urinary obstruction, urologic dysfunc-
tion, and bladder catheterization. Routine
urine screening for catheter-acquired as-
Suspected Urinary Tract Infection
ymptomatic bacteriuria should not be per-
Urinary tract infection (UTI) commonly formed except in specific populations, such
precipitates further infectious sequelae and as pregnant women and patients undergoing
clinical deterioration in the neurologic ICU. urologic procedures in which visible muco-
Typical signs and symptoms of a UTI are sal bleeding is anticipated. Specifically, in pa-
listed in Table 19.9. However, the diagnosis tients with indwelling urethral catheters as
well as in patients with neurogenic bladder
managed with intermittent catheterization,
the screening and treatment of catheter-ac-
Table 19.9 Signs and symptoms of urinary tract
quired asymptomatic bacteriuria are not rec-
infection
ommended in the absence of clinical signs or
New onset or worsening of fever, and at least one symptoms suggestive of infection.
of the following: The laboratory assessment for UTI in-
• Rigors
cludes obtaining a urine sample for micro-
scopic examination (chemistries, blood,
• Altered consciousness pyuria) and culture. In patients with symp-
toms of sepsis, a Gram stain of the urine
• Malaise
may be indicated. In particular, a urine
• Lethargy of unknown etiology sample is necessary before antimicrobial
pharmacotherapy is initiated to distinguish
• Flank pain among the diversity of potential causative
• Costovertebral angle tenderness pathogens and the potential presence of
antimicrobial resistance. For patients with
• Acute hematuria an indwelling catheter, samples should be
acquired from the port itself, not the drain-
• Pelvic discomfort
age bag. Urine samples should be processed
• Dysuria promptly because bacterial multiplication
may cause the laboratory to overestimate
• Urgent or frequent urination the true pathogenic burden. Rapid urine
• Suprapubic pain or tenderness dipsticks are not appropriate for the inves-
278 tigation of a possible catheter-acquired UTI.
Pyuria in the catheterized patient is patient requests catheter placement. If an
not diagnostic of bacteriuria or UTI. Along indwelling catheter has been in place when
with odor and cloudiness, the presence or UTI symptoms develop and the catheter is
absence of pyuria is not necessarily a reli- still indicated, replacing the catheter may
able differentiator of catheter-acquired hasten recovery from the infection and re-
asymptomatic bacteriuria from catheter- duce the risk for future catheter-acquired
associated UTI. The absence of pyuria in a bacteriuria or catheter-acquired UTI.
symptomatic patient, however, is evidence Intermittent catheterization can always

arguing against a diagnosis of catheter-ac- be considered as a potential alternative to
quired UTI. Yeast and enterococci tend to short- or long-term indwelling catheter-
cause less pyuria, whereas gram-negative ization. Silver alloy or antimicrobial-coated
bacteria tend to produce more pyuria.32,33 urinary catheters may be considered be-
Regardless of whether it is symptomatic, cause they delay the onset of bacteriuria,
true bacteriuria or candiduria in a cath- but the data are insufficient to recommend
eterized patient will present with a colony such devices for routine use.
count of 103 CFU/mL or higher in culture. Systemic antimicrobial pharmacother-
However, because the risk for the acquisi- apy should not be administered routinely
tion of bacteriuria in a catheterized patient for prophylaxis in patients with indwell-
is cumulative, at 7% per day, many patients ing catheters, even those undergoing sur-
with extended ICU stays will have bacteri- gical procedures. The risk of selecting for
uria. Similarly, low colony counts of 1,000 pathogens with antimicrobial resistance is
CFU/mL will increase to 100,000 CFU/mL- substantial.
within 48 hours.33,34 Neither a high patho- Hospitals, long-term care facilities, and
gen count nor pyuria is evidence that UTI associated institutions play an important
is the source of fever, and UTI accounts for role in promoting the judicious and re-
the minority of fevers identified in the ICU. sponsible use of urinary catheters. Spe-
In a patient with an indwelling urethral cifically, institutions should provide a list
or suprapubic catheter or in a patient un- of indications for indwelling catheters and
dergoing intermittent catheterization, a educate their staff on those indications.
catheter-acquired UTI can be diagnosed Regular assessment of staff adherence to
if1 signs or symptoms of UTI exist with no evidence-based policies on catheteriza-
other identifiable source and if two colony tion is important. Portable bladder scan-
counts of a bacterial species of 103 CFU/mL ners can be very useful in determining if
are present in a single catheter urine sam- catheterization is necessary for postop-
ple or in a midstream voided urine sample erative patients. Urinary catheters should
if the patient has been decatheterized in be removed as soon as they are no longer
the last 48 hours. If no clinical signs or indicated, and nurse- or physician-based
symptoms of UTI exist but colony counts of electronic reminder systems or automatic
a single bacterial species of more than 105 stop orders may be effective in reducing in-
CFU/mL are found on urine culture in such appropriate prolonged catheterization.
a patient, a diagnosis of catheter-acquired The use and management of blad-
asymptomatic bacteriuria is appropriate. der catheterization are complicated, ever
changing, and plagued by uncertainty; in-
Catheter Management terested readers are encouraged to refer to
Hooton et al1 for more details on this topic.
The overarching goal of catheter manage-
ment is to reduce the frequency of cath-
Treatment
eterization. Indwelling catheters should
be placed only when they are absolutely The treatment of UTI is guided by a recent,
indicated. Catheters are not indicated for fresh urine sample from a newly placed
urinary incontinence except when all other urinary catheter or a straight catheteriza-
approaches have been ineffective and the tion. Patients whose catheter has been re-
279
cently discontinued may have a urinalysis tion. There are many noninfectious causes
and culture of a voided midstream urine of hospital-based diarrhea, such as tube
sample to determine if they are infected feedings. The antibiotics most frequently
antimicrobial pharmacotherapy is deter- associated with C. difficile diarrhea are
mined and initiated. Pyuria, foul odor, and clindamycin, cephalosporins, and fluoroqui-
cloudy urine are not indications for anti- nolones; however, any antibacterial agent
microbial treatment in those who are as- may be the instigating factor for illness.
ymptomatic1 (see Table 19.9). However, in
neurologically impaired patients, this dis- Assessment
tinction may be difficult to determine.
In patients with established catheter-ac- In the setting of a suspected gastroin-
quired UTI who exhibit prompt resolution testinal infection, a stool sample should
of symptoms after initiation of antimi- be collected for laboratory assessment.
crobial pharmacotherapy, 7 days of treat- These samples should be diarrheal or an
ment is recommended.1 In those patients unformed stool, except in the case of sus-
with a delayed therapeutic response, 10 pected ileus secondary to C. difficile. Assays
to 14 days of treatment is recommended.1 available include enzyme-linked immuno-
These recommendations stand irrespective sorbent assay (ELISA) screening for toxin A
of whether the patient remains catheter- and B, tissue culture, and polymerase chain
ized. Pharmacotherapy should be selected reaction (PCR)–based technology.2 Tissue
based on the laboratory findings to limit culture assay is the most sensitive and con-
the antimicrobial spectrum for treatment. sidered the clinical gold standard test but is
If empiric treatment is required, the phar- not performed at most medical centers. If
macotherapy should be selected based on the ELISA screen is negative, a repeat ELISA
Gram stain results, previous culture results should be automatically conducted if the
(if available), and the local epidemiology. level of clinical suspicion of disease is high.
Older patients who develop a catheter- Studies suggest that PCR testing is faster,
acquired UTI without pyelonephritis after more sensitive, and more specific than oth-
an indwelling catheter has been removed er current methods.2
may be treated with a 3-day course of an- If severe illness is present and results
tibiotics.1 In addition, women with cath- of tests to confirm C. difficile infection are
eter-acquired asymptomatic bacteriuria negative, inconclusive, or not available, a
that persists for more than 48 hours after flexible sigmoidoscopy study is a reason-
the removal of a short-term indwelling able next diagnostic alternative. Empiric
catheter may be considered candidates for treatment with oral vancomycin can be
antimicrobial pharmacotherapy to reduce considered while diagnostic results are
the risk for developing a future catheter- awaited and should be initiated as soon
acquired UTI. as the diagnosis is suspected or if the in-
fection is severe or complicated. Warning
signs of severe infection include a serum
Suspected Gastrointestinal Infection
lactate level at or above 5 mmol/L and leu-
Any patient with fever or leukocytosis and kocytosis with a cell count above 50,000/
diarrhea who received antibacterial treat- µL.2 These signs should prompt careful
ment or chemotherapy within the 60 days consideration for subtotal colectomy with
preceding the onset of symptoms should preservation of the rectum. Early suspicion
undergo an assessment for gastrointestinal and early testing should avoid the need for
infection, especially gastrointestinal infec- surgical intervention.
tion due to Clostridium difficile.2,3,35 Diarrhea Patients who did not present to the hos-
is defined as stool that fits the shape of its pital with diarrhea and who are immuno-
container, but patients should have two or competent rarely require stool cultures for
more unformed stools per day before being other enteric pathogens (e.g., ova and para-
considered for testing for C. difficile infec- sites). Cultures for other pathogens should
280
be ordered only if clinically indicated and Table 19.10 Pharmacotherapy of Clostridium difficile
epidemiologically appropriate, such as in infection2
the case of an immunocompromised host. Discontinue inciting/nonessential antimicrobial
Testing for cure of C. difficile infection is agents.
not recommended, nor is testing in asymp-
tomatic patients. In general, repeat laborato- Antiperistaltic agents are not indicated.
ry testing of stool samples should be avoided. Initial episode mild to moderate:

Treatment • Metronidazole, 500 mg orally 3 times per day
for 10–14 days
Oral metronidazole is the first line of treat-
ment for mild disease. Patients with mod- Initial episode moderate to severe:
erate to severe disease or a complicated • Vancomycin, 125 mg orally 4 times per day for
clinical status should receive oral vancomy- 10–14 days
cin. Oral fidaxomicin has recently become
available for the treatment of C. difficile in- Severe, complicated:
fection but has not been shown to be supe- • Vancomycin, 500 mg orally 4 times per day
rior to vancomycin for acute treatment, and
the tablets cannot be crushed and placed • Vancomycin, 500 mg in 100 mL of normal saline
in gastrostomy tubes for administration.36 per rectum every 6 hours
In general, empiric treatment is not recom- • Metronidazole, 500-mg intravenous bolus every
mended unless moderate to severe disease 8 hours
is present. Treatment will not affect ELISA
or PCR laboratory testing. Pharmacothera-
py for a laboratory-confirmed, clinically se-
vere, or complicated infection is described
in Table 19.10.2 The first recurrence after administration of concomitant antibiot-
treatment should be treated with the same ics.16 No evidence exists suggesting that
regimen as the initial episode but stratified the use of probiotics reduces risk in hospi-
according to disease severity as indicated in talized patients, and they may actually in-
Table 19.10. Second or third recurrences of crease the risk for bloodstream infections
infection should be treated with a tapered in immunocompromised hosts.
or pulse regimen of vancomycin. Of note,
it is important to avoid the use of metroni-
Special Conditions
dazole beyond the first recurrence because
the cumulative dose may increase the risk C. difficile infection is a serious epidemio-
for neurotoxicity. Antiperistaltic agents are logic problem in the neurologic ICU, and
not indicated and may actually mask other enhanced contact and isolation precau-
symptoms or even trigger toxic megacolon.2 tions should be implemented. Health care
Minimizing the frequency, duration, workers and neurologic ICU visitors must
and intensity of concomitant antimicrobial use gloves and gowns upon entry into the
pharmacotherapy, in addition to reducing room of a patient with C. difficile infection,
the number of agents used, is important and soap and water should be used for
in decreasing the risk for C. difficile infec- hand washing because alcohol-based hand
tions and recurrences. In patients requir- gels do not effectively kill spores. Judicious
ing continued antimicrobial therapy for an antimicrobial selection is of key impor-
independent infection, no strong evidence- tance. Antimicrobials should be chosen
based recommendations currently exist for that target the pathogens identified, and
the prevention of recurrent C. difficile in- their selection should be based on the local
fection. However, expert opinion suggests epidemiology. Cephalosporin, clindamy-
that metronidazole or vancomycin may be cin, and fluoroquinolone use in particular
continued for 7 days after the duration of should be limited where possible.
281
Suspected Sinusitis duction, are not clinically recommended
because of their potential adverse effects.
The assessment of suspected sinusitis in
All of these antipyretic agents require in-
the neurologic ICU does not differ sub-
tact thermoregulatory mechanisms. Anti-
stantially from that performed outside the
pyretics are more likely to be ineffective if
neurologic ICU. Nevertheless, it is impor-
neurologic injury has resulted in impaired
tant for clinicians to be aware of the risk
thermoregulation, as is often the case in
for sinusitis in patients with a fever of un-
the neurologic ICU. In stroke patients, oral
known origin, particularly those patients
antipyretics have been shown to be only
with nasotracheal or orotracheal intuba-
marginally effective, and nonpharmacolog-
tion.37,38 The use of nasogastric tubes for
ic measures are actually more effective.39
extended time periods should be avoided
Pyrexia refractory to pharmacologic
to reduce the risk for nosocomial sinusitis.
measures requires cooling, either external-
If the clinical evaluation demonstrates that
ly or internally. Effective external cooling
a fever is present and sinusitis is suspected
should take advantage of the four modes of
as the cause, computed tomography (CT) of
heat loss: evaporation (e.g., sponge baths),
the facial sinuses is recommended.3 Minor
conduction (e.g., ice packs), convection
CT abnormalities of the sinuses are not un-
(e.g., cooling blanket), and radiation (e.g.,
common, and these abnormalities should
skin exposure). Internal cooling can be ef-
be carefully scrutinized before the diagno-
fected with a cold saline infusion centrally.
sis of sinusitis is made. Empiric treatment
Nonpharmacologic cooling will reduce
for sinusitis can be initiated based on the
body temperature below the physiologic
relative time course of the patient’s ad-
set point, which may induce thermogen-
mission to the hospital and whether the

esis in the form of shivering. Medications
patient has received any prior antibiotic
such as meperidine, dantrolene, propofol,
therapy. If the patient does not respond to
dexmedetomidine, and paralytics may be
antibiotic treatment, puncture and aspira-
useful adjuncts to help control shivering.
tion of the involved sinuses under aseptic
Infection can be difficult to detect when
conditions should be considered. Gram
fever, a cardinal clinical sign, is suppressed.
stain and culture of the aspirate can be
Unfortunately, no standards have been es-
performed to determine both the causative
tablished for infection surveillance. Moni-
agent and the antimicrobial susceptibility
toring the patient with daily white blood
of that agent. Sphenoid sinusitis usually re-
cell counts or chest radiographs, an occa-
quires more aggressive medical and some-
sional urinalysis, and blood cultures for an
times surgical treatment.
abruptly or steadily increasing white cell
count seems reasonable, but there are no
Induced Normothermia evidence-based data to support these prac-
The best evidence available suggests that tices at this time.
induced normothermia in the setting of
neurologic injury is beneficial.8,9 When
compared with normothermia, hyperther- ■■ Conclusion
mia has been associated with worse neu-
rologic outcomes in both stroke and brain Guidelines have been established for the
injury patients, and induced hypothermia diagnosis and management of certain in-
is associated with numerous morbidities fectious diseases, and these guidelines may
despite its effectiveness in neuroprotection prove useful in the neurosurgical critical
in several experimental models. care unit. However, there are also limita-
Pharmacologic means to avoid pyrexia tions described in the literature and occa-
include acetaminophen, aspirin, and other sional controversy. This chapter provides a
nonsteroidal antiinflammatory drugs. Cor- review of the current literature and high-
ticosteroids, although effective in fever re- lights key tenets of infection diagnosis and
282
treatment strategies. It is imperative that 11. D imopoulos G, Falagas ME. Approach to the fe-
brile patient in the ICU. Infect Dis Clin North Am
the clinician consider the circumstances
2009;23(3):471–484 PubMed
surrounding the patient’s illness and the 12. R iedel S, Carroll KC. Blood cultures: key elements
pathway needed to optimize care, using for best practices and future directions. J Infect
the current evidence where applicable. Chemother 2010;16(5):301–316 PubMed
13. S afdar N, Maki DG. Inflammation at the inser-
tion site is not predictive of catheter-related
References bloodstream infection with short-term, non-
cuffed central venous catheters. Crit Care Med

1. H ooton TM, Bradley SF, Cardenas DD, et al; In-
2002;30(12):2632–2635 PubMed
fectious Diseases Society of America. Diagnosis,
14. S akushima K, Hayashino Y, Kawaguchi T, Jackson
prevention, and treatment of catheter-associated
JL, Fukuhara S. Diagnostic accuracy of cerebrospi-
urinary tract infection in adults: 2009 Interna-
nal fluid lactate for differentiating bacterial men-
tional Clinical Practice Guidelines from the Infec-
ingitis from aseptic meningitis: a meta-analysis. J
tious Diseases Society of America. Clin Infect Dis
Infect 2011;62(4):255–262 PubMed
2010;50(5):625–663 PubMed
15. Srinivas D, Veena Kumari HB, Somanna S,
2. Cohen SH, Gerding DN, Johnson S, et al; Society
Bhagavatula I, Anandappa CB. The incidence of
for Healthcare Epidemiology of America; Infec-
postoperative meningitis in neurosurgery: an in-
tious Diseases Society of America. Clinical prac-
stitutional experience. Neurol India 2011;59(2):
tice guidelines for Clostridium difficile infection in
195–198 PubMed
adults: 2010 update by the Society for Healthcare
16. L ietard C, Thébaud V, Besson G, Lejeune B. Risk
Epidemiology of America (SHEA) and the Infectious
factors for neurosurgical site infections: an
Diseases Society of America (IDSA). Infect Control
18-month prospective survey. J Neurosurg 2008;
Hosp Epidemiol 2010;31(5):431–455 PubMed
109(4):729–734 PubMed
3. O’Grady NP, Barie PS, Bartlett JG, et al; American
17. D ashti SR, Baharvahdat H, Spetzler RF, et al. Oper-
College of Critical Care Medicine; Infectious Dis-
ative intracranial infection following craniotomy.
eases Society of America. Guidelines for evalua-
Neurosurg Focus 2008;24(6):E10 PubMed
tion of new fever in critically ill adult patients:
18. M cClelland S III, Hall WA. Postoperative central
2008 update from the American College of Criti-
nervous system infection: incidence and associ-
cal Care Medicine and the Infectious Diseases
ated factors in 2111 neurosurgical procedures.
Society of America. Crit Care Med 2008;36(4):
Clin Infect Dis 2007;45(1):55–59 PubMed
1330–1349 PubMed
19. B arker FG II. Efficacy of prophylactic antibiotics
4. Niederman MS, Craven DE, Bonten MJ, et al;
against meningitis after craniotomy: a meta-
American Thoracic Society; Infectious Diseases
analysis. Neurosurgery 2007;60(5):887–894, dis-
Society of America. Guidelines for the manage-
cussion 887–894 PubMed
ment of adults with hospital-acquired, ven-
20. Z arrouk V, Vassor I, Bert F, et al. Evaluation of the
tilator-associated, and healthcare-associated
management of postoperative aseptic meningitis.
pneumonia. Am J Respir Crit Care Med 2005;
171(4):388–416 PubMed
21. L eib SL, Boscacci R, Gratzl O, Zimmerli W. Predic-
5. Mandell LA, Wunderink RG, Anzueto A, et al; In-
tive value of cerebrospinal fluid (CSF) lactate level
fectious Diseases Society of America; American
versus CSF/blood glucose ratio for the diagnosis
Thoracic Society. Infectious Diseases Society of
of bacterial meningitis following neurosurgery.
America/American Thoracic Society consensus
guidelines on the management of community-
22. H onda H, Jones JC, Craighead MC, Diringer MN,
acquired pneumonia in adults. Clin Infect Dis
Dacey RG, Warren DK. Reducing the incidence of
2007;44(Suppl 2):S27–S72 PubMed
intraventricular catheter-related ventriculitis in
6. Mermel LA, Allon M, Bouza E, et al. Clinical prac-
the neurology-neurosurgical intensive care unit
tice guidelines for the diagnosis and manage-
at a tertiary care center in St Louis, Missouri: an
ment of intravascular catheter-related infection:
8-year follow-up study. Infect Control Hosp Epi-
2009 update by the Infectious Diseases Society of
demiol 2010;31(10):1078–1081 PubMed
America. Clin Infect Dis 2009;49(1):1–45 PubMed
23. W ong GK, Ip M, Poon WS, Mak CW, Ng RY. Anti-
7. Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice
biotics-impregnated ventricular catheter versus
guidelines for the management of bacterial menin-
systemic antibiotics for prevention of nosocomial
gitis. Clin Infect Dis 2004;39(9):1267–1284 PubMed
CSF and non-CSF infections: a prospective ran-
8. Linares G, Mayer SA. Hypothermia for the treat-
domised clinical trial. J Neurol Neurosurg Psy-
ment of ischemic and hemorrhagic stroke. Crit
chiatry 2010;81(10):1064–1067 PubMed
Care Med 2009;37(7, Suppl):S243–S249 PubMed
24. L ozier AP, Sciacca RR, Romagnoli MF, Connolly
9. Badjatia N. Hyperthermia and fever control in
ES Jr. Ventriculostomy-related infections: a
brain injury. Crit Care Med 2009;37(7, Suppl):
critical review of the literature. Neurosurgery
S250–S257 PubMed
2008;62(Suppl 2):688–700 PubMed
10. Krieger DW, De Georgia MA, Abou-Chebl A, et al.
25. F riedman WA, Vries JK. Percutaneous tunnel ven-
Cooling for acute ischemic brain damage (cool
triculostomy. Summary of 100 procedures. J Neu-
aid): an open pilot study of induced hypother-
rosurg 1980;53(5):662–665 PubMed
mia in acute ischemic stroke. Stroke 2001;32(8):
26. Wong GK, Poon WS, Wai S, Yu LM, Lyon D, Lam
1847–1854 PubMed
JM. Failure of regular external ventricular drain
283
exchange to reduce cerebrospinal fluid infection: 33. Stark RP, Maki DG. Bacteriuria in the catheterized
result of a randomised controlled trial. J Neurol Neu- patient. What quantitative level of bacteriuria is rel-
rosurg Psychiatry 2002;73(6):759–761 PubMed evant? N Engl J Med 1984;311(9):560–564 PubMed
27. Scheithauer S, Bürgel U, Bickenbach J, et al. Exter- 34. M aki DG, Tambyah PA. Engineering out the risk
nal ventricular and lumbar drainage-associated for infection with urinary catheters. Emerg Infect
meningoventriculitis: prospective analysis of Dis 2001;7(2):342–347 PubMed
time-dependent infection rates and risk factor 35. F ekety R. Guidelines for the diagnosis and man-
analysis. Infection 2010;38(3):205–209 PubMed agement of Clostridium difficile-associated
28. Lo CH, Spelman D, Bailey M, Cooper DJ, Rosen- diarrhea and colitis. American College of Gastro-
feld JV, Brecknell JE. External ventricular drain enterology, Practice Parameters Committee. Am J
infections are independent of drain duration: an Gastroenterol 1997;92(5):739–750 PubMed
argument against elective revision. J Neurosurg 36. L ouie TJ, Miller MA, Mullane KM, et al; OPT-80-
2007;106(3):378–383 PubMed 003 Clinical Study Group. Fidaxomicin versus
29. Beer R, Pfausler B, Schmutzhard E. Manage- vancomycin for Clostridium difficile infection. N
ment of nosocomial external ventricular drain- Engl J Med 2011;364(5):422–431 PubMed
related ventriculomeningitis. Neurocrit Care 37. H olzapfel L, Chevret S, Madinier G, et al. Influence
2009;10(3):363–367 PubMed of long-term oro- or nasotracheal intubation on
30. Leung GK, Ng KB, Taw BB, Fan YW. Extended nosocomial maxillary sinusitis and pneumonia:
subcutaneous tunnelling technique for exter- results of a prospective, randomized, clinical tri-
nal ventricular drainage. Br J Neurosurg 2007; al. Crit Care Med 1993;21(8):1132–1138 PubMed
21(4):359–364 PubMed 38. v an Zanten AR, Dixon JM, Nipshagen MD, de Bree
31. Raghavendran K, Nemzek J, Napolitano LM, R, Girbes AR, Polderman KH. Hospital-acquired
Knight PR. Aspiration-induced lung injury. Crit sinusitis is a common cause of fever of unknown
Care Med 2011;39(4):818–826 PubMed origin in orotracheally intubated critically ill pa-
32. Tambyah PA, Maki DG. The relationship between tients. Crit Care 2005;9(5):R583–R590 PubMed
pyuria and infection in patients with indwelling uri- 39. Wrotek SE, Kozak WE, Hess DC, Fagan SC. Treatment
nary catheters: a prospective study of 761 patients. of fever after stroke: conflicting evidence. Pharma-
Arch Intern Med 2000;160(5):673–677 PubMed cotherapy 2011;31(11):1085–1091 PubMed
284
Index
Note: Page numbers followed by f and t indicate figures and tables, respectively.
A supportive care and, 101

Abscess(es) surgical treatment of, 100
brain treatment of, 100–101
amebic, 89 in blastomycosis, 74
anatomic distribution of, 90 candidal, 69, 73–74
clinical presentation of, 90 treatment of, 78
incidence of, 89 in coccidioidomycosis, 70
prognosis for, 91 computed tomography of, 35
in aspergillosis, 71, 72f, 74 culture, 25–26, 99
treatment of, 78 development of, 40–41
aspiration, 25–26, 99, 99f, 100 diagnosis of, 25–26
bacterial, 95–103, 111 fungal, 68, 73–74
antibiotics for, 100 biopsy of, 77
aspiration of, 99, 99f, 100 causative organisms, 68, 72–73
capsular stage, 97, 98f diagnosis of, 25–26
clinical presentation of, 98 imaging, 75–77, 76f
complications of, 101–102 risk factors for, 68
culture, 99 surgical management of, 77
development of, stages, 97 in hisplasmosis, 74
diagnosis of, 25–26, 98–99 in HIV-infected (AIDS) patients, 26t, 95,
epidemiology of, 95 96
etiologic agents, 95–96 imaging of, 40–42
follow-up for, 102 in immunocompromised patients,
in HIV-infected (AIDS) patients, 95, 96 microbiology, 248
imaging of, 41–42, 41f, 98f, 99, 99f immunology, 26
intraventricular rupture of, 101 intraventricular, shunt and, 47
laboratory investigation, 99 microbiology, 24–25, 26t
mortality rate for, 95 in mucormycosis, 71, 72, 72f, 74, 74f
neonatal, and hydrocephalus, 101– mycobacterial, diagnosis of, 25–26
102 nocardial, 24, 96
neonatal, clinical presentation of, 98 diagnosis of, 25–26
outcomes with, 102 odontogenic, 97
pathophysiology of, 97–98 microbiology, 24
polymicrobial, 96 otogenic, microbiology, 24
recurrent, 102 in pediatric patients, 46, 234–235
risk factors for, 95, 96–97 medical management of, 235–237
sites of, 97 surgical management of, 237–239,
stereotactic drainage of, 100 239f
Abscess(es), brain (continued) psoas, with spinal epidural abscess, 166
polymicrobial, 96 retropharyngeal, with spinal epidural
postoperative, 46 abscess, 166
incidence of, 24 spinal epidural, 126, 163–176
microbiology, 24 after diskography, 175
risk factors for, 24, 26t anatomical considerations with, 164
Scedosporium, 72, 74 bacterial, unusual species involved in,
treatment of, 77, 79 172–173
sterile on culture, 96 catheter-related, 175
subdural empyema and, 125 clinical presentation of, 151, 166
Toxoplasma gondii, 96, 97f diagnosis of, 27, 166–169
tuberculous, 24 distribution of involved spinal segments,
and tumor, differentiation of, 98–99 164
cranial epidural, 125 in elderly, 164
clinical features of, 126 epidemiology of, 164
diagnosis of, 27, 126 fungal, 165, 171, 173–174
epidemiology of, 125 historical perspective on, 163
imaging of, 126–129, 129f–130f imaging of, 167–168, 168f
laboratory investigation, 126 incidence of, trends in, 163, 164
microbiology, 27, 128t kyphoplasty-related, 176
mortality rate for, 131 laboratory investigation, 166–167
otogenic, 128t management of, 151
pathogenesis of, 125–126 microbiologic diagnosis of, 169
pathophysiology of, 125–126 microbiology, 27, 164–165, 172–174
in pediatric patients, 233–239 mortality rate for, 172
medical management of, 236 mycobacterial, 171
surgical management of, 237–239 neurologic progression during medical
postoperative, 128t, 201–202 therapy, 171
posttraumatic, 128t outcomes with, 171–172
prognosis for, 131 in parasitic infection, 174
risk factors for, 125–126 pathogenesis of, 165–166
Index
sinusitis and, 128t, 234 postoperative, 165, 174–175

subdural empyema and, 125 prognosis for, 171–172
and suppurative intracranial risk factors for, 164t
thrombophlebitis, 27 and secondary extraspinal infection, 166
surgical management of, 131 sources of, 165
treatment of, 129–131 and spinal (vertebral) osteomyelitis, 149
work-up for, 126 treatment of, 163–164, 169–171
dental, and vertebral column infections, 149 tuberculous, 165, 172–173
hepatic, in amebiasis, 90 vertebroplasty-related, 176
and infectious intracranial aneurysms, 136t spinal intramedullary, 163, 177–179
intraparenchymal, in pediatric patients, spinal subdural, 163, 176–177
233–239, 235 after diskography, 175
medical management of, 236–237 stitch, 201
surgical management of, 237–239 Absidia spp., 71, 250–251
paraspinal muscle, with spinal epidural Acanthamoeba spp., 89–91
abscess, 166 diagnostic tests for, 24
paravertebral, 159 meningitis, 19, 22
management of, 155 Acinetobacter spp., shunt infection, 21
and spinal (vertebral) osteomyelitis, 149 Acinetobacter baumannii
pharyngeal, and vertebral column hardware infection, 22
infections, 149 meningitis, 111
post-meningitic, in pediatric patient, 234 Acquired immunodeficiency syndrome. See
postoperative intracerebral, 203–204 HIV-infected (AIDS) patients
286
Acrophialophora fusispora, 73 epidemiology of, 89
Actinomyces spp. etiology of, 89–90
brain abscess, 26t outcomes with, 91
meningitis pathogenesis of, 89–90
diagnostic tests for, 23t prevention of, 91
risk factors for, 23t risk factors for, 18t
spinal intramedullary abscess, 177 treatment of, 90–91
Actinomyces israelii, spinal epidural abscess, American trypanosomiasis, in
172 immunocompromised patients,
Acute transverse myelitis, 51 257–258
in schistosomiasis, 88 Aminoglycosides, 32t
viral causes of, 51–52, 54, 58 resistance to, 31, 32t
Acyclovir Amphotericin B
for herpes B infection, 62t for amebiasis, 91
for HSV infection, 53, 62t, 64 for blastomycosis, 78
for VZV infection, 62t, 64 for cryptococcal infection, 78
Adenovirus lipid complex, for mucormycosis, 78
CNS infection lipid complex with flucytosine, for
diagnosis of, 62t candidal infection, 78
treatment of, 62t liposomal
meningitis, 55 for candidal infection, 78
meningoencephalitis, 55 for histoplasmosis, 78
Adhesion molecule(s), and transendothelial for mucormycosis, 78
migration of lymphocytes into CNS, Amphotericin B deoxycholate
8–9 for aspergillosis, 78
Age. See also Elderly; Neonate(s); Pediatric for candidal infection, 78
patients for mucormycosis, 78
and antibiotic dosage and administration, Ampicillin-sulbactam, prophylactic, in
108t neurosurgery, 187
and bacterial meningitis, 107, 108t Anaerobes
and CSF protein level, 115 cranial epidural abscess, 128t
Index
and diskitis, 147, 149 shunt infection, 21
and focal intracranial infectious lesions in spinal epidural abscess, 165
pediatric patients, 233–234 spinal infection, 27
and shunt infection, 209 subdural empyema, 26, 127t
and surgical site infections, 197 vertebral column infection, antibiotic
AIDS (acquired immunodeficiency syndrome). treatment of, 158
See HIV-infected (AIDS) patients Aneurysm(s). See also Infectious intracranial
Albendazole aneurysm(s)
for cysticercosis, 83 mycotic, 133
for neurohydatidosis, 85 in aspergillosis, 71, 71f, 72f
Alcoholism in coccidioidomycosis, 70
and meningitis, 113 in pediatric patients, 46
and spinal subdural abscess, 176 Angiography. See also Magnetic resonance
and vertebral column infections, 147 angiography (MRA)
Alcohol rubs, for preoperative hand with infectious intracranial aneurysm,
cleansing, 150 142–143, 142f
Alice in Wonderland syndrome, 61 Angiostrongylus cantonensis
Allergy(ies), to antibiotics, 31, 117, 185–186 diagnostic tests for, 18t
AMA. See Abscess(es), brain, amebic meningitis, 19
Amebiasis, 81t, 89–91 CSF findings in, 17t
clinical presentation of, 90 diagnostic tests for, 21, 23t
diagnosis of, 90 risk factors for, 18t, 23t
diagnostic tests for, 18t risk factors for, 18t, 23t
287
Anorexia for vertebral column infection, 147, 155,
with vertebral column infection, 151 157–159
in viral infection, 61 monitoring, 158–159
Antibiotic(s) outcomes with, 159
administration of Antibiotic-impregnated materials, 33
duration of, 32 Antibiotic prophylaxis, 30–31
timing of, 32 with CSF fistulas, 192
allergy to, 31, 117, 185–186 for DBS hardware-related infections, 224
for bacterial brain abscess, 100 neurosurgical, 185–195
for bacterial meningitis, 108t, 116–118 CDC recommendations for, 185, 186t
bacteriocidal, 31 in clean-contaminated procedures,
bacteriostatic, 31 187–188
b-lactam, 32t in clean procedures, 186–187
adverse effects and side effects of, 31 clinical data regarding, 186–188
resistance to, 31, 32t with CSF shunts, 190–191
broad-spectrum, misuse of, 186 duration of, 188–189
classification of, 31, 32t efficacy of, 186–188
and CSF findings, 116, 126 with external CSF drains, 189–190
for DBS hardware-related infection, 223–224 with implanted foreign bodies, 190–191
for dirty or contaminated wounds, 188 risks associated with, 185–186
dosage and administration of, by age timing of, 185, 188–189
group, 108t for postoperative spinal infection, 150
for epidural and subdural infections, principles of, 185–186
129–131 for shunt placement, 190–191, 214, 242
for infectious intracranial aneurysm, in spinal neurosurgery, 191–192
141–143, 142t, 144f and surgical site infections, 197
and infectious intracranial aneurysm timing of administration of, 32–33
formation, 137 topical, 192–193
for intracranial abscesses, in pediatric Antibiotic resistance, 31, 186
patients, 235–237 mechanism of, 31, 32t
intrathecal administration of, 31 spread, control of, 32
Index
intraventricular administration of, 31 Anticonvulsant(s)

for shunt placement, 214 for cysticercosis, 83
mechanism of action of, 31, 32t indications for, with epidural and subdural
misuse of, 30 infections, 129
narrow-spectrum prophylactic
appropriate use of, 30 in amebiasis, 91
for surgical prophylaxis, 186 with bacterial brain abscess, 100, 101
penetration into central nervous system, with epidural and subdural infections, 129
31, 186–187 in fungal infection, 79
perioperative, and prevention of Antifungal therapy, 77–79
postoperative spinal infection, 150 Antigen-presenting cell(s)
peripartum, for prevention of neonatal in CNS, 4–5
group B streptococcal infection, 110 perivascular, in CNS, 4–5
for pulmonary infection, 277–278, 277t APC. See Antigen-presenting cell(s)
for shunt infection, 211–213 Aphasia
in pediatric patients, 243 in bacterial meningitis, in adults, 114
spectrum of, 31, 32t with fungal brain abscess, 73
for spinal epidural abscess, 169, 170–171 in viral infection, 61
for spinal intramedullary abscess, 178–179 Arachnoiditis, in cysticercosis, 82, 83
for spinal subdural abscess, 177 Arbovirus(es), 55–57, 56t
for subdural empyema, 203 CNS infection
susceptibility testing, 117 diagnosis of, 62t
therapy with, principles of, 30 mortality rate for, 64
288
prevention of, 62t, 63 with spinal subdural abscess, 176–177
treatment of, 62t with vertebral column infection, 150
encephalitis, seasonal distribution of, 51 Bacterial infection(s). See Abscess(es), brain,
Arterial thrombosis, in cysticercosis, 82 bacterial; Meningitis, bacterial;
Arteriovenous malformation, pulmonary, specific bacteria
hereditary hemorrhagic Bacteroides spp.
telangiectasia and, 96, 97f brain abscess, 26t, 95, 96f
Aspergillosis, 24–25. See also Aspergillus cranial epidural abscess, 128t
spp.; Aspergillus flavus; Aspergillus subdural empyema, 127t
fumigatus Bactiseal, 33
CNS involvement in, 70–71 Balamuthia spp., 89, 91
diagnostic tests for, 152 diagnostic tests for, 24
disseminated, 70–71 Balamuthia mandrillaris, 89–90
histology of, 77 Bartonella henselae, diagnostic tests for, 152
in HIV-infected (AIDS) patients, 249–250 Basilar leptomeningitis
in HSCT recipients, 264 in coccidioidomycosis, 70
imaging of, 42, 45f, 75–76, 76f in histoplasmosis, 70
in immunocompromised patients, 249–250 treatment of, 77
intralesional hemorrhage in, 42, 45f Batson plexus, 149
laboratory investigation of, 75 BBB. See Blood–brain barrier
prognosis for, 79 Behavioral change, with infectious
risk factors for, 71 intracranial aneurysms, 139, 139t
spinal epidural abscess in, 173 Bilharziasis. See also Schistosomiasis
treatment of, 78, 250 spinal epidural abscess in, 174
surgical, 77 Biofilm, and shunt infection, 210
vertebral column infection, antibiotic Biopsy. See also Brain biopsy
treatment of, 158 in amebiasis, 90
vertebral osteomyelitis in, 149 with brain abscess, 77
Aspergillus spp. See also Aspergillosis CT-guided
blood vessel wall invasion, 71, 71f of spinal epidural abscess, 168
brain abscess, 26t, 68, 74 in vertebral column infection, 152
Index
hyphae of, 68, 68f, 71f, 77 in cysticercosis, 82
laboratory identification of, 75 open
meningitis, 68 of spinal epidural abscess, 168
in organ transplant recipients, 264–265 in vertebral column infection, 152
Aspergillus flavus, 71 percutaneous, of spinal epidural abscess,
Aspergillus fumigatus, 71, 71f. See also 168
Aspergillosis rectal, in schistosomiasis, 88
in infectious intracranial aneurysms, 138, Bipolaris hawaiiensis, 73
138f Bipolaris spicifera, 73
sinusitis, 137f Blastomyces dermatitidis. See also
Asplenia, and meningitis, 113 Blastomycosis
Astrocytoma(s), T cells in, 7 geographic distribution of, 69, 147
Ataxia, in schistosomiasis, 88 Blastomycosis. See also Blastomyces
ATM. See Acute transverse myelitis dermatitidis; Chromoblastomycosis
Autoimmune disease(s), of central nervous brain abscess in, 74
system, 3 diagnosis of, 73, 74
Azithromycin, 32t geographic distribution of, 69, 147
imaging of, 75
B in immunocompromised patients, 252
Back pain meningitis in, 74
chronic, with vertebral column infection, 159 diagnostic tests for, 23t
in schistosomiasis, 88 risk factors for, 23t
with spinal epidural abscess, 166 spinal epidural abscess in, 173–174
289
Blastomycosis (continued) Brain herniation, in schistosomiasis, 88
treatment of, 78 Brainstem, encephalitis, in EBV infection, 54
surgical, 77 Brain tumor(s). See also Glioma(s)
vertebral column infection, antibiotic and abscess, differentiation of, 98–99
treatment of, 158 Bronchoalveolar lavage (BAL), 276
vertebral osteomyelitis in, 149 Brucella spp. See Brucellosis (Brucella spp.)
Blood–brain barrier, 4, 31 Brucellosis (Brucella spp.)
antibiotics and, 187 diagnostic tests for, 152
chemokine expression and function at, geographic distribution of, 147
9–11 risk factors for, 27
chemokine receptor expression and spinal epidural abscess, 172
function at, 9–11 spinal intramedullary abscess, 177
diapedesis across, 8f, 9 vertebral column infection, 149
structure of, 8f antibiotic treatment of, 158
T cell transport across, 7 Bruton disease, and viral infection, 60
Blood–cerebrospinal fluid barrier, 4 BSE. See Bovine spongiform encephalopathy
antibiotics and, 186–187 (BSE)
T cell transport across, 7
Blood culture C
“do’s” and “don’ts” for, 272t California encephalitis group of viruses,
in infectious intracranial aneurysms, 138, encephalitis, 25t
139t California encephalitis virus, 55
in meningitis, 20 California serogroup virus(es), 56, 56t
with postoperative vertebral column Candida spp., 69. See also Candidiasis
infection, 153 (Candida spp.)
in shunt infection, 22 Candida albicans, 69. See also Candidiasis
with spinal epidural abscess, 169 (Candida spp.)
triggers for, 271, 272t in infectious intracranial aneurysms, 138
with vertebral column infection, 152 laboratory identification of, 75
in vertebral osteomyelitis, 27 Candida krusei, 69. See also Candidiasis
Blood–spinal cord barrier, T cell transport (Candida spp.)
Index
across, 7 Candidiasis (Candida spp.)

Bloodstream infection, in ICU patient, brain abscess, 24, 26t
270–273 clinical features of, 73
Body temperature. See also Fever; Induced CNS involvement in, 69
normothermia diagnosis of, 74, 75, 152
and infectious work-up, in neurologic ICU in HSCT recipients, 264
patient, 269–270, 270t–271t in immunocompromised patients,
monitoring, in neurologic ICU patient, 269 252–253
and neurologic outcome, 269 infection of DBS hardware, 222
Bone flap infection, 201–202 infectious intracranial aneurysms, 138
Borrelia burgdorferi, 111. See also Lyme laboratory identification of, 75
meningitis meningitis
diagnostic tests for, 18t diagnostic tests for, 23t
meningitis, 19 risk factors for, 23t
diagnostic tests for, 21 in organ transplant recipients, 264–265
risk factors for, 18t prognosis for, 79
Bovine spongiform encephalopathy (BSE), 59 sequelae, 79
imaging in, 39, 40f shunt infection, 21, 210
Brain biopsy spinal epidural abscess, 173
with abscess, 77 spinal infection, 27
in cysticercosis, 82 spinal intramedullary abscess, 177
in HSV encephalitis, 63, 64 systemic, 69
in prion disease, 60 treatment of, 78, 158
290
vertebral column infection, antibiotic in pediatric patients, 46
treatment of, 158 with ruptured infectious intracranial
vertebral osteomyelitis, 149 aneurysm, 140
CAP. See Pneumonia, community-acquired venous, magnetic resonance imaging of,
Carotid artery, in rhinocerebral 36, 36f
mucormycosis, 74 Cerebral ischemia, in coccidioidomycosis, 70
Cat-scratch fever, diagnostic tests for, 152 Cerebritis
Cavernous sinus thrombosis in bacterial brain abscess development, 97
and infectious intracranial aneurysms, in bacterial meningitis, in elderly, 114,
136t, 137, 140, 141 115f
in pediatric patients, 46 imaging in, 40–42
CCL2, expression and function at blood–brain in pediatric patients, 46
barrier, 10–11 postoperative, 46
CCL19, expression and function at blood–brain stages of, 40–41
barrier, 9–10 with subdural empyema, 126
CCL21, expression and function at blood–brain Cerebrospinal fluid (CSF)
barrier, 9–10 analysis, 126
CDC. See Centers for Disease Control and in amebiasis, 90
Prevention (CDC) in bacterial meningitis, 20
Cefotaxime, prophylactic, in neurosurgery, contraindications to, 27
187 in cysticercosis, 82
Ceftriaxone, prophylactic, in neurosurgery, in EBV infection, 54
187 in encephalitis, 24, 25t
Cellulitis. See also Orbital cellulitis in enterovirus infection, 54–55
and infectious intracranial aneurysms, 136t in fungal infection, 74, 75
and spinal subdural abscess, 176 in fungal meningitis, 24
Centers for Disease Control and Prevention in HSV infection, 53
(CDC) in lymphocytic choriomeningitis virus
recommendations for neurosurgical infection, 58
antibiotic prophylaxis, 185, 186t in meningitis, 16, 17t, 115
recommendations for prevention of in neurologic ICU patient, 274–275
Index
surgical site infections, classification in rabies, 57
of, 185, 185t in schistosomiasis, 88
Viral Exanthems and Herpesvirus Branch, in shunt infection, 21–22, 211, 241
contact information for, 54 with spinal epidural abscess, 167
Central cord syndrome, with spinal epidural with spinal intramedullary abscess, 177
abscess, 165 in suspected meningitis, 19, 20t
Cephalosporin(s), 32t in tuberculous meningitis, 17t, 22–23,
prophylactic, in neurosurgery, 186–187 116t
Cerebellar ataxia in viral meningitis, 19–20
in Lyme meningitis, 115 appearance, 16
in VZV infection, 54 in bacterial meningitis, 116t
Cerebellitis, EBV-associated, 54 culture
Cerebral edema fungal, 24
with bacterial abscess, 100, 100f in infectious intracranial aneurysms,
in chronic meningitis, 73 138
management of, 61 in meningitis, 17, 20
with subdural empyema, 127–129 in shunt infection, 22, 211
treatment of, 79 viral, 24
Cerebral infarction fistula(s), antibiotic prophylaxis with, 192
in coccidioidomycosis, 70 glucose level, 115, 116t
computed tomography of, 35 in meningitis, 17, 17t, 20
in cysticercosis, 82 in neonates, 115
in fungal infection, 248–249 Gram stain, 116
291
Cerebrospinal fluid (CSF) (continued) Chlorhexidine-based scrubs, for preoperative
leakage, 192 hand cleansing, 150
management of, 204 Chorea, in Lyme meningitis, 115
and postoperative meningitis, 204 Chromoblastomycosis, and infectious
and surgical site infections, 197–198 intracranial aneurysms, 138
in Lyme meningitis, 116, 116t Ciprofloxacin, 32t
opening pressure, 16, 115, 116t Cirrhosis
protein level, 116t and spinal epidural abscess, 164, 166–167
age dependence of, 115 and vertebral column infections, 147
in meningitis, 17, 17t, 20 Citrobacter spp.
in viral meningitis, 116t brain abscess, 95
WBC count, 115–116, 116t meningitis, 111
factors affecting, 17 Citrobacter koseri, meningitis, 111
in meningitis, 16–17, 17t, 20, 115–116 CJD. See Creutzfeldt-Jakob disease (CJD)
Cerebrospinal fluid (CSF) shunt. Cladophialophora bantiana, 72–73
See also Shunt infection; Clinical pulmonary infection score, 276, 277t
Ventriculoperitoneal shunt Clostridium spp.
antibiotic-impregnated tubing for, 33, 214 brain abscess, 24, 26t
antibiotic prophylaxis with, 190–191 and cranial epidural abscess, 128t
components of, 208 and subdural empyema, 127t
failure rates, 208 Clostridium difficile
health care costs of, 208 colitis, antibiotic prophylaxis and, 186
malfunction, 208, 210, 240 infection
placement in neurologic ICU patient, 280–281
complications of, 208 treatment of, 281, 281t
frequency of, 208 Clostridium perfringens, vertebral column
and surgical site infections, 198 infection, 151
and ventricular empyema, 47 Cloxacillin, prophylactic, in neurosurgery, 187
and ventriculitis, 47 CMV. See Cytomegalovirus (CMV)
Chagas disease, in immunocompromised Coccidioides spp. See also Coccidioidomycosis
patients, 257–258 laboratory identification of, 75
Index
Chemokine(s) Coccidioides immitis, 70, 251. See also

in activation and firm adhesion of Coccidioidomycosis
leukocytes to endothelium, 9 meningitis
expression and function at blood–brain diagnostic tests for, 23t
barrier, 9–11 risk factors for, 23t
secretion of, by microglia, 5–6 Coccidioides posadasii, 251
Chemokine receptor(s) Coccidioidomycosis
CCR2, expression and function at blood– clinical features of, 73
brain barrier, 10–11 CNS involvement in, 70
CCR7, expression and function at blood– diagnosis of, 23t, 73
brain barrier, 9–10 disseminated, 70
CXCR3, expression and function at blood– geographic distribution of, 68, 147
brain barrier, 11 in immunocompromised patients, 251–252
CX3CR1, expression and function in pulmonary involvement in, 70
central nervous system, 11 risk factors for, 23t
CXCR4, expression and function at blood– spinal epidural abscess in, 173
brain barrier, 10 spinal involvement in, 70
expression and function at blood–brain vertebral osteomyelitis in, 149
barrier, 9–11 Cochlear implant, 112–113
Chemotherapy, and surgical site infections, 197 Colorado tick fever virus, 55, 56–57, 56t
Chills, with vertebral column infection, 151 Coma, in viral infection, 61
Chlorhexidine-alcohol, for preoperative skin Complement deficiency, and meningitis,
cleansing, 150 113–114
292
Computed tomography (CT), 35. See also Cranial nerve palsy(ies)
Biopsy, CT-guided in bacterial meningitis, in adults, 114
of aspergillosis, 75 in chronic meningitis, 73
of bacterial brain abscess, 99, 99f with infectious intracranial aneurysms,
of bacterial meningitis, 35 139, 139t
of blastomycosis, 75 in Lyme meningitis, 115
of brain abscess, 41 with subdural empyema, 126
of cavernous sinus thrombosis, 46 C-reactive protein (CRP), 126
of cerebral abscess, in pediatric patient, 235 with bacterial meningitis, 20–21
of cerebritis, 40–41 intracranial infection and, 200
of cryptococcal infection, 75 postoperative level, 152, 167, 200
of cysticercosis, 46f, 82–83 with shunt infection, 211, 241
of DBS hardware-related infection, 222 with spinal epidural abscess, 166–167
of echinococcosis, 84–85, 85f with spinal surgical site infection, 217
of epidural and subdural infections, with vertebral column infection, 152
126–129, 129, 129f with vertebral osteomyelitis, 27
of extra-axial abscess, in pediatric patient, Creutzfeldt-Jakob disease (CJD), 59
234 clinical presentation of, 59–60
of herpes encephalitis, 38 growth hormone preparations and, 59
of histoplasmosis, 75 imaging in, 39
of HIV encephalitis, 42 sporadic, 59
of intracranial infection, 200 variant, 59
of mucormycosis, 251 clinical presentation of, 60
of neurocysticercosis, 42–43, 46f, 47f imaging in, 39, 40f
of osteomyelitis, 46 CRP. See C-reactive protein (CRP)
of pediatric patients, 44–45 Cryptococcosis
of progressive multifocal diagnosis of, 73, 74
leukoencephalopathy, 42, 43f diagnostic tests for, 23t, 152
of shunt infection, 211 in HIV-infected (AIDS) patients, 70, 258–260
of spinal epidural abscess, 167–168 imaging of, 75
of spinal surgical site infection, 217–218 laboratory investigation of, 75
Index
of subdural empyema, 234 prognosis for, 79
of vertebral column infection, 153, 154f, 155 risk factors for, 23t, 69–70
Confusion treatment of, 78
in bacterial meningitis, in adults, 114 surgical, 77
in chronic meningitis, 73 Cryptococcus gattii, meningitis, 68
Congenital heart disease, and infectious Cryptococcus neoformans, 69–70. See also
intracranial aneurysm, 139, 139t Cryptococcosis
Conjugation, bacterial, 31–32 brain abscess, 26t
Corticosteroid(s). See Steroid(s) in HIV-infected (AIDS) patients, 258
Corynebacterium spp. meningitis, 68
postoperative vertebral column infection, diagnostic tests for, 23t
150 risk factors for, 23t
shunt infection, 209, 210t CSF. See Cerebrospinal fluid (CSF)
spinal epidural abscess, postoperative, 175 CT. See Computed tomography (CT)
Coxsackievirus A7, 55 CTL. See Cytotoxic T lymphocytes (CTL)
CPIS. See Clinical pulmonary infection score Culture(s). See also Blood culture;
Cranial nerve(s) Cerebrospinal fluid (CSF), culture
in EBV infection, 54 of brain abscess, 25–26, 99
in polio, 64–65 of DBS hardware-related infection, 222
in progressive multifocal of epidural abscess, 27, 126
leukoencephalopathy, 58 with postoperative vertebral column
in rabies, 57 infection, 153
in rhinocerebral mucormycosis, 74 results, and antibiotic administration, 32
293
Culture(s) (continued) Decubitus ulcer(s)
with spinal epidural abscess, 169 and spinal epidural abscess, 165
sputum, in infectious intracranial and vertebral column infections, 149
aneurysms, 138 Deep brain stimulation
of subdural empyema, 27, 126 clinical applications of, 219–220
tissue, in vertebral osteomyelitis, 27 complications of, 220
with vertebral column infection, 152 hardware-related infections, 219–224
Cunninghamella spp., 250–251 clinical presentation of, 222
Curvularia pallescens, 73 definition, 222
CX3CL1, expression and function in central diagnosis of, 222
nervous system, 11 epidemiology of, 220
CXCL9, expression and function in central imaging of, 222
nervous system, 11 laboratory investigation, 222
CXCL10, expression and function in central management of, 223–224
nervous system, 11 microbiology, 221–222
CXCL11, expression and function in central outcomes with, 224
nervous system, 11 pathogenesis of, 221–222
CXCL12 prevention of, 224
expression and function in central nervous risk factors for, 220–221
system, 10 reversibility, 220
isoforms, expression and function in single procedure, 220
central nervous system, 10 staged procedure, 220
Cyst(s). See also Cysticercosis system for, 220
brain, in echinococcosis, 84 Deep venous thrombosis, and infectious
Cysticercosis, 81–83, 81t intracranial aneurysms, 136t
clinical presentation of, 82 Dendritic cells, perivascular, in CNS, 4–5
diagnosis of, 82–83 Dental infection, and infectious intracranial
epidemiology of, 81–82 aneurysms, 136t
mortality rate for, 82, 83 Dental surgery, and bacterial brain abscess, 97
outcomes with, 83 Dermal sinus, congenital, and spinal abscess,
pathogenesis of, 82 176, 176f
Index
prevention of, 83 Dermoid cyst(s), and bacterial brain abscess, 96

spinal epidural abscess in, 174 Dexamethasone
spinal involvement in, 82, 83 adjunctive, in meningitis treatment, 117
treatment of, 83 and brain abscess, 100
Cystic fibrosis, and bacterial brain abscess, 96 Diabetes mellitus
Cytomegalovirus (CMV) and bacterial brain abscess, 96
acute transverse myelitis, 52 and meningitis, 113
CNS infection and spinal epidural abscess, 164
diagnosis of, 62t and spinal subdural abscess, 176
risk factors for, 54 and surgical site infections, 197
treatment of, 62t and vertebral column infections, 147
encephalitis, 25t Diapedesis, of leukocytes, across vascular
meningitis, 19 endothelium, 8f, 9
diagnostic tests for, 18t, 20 Diphtheria spp., in infectious intracranial
risk factors for, 18t aneurysms, 138
meningoencephalitis, 54 Diskitis, 147. See also Vertebral column
in HIV-infected (AIDS) patients, 54 infection(s)
in organ transplant recipient, 263 after diskography, 175
Cytotoxic T lymphocytes (CTL), 7 age distribution of, 147, 149
clinical presentation of, 150–151
D distribution of involved spinal segments
DBS. See Deep brain stimulation in, 149
DCs. See Dendritic cells epidemiology of, 147
294
fungal, 149 EITB. See Enzyme-linked
imaging of, 153–155 immunoelectrotransfer blot (EITB)
incidence of, 147 Elderly
laboratory investigation, 152 bacterial meningitis in, 108, 108t, 114, 115f
microbiology, 149 demographics of, in U.S., 214
outcomes with, 159 spinal epidural abscess in, 164
pain with, 150–151 spinal surgery in, trends in, 214
postoperative, pain with, 151 Electroencephalography, in diagnosis of HSV
risk factors for, 147, 149 infection, 53
and spinal epidural abscess, 164 ELISA. See Enzyme-linked immunosorbent
treatment of, 155–159 assay (ELISA)
Diskography, infection after, 175 Encephalitis. See also Meningoencephalitis
Double gloving, 150, 242 arboviral, 55, 56
Dowling method, for hydrodissection of aseptic, 19
hydatid cyst, 85, 86f bacterial
Dracunculiasis, spinal epidural abscess in, diagnostic tests for, 25t
174 risk factors for, 25t
in coccidioidomycosis, 70
E in cysticercosis, 82
EAE. See Experimental autoimmune diagnostic tests for, 24, 25t
encephalomyelitis (EAE) enteroviral, 55
Eastern equine encephalitis (EEE) virus granulomatous amebic, 89–91
encephalitis, 25t herpes simplex virus, 53
infection, 55, 56t imaging of, 38, 39f
mortality rate for, 64 imaging of, 38, 39f
EBV. See Epstein-Barr virus (EBV) limbic, 38
Echinococcosis, 81t, 83–87 microbiology, 24, 25t
alveolar, 83 necrotizing hemorrhagic, Sappinia
clinical presentation of, 84 diploidea, 89
cystic, 83 risk factors for, 24, 25t
diagnosis of, 84–85 in schistosomiasis, 88
Index
epidemiology of, 83–84 subacute granulomatous, in amebiasis, 90
etiology of, 84 tuberculous, 25t
mortality rate for, 87 varicella-zoster virus, 54
outcomes with, 87 viral, 51
pathogenesis of, 84 clinical presentation of, 60–63
polycystic, 83 complications of, 64
recurrence, 87 diagnostic tests for, 25t
spinal involvement in, 84–85, 86f, 87f, 174 mortality rate for, 64
treatment of, 85, 86f prognosis for, 64
vertebral osteomyelitis in, 149 risk factors for, 25t
Echinococcus spp. See also Echinococcosis seasonal distribution of, 51
life cycle of, 84 treatment of, 62t, 64
Echinococcus granulosus, 83, 84 Encephalopathy, with fungal brain abscess,
spinal epidural abscess, 174 73
Echinococcus multilocularis, 83 Endocarditis
Echinococcus oligarthrus, 83 and infectious intracranial aneurysms,
Echinococcus vogeli, 83 136, 136t, 139, 139t
Echocardiography, with vertebral column staphylococcal, and CNS infection, 110
infection, 152 and vertebral column infections, 147, 149,
Echovirus, meningitis 152
diagnostic tests for, 23t Endovascular treatment, for infectious
risk factors for, 23t intracranial aneurysm, 142, 142t, 143
Echovirus 9, encephalitis, 55 End-stage renal disease (ESRD). See Renal failure
295
Entamoeba histolytica, 89–91 diagnosis of, 62t
brain abscess, 25 treatment of, 62t
Enterobacter spp. encephalitis, 25t, 54
and cranial epidural abscess, 128t in HIV-infected (AIDS) patients, 258
infection of DBS hardware, 221–222 meningitis, 19
and subdural empyema, 127t diagnostic tests for, 18t, 20
Enterobacter cloacae, surgical site infection, risk factors for, 18t
217 meningoencephalitis, 52, 61
Enterobacteriaceae, brain abscess, 26t in organ transplant recipient, 263
Enterococcus spp. Erythrocyte sedimentation rate, 126
diskitis, 149 with cirrhosis, 166–167
in infectious intracranial aneurysms, 138, postoperative level, 152, 167
138t with spinal epidural abscess, 166–167,
shunt infection, 209, 210t, 243, 244 167f, 171
in pediatric patients, 240 with spinal surgical site infection, 217
spinal epidural abscess, 165 with vertebral column infection, 152
Enterococcus faecalis, surgical site infection, with vertebral osteomyelitis, 27
217 Escherichia coli
Enterovirus(es) brain abscess, 24, 95
acute transverse myelitis, 52 in infectious intracranial aneurysms, 138
CNS infection, 54–55 meningitis, 19, 108, 111
diagnosis of, 62t neonatal, 107, 108t
risk factors for, 60 shunt infection, 21, 209, 210t, 244
and seizures, 64 spinal epidural abscess, 165
treatment of, 62t spinal infection, 27
encephalitis, 55 and subdural empyema, 127t
meningitis, 54–55 vertebral column infection, antibiotic
clinical presentation of, 60 treatment of, 158
diagnostic tests for, 20 vertebral osteomyelitis, 149
seasonal distribution of, 51 Exophiala dermatitidis, 73
nonpolio Experimental autoimmune
Index
diagnostic tests for, 18t encephalomyelitis (EAE), 3

encephalitis, 25t chemokine expression and function in, 10–11
risk factors for, 18t natural killer cells and, 7
Enterovirus 70, 55 pathophysiology of, 4, 6, 8, 9
Enterovirus 71, encephalitis, 55 T cells in, 6–7
Enzyme-linked immunoelectrotransfer blot External ventricular drain(s). See also
(EITB), in cysticercosis, 82 Cerebrospinal fluid (CSF) shunt
Enzyme-linked immunosorbent assay antibiotic-impregnated, 33
(ELISA), in cysticercosis, 82 antibiotic prophylaxis and, 189–190
Ependymitis, shunt and, 47
Epidural empyema, in pediatric patients, 46 F
Epidural hemorrhage, with ruptured Fatal familial insomnia, 59
infectious intracranial aneurysm, Febrile illness, arboviral, 55
139t Fecal incontinence, with spinal epidural
Epidural infection(s), 125–132 abscess, 166
Epilepsy. See also Seizure(s) Fever
cysticercosis and, 81 with amebiasis, 90
in echinococcosis, 84 with arboviral infection, 55
viral infection and, 64 with bacterial meningitis
Epstein-Barr virus (EBV) in adults, 114
acute transverse myelitis, 52 in infants/young children, 114
cerebellitis, 54 with cranial epidural abscess, 126
CNS infection with enteroviral infection, 54, 60
296
with histoplasmosis, 70 in HSCT recipients, 264
with infectious intracranial aneurysms, in immunocompromised patients,
139, 139t, 140 248–249
management of, principles of, 269 incidence of, 68
with neonatal meningitis, 114 laboratory identification of, 75
in patient with catheter microbiology, 74
diagnosis of, 273, 273f in organ transplant recipient, 263
management of, 273, 273f pathogenesis of, 69–73
postoperative, 151 primary (endemic), in
in ICU patient, 274 immunocompromised patients, 251
with rabies, 57 risk factors for, 68
with schistosomiasis, 88 sequelae, 79
with shunt infection, 210 spinal epidural abscess in, 165, 173–174
with spinal epidural abscess, 166 and surgical site infection, 200
with spinal subdural abscess, 176–177 treatment of, 77–79, 249
with subdural empyema, 126 medical, 77–79
suspected noninfectious, in ICU patient, Furuncles, and spinal subdural abscess, 176
273–274 Fusarium spp., hyphae of, 77
with vertebral column infection, 151 Fusobacterium spp., brain abscess, 26t
with viral infection, 61 Fusobacterium necrophorum, molecular
Fluconazole detection of, 26
for amebiasis, 91
for candidal infection, 78 G
for cryptococcal infection, 78 GAE. See Encephalitis, granulomatous
Flucytosine amebic
for amebiasis, 91 Ganciclovir, for CMV infection, 62t, 64
for cryptococcal infection, 78 Gas, instraspinal, 177
Fluke(s), 81t Gastrointestinal infection, in neurologic ICU
Fluoroquinolones, 32t patient, 280–281
penetration of blood–brain barrier, 31 Gatifloxacin, 32t
Focal neurologic deficit(s) Gentamycin, 32t
Index
with bacterial brain abscess, 98 Gerstmann-Sträussler-Scheinker disease,
with bacterial meningitis, in adults, 114 59
with cranial epidural abscess, 126 Glioblastoma multiforme, T cells in, 7
with schistosomiasis, 88 Glioma(s)
with subdural empyema, 126 pseudo-progression, 204
Fontanelle(s), bulging, in neonatal T cells in, 7
meningitis, 114 Glomerulonephritis, with shunt infection,
Foreign body(ies), implanted. See Implanted 210
device(s) Glycopeptides, 32t
Foscarnet, for CMV infection, 64 Gnathostoma spingerum, meningitis, 19
Fungal infection(s), 68–80. See also specific GPCR. See G protein–coupled receptor(s)
infection G protein–coupled receptor(s), in activation
clinical features of, 73–74 and firm adhesion of leukocytes to
of CSF shunt, in pediatric patients, endothelium, 9
240–241 Gram-negative bacilli. See also specific
of DBS hardware, 222 bacteria
delayed diagnosis of, 68 aerobic
diagnosis of, 75–77 and cranial epidural abscess, 128t
epidemiology of, 68 and subdural empyema, 26, 127t
etiology of, 69–73 meningitis
geographic distribution of, 68–69 diagnostic tests for, 20
histology, 77 neonatal, 107–108
in HIV-infected (AIDS) patients, 38, 73 spinal intramedullary abscess, 177
297
Gram-negative bacteria. See also specific Hallucinations, in viral infection, 61
bacteria Halo pin placement, and bacterial brain
enteric, meningitis caused by, 111 abscess, 97
infectious intracranial aneurysms, 138, HAM. See Myelopathy, HTLV-1-associated
138t HAP. See Pneumonia, hospital-acquired
shunt infection, 21, 209, 210t Hardware infection(s), 221–224. See also
spinal epidural abscess, 165 Deep brain stimulation, hardware-
surgical site infection, 217 related infection
Gram-negative rods. See also specific bacteria diagnosis of, 22
aerobic, meningitis caused by, 111 microbiology, 22
brain abscess, 26t HCAP. See Pneumonia, health care-
diskitis, 149 associated
hardware infection, 22 Headache
meningitis, 108 with amebiasis, 90
diagnostic tests for, 18t with bacterial brain abscess, 98
risk factors for, 18t with bacterial meningitis
shunt infection, 244 in adults, 114
spinal infection, 27 in infants/young children, 114
vertebral column infection with chronic meningitis, 73
antibiotic treatment of, 158 with cranial epidural abscess, 126
postoperative, 150 with echinococcosis, 84
vertebral osteomyelitis, 149 with enteroviral infection, 55, 60
Gram-positive bacteria. See also specific with fungal brain abscess, 73–74
bacteria with HSV meningitis, 53
infection of DBS hardware, 222 with infectious intracranial aneurysms,
shunt infection, 209, 210t 139, 139t
Gram-positive cocci, vertebral column with Lyme meningitis, 115
infection, antibiotic treatment of, 158 with schistosomiasis, 88
Granuloma(s). See also Tuberculosis with shunt infection, 210
in aspergillosis, 70 with subdural empyema, 126
in coccidioidomycosis, 70 with viral infection, 61
Index
in fungal infections, 248–249 Hearing loss, meningitis-related, 118

in histoplasmosis, 70 prevention of, 117
Guillain-Barré-like syndrome Heart disease, cyanotic, and bacterial brain
in lymphocytic choriomeningitis virus abscess, 96
infection, 58 Helminths, 81t
in polio, 65 brain abscess, 25
Guillain-Barré syndrome, and rabies, diagnostic tests for, 18t
differentiation of, 57 risk factors for, 18t
Hematoma, intracerebral, in aspergillosis,
H 71, 72f
Haemophilus spp., brain abscess, 26t Hematopoietic cells, in CNS, 4
Haemophilus influenzae Hematopoietic stem cell transplantation, and
brain abscess, 95 infection, 262, 264
meningitis, 19, 108, 109 Hemiparesis
diagnostic tests for, 18t, 20 with bacterial meningitis
risk factors for, 18t in adults, 114
sequelae, 118 in elderly, 114
treatment of, 117 with subdural empyema, 126
shunt infection, 243 Hemorrhagic fever, arboviral, 55
and subdural empyema, 127t Hereditary hemorrhagic telangiectasia
vaccine against, 107, 109 (HHT)
vertebral column infection, 149 and bacterial brain abscess, 96
Hair removal, and surgical site infection, and pulmonary arteriovenous
298 198–199 malformation, 96, 97f
Herpes B virus bacterial brain abscesses in, 95, 96
CNS infection brain abscess in, microbiology, 26t
diagnosis of, 62t CMV meningoencephalitis in, 54
prevention of, 62t CNS infections in, 258–262
treatment of, 62t CNS lymphoma in, 258, 259
encephalitis, 54, 61 coinfections in, 258–262
Herpes simplex virus (HSV) cryptococcal meningoencephalitis in, 70
acute transverse myelitis, 52 cryptococcosis in, 259–260
CNS infection Epstein-Barr virus in, 258
diagnosis of, 62t fungal infections in, 73
treatment of, 62t fungal meningitis in, imaging of, 38
encephalitis, 25t, 52, 53, 53f, 61 histoplasmosis in, 252
diagnostic tests for, 20 imaging in, 38, 42
and epilepsy, 64 immune reconstitution inflammatory
hemorrhage with, 38 syndrome in, 261
imaging of, 38, 39f JC virus in, 258, 261–262
pathogenesis of, 52 meningitis in, 111, 113
progression of, 53, 53f, 61–63, 61f, 63f neurocysticercosis in, 256–257
risk factors for, 60 parasitic infections in, 258–259
treatment of, 64 pneumococcal meningitis in, 113
meningitis, 53 progressive multifocal
diagnostic tests for, 18t leukoencephalopathy in, 58, 258,
risk factors for, 18t 261–262, 263f
Herpesvirus(es), 52–54. See also Human spinal epidural abscess in, 164t
herpesvirus (HHV) spinal subdural abscess in, 176
in organ transplant recipient, 263 toxoplasmosis in, 255, 259
HIB. See Haemophilus influenzae tuberculosis in, 259, 260–261
Histoplasma spp. See also Histoplasmosis spinal, 173
laboratory identification of, 75 vertebral column infections in, 147
Histoplasma capsulatum, 70. See also vertebral osteomyelitis in, 149
Histoplasmosis Hockey stick sign, in variant Creutzfeldt-
Index
meningitis Jakob disease, 39, 40f
diagnostic tests for, 23t, 24 Homonymous hemianopsia, with subdural
risk factors for, 23t empyema, 126
pulmonary infection, 69–70 Hospital-acquired pathogens, 16
Histoplasmosis HSCT. See Hematopoietic stem cell
clinical features of, 73 transplantation
CNS involvement in, 70 HSV. See Herpes simplex virus (HSV)
diagnostic tests for, 23t, 24 HTLV. See Human T-cell lymphotropic virus
disseminated, 70 (HTLV)
geographic distribution of, 68–69 Human herpesvirus (HHV)
in HIV-infected (AIDS) patients, 252 HHV-6, encephalitis, 25t
imaging of, 75 meningitis, 19
in immunocompromised patients, 252 diagnostic tests for, 20
meningitis, 22, 23t, 24 Human immunodeficiency virus (HIV).
pulmonary involvement in, 69–70 See also HIV-infected (AIDS)
risk factors for, 23t patients
spinal involvement in, 70, 149 acute transverse myelitis, 52
treatment of, 78 encephalitis, imaging of, 42
surgical, 77 meningitis, 19
vertebral osteomyelitis in, 149 diagnostic tests for, 18t
HIV. See Human immunodeficiency virus risk factors for, 18t
(HIV) polymerase chain reaction (PCR) for, 24
HIV-infected (AIDS) patients Human T-cell lymphotropic virus (HTLV)
aspergillosis in, 249–250 acute transverse myelitis, 52 299
Human T-cell lymphotropic virus (HTLV) of DBS hardware-related infection, 222
(continued) of echinococcosis, 84–85, 85f, 86f
CNS infection of encephalitis, 38, 39f
diagnosis of, 62t of epidural and subdural infections,
treatment of, 62t 126–129, 128f, 129f–130f
HTLV-1, 58–59 of fungal infection, 75–77, 76f
and strongyloidiasis, 257 of fungal meningitis, 38
HTLV-2, 59 of HSV infection, 53, 53f, 61–63, 61f, 63f
Hydatid cyst(s), 84 in immunocompromised patients, 42, 43f,
hydrodissection of (Dowling method), 85, 44f, 45f
86f of meningitis, 35–38, 37f, 38f
Hydatid disease, spinal epidural abscess in, in prion diseases, 39, 40f
174 of progressive multifocal
Hydatidosis, cystic, 83–87 leukoencephalopathy, 58
Hydrocephalus of schistosomiasis, 88
in adults, 208 of shunt infection, 211
with bacterial brain abscess, 101–102, of spinal epidural abscess, 167–168, 168f
101f of spinal instrumentation-related
with bacterial meningitis, in elderly, 114 infection, 217–218, 217f
with Candida meningitis, 73 of spinal intramedullary abscess, 177, 178f
with chronic meningitis, 73 of spinal subdural abscess, 176–177
with coccidioidomycosis, 70 of tuberculous meningitis, 37, 38f
computed tomography of, 35 of vertebral column infection, 153–155,
with cysticercosis, 82, 83 154f
epidemiology of, 208 Immigrants, neurocysticercosis in, 42–43,
etiology of, 208 46f–48f
with fungal infection, treatment of, 77 Immune cells, in CNS, 4–7
imaging of, 46f, 47f Immune reconstitution inflammatory
with lymphocytic choriomeningitis virus syndrome, 261, 262
infection, 58 Immune response, in central nervous
in pediatric patients, 208 system, 3
Index
treatment of, 208 Immunocompromised patient(s). See also

with viral infection, 64 HIV-infected (AIDS) patients;
Hydrophobia, in rabies, 57 Immunosuppressed patient(s)
Hyperbaric oxygen, for mucormycosis, 79 American trypanosomiasis in, 257–258
Hyperimmunoglobulin M syndrome, and aspergillosis in, 249–250
viral infection, 60 blastomycosis in, 252
Hypogammaglobulinemia candidiasis in, 252–253
and meningitis, 113 Chagas disease in, 257–258
and viral infection, 60 CNS infections in, 247–268
clinical presentation of, 247–248
I imaging of, 42, 43f, 44f, 45f
ICP. See Intracranial pressure microbiology, 247
IIA. See Infectious intracranial aneurysm(s) prevention of, 248
Imaging, 35–48. See also specific imaging treatment of, 248
modality coccidioidomycosis in, 251–252
of bacterial brain abscess, 98f, 99, 99f histoplasmosis in, 252
of bacterial meningitis, 108, 108f, 114, leishmaniasis in, 258
115f mucormycosis in, 250–251
of brain abscess, 40–42 mycoses in, primary (endemic), 251
of cerebral abscess, in pediatric patient, nocardiosis in, 253–254, 254f
235 parasitic infections in, 254–258
of cerebritis, 40–42 schistosomiasis in, 258
of cysticercosis, 82–83 spinal epidural abscess in, 164
300
strongyloidiasis in, 257 Infectious mononucleosis, neurologic
and surgical site infections, 197 complications of, 54
toxoplasmosis in, 254–255, 256f Inflammation
zygomycosis in, 250–251 in bacterial brain abscess development,
Immunologic privilege, 3 97–98
Immunosuppressed patient(s). See also in central nervous system, chemokine
Immunocompromised patient(s) expression in, 10
bacterial brain abscesses in, 95, 96 markers of
CNS infections in, 247 in bacterial meningitis, 20–21
fungal infections in, 68, 73 with spinal epidural abscess, 166–167
and meningitis, 113 in vertebral column infection, 151–152
progressive multifocal with vertebral osteomyelitis, 27
leukoencephalopathy in, 58 with subdural empyema, 126
spinal epidural abscess in, 164 Influenza, and seizures, 64
vertebral column infections in, 147 Integrin(s), in activation and firm adhesion
Immunosurveillance, of central nervous of leukocytes to endothelium, 9
system, 3 Intercellular cell adhesion molecule (ICAM)
Implanted device(s), 208–230. See also ICAM-1, and transendothelial migration of
Cerebrospinal fluid (CSF) shunt lymphocytes, 8–9
antibiotic prophylaxis with, 190–191 ICAM-2, and transendothelial migration of
imaging of, 46–47 lymphocytes, 8–9
and surgical site infections, 197, 198 Interferon-a, for HTLV-1 infection, 59, 62t
Induced normothermia, in neurologic ICU Interferon gamma release assay, 23
patient, 282 Interleukin-1 receptor-associated kinase (IRAK)-
Infectious intracranial aneurysm(s) 4, deficiency, and meningitis, 113
anatomic distribution of, 136, 136t, Intracranial pressure
140–141 increased, 75
associated infections, 136, 136t in amebiasis, 90
clinical presentation of, 139–140, 139t in cysticercosis, 82
cryptogenic (primary), 137 in viral infection, 64
epidemiology of, 133–136, 139 monitoring, 61, 64
Index
extravascular sources, 137 Intraparenchymal hemorrhage, with
and clinical presentation, 140 ruptured infectious intracranial
fungal, 138 aneurysm, 139t, 140, 140f
management of, 142 Intrathecal pump infection(s), 219
mortality rate for, 141 Intravenous drug use
outcomes with, 141 and bacterial brain abscess, 97
risk factors for, 139 and spinal epidural abscess, 164, 164t, 165
histopathology of, 137, 137f and vertebral column infections, 147
incidence of, trend in, 133 Intraventricular hemorrhage, with ruptured
intravascular sources, 136–137 infectious intracranial aneurysm,
literature review on, 133, 134t–135t 139t, 140
microbiology, 138, 138t IRIS. See Immune reconstitution
mortality rate for, 141 inflammatory syndrome
multiple, 141 Irritability
management of, 143 with bacterial meningitis, in infants/young
natural history of, 141 children, 114
outcomes with, 140 with shunt infection, 210
pathogenesis of, 136–137 with viral infection, 61
in pediatric patients, 133–136 Itraconazole
risk factors for, 133, 139, 139t for aspergillosis, 78
rupture, 139–140, 139t for blastomycosis, 78
mortality rate with, 141 for cryptococcal infection, 78
treatment of, 141–143, 142t, 144f for histoplasmosis, 78
301
J Leukocyte margination, 7
Jamestown Canyon virus, 56, 56t Leukocytosis, with vertebral column
Japanese encephalitis virus, infection infection, 152
epidemiology of, 51 Level of consciousness, altered. See also
prevention of, 63–64 Mental status, altered
and seizures, 64 with amebiasis, 90
JC virus. See also Progressive multifocal with fungal brain abscess, 73–74
leukoencephalopathy (PML) with viral infection, 61
CNS infection, 58 Levofloxacin, 32t
diagnosis of, 62t Linezolid, 31, 32t
treatment of, 62t Listeria spp., spinal intramedullary abscess,
encephalitis, 25t 177, 179
in HIV-infected (AIDS) patients, 258, 261–262 Listeria monocytogenes
meningitis, 19, 108, 108t, 110–111
K diagnostic tests for, 18t, 20
Ketoconazole, for blastomycosis, 78 neonatal, 107, 108t
Klebsiella spp. risk factors for, 18t
brain abscess, 24 sequelae, 118
infection of DBS hardware, 222 treatment of, 117
in infectious intracranial aneurysms, 138 and subdural empyema, 127t
meningitis, 19, 111 LP. See Lumbar puncture
shunt infection, 209, 210t Lumbar drain(s), antibiotic prophylaxis and,
spinal epidural abscess, 165 190
Klebsiella pneumoniae Lumbar puncture, 35
brain abscess, 95 contraindications to, 27, 126, 167
in infectious intracranial aneurysms, 138 indications for, 115
shunt infection, 21 magnetic resonance imaging after, 36
Kuru, 59 Lyme meningitis, 19, 111. See also Borrelia
Kyphoplasty, infection after, 176 burgdorferi
Kyphosis, with tuberculous vertebral clinical presentation of, 114–115
osteomyelitis, treatment of, 155 CSF findings in, 17t, 116, 116t
Index
diagnostic tests for, 21, 116

L treatment of, 117
La Crosse virus, 51, 56, 56t Lymphocyte function-associated antigen
b-Lactamase, 31, 32t (LFA), LFA-1, and transendothelial
Leishmania donovani, 258 migration of lymphocytes, 9
Leishmania infantum, 258 Lymphocytic choriomeningitis virus
Leishmaniasis, 254 acute transverse myelitis, 58
in immunocompromised patients, 258 infection, 58
Lethargy diagnosis of, 62t
with amebiasis, 90 prevention of, 62t
with bacterial brain abscess, 98 treatment of, 62t
with bacterial meningitis Lymphoma(s), CNS, in HIV-infected (AIDS)
in adults, 114 patients, 258, 259
in infants/young children, 114
with neonatal meningitis, 114 M
with shunt infection, 210 Macaques, herpes B virus, 54
with viral infection, 61 Macrolides, 32t
Leukocyte(s) for amebiasis, 91
activation and firm adhesion to resistance to, 31, 32t
endothelium, 8f, 9 Macrophage(s), perivascular, in CNS, 4–5
diapedesis (transendothelial migration), Macrophage inflammatory protein (MIP),
8f, 9 MIP-3b, 9–10
tethering and rolling on endothelium, 7–9, Magnetic resonance angiography (MRA),
302 8f indications for, 37, 38
Magnetic resonance imaging (MRI), 35 Magnetic resonance spectroscopy
of amebiasis, 90 of bacterial brain abscess, 99
of aspergillosis, 42, 45f, 75, 76f of brain abscess, 41–42
of bacterial brain abscess, 98f, 99 of HIV encephalitis, 42
of bacterial meningitis, 35–37, 108f of mucormycosis, 251
of blastomycosis, 75 of toxoplasmosis, 42
of brain abscess, 41 Magnetic resonance venography, indications
of Candida infection, 75 for, 37
of cavernous sinus thrombosis, 46 Major histocompatibility complex (MHC),
of cerebral abscess, in pediatric patient, 235 class II molecules, microglia and, 5
of cerebritis, 40–41 Malaise
of cryptococcal infection, 75 with amebiasis, 90
of cysticercosis, 46f, 82–83 with enteroviral infection, 60
of DBS hardware-related infection, 222 with infectious intracranial aneurysms,
diffusion-weighted (DWI), 36, 36f, 37, 38f, 139, 139t
47 with spinal epidural abscess, 166
of brain abscess, 41, 41f with vertebral column infection, 151
of echinococcosis, 85, 85f, 86f Malaria, 81t, 254
of epidural and subdural infections, 126, Malignancy
129, 129f–130f and meningitis, 113
of extra-axial abscess, in pediatric patient, and vertebral column infections, 147
234 Malnutrition, and surgical site infections,
FLAIR, 35–36, 36f, 37, 37f, 38, 39, 39f, 40f, 197
41f, 44f–46f, 47, 47f, 48f Mantoux skin test, 116
of fungal meningitis, 38 Mastoiditis
of herpes encephalitis, 38, 39f and bacterial brain abscess, 97, 98f
of histoplasmosis, 75 and cranial epidural abscess, 128t
of HIV encephalitis, 42 and subdural empyema, 127t
of HSV infection, 53, 53f, 61–63, 61f, 63f and subdural infection, 125
of intracranial infection, 200 Measles
of mucormycosis, 76, 76f, 251 and seizures, 64
Index
of neurocysticercosis, 42–43, 46f, 47f, 48f and subacute sclerosing panencephalitis,
of nocardiosis, 253, 254f 65
of osteomyelitis, 46 vaccination against, 63
of pediatric patients, 44–45 Mebendazole, for neurohydatidosis, 85
in prion disease, 60 Mediastinitis, and vertebral column
of progressive multifocal infections, 149
leukoencephalopathy, 42, 43f, 262, Memory, decreased, in chronic meningitis,
263f 73
of schistosomiasis, 88 Meningeal infection(s), 107–124. See also
of shunt infection, 211 Meningitis
of shunt-related infection, 47 Meningioma(s), and surgical site infections,
of spinal epidural abscess, 167–168, 168f, 198
170, 172 Meningismus
of spinal instrumentation-related with amebiasis, 90
infection, 217–218, 217f with bacterial meningitis, in infants/young
of spinal intramedullary abscess, 177, 178f children, 114
of spinal subdural abscess, 176–177 with fungal brain abscess, 73
of subdural effusions, 234–235 with HSV meningitis, 53
of subdural empyema, 234 with infectious intracranial aneurysm,
of toxoplasmosis, 42, 44f 140
of tuberculous meningitis, 37, 38f with rabies, 57
of variant Creutzfeldt-Jakob disease, 39, 40f with shunt infection, 210
of vertebral column infection, 153–154, with subdural empyema, 126
154f, 155, 158–159 with viral meningitis, 60 303
Meningitis risk factors for, 23t
acute sequelae, 79
common organisms in, 18t carcinomatous, imaging of, 37
diagnostic tests for, 18t, 19, 20t caused by enteric gram-negative bacteria,
microbiologic diagnosis of, 19–21 111
adenoviral, 55 chronic, 22–24
amebic, 19, 22 clinical features of, 73
diagnostic tests for, 18t, 21, 24 diagnostic tests for, 22–24, 23t
risk factors for, 18t microbiology, 22, 23t
arboviral, 55, 56 coccidioidal, 22, 73
aseptic, 19, 51 CSF findings in, 17t
imaging of, 37, 37f diagnostic tests for, 23t, 24
in neurologic ICU patient, 275 laboratory investigation of, 75
postoperative, 204 risk factors for, 23t
bacterial, 35, 107 cryptococcal, 22
in adolescents, 108, 108t CSF findings in, 17t
in adults, 108, 108t diagnostic tests for, 23t, 24
age of patient and, 107, 108t imaging of, 38
anatomic risk factors for, 112–113 prognosis for, 79
chronic, 22–23, 23t risk factors for, 23t
clinical presentation of, 114–115 treatment of, 78
complications of, 118 CSF findings in, 16–17, 17t
CSF findings in, 17t, 116t in cysticercosis, 82
CSF leukocyte count in, 17 cytomegalovirus, 19
CSF neutrophil count in, 17 diagnosis of, 115–116
CSF opening pressure in, 16 enteroviral, 19, 54–55
demographics of, 107 clinical presentation of, 60
diagnostic tests for, 18t diagnostic tests for, 18t
in elderly, 108, 108t, 114, 115f risk factors for, 18t
epidemiology of, 107 fungal, 22, 24, 68, 248–249
etiology of, 107–111 causative organisms, 68
Index
geographic differences in, 107 clinical features of, 73

imaging of, 35–37, 114, 115f diagnostic tests for, 23t
immunologic risk factors for, 113–114 imaging of, 37, 38
incidence of, 107 microbiology, 23t
in infants and children, 108, 108t, 114 group B streptococcal, neonatal, 107, 108t,
microbiology, 18t, 19, 107–111, 108t 110
neonatal, 107–108, 108t, 110 Haemophilus influenzae type b, risk factors
clinical presentation of, 114 for, 113–114
pathogenesis of, 107–111 helminthic, 19
postoperative, 204 diagnostic tests for, 18t, 21
prognosis for, 118 risk factors for, 18t
risk factors for, 18t, 19, 111–114 herpes simplex virus, 19, 53
sequelae, 118 diagnostic tests for, 18t
and suppurative intracranial risk factors for, 18t
thrombophlebitis, 27 Histoplasma, 73
vaccines and, 107 hospital-acquired, 19
and bacterial brain abscess, 97 imaging of, 35–38, 37f, 38f
in blastomycosis, 74 in infant/young child, and subdural
diagnostic tests for, 23t empyema, 127t
risk factors for, 23t infectious, in neurologic ICU patient, 275
candidal, 73 and infectious intracranial aneurysms,
diagnostic tests for, 23t 136, 136t, 137, 139, 139t
prognosis for, 79 Listeria, sequelae, 118
304
lymphocytic choriomeningitis virus, 57 risk factors for, 18t
meningococcal, 109–110. See also Neisseria viral, 19
meningitidis clinical presentation of, 60–63
clinical presentation of, 114 common organisms of, 18t
geographic differences in, 107 CSF findings in, 17t, 116t
neonatal, 108 diagnostic tests for, 18t, 19–20, 23t
risk factors for, 113–114 epidemiology of, 51–52
sequelae, 118 etiology of, 52–60
treatment of, 117 imaging of, 37, 37f
Mollaret’s, 19 immunology, 20
neonatal microbiology, 18t, 19
bacterial, 107–108, 108t, 110 pathogenesis of, 52
clinical presentation of, 114 risk factors for, 18t, 23t
group B streptococcal, 110 seasonal distribution of, 51
meningococcal, 108 treatment of, 62t, 63–64
pneumococcal, 108 Meningitis belt, 107
staphylococcal, 108 Meningococci. See Neisseria meningitidis
and subdural empyema, 127t Meningoencephalitis
parasitic adenoviral, 55
diagnostic tests for, 23t amebic, CSF findings in, 17t
risk factors for, 23t cryptococcal, 69–70, 69f
in pediatric patients, 44–46 clinical features of, 73
pneumococcal, 109. See also Streptococcus enteroviral, chronic, in
pneumoniae hypogammaglobulinemia, 113
clinical presentation of, 114 lymphocytic choriomeningitis virus, 57
in HIV-infected (AIDS) patients, 113 primary amebic, 89–91
neonatal, 108 spinal subdural abscess and, 177
risk factors for, 113–114 viral, 51
sequelae, 118 clinical presentation of, 61
treatment of, 117 epidemiology of, 51–52
postoperative, 19, 46, 202, 204 etiology of, 52–60
Index
chronic, 23 pathogenesis of, 52
in Scedosporium infection, 72 treatment of, 62t, 63–64
with spinal subdural abscess, 177 Mental status, altered. See also Level of
spirochetal, 19 consciousness, altered
diagnostic tests for, 18t, 21 with bacterial meningitis
risk factors for, 18t in adults, 114
staphylococcal, 110 in elderly, 114
neonatal, 108 in infants/young children, 114
syphilitic, 19 with cranial epidural abscess, 126
diagnostic tests for, 21 with infectious intracranial aneurysms,
treatment of, 116–118 139, 139t
tuberculous, 22, 111 with spinal subdural abscess, 177
CSF findings in, 17t, 22–23, 116t with subdural empyema, 126
diagnostic tests for, 18t, 22–23, 23t, Meropenem, 32t
116 Metabolic factors, and surgical site
imaging of, 37, 38f infections, 197
and infectious intracranial aneurysm, Metastatic disease, and surgical site
141, 141f infections, 198
in pediatric patients, 45 Methicillin-resistant Staphylococcus aureus
risk factors for, 18t, 23t (MRSA), 31, 186
treatment of, 117–118 antibiotic treatment of, 158
varicella-zoster virus, 19, 54 control of, 32
diagnostic tests for, 18t surgical site infection, 216–217
305
Methicillin-sensitive Staphylococcus aureus Multiple sclerosis (MS), 4
(MSSA), vertebral column infection, chemokine expression and function in,
antibiotic treatment of, 158 10–11
Methylmethacrylate, in vertebroplasty/ T cells in, 6–7
kyphoplasty, and infection, 176 Mumps
Metronidazole, 32t encephalitis, 19
for E. histolytica brain abscess, 91 meningitis, 19
Miconazole, for amebiasis, 91 diagnostic tests for, 18t, 20
Microbiological diagnosis, 16–29 risk factors for, 18t
specimen collection for, 16–17 meningoencephalitis, 51–52
specimen selection for, 16–17 and seizures, 64
Micrococcus spp., infection of DBS hardware, vaccination against, 51–52, 63
222 Mycobacteria. See also Mycobacterium
Microglia tuberculosis
chemokine secretion by, 5–6 brain abscess, 26t
in CNS, 4–6 in infectious intracranial aneurysms, 138,
functions of, 5 138t
and neurons, interactions of, 5, 6f nontuberculous, brain abscess, 24
perivascular, in CNS, 4–5 risk factors for, 27
Microsporidiosis, 254 stains for, 22
Microvasculature, of central nervous system, Mycobacterium tuberculosis, 111. See also
3–4 Tuberculosis
Mini-BAL, 276 brain abscess, 24
contraindications to, 276, 277t encephalitis, 25t
Mollaret’s meningitis, 19 meningitis. See Meningitis, tuberculous
Mondini dysplasia, 112, 112f spinal epidural abscess, 165
Mononeuritis multiplex, in Lyme meningitis, Mycoplasma hominis, molecular detection
115 of, 26
Mosquito vector(s), and viral infection, 51, Mycoplasma pneumoniae, encephalitis, 25t
55–56, 56t Mycoses. See also Fungal infection(s)
Motor deficit(s) primary (endemic), in
Index
with infectious intracranial aneurysms, immunocompromised patients, 251

139, 139t Mycotic aneurysm. See Aneurysm(s), mycotic
with spinal epidural abscess, 166 Myelitis. See also Acute transverse myelitis
MRI. See Magnetic resonance imaging (MRI) in cysticercosis, 82
MRSA. See Methicillin-resistant infection-associated, with viral infection, 51
Staphylococcus aureus (MRSA) in Lyme meningitis, 115
Mucor spp., 71, 250–251. See also Myelography
Mucormycosis contraindications to, 153
brain abscess, imaging of, 76, 76f CT, of spinal epidural abscess, 168
in infectious intracranial aneurysms, 138 Myeloid differentiation (MyD) factor 88,
Mucormycosis, 24–25, 71–72, 72f. See also deficiency, and meningitis, 113
Mucor spp. Myelopathy
histology of, 77 HTLV-1-associated, 58–59
in immunocompromised patients, with schistosomiasis, 88
250–251 with viral infection, 51
laboratory investigation of, 75
meningitis, imaging of, 38 N
prognosis for, 79 Naegleria fowleri, 89–91
rhinocerebral diagnostic tests for, 18t
clinical features of, 74 meningitis, 19
imaging of, 75–77, 76f risk factors for, 18t
treatment of, 78–79 National Nosocomial Infections Surveillance
surgical, 77 (NNIS) risk index, 199
306
Natural killer (NK) cells Neurocysticercosis, 256–257
in central nervous system, 7 colloidal stage, 42–43, 47f, 48f
in experimental autoimmune encephalitic, 43
encephalomyelitis, 11 granular nodular stage, 43
Nausea in HIV-infected (AIDS) patients, 256–257
with amebiasis, 90 imaging in, 42–43
with bacterial brain abscess, 98 nodular calcified stage, 43
with chronic meningitis, 73 racemose, 42, 46f
with cranial epidural abscess, 126 stages of, 42–43
with infectious intracranial aneurysms, and tuberculosis, concomitant, 43
139, 139t vesicular stage, 42, 46f
with rabies, 57 Neuroimaging. See Imaging; specific imaging
with schistosomiasis, 88 modality
with shunt infection, 210 Neurologic deficit(s). See also Cranial
with subdural empyema, 126 nerve palsy(ies); Focal neurologic
with viral infection, 61 deficit(s)
Near-complications, 199–200 with spinal epidural abscess, 165–166
Neck pain, with vertebral column infection, 150 with spinal subdural abscess, 176–177
Neck stiffness. See also Nuchal rigidity Neurologic intensive care unit
with bacterial meningitis CNS infection in, assessment for, 274–275,
in adults, 114 274t
in infants/young children, 114 systemic infections in, 269–284
with shunt infection, 210 signs and symptoms, 270t
Negri bodies, 57 work-up for, 269–270, 270t–271t
Neisseria spp., recurrent infections, Neuron(s), developing
complement deficiency and, 114 apoptosis, 5
Neisseria meningitidis microglia and, 5, 6f
carriers, 109 Neurosarcoidosis, imaging of, 37
meningitis, 19, 108, 108t Neurosurgery. See also Surgery
diagnostic tests for, 18t, 20 and bacterial brain abscess, 97
geographic differences in, 109–110 clean-contaminated procedures, 187–188,
Index
risk factors for, 18t 198
serogroups, 109–110 clean procedures, 187–188, 198
shunt infection, 243 contaminated procedures, 187–188, 198
and subdural empyema, 127t Neurosurgical patient(s), imaging in, after
vaccine against, 107 craniotomy/craniectomy, 46
Neonate(s) Neurosyphilis, 19
bacterial brain abscess in CSF findings in, 17t
clinical presentation of, 98 diagnostic tests for, 21
and hydrocephalus, 101–102 gummatous, 19
CSF glucose level in, 115 parenchymatous, 19
meningitis in Neutrophilia, with vertebral column
bacterial, 107–108, 108t, 110 infection, 152
clinical presentation of, 114 Night sweats
Escherichia coli, 107, 108t with spinal epidural abscess, 166
gram-negative bacillary, 107–108 with vertebral column infection, 151
group B streptococcal, 107, 108t, 110 Nipah virus, 52
Listeria monocytogenes, 107, 108t Nitroamidazole, 32t
meningococcal, 108 NK cells. See Natural killer (NK) cells
Pasteurella spp., 108 NNIS. See National Nosocomial Infections
pneumococcal, 108 Surveillance (NNIS) risk index
staphylococcal, 108 Nocardia spp. See Nocardiosis (Nocardia spp.)
Streptococcus agalactiae, 107 Nocardia asteroides, spinal epidural abscess,
and subdural empyema, 127t 172
307
Nocardiosis (Nocardia spp.) outcomes with, 159
brain abscess, 26t, 95–96, 96f pain with, 150–151
diagnosis of, 25–26 pathogenesis of, 149
in immunocompromised patients, 253–254, risk factors for, 147
254f sequelae, 159
meningitis and spinal epidural abscess, 164
diagnostic tests for, 23t treatment of, 155–159, 157f
risk factors for, 23t Otitis media
in organ transplant recipients, 263, 265 chronic, and subdural infection, 125
spinal epidural abscess, 172 and cranial epidural abscess, 128t
spinal intramedullary abscess, 177 recurrent, and bacterial brain abscess, 97
Nuchal rigidity. See also Neck stiffness and subdural empyema, 127t
in elderly, 114 Oxacillin, prophylactic, in neurosurgery, 187
in meningitis, 114 Oxamniquine, for schistosomiasis, 89
Nucleic acid amplification tests. See also Oxazoladinones, 32t
Polymerase chain reaction (PCR)
in bacterial meningitis, 21 P
in shunt infection, 22 Pain. See also Back pain; Radicular pain
in viral meningitis, 20 chronic, with vertebral column infection,
Nutritional status, and surgical site 159
infections, 197 neck, with vertebral column infection, 150
ocular, with infectious intracranial
O aneurysm, 140
Obesity with spinal epidural abscess, 166
and spinal epidural abscess, 164t with vertebral column infection, 150–151
and surgical site infections, 197 PAM. See Meningoencephalitis, primary
Ochroconis gallopava, 73 amebic
Ocular pain, with infectious intracranial Papilledema, 73
aneurysm, 140 with bacterial brain abscess, 98
Ophthalmoplegia, with infectious with echinococcosis, 84
intracranial aneurysm, 140 with fungal meningitis, 73
Index
Opsoclonus-myoclonus, in Lyme meningitis, with subdural empyema, 126

115 Paralysis. See also Hemiparesis
Orbital cellulitis, and infectious intracranial acute flaccid
aneurysms, 136, 136t, 137, 140 arboviral, 55, 56
Organ transplant recipient(s) enteroviral, 55
bacterial brain abscesses in, 95, 96 in rabies, 57
fungal infections in, 73 in polio, 64–65
infections in, 262–264, 264–265 with spinal epidural abscess, 166
Osteomyelitis Paramyxoviridae, encephalitis, 51–52
and infectious intracranial aneurysm Paraplegia, in coccidioidomycosis, 70
formation, 137 Parasitic infection(s), 81–94, 81t. See also
postoperative, 46 specific parasite
spinal (vertebral), 147, 163. See also in HIV-infected (AIDS) patients, 258–259
Vertebral column infection(s) in immunocompromised patients, 254–258
clinical presentation of, 150–151 spinal epidural abscess in, 174
delayed diagnosis of, 151 vertebral osteomyelitis in, 149
diagnosis of, 27 Parechovirus(es), CNS infection, 54–55
distribution of involved spinal segments Paroxysmal lateral epileptiform discharges
in, 149 (PLEDs), in HSV infection, 53
imaging of, 153–155 Pasteurella spp., meningitis, neonatal, 108
incidence of, 147 Pasteurella multocida, meningitis, 111
laboratory investigation, 152 PCR. See Polymerase chain reaction (PCR)
microbiology, 27, 149 PCT. See Procalcitonin
308
Pediatric patients, 233–246 Pneumonia
bacterial meningitis in, 108, 108t, 114 community-acquired, 276, 276t
cranial epidural abscess in, 233–239 health care-associated, 276, 276t
focal intracranial infectious lesions in, hospital-acquired, 276, 276t
233–239 in neurologic ICU patient, 276–278
age distribution of, 233–234 types of, 276, 276t
epidemiology of, 233–234 ventilator-associated, 276, 276t
imaging of, 233 Polio-like outbreaks, 55
mortality rate for, 233 Poliomyelitis, 55
postoperative, 234 bulbospinal, 64–65
imaging of, 44–46 complications of, 64–65
intraparenchymal abscess in, 233–239 prevention of, 62t, 63
meningitis in, and subdural empyema, vaccination against, 63
127t Polymerase chain reaction (PCR)
shunt infection in, 233, 239–244 for amebiasis, 90
incidence of, 209 in bacterial meningitis, 21
subdural empyema in, 233–239 for Balamuthia, 24
Penicillin(s), 32t for Candida albicans, 75
Pentamidine, for amebiasis, 91 for cytomegalovirus, 24
Peptostreptococcus spp., in infectious for enterovirus, 55
intracranial aneurysms, 138 for Epstein-Barr virus, 24, 54
Personality changes for herpes simplex virus, 20, 24, 53
with fungal brain abscess, 73 for HHV-6, 24
with viral infection, 61 for HIV, 24
Petechiae, with infectious intracranial for JC virus, 24, 58
aneurysms, 139, 139t for lymphocytic choriomeningitis virus,
Petriellidium boydii, in infectious intracranial 58
aneurysms, 138 in microbiological diagnosis of brain
Pharyngitis abscess, 26
in enteroviral infection, 54 for microbiologic diagnosis of spinal
and infectious intracranial aneurysm epidural abscess, 168
Index
formation, 137 in shunt infection, 22
Phlebitis, and infectious intracranial for varicella-zoster virus, 24
aneurysms, 136t in viral meningitis, 20
Photophobia Posaconazole
with enteroviral meningitis, 54 for aspergillosis, 78
with HSV meningitis, 53 for mucormycosis, 78–79
with subdural empyema, 126 Positron emission tomography (PET),
with viral meningitis, 53–54, 60 [18F]fluorodeoxyglucose, of
Piperacillin, prophylactic, in neurosurgery, vertebral column infection,
187 155
Plain film radiograph(s) Postoperative infection(s), 19, 23, 46. See also
of spinal epidural abscess, 167 Antibiotic prophylaxis
of vertebral column infection, 153, 154f, and cranial epidural abscess, 128t
155 and infectious intracranial aneurysms,
Plasmid(s), and antibiotic resistance, 31–32 136, 136t, 137
PLEDs. See Paroxysmal lateral epileptiform intracranial, 196–207
discharges (PLEDs) epidemiology of, difficulties of, 196
Pleural effusion(s), with spinal epidural literature on, 196–197
abscess, 166 microbiology of, 16
PML. See Progressive multifocal risk factors for, 186
leukoencephalopathy (PML) spinal epidural abscess, 175
Pneumococci. See Streptococcus and subdural empyema, 26, 127t, 202–203,
pneumoniae 202f, 203f
309
Postoperative infection(s) (continued) Proteus mirabilis, surgical site infection, 217
vertebral column, 149–150 Protozoa, 81t
microbiology, 150 brain abscess, 25
outcomes with, 159 in HSCT recipients, 264
pain in, 151 PrPc protein, 59–60
prevention of, 150 Pseudallescheria boydii, 72
risk factors for, 147–148, 150 in infectious intracranial aneurysms, 138
treatment of, 155, 156–158 Pseudomonas spp. See also Pseudomonas
Pott disease, 27, 147, 148f aeruginosa
Pott puffy tumor, 234 brain abscess, 24, 95
Powassan virus, 55, 56, 56t infection of DBS hardware, 22, 222
Praziquantel shunt infection, 21, 209, 210t, 243
for cysticercosis, 83 surgical site infection, 217
for schistosomiasis, 88–89 Pseudomonas aeruginosa
Prevotella spp., brain abscess, 26t brain abscess, 24, 95
Prion disease, 59–60 and cranial epidural abscess, 128t
diagnosis of, 62t hardware infection, 22, 222
imaging in, 39, 40f in infectious intracranial aneurysms, 138,
treatment of, 62t 138t
Procalcitonin, serum, in bacterial meningitis, meningitis, 19, 111
20–21 shunt infection, 21, 209, 210t, 243
Progressive multifocal leukoencephalopathy spinal epidural abscess, 165
(PML), 58 spinal infection, 27
in HIV-infected (AIDS) patients, 58, 258, and subdural empyema, 127t
261–262, 263f vertebral column infection, antibiotic
imaging in, 42, 43f treatment of, 158
mortality rate for, 64 vertebral osteomyelitis, 149
in organ transplant recipients, 265 Pseudotumor cerebri, in Lyme meningitis, 115
Propionibacterium spp. Pulmonary infection, in neurologic ICU
and cranial epidural abscess, 128t patient, 276–278
and subdural empyema, 127t Pulvinar sign, in variant Creutzfeldt-Jakob
Index
Propionibacterium acnes disease, 39

brain abscess, 24, 26t, 96 Purified protein derivative (PPD), 116
hardware infection, 22 Pyelonephritis, and vertebral column
infection of DBS hardware, 222, 223 infections, 149
meningitis Pyocephalus, shunt and, 47
diagnostic tests for, 18t
risk factors for, 18t R
organ/space surgical site infection, 202 Rabies
postoperative vertebral column infection, clinical presentation of, 57
150 diagnosis of, 57, 62t
shunt infection, 21, 190, 209, 210t, 243, encephalitis, 52, 61
244 pathogenesis of, 52
in pediatric patients, 240 furious, 57
spinal epidural abscess, 165 incubation period for, 57
postoperative, 175 mortality rate for, 64
spinal infection, 27 paralytic, 57
subdural empyema, 26 post-exposure prophylaxis, 57, 62t, 63
surgical site infection, 200 prevention of, 62t, 63
vertebral column infection, 151, 153 sources of, 57
Proptosis, with infectious intracranial survival, 57–58
aneurysm, 140 transmission of, 57
Proteus spp. treatment of, 58, 62t
brain abscess, 24, 95 Milwaukee protocol for, 57–58
310 shunt infection, 209, 210t Radiation, and surgical site infections, 197
Radicular pain outcomes with, 89
with spinal epidural abscess, 166 pathogenesis of, 87–88
with vertebral column infection, 150 spinal involvement in, 87–89
Radiology, 35–48. See also Imaging treatment of, 88–89
Radionuclide imaging SEA. See Abscess(es), spinal epidural
of cerebral abscess, in pediatric patient, 235 Secondary lymphoid tissue chemokine, 9–10
of spinal epidural abscess, 167 Seizure(s). See also Epilepsy
of vertebral column infection, 154–155 with amebiasis, 90
Ramichloridium mackenziei, 73 with bacterial brain abscess, 101
Rash, in bacterial meningitis, in infants/ with bacterial meningitis
young children, 114 in adults, 114
Red man syndrome, 31 in elderly, 114
Renal failure in infants/young children, 114
and spinal epidural abscess, 164, 164t with cranial epidural abscess, 126
and vertebral column infections, 147 with fungal brain abscess, 73–74
Reye syndrome, 54 with HSV encephalitis, 64
Rheumatic heart disease, and infectious with infectious intracranial aneurysms,
intracranial aneurysm, 139, 139t 139, 139t
Rhizomucor spp., 250–251 with neonatal meningitis, 114
Rhizopus spp., 71, 250–251 with schistosomiasis, 88
Rhizopus arrhizus, 72 with shunt infection, 210
Rhizopus oryzae, 72 with subdural empyema, 126
Rifampin, for amebiasis, 91 with viral infection, 61, 64
Roundworm(s), 81t Selectin(s), and tethering and rolling of
leukocytes on endothelium, 8
S Septicemia, with spinal epidural abscess, 166
St. Louis encephalitis virus Serratia spp., infection of DBS hardware, 222
encephalitis, 25t Serratia marcescens, in infectious intracranial
infection, 55–56, 56t aneurysms, 138
mortality rate for, 64 Shaving, of surgical site, 198–199
meningitis Shunt infection
Index
diagnostic tests for, 18t Candida-related, 73
risk factors for, 18t treatment of, 77
Salmonella spp. clinical presentation of, 210
meningitis, 108, 111 diagnosis of, 21–22, 210–211
spinal epidural abscess, 165 epidemiology of, 209
vertebral column infection, 149 fungal, 210
Sappinia diploidea, 89 imaging of, 211
Scedosporium spp., brain abscess, 26t management of, 211–213
Scedosporium apiospermum, 72, 74 microbiology, 21, 209–210, 210t
hyphae of, 77 outcomes with, 213–214
Scedosporium prolificans, hyphae of, 77 pathogenesis of, 209–210
Schistosoma haematobium, 87–88, 258 in pediatric patients, 239–244
Schistosoma intercalatum, 87 clinical presentation of, 240
Schistosoma japonicum, 87–88, 258 diagnosis of, 241
Schistosoma mansoni, 87–88, 258 epidemiology of, 239
spinal epidural abscess, 174 fungal, 240–241
Schistosoma mekongi, 87 health care costs of, 239
Schistosomiasis, 81t, 87–89, 254 laboratory investigation, 241
clinical presentation of, 88 management of, 241–244
diagnosis of, 88 microbiology, 240
epidemiology of, 87 postoperative, 240
etiology of, 87–88 prevention of, 241–242
in immunocompromised patients, 258 reinfection, 243
mortality rate for, 87 sequelae, 239 311
Shunt infection (continued) Spinal cord
polymicrobial, 209–210, 210t cysticercosis and, 82
prevention of, 214 intramedullary abscess. See Abscess(es),
antibiotic prophylaxis for, 190–191 spinal intramedullary
risk factors for, 209 viral infection and, 51
Shunt nephritis, 240 Spinal epidural abscess. See Abscess(es),
Shunt tap, 211, 241 spinal epidural
Shunt tubing, antibiotic-impregnated, 33 Spinal epidural catheter, and infection, 175
Sickle cell disease, and vertebral column Spinal instrumentation
infection, 149 and epidural abscess, 174–175
Single-photon emission computed infections associated with, 214–219
tomography (SPECT), of vertebral classification of, 214, 215t
column infection, 154–155 clinical presentation of, 217
Sinusitis, 137f epidemiology of, 214–216
and cranial epidural abscess, 128t, 234 imaging of, 217–218, 217f
and focal intracranial infectious lesions, in laboratory investigation, 217
pediatric patients, 234 microbiology, 216–217
and infectious intracranial aneurysm patient-related factors and, 214–216
formation, 137 prevention of, 215–216
intracranial complications, in pediatric procedure-related factors and, 216
patients, 45–46, 234 risk factors for, 214–216
in neurologic ICU patient, 282 treatment of, 218–219
recurrent, and bacterial brain abscess, 97 work-up for, 217–218
and subdural empyema, 125, 127t Spinal nerve block, and spinal epidural
Sinus tenderness abscess, 164t
with cranial epidural abscess, 126 Spinal neurosurgery, antibiotic prophylaxis
with subdural empyema, 126 in, 191–192
Skin flora. See also specific bacteria Spinal subdural abscess. See Abscess(es),
infection of DBS hardware, 222 spinal subdural
and shunt infection, 210 Spine, surgical site infections, risk factors for,
Skin infection, and vertebral column 148
Index
infections, 149 Spirochetes

Skin lesions, in amebiasis, 90 diagnostic tests for, 18t
Solid organ transplant recipient(s). See also risk factors for, 18t
Organ transplant recipient(s) Spondylitis, tuberculous, 27
infections in, 264–265 diagnosis of, 153
Space-occupying lesions, in fungal infections, Spondylodiskitis, pyogenic, 147. See also
248–249 Vertebral column infection(s)
Spastic paraparesis. See also Tropical spastic antibiotic therapy for, outcomes with, 159
paraparesis (TSP) diagnosis of, 27
HTLV-2 and, 59 microbiology, 27
Specimen(s), for diagnosis mortality rate for, 159
collection of, 16 Sporothrix schenckii, meningitis
selection of, 16 diagnostic tests for, 23t
Speech difficulty risk factors for, 23t
with infectious intracranial aneurysms, Sporotrichosis, diagnosis of, 73
139, 139t Sputum culture, in infectious intracranial
with subdural empyema, 126 aneurysms, 138
Spinal canal infection(s), 163–181. See SSIs. See Surgical site infection(s)
also Abscess(es), spinal epidural; SSPE. See Subacute sclerosing
Abscess(es), spinal intramedullary; panencephalitis (SSPE)
Abscess(es), spinal subdural Staphylococci (Staphylococcus spp.)
imaging of, 163 brain abscess, 95, 97–98
microbiology, 163 coagulase-negative
312 risk factors for, 163 infection of DBS hardware, 222
meningitis, 19 surgical site infection, 217
diagnostic tests for, 18t, 23t Staring eyes, in bacterial meningitis, in
risk factors for, 18t, 23t infants/young children, 114
organ/space surgical site infection, 202 Steroid(s). See also Dexamethasone
shunt infection, 21, 209–210, 210t, 243 for amebiasis, 91
spinal infection, 27 for cerebral edema
surgical site infection, 200 with bacterial abscess, 100
vertebral column infection, antibiotic in fungal infection, 79
treatment of, 158 for cysticercosis, 83
and cranial epidural abscess, 128t for schistosomiasis, 89
endocarditis, and CNS infection, 110 for spinal intramedullary abscess, 179
in infectious intracranial aneurysms, 138, and surgical site infections, 197
138t Stitch abscess, 201
spinal intramedullary abscess, 177 Streptococci (Streptococcus spp.)
subdural empyema, 26 aerobic
and subdural empyema, 127t and cranial epidural abscess, 128t
Staphylococcus aureus. See also Methicillin- and subdural empyema, 127t
resistant Staphylococcus anaerobic/microaerophilic
aureus (MRSA); Vancomycin- and cranial epidural abscess, 128t
intermediate Staphylococcus aureus and subdural empyema, 127t
(VISA); Vancomycin-resistant brain abscess, 24, 26t, 95, 96, 98f
Staphylococcus aureus (VRSA) diskitis, 149
brain abscess, 24, 26t group A, meningitis, 108, 110
diskitis, 149 group B
hardware infection, 22 meningitis, 108, 110
infection of DBS hardware, 222, 223 neonatal, 107, 108t, 110
in infectious intracranial aneurysms, 138, treatment of, 117
138t and subdural empyema, 127t
meningitis, 19, 110 a-hemolytic
diagnostic tests for, 18t and cranial epidural abscess, 128t
risk factors for, 18t in infectious intracranial aneurysms, 138
Index
methicillin-sensitive, antibiotics for, 30 and subdural empyema, 127t
organ/space surgical site infection, 202 g-hemolytic, in infectious intracranial
postoperative vertebral column infection, aneurysms, 138
150 in infectious intracranial aneurysms, 138,
shunt infection, 21, 190, 209, 210t, 243, 138t
244 meningitis, 19
in pediatric patients, 240 spinal epidural abscess, 165
spinal epidural abscess, 164–165 spinal intramedullary abscess, 177
postoperative, 174 subdural empyema, 26
spinal subdural abscess, 176 vertebral column infection, antibiotic
spinal subdural empyema, 27 treatment of, 158
spondylodiskitis, 27 viridans group, shunt infection, 209, 210t
surgical site infection, 200, 216 Streptococcus agalactiae, meningitis, 108,
vertebral column infection, antibiotic 110
treatment of, 158 diagnostic tests for, 18t
vertebral osteomyelitis, 27, 149 neonatal, 107
Staphylococcus epidermidis risk factors for, 18t
infection of DBS hardware, 222 Streptococcus bovis, in infectious intracranial
in infectious intracranial aneurysms, 138 aneurysms, 138
postoperative vertebral column infection, Streptococcus milleri, brain abscess, 95
150 Streptococcus mitis, in infectious intracranial
shunt infection, 190, 209, 210t aneurysms, 138, 138t
spinal epidural abscess, 165 Streptococcus mutans, in infectious
postoperative, 174–175 intracranial aneurysms, 138, 138t 313
Streptococcus pneumoniae polymicrobial, 26
in infectious intracranial aneurysms, 138 postoperative, 26, 127t, 202–203, 202f,
meningitis, 19, 108, 108t, 109 203f
and cochlear implant, 113 posttraumatic, 26, 127t
diagnostic tests for, 18t, 20 prognosis for, 131
in immunodeficient patients, 113 retrograde thrombophlebitis and, 125
risk factors for, 18t risk factors for, 26, 125
treatment of, 117 sequelae, 131
shunt infection, 209, 210t, 243 sinusitis and, 125, 127t
spinal epidural abscess, 165 sources of, 127t
and subdural empyema, 127t spinal
vaccine against, 107, 109 diagnosis of, 27
Streptococcus pyogenes microbiology, 27
in infectious intracranial aneurysms, 138 and suppurative intracranial
meningitis, 108, 110 thrombophlebitis, 27
Streptococcus sanguinis, in infectious surgical management of, 131
intracranial aneurysms, 138, 138t treatment of, 129–131
Streptococcus sanguis, shunt infection, 243 tuberculous, 125
Streptococcus viridans work-up for, 126
in infectious intracranial aneurysms, 138, Subdural infection(s), 125–132
138t Sulfadiazine, for amebiasis, 91
spinal epidural abscess, 165 Sulfa drugs, for amebiasis, 91
Strongyloides stercoralis, 254, 257 Sulfur granules, 172
Strongyloidiasis, in immunocompromised Surgery. See also Neurosurgery
patients, 257 for DBS hardware-related infection, 223–224
Subacute sclerosing panencephalitis (SSPE), for infectious intracranial aneurysm,
65 142–143, 142t, 144f
Subarachnoid hemorrhage intracranial, and bacterial brain abscess,
in aspergillosis, 71 97
with ruptured infectious intracranial for intracranial abscesses, in pediatric
aneurysm, 139t, 140, 140f patients, 237–239, 239f
Index
Subdural effusion(s) prior spinal, and spinal epidural abscess,

computed tomography of, 35 164t
in pediatric patients, 45, 234–235 for shunt infection, 211–213
Subdural empyema, 37, 111, 125 spinal, epidural abscess after, 174–175
in bacterial meningitis, in elderly, 114, for spinal epidural abscess, 169–170, 171
115f for spinal intramedullary abscess, 178, 179
clinical features of, 126 for spinal subdural abscess, 177
computed tomography of, 35, 127, 128f for subdural empyema, 203
and cranial epidural abscess, 27 in treatment of infection, 30
diagnosis of, 126 for vertebral column infection, 147,
epidemiology of, 125 155–157, 157f
imaging of, 126–129, 128f Surgical site, shaving of, 198–199
laboratory investigation, 126 Surgical site infection(s), 196. See also
magnetic resonance imaging of, 36, 36f, Spinal instrumentation, infections
129 associated with
microbiology, 26, 127t classification of, 199, 214
mortality rate for, 131 in cranial surgery, 199–200
osteomyelitis and, 125 extradural, 199
pathogenesis of, 125 hair removal and, 198–199
pathophysiology of, 125 imaging of, 46, 200
in pediatric patients, 46, 233–239, 234 incisional, 199, 200–201
medical management of, 236, 237f deep, 201, 214, 215t
surgical management of, 237–239 superficial, 200–201, 214, 215t
314
intradural, 199 Toxoplasmosis, 81t
in lumbar spine, 214, 215f brain abscess in, 24, 26t, 96, 97f
microbiology, 200 and Chagas disease, 257
organ-related (organ/space), 199, 200, 202, in HIV-infected (AIDS) patients, 259
214 in HSCT recipient, 264
CDC definition, 202 imaging in, 42, 44f
microbiology, 202 in immunocompromised patients, 254–255,
risk factors for, 197–198 256f
patient-related, 197 immunology, 26
procedure-related, 197–198 in organ transplant recipient, 263
risk for, estimating, 199 spinal intramedullary abscess, 177
spinal instrumentation-related, 214, 215f Transmissible spongiform encephalopathy
time to manifestation, 200 (TSE), 59–60
underreporting of, 199–200 clinical presentation of, 59–60
Suture(s), antibiotic-coated, 33 diagnosis of, 60
Syndrome of inappropriate antidiuretic iatrogenic, 59–60
hormone secretion (SIADH), in viral mortality rate for, 64
infection, 64 prevention of, 60
Syphilis. See also Neurosyphilis; Treponema Transplant recipient(s). See
pallidum Immunosuppressed patient(s);
meningovascular, 19 Organ transplant recipient(s)
Transverse myelitis. See Acute transverse
T myelitis
Taenia solium, 42, 81, 256. See also Trauma
Cysticercosis penetrating
life cycle of, 82 and cranial epidural abscess, 128t
Tapeworm(s), 81t and subdural empyema, 127t
Target sign, in toxoplasmosis, 42 and spinal epidural abscess, 164t
T cells (T lymphocytes) and vertebral column infections, 148, 149
in cerebrospinal fluid, 6 Treponema pallidum. See also Syphilis
migration into CNS, 4–5, 5–6, 6–7 diagnostic tests for, 18t
Index
routes for, 7 meningitis, 19
recruitment into central nervous system, diagnostic tests for, 21
7–9 risk factors for, 18t
transendothelial migration into CNS, 7–9, Trimethoprim-sulfamethoxazole,
8f prophylactic, in neurosurgery, 187
Tetracycline Tropical spastic paraparesis (TSP), 58–59
for amebiasis, 91 Trypanosoma cruzi, 257
resistance to, 31, 32t brain abscess, 25
Thrombophlebitis, suppurative intracranial in organ transplant recipients, 265
diagnosis of, 27 Trypanosomiasis, 81t, 254
microbiology, 27 TSE. See Transmissible spongiform
Tick(s), and viral infection, 56–57, 56t encephalopathy (TSE)
Tickborne encephalitis virus, 56t TSP. See Tropical spastic paraparesis (TSP)
Tissue culture, in vertebral osteomyelitis, 27 Tuberculin skin test, 23, 152–153
TLRs. See Toll-like receptor(s) (TLRs) Tuberculosis. See also Mycobacterium
Tobacco use, and surgical site infections, 197 tuberculosis; Pott disease
Tobramycin, 32t antibiotic treatment of, 158
Toll-like receptor(s) (TLRs), signaling defects, in HIV-infected (AIDS) patients, 259,
and viral infection, 60 260–261
Tonsillitis, and infectious intracranial spinal, 173
aneurysm formation, 137 meningitis. See Meningitis, tuberculous
Torulopsis glabrata, 69 and neurocysticercosis, concomitant, 43
Toxoplasma spp. See Toxoplasmosis in organ transplant recipient, 263
315
Tuberculosis (continued) CNS infection, 54
in organ transplant recipients, 264–265 diagnosis of, 62t
spinal, 147, 148f prevention of, 62t
treatment of, 173 and seizures, 64
spinal epidural abscess, 172–173 treatment of, 62t
subdural empyema, 125 encephalitis, 25t, 54
treatment of, 117–118, 158, 173 meningitis, 54
vertebral column infection, 149, 155. See diagnostic tests for, 18t, 20
also Spondylitis, tuberculous risk factors for, 18t
antibiotic treatment of, 158 Vascular anatomy, of central nervous system,
3–4
U Vasculitis
Ultrasound, 35 in amebiasis, 90
of intraparenchymal abscess, in pediatric in cysticercosis, 82, 83
patient, 235 and infectious intracranial aneurysms, 136t
of pediatric patients, 44–45 in schistosomiasis, 88
of subdural effusion, 234 vCJD. See Creutzfeldt-Jakob disease (CJD),
Urinary catheter(s), in neurologic ICU variant
patient, management of, 279 VDRL. See Venereal Disease Research
Urinary incontinence, with spinal epidural Laboratory (VDRL) test
abscess, 166 Venereal Disease Research Laboratory
Urinary retention, with spinal epidural (VDRL) test, cerebrospinal fluid, 21
abscess, 166 Venezuelan equine encephalitis (VEE) virus,
Urinary tract infection(s) (UTI) 55, 56t
and infectious intracranial aneurysms, Ventricular drain
136t antibiotic prophylaxis and, 189–190
in neurologic ICU patient, 278–280 external, with bacterial brain abscess, 101,
signs and symptoms, 278, 278t 101f
and vertebral column infections, 149 Ventricular empyema, shunt and, 47
US. See Ultrasound Ventriculitis
UTI. See Urinary tract infection(s) (UTI) acute, 19–21
Index
with bacterial brain abscess, 101

V in bacterial meningitis, in elderly, 114,
Vaccine(s) 115f
against bacterial infections, 107 chronic, 22–24
against viral infections, 62t, 63–64 in neurologic ICU patient, 275
Vacuum-assisted closure (VAC), for spinal postoperative, 202, 204
surgical wound, 155, 218 in Scedosporium infection, 72
Valvular heart disease, and infectious shunt and, 47
intracranial aneurysm, 139, 139t Ventriculoatrial shunt, infection, 240
Vancomycin, 32t pathogenesis of, 210
with gentamicin, prophylactic, in rates of, 209
neurosurgery, 187 Ventriculoperitoneal shunt. See also
penetration of blood–brain barrier, 31 Cerebrospinal fluid (CSF) shunt
prophylactic, in neurosurgery, 187 infection, 47
and red man syndrome, 31 pathogenesis of, 210
Vancomycin-intermediate Staphylococcus rates of, 209
aureus (VISA), 31 Ventriculopleural shunt, infection, rates of, 209
Vancomycin-resistant enterococci (VRE), 31 Vertebral column, vascular anatomy, 149
Vancomycin-resistant Staphylococcus aureus Vertebral column infection(s), 147–162. See
(VRSA), 31 also Diskitis; Osteomyelitis, spinal
VAP. See Pneumonia, ventilator-associated (vertebral); Spondylodiskitis
Varicella-zoster virus (VZV) clinical presentation of, 150–151
acute transverse myelitis, 52, 54 demographics, 147–148
316
diagnosis of, 151–155 with schistosomiasis, 88
differential diagnosis, 151 with shunt infection, 210
epidemiology of, 147–148 with subdural empyema, 126
etiology of, 148–150 Voriconazole
imaging of, 153–155, 154f for aspergillosis, 78, 250
incidence of, 147–148 for Scedosporium brain abscess, 79
laboratory investigation, 151–153 VRE. See Vancomycin-resistant enterococci
microbiology, 148–150 (VRE)
misdiagnosis of, 151 VRSA. See Vancomycin-resistant
outcomes with, 159 Staphylococcus aureus (VRSA)
pathogenesis of, 148–150 VZV. See Varicella-zoster virus (VZV)
postoperative, 149–150
microbiology, 150 W
outcomes with, 159 Weakness, with spinal epidural abscess, 166
pain in, 151 Western equine encephalitis (WEE) virus,
prevention of, 150 infection, 55, 56t
risk factors for, 147–148, 150 mortality rate for, 64
treatment of, 155, 156–158 West Nile virus
radiographic signs of, 153 acute transverse myelitis, 52
risk factors for, 147 CNS infection, 51, 55, 56, 56t
treatment of, 155–159 encephalitis, 25t, 51
Vertebroplasty, infection after, 176 infection, T cells in, 7
Vertical laminar airflow, 150 meningitis
Vicryl Plus, 33 diagnostic tests for, 18t
Viral infection(s), 51–67. See also specific risk factors for, 18t
infection meningoencephalitis, 19
clinical presentation of, 60–63 White blood cell count
complications of, 64–65 with spinal epidural abscess, 166–167
in HSCT recipients, 264 with spinal surgical site infection, 217
mosquito-borne, 51 with vertebral column infection, 152
Index
prevention of, 62t, 63–64 WNV. See West Nile virus
prognosis for, 64–65 Wound(s)
risk factors for, 60 classification of, 198
sequelae, 64–65 closure, hair management in, 199
treatment of, 61, 62t, 63–64 dirty or contaminated, 188, 198
VISA. See Vancomycin-intermediate Wound drainage, with postoperative
Staphylococcus aureus (VISA) vertebral column infection, 151
Vision Wound infection. See also Surgical site
decreased infection(s)
with chronic meningitis, 73 after spinal surgery, 174
with subdural empyema, 126 CDC criteria for, 200
double, in chronic meningitis, 73 postoperative, 126
Visual field defects, in bacterial meningitis,
in adults, 114 X
Vomiting X-linked agammaglobulinemia, and viral
with amebiasis, 90 infection, 60
with bacterial brain abscess, 98
with bacterial meningitis, in infants/young Z
children, 114 Zidovudine, for HTLV-1 infection, 59, 62t
with chronic meningitis, 73 Zygomycosis, in immunocompromised
with cranial epidural abscess, 126 patients, 250–251
with infectious intracranial aneurysms,
139, 139t
317

Foc

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Foc

Uploaded by

Copyright:

Available Formats

Neurosurgical Infectious Disease

Surgical and Nonsurgical Management

Walter A. Hall, MD, MBA

Peter D. Kim, MD, PhD

Executive Editor: Kay Conerly

Library of Congress Cataloging-in-Publication Data

Also available as an e-book:

II Etiologic Agents

IV Neurosurgical Issues

Ian Mutchnick and Thomas M. Moriarty

Ali Akhaddar, MD Zvi R. Cohen, MD

Kunal M. Patel, MD Dino Terzic, MD

Roberto Spiegelmann, MD Peter C. Warnke, MD

blood molecules are prevented from enter-

1 Immunology of the Central Nervous System

deficient mice, which significantly reduced different T-cell-receptor (TCR) specificities,

1 Immunology of the Central Nervous System

Natural Killer (NK) Cells Tethering and Rolling of Leukocytes on

1 Immunology of the Central Nervous System

1 Immunology of the Central Nervous System

immune responses in brain is promoted by local Neuroscience 1985;15(2):313–326 PubMed

1 Immunology of the Central Nervous System

vasc Res 1996;32(4):733–742 PubMed 7118–7122 PubMed

1 Immunology of the Central Nervous System

The central nervous system (CNS) may Cerebrospinal Fluid

WBC count Primary Glucose Protein

Normal range 0–5a 0.6b < 50

2 Microbiological Diagnosis of Central Nervous System Infections

Acute bacterial meningitis 1,000–5,000 Neutrophilic < 40 100–500

Neurosyphilis >10 Mononuclear Decreased Elevated

Lyme meningitis < 500 Mononuclear Normal < 620

Primary amebic meningoencephalitisc Elevated Neutrophilic Decreased Elevated

Angiostrongylus cantonensis meningitis Elevated Eosinophilic Normal Elevated

Tuberculous meningitis 50–300 Mononuclear < 45 50–300

Cryptococcal meningitis 20–500 Mononuclear < 40 > 45

Coccidioidal meningitis < 700 Mononuclear or Decreased Elevated

-8), cause aseptic meningitis and encephali-

2 Microbiological Diagnosis of Central Nervous System Infections

HSV-1, HSV-2, VZV PCR

CMV Immunocompromised PCR

Epstein-Barr virus Immunocompromised PCR

Mumps virus Unimmunized Complement fixation,

West Nile virus United States WNV-specific IgM

HIV Sexual contact, HIV ELISA (negative

Streptococcus pneumoniae Bacterial culture Blood culture

Neisseria meningitidis Bacterial culture Blood culture

Streptococcus agalactiae Bacterial culture

Haemophilus influenzae Bacterial culture

Listeria monocytogenes Bacterial culture Blood culture

Staphylococcus aureus Surgical procedures Bacterial culture

Coagulase-negative Surgical procedures Bacterial culture

Gram-negative rods Surgical procedures Bacterial culture

Propionibacterium acnes Surgical procedures Bacterial culture

Mycobacterium tuberculosis Prior residence or travel AFB culture

Treponema pallidum Sexual contact VDRL

Borrelia burgdorferi Tick bite Western blot ELISA (screening)

Naegleria fowleri Swimming in freshwater CSF wet mount, PCR

Angiostrongylus cantonensis Travel history to the South Microscopic exam

Immunology Cerebrospinal Fluid Culture

Paired serology is diagnostic for herpes

2 Microbiological Diagnosis of Central Nervous System Infections

2 Microbiological Diagnosis of Central Nervous System Infections

Actinomyces Immunocompromise, Anaerobic culture Pathology

Nocardiaa Immunocompromise Culture

the diagnosis may be missed using routine ■■ Subdural Empyema/

■■ F ocal Central Nervous acterized pathologically by tissue