A Dead Disease, As Illustrated By The Illness Of Georgiana, Duchess Of Devonshire I. G Schraibman, Sale, Cheshire, U.K.

This article has been posted with the permission of Dr Schraibman

Lady Georgiana Spencer (1757 – 1806) was a lovely and much-loved child. She was pretty, intelligent and confident, but at the same time respectful and obedient. In 1774 she married the most eligible bachelor in the land, the fifth Duke of Devonshire. Her family was slightly lower in social status than the Devonshires, but, far from being intimidated, she blossomed, became her own person, and was eventually known and loved not only by those of her own class but by the people of England.

She was the fashion icon of her day, the leader of the bon ton, and her raiment was the subject of discussion and imitation in all fashionable circles. She used her intelligence and position to afford considerable support to Charles Fox and the Whigs. Her only known fault was gambling, in which she was joined by most of the aristocracy, including her friend, the Prince of Wales; at one stage, Georgiana was indebted to the tune of £6,000,000 at today’s values!

In late July 1796, at the height of her powers and in excellent health, she was stricken with a severe and agonizing illness, which was thought likely to kill her. However, she made a recovery to almost complete normality over the course of many months.

The Duchess’s Illness

She had suffered from “migraine” for years, but about 26 July she was forced to bed by a particularly severe headache. Her right eye swelled to the “size of an apricot”. Dr. Warren, her personal physician, summoned three of the most widely known medical luminaries of the time, including John Gumming, Senior Surgeon to the King. They were flummoxed, but this did not inhibit them from applying increasingly desperate measures; one worthy, in an attempt to increase blood flow to the head to counteract the inflammation, squeezed her neck, almost strangling her! The only effective measure they could supply was laudanum. Her children were dispatched elsewhere so they could not hear their mother’s screams.

Although she was usually a prolific letter writer, Georgiana was beyond such communication; neither are there letters from friends or the doctors. The only clear account available is by Lady Spencer, her mother, who wrote on 4 August, after a visit:

“the inflammation has been so great that the eye, the eyelids and the adjacent parts were swelled to the size of your hand doubled and projecting forwards from the face …. a small ulcer has formed on top of the cornea and has burst and as far as that reaches the injury is not to be recovered – if the inflammation should increase, the ulcer form again, and again burst, it would destroy the whole substance of the eye, which would then sink …… The eyelids are still much swelled and scarred with the leeches and the little opening between them is always filled with a thick white matter.”

She went on to praise her daughter’s stoicism, reporting that Georgiana “had prayed most earnestly for a perfect submission to God’s will”.

The Diagnosis

The dominant symptoms of severe headache followed byproptosis, chemosis of the eyelids and loss of vision suggested cavernous sinus thrombosis (CST). Differential diagnosis includes orbital cellulitis, orbital tumor, severe sinusitis and possibly carotid cavernous fistula. Orbital cellulitis does not cause proptosis. An orbital tumor is unlikely because of the almost complete recovery. She was not known to suffer from pre-existing sinus trouble and there is no record of any infective locus in the head and neck. A fistula is possible, as these often thrombose spontaneously, but there is no record of the characteristic pulsating exophthalmos, although this could have been missed.

Cavernous Sinus Thrombosis

The cavernous sinuses lie on each side of the pituitary fossa, connected by the intercavernous sinuses in front of and behind the pituitary stalk. they are connected to the other dural sinuses and drain into the internal jugular vein. Their extracranial connections are most important because they drain he face in the area supplied by the maxillary and ophthalmic divisions of the trigeminal nerve and communicate with the veins surround the ear via the pterygoid plexus. In the lateral wall of the cavernous sinus run the second, third and fourth cranial nerves and the maxillary division of the fifth; in the centre is the carotid artery, below which is the sixth cranial nerve, supplying the rectus externus. There must have been a lapse in evolutionary design to route the venous drainage of the most bacteria-ridden sites in the head and neck into the cranial cavity.

Clinical Course

The first symptom is unrelenting headache with vomiting. Proprosis and chemosis appear soon and abducens paralysis is invariably the first neurological sign, followed by ophthalmoplegia and corneal ulceration. If the interior can be visualized, papilloedema, venous congestion and haemorrhages can be seen. Thrombosis of the jugular veins may supervene, if the patient does not perish from septicaemia first. The causative organisms are Staphylococcus aureus, S. haemolyticus and pneumococci.

The condition was first reported at postmortem by Duncan in 1821 and in vivo by Vigla in 1839. An estimated 300 cases had been reported by 1918, 350 by 1931 and 40 by 1936. A distinction was made between fulminant and non-fulminant cases, with a better prognosis in the latter. The overall survival was said to be 7% but the range quoted from world literature was 5 – 16%, the majority of reports were under 10%. Fifty-eight recoveries were recorded up to the time of the 1936 review. Only eight cases were recorded in 6,250 general admissions; of these, plus four others, only one survived. Although a relatively rare condition, CST was rightly feared in pre-antibacterial days.

Cavernous Sinus Thrombosis – A Dead Disease

Medical students of 50 years ago were warned of the danger of interfering with minor infective lesions in the area of distribution of the maxillary and ophthalmic nerves (the “dangerous area of the face”), and this lesson is still carried in some anatomical texts but no longer in clinical ones. A symposium held at the Royal Society of Medicine, the proceedings of which were published in 1998, on the subject of cerebral thrombosis makes no mention of CST. It is not mentioned in four current textbooks of medicine (Oxford Textbook of Medicine, 1996; Rees and Williams, 1995; Principles of Internal Medicine, 1998; Internal Medicine, 1994). A survey of the Index Medicus throughout its years of publication (1879 – 1999) was carried out; it is very difficult to be precise as to the numbers of references to CST before 1918, but in that year 12 references are found, rising to 38 in 1930 but then falling to 20 in 1942, 14 in 1948, 6 in 1960, and only 1 in 1969; after this there are none at all.

The first antibacterial agent, Prontosil, was introduced in 1933, but it was toxic and was soon replaced with safer sulphanilamide, but even in 1940 only 5 of 12 cases were treated with this substance. The first recorded use of sulphanilamide in CST was in 1939 and the first use of penicillin was in 1944.

Since then, widespread use of antibiotics in the early stages of infectivity in the head and neck has eliminated CST from the medical lexicon, in parallel with the decline of severe middle-ear disease, mastoiitis and purulent sinusitis. A feared killer has been vanquished.

Conclusion

At the age of 35, Georgiana developed a serious and life-threatening condition of her right eye (the left was involved to a lesser degree), which, from the description provided by her mother and the knowledge subsequently accumulated, was most likely to be CST. In view of her survival against long odes, it must have been of the non-infective variety. This disease has disappeared from modern medical experience owing to the availability of antibiotics and their application at the early stage of infective conditions of the head and neck.

Acknowledgements: I would like to congratulate and thank Amanda Foreman for her superb biography of Georgiana, which first aroused my interest in this subject. I would like to thank the Trustees of the Chatsworth Settlement for permission to reproduce Figures 1 and 2 and Churchill Livingstone for Figures 3 and 4. Mr. Peter Blore of the Media Centre, Manchester University, exercised his considerable skills to help in producing the illustrations.

References

1. Foreman A. Georgiana, Duchess of Devonshire. London: Harper Collins, 1998.

2. Lady Margaret Spancer, 1796, paper No. 1357, Chatsworth Collection, courtesy of the Trustees.

3. Duncan, A. Contribution to Morbid Anatomy. Edinburgh, 1821: 17,334.

4. Vigla EN. De la Morse Algue chez l’homme. Theses de l’Ecole de Medecine, Paris, 1839.

5. Smith D. Cavernous sinus thrombosis with notes of five cases. Arch Ophthalmol 1918;47;482-93.

6. Brown, WGS. Cavernous sinus thrombosis. Lancet 1931; 960-5.

7. Grove WE. Septic and aseptic types of cavernous sinus thrombosis. Arch Otolaryngol 1936; 24; 29 – 50.

8. Chisholme JJ, Watkins SS. Twelve cases of thrombosis of the cavernous sinus. Arch Surg 1920; 1; 483 – 512.

9. Pirkey WP. Thrombosis of the cavernous sinus. Arch Otolaryngol 1950;51; 917 – 24

10. Journal of Medical Biography