General paralysis of the insane, a syndrome of mental disorder and weakness occurring in tertiary syphilis, is also known as dementia paralytica, Bayle disease, parenchymal syphilis and symptomatic neurosyphilis.  It is a rare disease in western general adult psychiatry these days but, at the height of its powers, it is thought that it accounted for up to 20% of patients in asylums.  

In brief: syphilis is a chronic sexually transmitted disease, caused by the bacterium Treponema pallidum, resulting in the formation of lesions throughout the body.  As well as being sexually transmitted the infection can also be transmitted from mother to the developing fetus (congenital syphilis). 

The primary symptom is a hard ulcer (chancre) at the site of infection (i.e the penis or vagina) and this forms 2-4 weeks following exposure.  Secondary symptoms develop about two months after this infection and include fever, malaise general enlargement of lymph nodes and a faint red rash on the chest.  Then, after a period of time somewhere between some months to many years the disease enters its tertiary phase with widespread formation of tumour like masses (gummas).  These can cause serious damage to the heart or blood vessels (cardiovascular syphilis) or to the brain (neurosyphilis) resulting in tabes dorsalis, blindness and general paralysis of the insane. 

The onset of GPI is usually gradual with depression as the dominant symptom.  There is then a slowly progressive memory and intellectual impairment.  Frontal lobes are particularly involved, resulting in characteristic personality change with disinhibition, uncontrolled excitement and over activity which may be mistaken for hypomania.  Grandiose delusions are present in 10%.  Physically there is slurred speech, a tremor of the lips and tongue, and Argyll Robinson pupil** in 50%.  As the condition progresses there is increased leg weakness leading to spastic paralysis. Patients become completely incapacitated, bedridden, and die, the process taking about three to five years on average.

The first clearly identified examples of paresis among the insane were described in Paris after the Napoleonic wars and general paresis of the insane was first described as a distinct disease in 1822 by Antoine Laurent Jesse Bayle.  Originally, the cause was (charitably) believed to be an inherent weakness of character or constitution.  While Esmarch and Jessen had asserted as early as 1857 that syphilis caused general paresis, progress toward the general acceptance by the medical community of this idea was only accomplished later by Alfred Fournier. In 1913 all doubt about the syphilitic nature of paresis was finally eliminated when Noguchi and Moore demonstrated the syphillitic spirochaetes in the brains of paretics.

In 1927 Julius Wagner-Jauregg was given the first and only Nobel Prize awarded to a psychiatrist.  This was for work done in 1917 by which time he had been selflessly studying the the relationship between fever and psychosis 30 years.  Wagner-Jauregg had exposed three neurosyphilitic patients to malaria drawn from the blood of a wounded soldier.  The resulting high fever killed the syphilis spirochetes, leading to their recovery (the fate of the soldier is not recorded).  Given that there were few cures for anything in 1917, Wagner-Jauregg’s achievement was a milestone in psychiatric and medical science.  There was now a reliable, albeit risky, cure for neurosyphilis.

After WWII the use of penicillin to treat syphilis has made general paresis a rarity and now even patients manifesting early symptoms of actual general paresis are capable of full recovery with a course of penicillin. The disorder is now virtually unknown outside  third world countries, although it has been reported in western HIV sufferers.   I was recently told by someone who should know about these things, that it is no longer routine to test for syphilis in sufferers of dementia. 

If you can get hold of it Hare (1959) has written an interesting historical analysis. 

Trivia: 
Murderous Ugandan dictator Idi Amin is thought to have died from neurosyphilis

Also check out:
Tuskegee Syphilis Study - a clinical study, conducted between 1932 and 1972 in Tuskegee Alabama in which 399 poor and mostly illiterate African Americans were studied to observe the natural progression of the syphilis if left untreated.  Wikipedia page / List Universe: Top ten evil human experiments #3

* I’ve always thought this is an extremely evocative name for a disease (although I grant the use of the word ‘insane’ is archaic and potentially un-PC)

** non medics - these are known, rather tastelessly, as prostitute’s pupils as they accommodate, but don’t react (to light)… 

Frontier Psychiatrist is sick today, and has been off work.  Ordinarily I might enjoy a day in front of the television working through a box set of Prison Break but I’ve been feeling really low all day.  I knew things weren’t right when I got up this morning and and simply stared at my toast rather than eating it. 

But what better time to examine physical illnesses (’organic causes’) that cause psychiatric symptoms?

Psychiatry and physical medicine have a complicated relationship.  Psychiatric and physical disease can occur at the same time by chance or physical disease can cause psychiatric symptoms and vice versa. Psychiatric medications also have a large number of side effects.  

Whenever a patient comes into the hospital with psychiatric problems, a full ‘work-up’ should include looking for a physical cause for the problem.  Psychiatrists were a bit rubbish at doing this, but are getting better; the hospital where I work audits whether patients admitted have a physical examination whilst they are on the ward. Patients usually get blood tests and often a CT scan, especially if the presentation is atypical.

Depression has a lot of organic causes: cancer, infection, neurological disorders including dementia, diabetes, thyroid disease, Addisons disease, and systemic lupus erythematosis.  Just having one of these diseases in themselves may be a cause for depression as they can result in substantial disability.  Psychiatry blogger Lake Cocytus tells a tale of delayed diagnosis of metastatic breast cancer due to confusion with depression. 

Anxiety also has a number of organic causes: hyperthyroidism, hyperventilation, phaeochromocytoma, neurological disorders and drug withdrawal. 

Finally, psychosis may also be triggered by an organic cause and these include neurological conditions (e.g. epilepsy and strokes), metabolic conditions (e.g. porphyria), endocrine conditions (e.g. hyper- or hypothyroidism), renal failure, electrolyte imbalance (especially calcium), or autoimmune disorders.