in Misc.

General paralysis of the insane* and psychiatry’s only Nobel Prize


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

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)… 


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  1. Love the ‘prostitute’s pupils’… definately a little nugget of knowledge to be stored :>

    Would it be fair to say that the symptoms of syphilis could be similar to those experienced by some people with brain tumours caused by, say, cancer? On reading your comments, it sounded like the physical problem within the brain – i.e. a mass that shouldn’t be there – is presumably the same in both cases. But I don’t think I’ve ever heard about people with brain tumors becoming insane. Or is that because it would be ‘un-PC’ to talk about it?

  2. It is interesting how many people from history are now being retrospectively diagnosed with neurosyphilis, like Hitler.

  3. You are a charlatan. Give up psychiatry and do something ethical.
    You are a pseudoscientist and a fascist. Shame on you.

  4. northernirelandexile:

    Different parts of the brain do different things, therefore the effect of a brain tumour will be related to the part of the brain that is affected. A tumour of the frontal lobes can cause psychiatric symptoms, with tumours of other parts of the brain this is less likely. Syphilis used to be known as ‘The Great Mimicker’ for its wide variety of clinic manifestations, so without modern scanning techniques (and a syphilis test) it would be difficult to tell GPI and a brain tumour apart.


    I am sympathetic to people who dislike psychiatrists, but there is no need to be rude. Please explain your objections more fully.

  5. Well I don’t see anything “pseudoscientific” about a thoughtful piece on the history of organic psychiatry in GPI – one of the few conditions that has a solid aetiology.

    I suspect “Sceptic”‘s agitation stems from wasting too much money on “courses”.

    Have you thought about doing a piece on cults FP?

  6. deClerambault…

    I think that you may be referring to the rabid bunch who accosted a friend and I on Tottenham Court Rd on Saturday, trying to have us attend a free screening of their own take on ‘science.’ From their pushy behaviour, I doubt that they have ever actually taken the time to consider others, so in my view – shame on them!!!

    FP – thanks for the explanation. (and for what it’s worth, I don’t think your posts are fascist, I think they are kind of fun. I only happened across this page when I was looking for the song by the Avalanches, but I enjoy reading it!)

  7. Actually, I rarely test for neurosyphilis. If one suspects it, do not use the screening test for primary and secondary syphilis—proceed directly to the MHA-TP, as the VDRL will be false 50% of the time in tertiary neurosyphilis.

  8. In repsone to one of the posts, yes, people with brain tumors can have psychotic features, psychosis being defined as a breach of reality testing—voices, visions, paranoid delusions, etc. It is, therefore, not always dramatic.

    In my experience, it does not always come at you in the media’s portrayal of psychosis, just as my work as a psychiatrist has nothing to do with the leather creaking, grandfather clock ticking portrayal of movies.

  9. You forgot the work on neurotransmission in giant squids—psychiatry’s second Nobel Prize.

  10. I think that you could argue that Moniz’s Nobel Prize in 1949 for his work on lobotomy was a Nobel Prize for psychiatry but I don’t think that neurotransmission in giant squids has had any effect on understanding of psychiatric disease…..

  11. Erik Kandel won the Nobel prize for medicine in 2000 – he is a psychiatrist. Neurotransmission has a central role in modern theory on mental illness – SSRIs etc etc.

  12. Thank you for the interesting piece, the history is fascinating! In South Africa we still routinely test all new psychiatric patients for Syphillis. It is quite common. I am currently treating a 20 year old man who has confirmed syphilitic meningitis. He presents with manic symptoms and bizarre delusions, but also has a strong history of metamphetamine abuse which may confound his current mental state. But the “great imitator” is being replaced by HIV over here.

  13. It most certainly IS still routine to test for syphilis in ALL psychiatric patients admitted to hospital whether or not they have symptoms of dementia. Syphilis can present in a variety of psychiatric symptoms including depression, mania and psychosis – not just cognitive impairment. Many cases of syphilis would still go undetected were it not routinely screened for. It has indeed made a resurgence in the last two decades. Many cases go undetected but unwittingly treated when people are given antibiotics for other ailments – thus arresting the syphilis without even knowing of the infection. There have been a good many elderly couples surprised to find that, usually, the husband was infected for decades, but the infection was never known. It is also still routine to test couples for syphilis before a marriage license is granted. And, of course, screening for syphilis is routine during pregnancy.

  14. Before a marriage licence is granted? How antiquated! If state asked to check me for syphilis test before I could get married I’d give it a miss on principle. Surely STD infection is a private matter…

  15. One of my hobbies is genealogy and I came across a death certificate from 1943 that listed cause of death as “General Paralysis of Insane”. Of course, this piqued my interest so I did a Google search and found your post. Thank you for an insightful post. The history of GPI was interesting to me since this happened in 1943 and you said, “After WWII…” So sad.

    To Frontier Psychiatrist – I would want to know if my future spouse had an STD. It’s for their own benefit as well as their future spouse and children that you would want to know. It’s not like they are going to post the results in the newspaper. Of course, I came to my husband as a trusting virgin. We’ve been married 33 yrs. Maybe there aren’t as many of those around any more. But we are still out here! 🙂

  16. Thanks for an interesting and informative post!

    My state no longer requires pre-marital screening simply because incidence is too low to justify the cost. However, syphilis was once the leading cause of death in my state and on the top 10 list for the US. Given that it could be cured, marital bloods made a great deal of public health sense – catch it (hopefully) before or soon after transmission and get rid of it. Once treated the license was issued.

    Also, fever can be a secondary symptom but isn’t always (I’ve rarely had pts recall a fever). Torso rash may or may not be present – I see far more palmer/plantar rashes than those on the torso. (I work in public health – I am not a physician or nurse.) Two months is rather minimal for secondary to appear. It can but it’s more accurate to say that secondary most often appears 4 weeks after the primary chancre resolves (the range is immediately after to 10 1/2 weeks after).

    I’m curious, Dr Joseph, how do you monitor efficacy of treatment without the VDRL or an RPR?

  17. The cause of death for my great grandfather was listed at “paralysis of the insane” He was a Civil War vet.
    How long is the dormancy possible? He died at age 47.
    His widow lived another 40 years but was blind the last 20 years of her life.

  18. Late latency (what you’re calling dormancy) can last indefinitely – some patients never enter tertiary. I had a patient for whom it lasted at least 30 years before that patient entered the tertiary stage (in that case the patient lost both hip joints).

    Just because your grandfather was infected does not necessarily mean your grandmother was. Syphilis is only infectious in the first year of infection (some authorities say two years but I’ve not seen any documented secondary cases that were so long from the date of inoculation), specifically when symptoms are present so it is quite possible for a veteran to have contracted syphilis during service and yet not passed it to his wife. There’s no way to know for certain, of course, but it is easily possible that her blindness was unrelated to syphilis.

  19. I found a death record for my great aunt showing she died from ‘General Paralysis of the Insane’, and apparently she’d had it for 11 years. My great uncle doesn’t seem to have been affected by syphilis, as he was in the army from 1911 till his death in 1917 from oedema of the glottis. I can’t help but wonder if she contracted it from my uncle, an affair, before she met him (she was almost thirty when she married him) or what. The two were only together for seven years before she was diagnosed, and apparently she’d had a child that died very young. I feel bad that she had to suffer, and for so long too.

  20. I’m sorry about your great aunt.

    There are some older texts that mention larynx involvement in tertiary (since syphilis can literally attack any part of the body in tertiary, it’s certainly plausible). It’s impossible to say for certain or even with a good guess as to the probability but it’s possible that your great uncle also died of syphilis or a complication of it.

    Tertiary has no hard and fast rules as to when it may occur. Most probably infection had been more than a year previous but even that is no guarantee. Primary and secondary are very predictable but tertiary is a wild card. It can onset quickly, slowly or not at all. As a result, it’s impossible to gauge when she might have been infected relative to anyone else.

  21. I have discovered that my grt, grt uncle died from GPI in 1917 after being discharged from the army (france) He had only been in France since March 1917, was discharged in July 1917, dying in January 1919. To me this sounds like he may have been suffering before being called up. His son died in WW2 but his daughter died in the 1953 from a brain haemorrhage,= aged 40. His grandson was born ‘deaf and dumb’. His wife wasn’t particularly young when she died, but who knows. I’m quite sad about this as his grandaughter who is in her 70’s recently contacted me through a family tree site, knowing nothing about her grandfather at all. She actually wasn’t researching him, not even knowing his name. I pointed her in his direction thinking she may be interested. I didn’t realise what GPI was, I thought it was some sort of shell shock. His grandaughter did some investigation and put me right. Poor lady. Does anyone think that he may have been infected before going to France. He seems to have been missing on most of the census except 1881 when he was two.

  22. Hi,

    It’s possible for neurosyphilis to onset within the first year of infection but that time frame is so short that if onset of tertiary (GPI in this case) was the reason for his discharge I’d expect a much earlier infection. If the GPI onset later it’s more probable that he contracted it in France but it could just as easily have been much earlier. Without his primary &/or secondary history it’s impossible to know when he contracted syphilis. If I had to guess, I’d bet on before he went to France but that’s just an educated guess based on the probabilities – it really is impossible to know for sure.

  23. Hi Phylis

    Thank you so much for your reply, you are certainly thinking along the same lines as myself.

    Last night I found records of someone matching his name and place of birth in an institution for deaf and dumb children in 1891 which may account for his absence on the census with his family. I wonder if he had other learning difficulties too. We shall never know.

    My theory, which obviously could be totally incorrect, is that something happened there or afterwards. He is still missing in 1901.

    When he signed up in 1916, we would have been in his 30’s which was strange. His records state he was only fit for home service. He married an older, widowed lady in 1911. He came from a large family who had repeatedly married into another large family (including the widow). Both families were neighbours and lived in rows of little victorian charity houses. Their lives were extremely hard. I am imagining he was only sent to France in 1917 when troops were getting thin on the ground. Poor, poor man. I cannot bear to think of how he suffered when returning home, being incarcerated in an asylum. Very interestingly, shortly after the war research was done in a clinic in our home town, namely the Mott Clinic, into the cure of Syphilis using malaria. I’m aware of the origins of the research and find it fascinating.

    Many thanks again

  24. Hi,

    You’re more than welcome.

    There may be another possibility – I didn’t really consider it last night but given his history it might – emphasis might – be possible that his wasn’t acquired syphilis but congenital. Congenital is almost a separate field and I don’t deal with it very often. I honestly don’t know if GPI could be an outcome in a congenital case – syphilis doesn’t always act the same in congenital – but I don’t know of any reason it couldn’t be. It might explain his early difficulties and why GPI onsets while he is so relatively young.

    But again, that’s mere conjecture – I don’t know how likely or even possible it would be.

    Best wishes with your studies. Merry Christmas!

  25. Hi there,

    That is a very interesting thought. This chap had 3 brothers who died in their 20’s. One had a son who died very young and I don’t, as yet know the causes of death but will delight my family over the christmas period by locating their death certificates.

    This man’s daughter died aged 40 of a brain haemorrhage and he had one grandson who died shortly after birth and a second who was born deaf and dumb.

    It’s all a bit odd but not entirely unusual given the age and conditions they lived in. I’m sort of wishing I hadn’t looked but at the same time the detective in me is rising to the fore.

    Thanks again and a merry christmas to you too!

  26. Lenin was already syphilitic when he arrived in Russia from Germany.

  27. This has become a fascinating thread. I came across it for the same reason as Kate. I’m doing some family genealogy and found my great grandfather died at age 47 In 1903 of “General Paralysis”. It doesn’t say ‘of the insane’ but I recently found reference to a petition for insanity. It seems to echo your great uncles situation Kate. Too bad the cure was found just ten years later. My G-grandfather’s second wife lived for many more years and appears to have had no complications. G-grandfather was born “0n high-seas” so maybe conditions contributed or else something later, which seems more probable.