General paresis of the insane: a diagnosis not to forget, 2025, Masud Husain

[Mij]

Just over 200 years ago something remarkable happened in post-Revolutionary Paris. Alienists, the forerunners of modern day psychiatrists and so-called because they cared for people alienated from society, had observed an alarming trend. A growing number of relatively young people—mostly men—had developed a startling, progressive illness. It was characterized by abnormal behaviour (sometimes referred to as mania and often associated with delusions of grandeur), cognitive decline and eventual dementia, gait disturbance leading to paralysis, and ultimately to death.

The mental institutions in Paris and elsewhere in France soon began to register that this hitherto unrecognized constellation of symptoms was a new condition. Moreover, it seemed utterly unresponsive to conventional psychological or physical treatments and always led to a terrible demise, usually within months, at the very most a couple of years.

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[Mij]

Although Alzheimer’s disease (AD) would perhaps not be the first consideration in the differential diagnosis of a patient presenting with GPI, it is interesting to note that many individuals in the Wang et al. study had hippocampal atrophy on MRI. Some also had evidence of amyloid positivity (on either CSF analysis or PET imaging) or elevated tau levels (in the CSF).

More likely than a clinical diagnosis of AD being made erroneously is the consideration of behavioural variant frontotemporal dementia and its overlap with movement disorders and amyotrophic lateral sclerosis (ALS). Further, if a neurological examination is not performed, some clinicians may diagnose a primary psychiatric diagnosis as the likely cause.

Late neurosyphilis remains an elusive entity and a challenging diagnosis to make unless we entertain it as a possibility. It remains a diagnosis not to forget.

 

[Hutan]

Bayle’s conclusion, considered subversive at the time, was that both the mental and physical symptoms and signs in these individuals were the direct result of the pathological changes in the brain. For Bayle, this seemed obvious. Surely it was the chronic inflammation that he had found that was the cause of the clinical manifestations. How could it be otherwise?

And it wasn’t only he who had observed such pathological changes. Others had also found the very same when they had performed post-mortems on such patients. However, their interpretation had been quite different. They tried to fit these pathological findings to suit Esquirol’s view of mental illness and suggested that the chronic inflammation was a complication—not a cause—of the madness observed in these individuals.

Eventually, of course, the cause was identified and later effective treatment for syphilis followed. But Bayle’s hypothesis that pathology within the brain could lead to mental illness, as well as physical signs and dementia, proved to be a landmark in medical history. It linked changes in the brain to behavioural manifestations observed in individuals who would otherwise be considered ‘lunatics’, raising the possibility that treatable, organic causes could trigger mental changes.

 

[Mij]

There was speculation that Florence Nightingale was believed to have suffered from ME. but later diagnosed with possible brucellosis or tertiary syphilis.