During the nineteenth century general paresis of the insane emerged as a new psychiatric disorder which was extremely common and completely devastating. While retrospective studies have found earlier instances of what may have been the same disorder, the first clearly identified examples of paresis among the insane were described in Paris after the Napoleonic Wars. Initially regarded as a complication of insanity by such influential psychiatrists as Jean-Etienne Dominique Esquirol, general paresis was first described as a distinct disease in 1822 by Antoine Laurent Jesse Bayle.

It is now known to be a late stage of the disease of syphilis.

General paresis most often struck people (men far more frequently than women) between twenty and forty years of age. Within a matter of months to a few years after the appearance of the first symptoms, it reduced its victims to a state of dementia and profound weakness. No treatment was known, and patients uniformly died. During the nineteenth century its prevalence came to be widely recognized. By 1877, for example, the superintendent of an asylum for men in New York reported that in his institution this disorder accounted for more than twelve percent of the admissions and more than two percent of the deaths.

While Esmarch and Jessen had asserted as early as 1857 that syphilis caused general paresis, progress toward the general acceptance of this idea was begun by the eminent nineteenth-century syphilographer Alfred Fournier (1832-1914). In 1913 all doubt about the syphilitic nature of paresis was finally eliminated when Noguchi and Moore demonstrated the spirochaetes in the brains of paretics. In 1917 Julius Wagner-Jauregg discovered that infecting paretic patients with malaria could halt the progression of general paresis. He won a Nobel Prize for this discovery in 1927. After World War II the use of penicillin to treat syphilis made general paresis a rarity.

But see: Tuskegee experiment