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above, some 15 to 20 years usually separate the onset of general paresis from the original infection The history of the disease is entwined with some of the major historical events in neuropsychiatry Haslam in 1798 and Esquirol at about the same time rst delineated the clinical state Bayle in 1822 commented on the arachnoiditis and meningitis, and Calmeil, on the encephalitic lesion Nissl and Alzheimer added details to the pathologic descriptions The syphilitic nature of the disease was suspected by Lasegue and others long before Schaudinn s discovery of the spirochete; it was nally con rmed by Noguchi in 1913 Kraepelin s monograph General Paresis (1913) is one of the classic reviews (see Merritt, Adams, and Solomon for these and other historical references) Once a major cause of insanity, accounting for some 4 to 10 percent of admissions to asylums (hence the term general paresis of the insane, or GPI), general paresis is now a rarity Since syphilis is acquired mainly in late adolescence and early adult life, the middle years (35 to 50) are the usual time of onset of the paretic symptoms Possibly the shortened life span of patients with AIDS has limited the emergence of general paresis, or the immunode ciency has altered the biologic reaction to the organism Congenital syphilitic paresis blights early mental development and results in late childhood and adolescent regression in both normal and mentally retarded children The clinical picture in its fully developed form includes dementia, dysarthria, myoclonic jerks, action tremor, seizures, hyperre exia, Babinski signs, and Argyll-Robertson pupils (page 242) However, more importance attaches to diagnosis at an earlier stage, when few of these manifestations are conspicuous The insidious onset of memory defect, impairment of reasoning, and reduction in critical faculties along with minor oddities of deportment and conduct, irritability, and lack of interest in personal appearance are not too different from the general syndrome of dementia outlined in Chap 21 One can appreciate how elusive the disease may be at any one point in its early evolution Indeed, with the currently low index of suspicion of the disease, diagnosis at this preparalytic stage is more often accidental than deliberate Although classic writings have stressed the development of delusional systems, most dramatically in the direction of megalomania, such symptoms are exceptional in the early or preparalytic phase More usual has been a simple dementia with weakening of intellectual capacities, forgetfulness, disorders of speaking and writing, and vague concerns about health In a few patients the rst hint of a syphilitic encephalitis, as mentioned earlier, may be facial quivering; tremulousness of the hands; indistinct, hurried speech; myoclonus; and seizures reminiscent of delirium or acute viral encephalitis As the deterioration continues into the paralytic stage, intellectual function progressively declines, and aphasias, agnosias, and apraxias intrude themselves Physical dissolution progresses concomitantly impaired station and gait, debility, unsteadiness, dysarthria, and tremor of the tongue and hands All these disabilities lead eventually to a bedridden state; hence the term paretic Other symptoms are hemiplegia, hemianopia, aphasia, cranial nerve palsies, and seizures with prominent focal signs of unilateral frontal or temporal lobe disease a syndrome known pathologically as Lissauer s cerebral sclerosis Normal-pressure hydrocephalus may be the basis of some of the cerebral symptoms Agitated, delirious, depressive, and schizoid psychoses are special psychiatric syndromes that can be differentiated from general paresis by the lack of mental decline, neurologic signs, and CSF ndings.

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