In 1857 Esmarch and Jessen were led by the clinical histories of their cases to conclude that syphilis was the cause of general paralysis; but their view gained ground very slowly. In France Charcot always rejected it, and D£jerine wrote in 1886, "Syphilis is very rarely found in the histories of general paralytics, and has no influence on the course of the affection; when found it is but a coincidence." Others have held, with Joffroy, that syphilis was a strong factor favoring the occurrence of general paralysis but not an essential cause of it.

Case histories alone were, naturally, insufficient to. establish the essential part played by syphilis in the etiology of general paralysis, a history of syphilitic infection being by no means always obtainable; but the case came to be strengthened on anatomical grounds by the similarity between the lesions of general paralysis and certain syphilitic lesions.

In 1897 Krafft-Ebing presented at the International Congress of Medicine in Moscow further important evidence. A physician, whose name was not mentioned, inoculated with syphilis nine general paralytics who had reached the last stage of the disease and in whose history syphilis had not been found; none of these developed a chancre.

1 Klippel. Lesions des poumons, du coeur, du foie et des reins dans la paralysie generale. Arch, de med. experim. et d'anat. path., July, 1892. - Angiolella. Lesions des petits vaisseaux de quelques organes dans la paralysie generate. II manicomio, 1895, Nos. 2 and 3.

The advent of the Wassermann reaction with the generally positive finding either in the blood, or in the cerebro-spinal fluid, or in both, led to the general acceptance of the view that in the absence of syphilis there can be no general paralysis. But the nature of the disease still seemed obscure; especially perplexing was its resistance to anti-syphilitic treatment in contrast with other syphilitic lesions. The disease was held to be a consequence and not a direct manifestation of syphilis, a "metasyphilitic" (Moebius) or "parasyphilitic" (Fournier) disorder, possibly in the nature of an autointoxication (Kraepelin).

Some, however, advanced the view, based on various considerations, that general paralysis was but a late and peculiar manifestation of still active syphilis.1 Others, notably Lambert and Dunlap,2 have insisted that a sharp line of demarcation cannot be drawn between general paralysis and cerebral syphilis and have brought to attention cases which, in clinical features as well as in post mortem findings, represent transition or combination forms.

The nature of the relationship between syphilis and general paralysis was finally settled by Noguchi and Moore,3 who found the treponema pallidum in brain sections from twelve out of a total of seventy cases of general paralysis examined by them. This finding has since been confirmed by many observers, so that general paralysis is now regarded as a lesion of syphilis affecting the brain and differing from other intracranial syphilitic lesions by the fact of its distribution being primarily parenchymatous, that of the others being meningeal, vascular, or interstitial.

1 Browning and McKenzie. On the Wassermann Reaction, and Especially its Significance in Relation to General Paralysis. Journ. of Mental Science, Vol. LV, 1909. - Plaut and Fischer. Die Lues-Paralyse Frage. Allg. Zeitschr. f. Psychiatrie, Vol. LXVI, 1909. - Rosanoff and Wiseman. Syphilis and Insanity. Amer. Journ. of Insanity, Jan. 1910.

2 C. I. Lambert. A Summary Renew of the Syphilitic and Metasyphilitic Cases in 152 Consecutive Autopsies. N. Y. State Hosp, Bulletin, Aug., 1912. - C. B. Dunlap. Anatomical Borderline between the so-called Syphilitic and Metasyphilitic Disorders. Amer. Journ. of Insanity, 1913.

3 Noguchi and Moore. A Demonstration of Treponema Pallidum in the Brain in Cases of General Paralysis. Journ. of Exper. Medicine, Vol. XVII, No. 2, 1913.

The clearer knowledge thus gained of the nature of general paralysis affords an explanation of its peculiar resistance to anti-syphilitic treatment: the pathogenic organisms are embedded in situations not reached by the medication.

There is still much in the etiology of general paralysis that is not well understood. The most important question demanding an answer is, Why do some syphilitics eventually develop general paralysis and others not? Probably not over 5% of syphilitics develop general paralysis.

In this connection one thinks, perhaps, first of all of a special predisposition. The view is often expressed that an inherited neuropathic constitution renders one more liable, on contracting syphilis, eventually to develop general paralysis, this view being based on the fact that in cases of general paralysis one finds rather frequently a family history of nervous or mental diseases, though not by any means so frequently as in the constitutional disorders. It is doubtful, however, if this view is really supported by the fact on which it has been based, as the latter is quite susceptible of a different interpretation, namely, that syphilis itself is more likely to be contracted by unrestrained, dissipated, and grossly immoral persons than by others, these traits being, in their turn, often among the manifestations of neuropathic constitutions. Thus, while a special susceptibility to the syphilitic virus may possibly have something to do with the development of general paralysis, the known facts do not seem to necessitate the assumption that the inherited neuropathic constitutions are especially related to this susceptibility.

Another view is that special strains of the syphilitic organism, more virulent toward nervous tissues, are responsible for the development of general paralysis and, perhaps, of other lesions of the nervous system, this view being based on the occasionally observed instances of conjugal paresis and of other instances of general paralysis occurring in two or more persons whose syphilitic infection can be traced to the same source. Such observations are, however, rare and, considering the great prevalence of syphilis, may be explained as coincidences.

Treponema pallidum in the Brain of General Paralysis.Treponema pallidum in the Brain of General Paralysis

Fig. 2. - Treponema pallidum in the Brain of General Paralysis. (Noguchi and Moore.)

That the distribution of an organism which is disseminated by the blood and lymphatic circulation and which is itself actively motile will vary in different cases according to mere chance would seem self evident; therefore it is not surprising that some cases of syphilis should have liver lesions, others bone lesions, still others lesions of the central nervous system, including general paralysis, etc., as their most prominent manifestations. Yet factors other than mere chance undoubtedly play a part in some cases. Head injury, for instance, has been shown by numerous carefully studied cases to be capable of starting general paralysis in a syphilitic person, acting, possibly, by opening a way for the migration of treponemata lodged in lymph spaces, interstitial tissues, or blood vessel walls into the brain parenchyma. Alcoholism has also been often mentioned as an exciting cause of general paralysis, but it is difficult to determine the exact part that is played by it in this connection.

It is a remarkable fact that in cases of tabes or of general paralysis the syphilis, during the years prior to the involvement of the central nervous system, runs a very mild course, often hardly furnishing evidence of its presence; secondary and, especially, tertiary manifestations (iritis, skin eruptions, gummata) are either slight or absent;1 and at autopsies in cases of general paralysis one seldom finds the lesions ordinarily observed in old syphilitics, such as endarteritis, arteriosclerosis, valvular heart lesions, aneurisms, infarctions, hepatic cirrhosis, etc. It would seem that in the cases destined to develop eventually tabes or general paralysis there is from the beginning a special distribution of the syphilitic infection. However this may be, the mildness of the manifestations usually leads to neglect of treatment, and that may certainly be said to increase the danger of tabes or general paralysis.

1 E. F. Snydacker. Absence of Iritis and Choroiditis among Syphilitics who have become Tabetic. Journ. Amer. Med. Assn., 1910.

Among other factors in the etiology of general paralysis the most important are sex, age, occupation, and environment.

Syphilis being more common in men than in women, general paralysis, too, occurs more commonly in men. Thus, during the year ending June 30, 1918, there were 3530 male and 3267 female first admissions to the New York state hospitals; among them were 725 male and 188 female cases of general paralysis, i.e., 20.5% and 5.8% of all admissions, respectively.1

The great majority of cases of general paralysis occur between the ages of thirty and sixty. Thus of a total of 913 cases of general paralysis among the first admissions to the New York state hospitals in the year ending June 30, 1918, but 62, or 6.8%, developed before the age of thirty, and but 45, or 4.9%, at sixty or over.1 Juvenile and even infantile cases are, however, sometimes met with, occurring generally on a basis of inherited syphilis.

All occupations do not equally predispose to syphilitic infection and, therefore, to general paralysis; unfortunately detailed and extensive statistics are not available. It is well known that army and navy officers, traveling salesmen, and railroad employees furnish a comparatively high proportion of cases of general paralysis, while the opposite is true of Catholic priests; Krafft-Ebing, for instance, saw among 2000 cases of general paralysis not one in a Catholic priest, while among his cases of insanity in army officers no less than 90% were cases of general paralysis.2 Among women professional prostitutes, naturally, furnish the highest proportion of cases of general paralysis.

1 Thirtieth Annual Report of the N. Y. State Hospital Commission, Albany,1919.

2 Quoted by Kraepelin. Psychiatric 8th Edition. Vol. II.

Syphilis occurs much more frequently in urban than in rural environments; accordingly, urban communities furnish a greater proportion of cases of general paralysis. Thus, according to the United States Census, cities of 100,000 and over furnished 9.6 and rural communities but 1.6 cases of general paralysis per 100,000 of the general population among the admissions to hospitals for the insane in the year 1910.1