Moore,1 who found the treponema pallidum in brain sections from twelve out of a total of seventy cases of general paresis examined by them. This finding has since been confirmed by many observers, so that general paresis 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 mainly parenchymatous, that of the others being meningeal, vascular, or interstitial.

The clearer knowledge thus gained of the nature of general paresis 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 paresis that is not well understood. The most important question demanding an answer is, Why do some syphilitics eventually develop general paresis and other not? Probably not over five per cent of syphilitics develop general paresis.

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 paresis, this view being based on the fact that in cases of general paresis 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

1 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.

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 paresis, 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 paresis 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 paresis 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.

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 paresis, 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 paresis 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 paresis, 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 paresis 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 paresis 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 paresis 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 almost certainly be said to increase the danger of tabes or general paresis.

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

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

Syphilis being more common in men than in women, general paresis too occurs more commonly in men. Thus, during the year ending September 30, 1914, there were 3338 male and 2927 female first admissions to the New York state hospitals; among them were 627 male and 147 female cases of general paresis, i.e., 18.8% and 5.0% of all admissions, respectively.1

The great majority of cases of general paresis occur between the ages of 30 and 60. Thus, of a total of 774 cases of general paresis among the first admissions to the New York state hospitals in the year ending September 30, 1914, but 49, or 6.3%, developed before the age of 30, and but 28, or 3.6%, at 60 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 paresis; 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 paresis, while the opposite is true of Catholic priests; Krafft-Ebing, for instance, saw among 2000 cases. of general paresis not a single one in a Catholic

1 Twenty-sixth Annual Report of the N. Y. State Hospital Commission, Albany, 1915.