(a) Tabetic type. The degeneration is localized in the posterior columns and is similar to the lesion of tabes; this has led many authors to look upon general paresis and tabes as two different localizations of the same morbid process.1

(b) Combined sclerosis. The degeneration involves both the posterior and the lateral columns. Moreover, the process here is more diffuse and affects simultaneously different systems of fibers (tract of Gowers, crossed pyramidal tract).

(C) Peripheral nerves. The lesions of the peripheral nerves consist in the phenomena of neuritis and atrophy, analogous to those encountered in tabes and in alcoholism.

(D) Viscera.

Three classes of lesions may be distinguished in the viscera:

(1) Lesions occurring merely as accidental complications: various infections, broncho-pneumonia, tuberculosis. The latter is rare and usually runs a slow

course.

(2) Lesions which are the direct consequences of the nervous disorders. These have been studied exhaustively by Klippel, who has termed them vasoparalytic lesions. They consist, according to this author, “in a high degree of congestion and capillary engorgement, capillary hemorrhages, and, by consequence, atrophic degeneration of epithelial tissues." 2

1 Nageotte. Tabes et Paralysie générale. Thèse de Paris, 1893. 2 Klippel. Lésions des poumons, du cœur, du foie et des reins dans la paralysie générale. Arch. de méd. expérim. et d'anat. path., July, 1892. Angiolella. Lésions des petits vaisseaux de quelques organes dans la paralysie générale. Il manicomio, 1895, Nos. 2 and 3.

(3) Diffuse vascular lesions identical in appearance with those of the cerebral vessels.

These lesions are met with chiefly in the kidneys, liver, and heart, and are often associated with degenerative lesions, such as fatty or cirrhotic liver, sclerotic kidney, or degenerated myocardium.

Etiology. In 1857 Esmarch and Jessen were led by the clinical histories of their cases to conclude that syphilis was the cause of general paresis, but their view gained ground very slowly. In France Charcot always rejected it, and Déjerine wrote in 1886, "Syphilis is very rarely found in the histories of general paretics, 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 paresis 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 paresis, 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 paresis 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 paretics who had reached the last stage of the disease and in whose history syphilis had not been found; none of these developed a chancre.

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 paresis. 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 paresis 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 paresis 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 paresis was finally settled by Noguchi and

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 LuesParalyse-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 Review 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.

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.