The technique of the Wassermann reaction as applied to the cerebro-spinal fluid consists in placing a certain quantity (.1 — .2 cc.) of the specimen to be tested in a tube and adding to it the proper amount (1 cc.) of extract of syphilitic or normal organs. I cc. of a 10 per cent solution of complement in the shape of guinea-pig serum is then added and the whole incubated at 37 C. for 30 minutes to give time for the complement to be bound. Then the hemolytic system, consisting of 1 cc. of a 5 per cent suspension of red-blood-cells of a sheep and two units, or twice the quantity necessary for complete hemolysis, of the heated serum of a rabbit immunized to sheep erythrocytes, is added. This rabbit serum will cause hemolysis of the sheep blood-cells if there is free complement in the tube, so the tube is again placed in the oven and observed at frequent intervals for several hours. If hemolysis occurs it shows that complement was not bound by the first ingredients and constitutes a negative reaction. The non-occurrence, or blocking, of hemolysis similarly would constitute a positive reaction, since it indicates that complement was absorbed in the first instance. Numerous controls are of course set out for each test. It will be seen that the process is a laborious one, necessitating as it does the immunizing and bleeding of animals, the making of extracts of organs, the washing of blood-cells, etc. One of the chief objections is that the ingredients are used in a fluid form. In this state they deteriorate steadily and have to be standardized, itself a time-consuming procedure, at nearly every series of experiments. In short, the test was possible only in a well-equipped laboratory and by trained workers. After a series of experiments, Noguchi'of Rockefeller Institute, has succeeded in so modifying and simplifying the technique that it bids fair to become almost a bed-side test. In the first place, he substituted for sheep blood in the hemolytic system, the blood from a human being. Thus, instead of requiring fresh sheep blood for each repetition, it is only necessary to prick the ear or finger of some individual who is known to be free from syphilis, let a few drops fall into a small tube of physiological salt solution, and we have our blood suspension. For the other components in the reaction he has succeeded in impregnating absorbent paper with the liver extract, with the serum of the rabbit which was immunized to human blood and with fresh guinea-pig serum or complement. Complement, especially, is very unstable and is active only for about three days in the fluid state, while when dried on paper it will retain its strength for months. These various papers are standardized in the laboratory so that small squares of certain dimensions represent, each, the required dose of that particular solution in the test. In paper form the substances will keep for long periods and, of course, are infinitely easier of manipulation. The substitution of the anti-human for the anti-sheep hemolytic system is a great advantage in that it does away with the difficulty which often arises from the presence in human blood-serum of a natural hemolysin for sheep blood. The possibility of preparing this paper form of the various components in the Wassermann reaction in large laboratories by pharmaceutical houses and its distribution by them, is apparent, and an extremely valuable diagnostic test for syphilis and general paralysis may thus be brought within the reach of any practising physician who possesses a little technical skill. With regard to the reliability of this reaction in the diagnosis of general paralysis, there have been some widely varying results by different workers. The majority, however, attest to its occurrence in from 60 to 75 per cent of all cases of that disease. In a communication about to be published, Noguchi and the writer have compared the Wassermann reaction with the butyric and other tests as applied to the spinal fluid. The Wassermann reaction, while not giving as high a percentage of positive results as the butyric acid reaction and the cell-count, is of undoubted value, and by eliminating some of the opportunities for error which now exist its efficiency will be much increased. In the series just mentioned, which consisted of about 200 cases, the Wassermann reaction gave 73 per cent of positive findings in general paralysis against 90 per cent which showed the butyric acid reaction and increased cell-content. A negative Wassermann reaction, then, is relatively of much less significance than the other tests, and doubtful reactions are very common. But a definitely positive result can be accepted without much question as meaning a syphilitic or metasyphilitic disorder of the central nervous system. Even in cases of acute inflammatory disease of the meninges in which the proteid and cell-content are very high, the Wassermann reaction is always negative. In two cases of psychoses other than general paralysis a positive reaction was obtained, but syphilis could not be excluded in their histories. Only four cases of spinal fluid from active lues without nervous involvement were examined, but all were negative. A certain number of such cases, however, have been found in the experience of others to give positive results, and this opens the question of whether these are the persons who, in later life, are prone to develop general paralysis. If such cases could be followed it would help much to clear up the subject of whether the nervous system is invaded at the time of the luetic attack or is subsequently involved. We may conclude, then, that in general paralysis and tabes, and in lues of the central nervous system, there exists in the cerebro-spinal fluid, besides an increase in cells and proteids, a characteristic which enables it to bind complement in the presence of certain lipoids. That this property is possessed also by syphilitic serum but appears to be absent in other conditions. That the detection of this substance not only aids in the diagnosis of general paralysis, but also is strong presumptive evidence of the relationship of this disease to syphilis. BIBLIOGRAPHY. 1. Bordet et Gengou: Annales de l'Inst. Pasteur, 1901. 2. A. Wassermann, A. Neisser und C. Bruck: Deutsche med. Wochenschrift, 1906, No. 12. 3. A. Wassermann und F. Plaut: Deutsche med. Wochenschrift, 1906, No. 44 4. H. Noguchi: Jour. of Experimental Medicine, 1909, March 1. A REVIEW OF THE RECENT STUDIES OF GENERAL PARESIS.* BY JAMES V. MAY, A. B., M. D., Assistant Physician, Binghamton State Hospital, Binghamton, N. Y. Perhaps nowhere within the wide domain of psychiatry have greater advances been made within the last few years than in our knowledge of general paresis. It constitutes at the present time practically the only psychosis which is accompanied by well-defined characteristic pathological changes which render postmortem demonstration and diagnosis possible. The gross changes found at autopsy, the thickening and adhesions of the dura, the occasional hemorrhagic membranes and exudates, the excess of cerebro-spinal fluid, the lepto-meningitis with adhesions, the regional atrophies and softenings, the diminished brain weight and the granulations in the ventricles are of themselves usually sufficient for diagnosis. The histological changes which take place have until recently been very vaguely and inadequately described. For our present comprehensive knowledge of the pathology of paresis we are largely indebted to the exhaustive researches of Nissl and Alzheimer. The latter has laid particular emphasis on the importance of plasma cells in the pia and vessel walls. The pia-arachnoid is always extensively infiltrated by plasma cells and lymphocytes, and shows occasional mast cells. The plasma cells are small and rounded or oval, with usually one and sometimes numerous nuclei. They are specially susceptible to degenerative changes, characterized by vacuolization, with the absorption at times of foreign substances, changes which cause them to resemble granule or waste product cells. Plasma cells are also found in brain syphilis, in tubercular meningitis, in carcinomatous and sarcomatous processes and in encephalitis,-due to lead and other poisons, as well as in idiocy and epilepsy. They occur so much more extensively, however, in paresis as to render a diagnosis comparatively easy, the other conditions in which they occur being * Read at the sixty-fifth annual meeting of the American Medico-Psychological Association, Atlantic City, N. J., June 1-4, 1909. excluded by pathological as well as clinical considerations. The presence of plasma cells is readily confirmed by selective stains which have been devised by Unna and Pappenheim. The characteristic meningeal infiltration, although present in practically all areas of the brain, is more marked in the frontal lobes. In the cortex the vessels seem to be greatly increased in number and show well-marked changes. Aside from an intimal proliferation and a budding of capillaries, there is nearly always an extensive infiltration of the adventitia by plasma cells, lymphocytes, some polynuclear and occasional mast cells. The plasma cells are usually very numerous. Their origin is questionable at the present time. In the superficial layer of the cortex there is almost always an increase of the neuroglia fibrils with numerous spider cells showing eccentric nuclei and large cell bodies. Anglade and Letreille' by means of a special stain have shown a conspicuous increase in neuroglia in the molecular layer of the cerebellar cortex. Rod-shaped cells, or "Stabchenzellen" as described by Nissl, with a long nucleus and only slight evidences of a cell body, are very common and seem to have some relation to the severity of the process. Satellite cells and "free nuclei " are often seen in the vicinity of the neurones. The nerve cells are frequently diminished in number in occasional areas with a proliferation of the glia. The definite changes in the neurones which have been described as acute alteration, grave alteration, rarefaction, shrinkage, sclerosis and pigment degeneration are all found in general paresis, but are not pathognomonic of the disease. Many cells are normal and some present the change known as axonal alteration. The cells appear to point in all directions, and there is often an obvious disturbance of the normal layering of the cortex. Areas of softening are often found, but Nissl denies the presence of gummata in paresis. Degeneration of the nerve fibres is shown early in the pyramidal layers and occurs later in the association and projection fields. The various lesions found in the cortex are shown to varying extents in the cord. The etiology of general paresis has proven as interesting a field of research for recent investigators as that of pathology. The bacterial origin of the disease as advocated by Ford Robertson' had led to considerable discussion at times. In cultures from the mucous membrane of the stomach and intestines, from the respira |