A Demonstration of Treponema Pallidum in the Brain in Cases of General Paralysis

s of the case records follow. J. C. ( Io3) , age fifty years ; durat ion of disease unknown. He was committed from the workhouse. There was much confusion; he was disoriented and his memory was extremely poor. The knee-jerks were unequal and exaggerated; the pupils sluggish and unequal. His speech was distorted, and there were marked tremors. Convulsions occurred. Death occurred af ter seven months in the hospital. C. M. ( io6) , age thir ty-nine years; durat ion unknown, but probably about four months. Syphilis ten years previously. W h e n he was admitted he was depressed and apprehensive; he had hallucinations of hear ing; he was disoriented, and his memory was very poor, with spells of marked confusion. The Noguchi, H., Jour. Am. Med. Assn., I912 , lix, I236. Hideyo Noguchi and J. W. Moore. 285 knee-jerks were normal, the pupils sluggish. There were ataxia, distorted speech, coarse tremors, and convulsions. He died after eleven months in the hospital. F. B. ( I I3) , age thirty-six years; duration before admission, fourteen months. Syphilis was denied. On admission he was dull, silly, mildly restless, and had occasional hallucinations. His memory showed marked discrepancies. The knee-jerks were absent, and the pupils slow to light and unequal. His speech was distorted, and he had convulsions. Later he developed a silly elation and deteriorated progressively. Death occur red 'a f te r fourteen months in the hospital. The total duration of the disease was thirty months. S. V. ( I3I ) , colored, age thirty-seven years; the duration of the disease before admission is unknown. Syphilis eight years previously. He was euphoric, his memory was very poor, and he was disoriented. The knee-jerks were much diminished, the pupils slightly slow, his speech ataxic, and there were coarse tremors. Later he developed typical expansive ideas and became very ataxic. Death occurred after twenty-seven months in the hospital. J. D. (I38), age thirty-three years; duration before admission, five months. He was admitted in an hallucinatory depression with nihilistic ideas and a history of a probable attempt at suicide. A complete mental status was impossible. The knee-jerks were exaggerated ; pupils unequal, Argyll-Robertson sign present ; there were marked tremors. The spinal fluid showed marked lymphocytosis. Death occurred after ten months in the hospital. F. M. (I59), age fifty-five years; duration of disease unknown. He was picked up on the street in a confused condition. He had absurd hypochondriacal ideas; " his insides were falling out," etc. He was disoriented and his memory was very poor. The knee-jerks were exaggerated, and the pupils sluggish. There were marked tremors, unsteadiness, and Romberg's sign. His speech was not seriously affected. Depression continued, and he insisted that he could not breathe or urinate, and that parts of him were dead. He died after four months in the hospital. The spinal fluid showed positive lymphocytosis and a positive W:assermann-Noguchi reaction. E. W. (I7o), age forty-four years; duration unknown. He had had syphilis. The psychosis was a simple deterioration with marked confusion and disorientation but no delusions. He was silly, his memory was poor, and there were occasional attacks of excitement. Thekneej e rks were diminished, and the pupils slightly slow. The speech showed extreme ataxia. Romberg's sign was present, and tremors were prominent. There were frequent convulsions. Death occurred after two months in the hospital. E. R. (23o), age forty-eight years; duration unknown. When admitted she was much demented, confused, completely disoriented, and her memory was poor. Her mood was one of silly elation. The knee-jerks were exaggerated, the pupillary reaction slow and of narrow range. There was marked distortion of speech and writing. There were coarse tremors and increasing ataxia. The spinal fluid showed marked pleocytosis. Death occurred after six months in the hospital. 286 Demonstration of Treponema pallidum in the Brain. M. M. (235), age forty-two years; duration uncertain. She had been blina from optic atrophy for two years before admission and had experienced occasional visual hallucinations, but definite mental symptoms seem to have begun only a few weeks before commitment, when she began to show a change of disposition and became forgetful. Syphilis probably occurred twenty years previously. Her husband was a paretic. On admission she was excited, resisting, and obscene. She seemed clear and gave correct answers in the orientation test but her memory showed marked discrepancies in time relations. The knee-jerks were absent, the pupils rigid, her speech drawling and distorted, no tremors, and only slight ataxia. The spinal fluid showed extreme lymphocytosis. She quieted down, and during the next two years showed a gradual deterioration without any particular mental trend. Ataxia increased steadily; she had occasional apoplectic attacks and convulsions. Death occurred after two years in the hospital. G. F. (236), age sixty years; duration before admission, one month. He became gradually childish, forgetful, and irritable. When admitted he was disoriented, and his memory was poor. The knee-jerks were absent, and the pupils unequal and slow; his speech was slurring and distorted. There were marked tremors and Romberg's sign. He deteriorated rapidly and died after four months in the hospital. M. D. (242), age thirty-seven years; duration eight months. The onset seemed to date from an injury to the head. There was a probable history of syphilis. He was depressed, confused, and had attempted suicide. His memory was poor, and he was much demented. The knee-jerks were exaggerated; and the pupils unequal and Argyll-Robertson sign present; his speech was ataxic. There were tremors and occasional convulsions. He died after four months in the hospital. The total duration of the disease was one year. F. B. (299) (figure I), age fifty-eight years; duration before admission, one month. There was a probable history of syphilis. He was depressed and whining, and had typical paretic ideas, such as that his bowels never moved, and that he had an incurable disease. He would point to a leg or an arm and say, " See, it's all dead, all gone,--there's no hope." His orientation and memory showed marked defects. The knee-jerks were slightly exaggerated, the pupils slow, his speech was distorted, and tremors were excessive. The spinal fluid showed pronounced lymphocytosis and a positive Wassermann-Noguchi reaction. Death occurred after eleven months in the hospital. N a t u r a l l y the first ques t ion that ar ises is, A r e these no t cases of cerebra l syphi l is in the n a r r o w e r sense? I n reply to this we can but rev iew br ief ly the d i f fe rent ia l points . T h e y all showed, in the i r c l inical course, a diffuse, p rogress ive de t e r i o r a t i on in all the men ta l fields, and no t the demence lacu~aire so o f t e n observed in syphi l i t ic b r a i n disease. T h e r e were i10 c ran ia l s y m p t o m s or o ther focal man i f e s t a t i ons . These po in ts are admi t t ed ly no t conv inc ing , for it is possible for an old syphi l i t ic e n d a r t e r i t i c m e n i n g i t i c cond i t i on to Hideyo Noguchi and J. W. Moore. 237 simulate paresis so closely as to be indistinguishable by its clinical features from the latter disease. It is upon the post-mortern findings that the diagnosis must depend. Anatomically the brains of our cases showed the usual pial thickening, more marked over the frontal convexity. In two it was also prominent over the gyri recti, cerebellum, and cisterna, but it did not assume the degree of meningitis usually seen in syphilis of the base. In one case (235) there was an old hemorrhagic membrane beneath the dura; in another (131) there was a marked preponderance of the paretic process in the right hemisphere, but these conditions were not represented clinically and the findings were otherwise typical. In the microscopic examination the meningeal process in all cases was diffuse, being more marked in the frontal region. The vessel infiltration was also diffuse and found at all depths of the cortex and in the marrow. Plasma cells were, in each case, numerous and usually outnumbered the lymphocytes. RQd cells were always present. The nerve cell alterations and changes in the neuroglia do not present differential characteristics and will not be enumerated. With regard to the vessels, a number of our cases, as in all general paralysis material, showed endarteritic changes. In six there was definite thickening of the vessel walls of the type described as syphilitic. In no instance did the intimal proliferation embarrass the lumen to any extent. In the remaining cases the vessels appeared normal. It seems hardly possible that the presence of the spiroch~etm could be traced to the luetic endarteritis, since they were not found associated, at least with those vessels which are visible with the Levaditi stain. In none of the cases were there softenings, and no gummata were found either in gross or microscopically. The spiroch~et~e were found in all layers of the cortex with the exception of the outer, or neuroglia layer. One was located at the border of this layer, 'but not within it. A few were found subcortically. Careful search of the pia failed to reveal any of the organisms. In all instances they seemed to have wandered into the nerve tissue. They were not found in the vessel sheaths and seldom in close proximity to the larger vessels. There seems to be no ratio between the number of spirocha~t~e and the severity of the 238 Demonstration of Treponema pallidum in the Brain. paretic process, a l though the case in which they were most numerous showed excessive paretic changes. Whe the r or not, by improving the technique, Treponema pallidum can be demonstra ted in a much higher percentage of paretic cases will be determined by fur ther investigations. EXPLANATION OF PLATE 5o. FIG. I. Treponema pallidum in the cortical layer of the right frontal area of the brain (case 299). Stained, with slight modification, by Levaditi's method. X I,100. THE JOURNAL OF EXPERIMENTAL MEDICINE VOL. XVII. PLATE 50.