Noguchi Ulohtftratinn of ttjc Waaarrmamt ©cat in fagri|iatrg William H. Holmes Reprinted from the Institution Quarterly, Vol. 4, No. 2 State Charities Commission Springfield, 111. The Noguchi Modification of the Wassermann Test in Psychiatry. By W. H. Holmes, M. D., Clinical Pathologist to the Psychopathic Institute. The technique of the various sero-diagnostic tests is a subject which has received its full share of attention in the literature. For that reason no description of the technique followed in this labora- tory will be given. The tests are made according to Noguchi’s modification of the original Wassermann method. The antigen used is an alcoholic extract of a syphilitic foetal liver, prepared and kindly furnished by Dr. W. H. Buhlig of Chicago. The object of this paper is to record the results obtained in this laboratory in cases of : (1) Typical General Paralysis. (2) Typical Tabes Dorsalis. (3) Typical Cerebro-spinal Syphilis. (4) Atypical cases of General Paralysis in which the test proved of value in arriving at a correct diagnosis. (5) Miscellaneous cases. Notwithstanding the fact that there has been an immense amount of work done in neurological serology, the exact value of the pro- „ ^ce^.ure is, in the minds of many, still somewhat in doubt. For that reason I have deemed it advisable to make a statistical study of the - available literature. The review is confined to three diseases, viz., paresis, tabes and cerebro-spinal syphilis. Doubtless many cases have been overlooked. A number have been purposely omitted be- cause I did not feel satisfied that they were typical cases. Other cases are omitted because it was not definitely stated whether the v blood serum or spinal fluid was examined. . (_fi From Table I it is readily seen that relatively few authors confirm the belief of Plaut,i who states “The serum in paresis always reacts positively.” Yet the average percentage in which the serum is positive is so high (90%) that one is justified in stating that a negative reaction of the serum makes a diagnosis of general paralysis highly doubtful. Referring again to Plaut’s work, we find that he believes a negative spinal fluid and a positive serum in a case of organic brain disease is more likely Table I — General Paralysis. •aAtirsod }uab .lad •inj^qnop PUB 9At}BS9JN oioteooo^ C-ips •C'-Ol -00 > I>lOOCOO(MO OOtNlMCOOOOi OCO * LO ' WO 0 C '(MW •SaS'BD JO 'ON •poqj 9 M UB9A OHHt>OJl>OOO^a5aiOOOOHOOOOHOOai05HH •t>OOO^C5 rHrHfHOOOOOOOOOrHT-HOrHrHOOOTHTH -OOOO O^O^CJiCJSO^O^O^O^O^CSC^CJiO^C^O^O^CJiO^CJiO^O^O^ • P'W Ph 3 - NvNS^ S S • N. o 2 o . o * 2 *^ 3 ^ , •+_> . TO ri+J ' ,• . ra 3 w 1 c$ cj ,Q W . lO^O w . C H ' u -r< ^ o >» t/2 ft VI *rH O-rt So 0 ^ 5 ' w 4 j P h p'l^ H P"H S d PSrrt d 1 ;! a d Cjf 3 3 ri! O 5 ^PrtlR -» »'g~ s®: d -i 43 o 3 be c o & z t* c3 •- ”o ®43 S3 CD is «g S3 M •r-. m 43 ci 0 ) _ to be cerebro-spinal syphilis than paresis. Directly opposed to this are the findings of Marie, Levaditi, and Yamanouchi, who give statistics of ninety cases of paresis which they classify as follows: Cerebro-spinal fluid. Bloom serum. Posi- Nega- Not ex- Posi- Nega- Not ex- tive. tive. amined. tive. tive. amined. Incipient stage, 25 cases 19 6 14 11 Fully dev. stage, 25 cases. . . . 8 17 20 5 , . . Late stage, 40 cases 3 20 17 34 4 They maintain that the reaction is more likely to be positive in the spinal fluid in the late stages of the disease but that as the disease progresses, the serum is less likely to be positive. As will be seen, my own results would lead me to believe that Plaut’s dic- tum is more nearly correct than are those of his critics. There are two sources of error which should receive careful consideration by those who obtain results diametrically opposite to those of other reliable workers. One is the possibility of technical errors; the other the possi- bility of an incorrect clinical diagnosis. Early in my work I was confronted with this question, “Are those cases which give a negative serum reaction, true cases of general paralysis?” Manifestly in many cases it can be answered only by autopsy and micros- copical examination of the brain. In other cases the subsequent course of the disease may show where we have been led astray. A case giving a nega- tive reaction in the spinal fluid was, in the opinion of every member of the staff of the hospital in which he was confined, a true case of general paraly- sis. In the course of time, he developed the following symptoms: marked nystagmus, scanning speech, intention tremor, cerebellar gait, spasticity, etc. The pupils were very small and diminished in activity to both light and accommodation. The above findings make the diagnosis of general paralysis very doubtful, and the presence of some other organic nervous dis- ease more probable. Another case was later classified as belonging to the Infective-Exhaustive group. Two others, in which the spinal fluid only was sent for examination, were classified as cerebro-spinal syphilis. The above cases are sufficient to show the extreme care necessary in making a clinical examination of patients before drawing conclusions as to the value of a serologic test. Among technical errors, I believe one of the most important is bacterial contamination of the specimens. Both sera and spinal fluids from known cases of general paralysis, sent to us by one hospital, invariably gave nega- tive reactions. We were at a loss to account for this fact, since specimens from other hospitals were giving uniformly satisfactory results. A micro- scopical examination of the specimens showed that some were grossly con- taminated by large sporulating bacilli resembling the B. subtilis. Some contained actively motile bacilli, and still others cocci of various kinds. For this reason, no cases of any kind from this hospital are included in our statistics, although, after the attention of the hospital staff was called to the contaminations, the results were much better. The 61 cases examined by me represent all stages of the malady. I could see no relationship of the intensity of the reaction in the serum or spinal fluid to the stage of the disease. The two fluids, in the majority of cases, reacted with almost equal intensity. In a few cases, the serum showed a more complete inhibition of hemolysis. The physical and mental signs and symptoms in these cases makes the diagnosis of general paralysis almost certain. Positive. Negative. Doubtful. 30 0 0 10 0 0 20 0 1 In 30 cases, blood serum only In 10 cases, spinal fluid only... In 21 cases, both fluids 5 Of 51 speciments of blood serum the reaction was therefore positive in 98 Der cent and of 31 specimens of spinal fluid it was positive in 96.7 per cent. The single case, in which the reaction was doubtful in both fluids, gave strongly positive findings otherwise. The ammonium sulphate and butyric acid tests were both positive and a cell count (Fuchs-Rosenthal method) showed 100 cells to the cubic millimeter. All 'the other fluids also gave positive cell counts and positive globulin tests. TABES. Five cases of typical tabes in which the blood was examined gave 2 posi- tive results. One of the positive cases gave a negative reaction when re- examined after a lapse of six months. No anti-syphilitic treatment had been given. From the following table it will be seen that the majqrity of Tabetics are syphilitic and that the blood serum reacts positively much more frequently than does the spinal fluid: Table II — Tabes Dorsalis. Name. Bloom serum. Cer. spinal fluid. No. of cases. Positive. Doubtful or negative. Per cent positive. No. of ■ cases. Positive. Doubtful or negative. Per cent positive. Assmann •. 11 6 5 54.5 3 2 1 66.6 Beltz 4 2 2 50 4 1 3 25 Citron 15 12 3 80 9 2 7 22 Eichelberg u. Pfortner 7 6 1 85 7 5 2 71 Edel . . 7 5 2 71 Eichelberg 49 27 22 55 Fraenkel-Heiden . 3 1 2 33 Hough 1 1 100 Klineberger 17 17 100 18 9 9 50 Kaplan 306 161 145 52.5 Lesser 61 34 27 55.7 Lederma.n 41 31 10 75 Noguchi - 125 85 40 68 Noguchi & Moore 11 6 5 54.5 Schutze (1) '. . 78 51 27 65 29 23 6 79 Nonne Plolzmann (2) 92 62 30 67 92 8 84 9 Plaut 14 11 3 78 11 7 4 63 Stertz 5 3 2 60 Zaloziecki 4 4 100 1 1 100 Wassermeyer & Bering 7 4 3 56 3 1 ' ’ '2 33 Williamson 5 4 1 80 Total 793 493 300 62 247 99 • 148 40 (1) Zeit. f. klin. Med. 65 Nos. 5 and 6; Berl. klin. Woch No. 5, 1907. (2) Monat. f. Psych, u. Nerv. Vol. 28, No. 2, 1910. CEREBRO-SPINAL SYPHILIS. Three cases of cerebro-spinal syphilis in which the spinal fluid only was examined gave negative reactions. There was an increase globulin con- tent in all. Of 4 cases in which the blood only was examined 3 were posi- tive and 1 was negative. The case giving a negative reaction had been in the Kankakee State Hospital nearly,a year and had been thoroughly treated. The small number of cases of cerebro-spinal syphilis examined by me does not permit the drawing of conclusions, but a study of the following statistics cannot fail to convince one that the spinal fluid is much more 6 likely to give a negative reaction than a positive one. This fact, of little value by itself, is in my opinion significant when associated with a positive cell count and an increased globulin content. Table III — CerebroSpinal Syphilis. Name. Blood serum. Cer. spinal fluid. No. of cases. Positive. Doubtful or negative. Per cent positive. No. of • cases. Positive. Doubtful or negative. • Per cent j positive. Assmann 10 9 1 90 8 4 4 50 Eichelberg & Pfortner 7 7 100 7 1 6 14 Hough 7 7 100 Kafka 2 1 . . ... 50 6 1 5 16 Klineberger 27 20 7 74 29 7 22 24 Ledermann 11 11 100 Rosanoff & Wisemann 1 1 . . 100 1 1 100 Stertz ' 3 2 66 8 ’ ’ *8 Wassermeyer & Bering 7 6 1 85 5 *"i 4 20 Williamson 3 3 100 Zaloziecki 4 2 2 50 1 . . Beltz 12 8 4 66 12 ”7 5 58 Plaut 20 19 1 95 20 3 17 15 Foerster 5 2 3 40 Fraenkel-Heiden 7 2 . 5 28 Marie, Levaditi & Yamanouchi. . . . 6 1 5 16 Schutze 4 4 Noguchi 5 3 2 60 Noguchi & Moore 6 3 3 50 Eichelberg .18 7 11 39 Total 123 98 25 80 139 41 98 29 In the followng table IV are reported a small group of cases in which the psychoses are of non-luetic origin. As with cerebro-spinal syphilis the material is too limited to draw conclusions, but the findings in Dementia Praecox and Manic Depressive insanity are in accord with those of other workers: Table IV. Blood serum. Cer. spinal fluid. Positive. Negative Positive. Negative. Cerebral thrombosis 0 2 Cerebral hemorrhage. . 0 2 Arteriosclerosis 0 9 0 3 Multiple sclerosis . 0 1 Huntington’s Chorea 0 2 Infective exhaustive psychoses 0 • 6 0 1 Alcoholism 0 3 0 1 Pellagra 0 2 Dementia praecox... 2 8 Manic depressive insanitv 1 3 Paranoic State 0 2 Idiocy 1 0 Mental defective 0 1 Epilepsy 0 1 Epilepsv with Secondarv svphilis 1 0 Unclassified 3 8 0 1 Totals 8 49 0 8 7 There remains then for further study a small group of cases, which at first were wrongly diagnosed, and in which the Wassermann test led to a revised and correct classification. Case 1. I. M. G. examined by Dr. S. N. Clark of the Kankakee State Hos- pital to whom I am indebted for the following account: Admitted April 28, 1911, age 38. No previous attacks. The history was obtained from her hus- band: Patient first showed signs of mental derangement in December, 1910. She was very nervous, excited and continually talking to herself. She suffered from very severe headaches which caused her to go from one physician to another seeking relief. Later she took up Christian Science, New Thought and other similar cults, but without any relief. In January, a physician examined hejr, and made a diagnosis of salpingitis. He sent her to hospital for operation and stated that this would result in recovery. In the hospital she was very noisy and they refused to allow her to stay. Since then she has gradually grown worse, becoming more and more irri- table and noisy, and has developed delusions? believing that her husband’s employer was going to kill him. Within the last few weeks before admis- sion she has come to believe that they are also going to kill her. The husband stated that for three days out of a week she would be apparently perfectly normal, working about the house as usual, whereas during the balance of the time she would undo everything that she had done. During the month of January she constantly lost in flesh. Her normal weight is 125 pounds, on admission it was 98 pounds. She has always recognized her husband and has been oriented for time and place. The husband stated that there have been no attacks during the seven years that he has known her, and he does not know of any previous to that time. Physically the patient was rather poorly developed and poorly nourished, muscles fairly firm. Mucous membranes were palb. Conjunctivse slightly icteric. No rough- ness of the tibial crests or other suggestion of luetic infection. Discolored spot on left lower shin. Apparent age 36. There was some cough and a few dry rales were to be heard at the left apex. Urine examination revealed a trace of albumen with many pus cells but was otherwise negative. The second aortic sound was accentuated but the pulse small, easily compress- ible, regular and 80 per minute. Slight hardening was perceptible in the palpable arteries. Digestive system negative. In the nervous syste,m special senses and cutaneous sensibility were normal. There was no abnormal de- gree of tenderness on pressure over nerve trunks or muscles. Sense of position and passive motion normal. Occasionally there seemed to be slight difficulty in approximating the fingers with the eyes closed. Finger-nose test well done. Slight difficulty in walking a straight line. Pupils were 2 mm. in diameter, equal, regular in outline, centrally placed and- reacted well to light and accommodation. Consensual reaction normal. Palpebral fissures equal and wider than normal. No nystagmus. There seemed to be a slight asymmetry in the facial muscles. Tongue protruded in the median line. Voice somewhat hoarse. No defect in articulation. The two sides of the body symmetrically developed. Dynamometer registered 102 in the right hand, 67 in the left. Slight tremor of fingers. Superficial reflexes normal. Deep reflexes, excepting the knee jerks which were normal, were exaggerated but equal on the two sides. No Babinski or Gordon’s reflexes. No disturbance of organic reflexes. Mentally the patient seemed to be clear and was correctly oriented for time, place and person but she did not very fully grasp the whole meaning of the situation. She talked freely, showing some disjtractibility by events in her surroundings together with marked circumstantialty. She con- tinued talking even when alone. At times she appeared slightly euphoric and showed considerable irritability. When questioned, she stated she felt sad because she was away from home, but otherwise well. She expressed a definite delusional trend with regard to persecutions, ill-systematised, to which she did not very adequately adjust herself, and also spoke somewhat * vaguely of visual and auditory hallucinations. No defects in memory or impressibility were definitely determined but she was unable to give a resume of a story read to her. This was thought to be the result of dis- 8 tracted attention and she was regarded as a case of manic depressive in- sanity. When her husband was interviewed by the writer, as the result of the intervention of a mutual friend, it was noticed that his left pupil was con- siderably larger than the right, there was a slight tremor of the lips, some speech defect, the right side of the mouth opened more widely than the left, and the right naso-labial fold was deeper than the left. Consequently a serologic examination was made upon his wife with the following results: Wassermann blood examination positive (4 plus). Spinal fluid examina- tion was made November 7th. Noguchi butyric acid test positive. Nonne- Apelt test positive. No reduction with Fehling’s solution. Cell count: 50 cells per cubic millimeter. 9 The further course of the case has left no room for doubt as to the nature of the disease. Case 2. S. C., age 28. History of loose and immoral life. Abrupt onset August 20, when she became nervous and was unconscious for 15 minutes. Physical examination on admission was absolutely negative. Mentally she was clear and well oriented. Showed a smiling, contented attitude with elevated mood but no marked press of activity. Her mental stream gave evidence of marked distractibility with numerous sound associations. She ivas clean and tidy in her habits, but somewhat careless of personal ex- posure. No delusions or sense falsifications were discovered. Her memory was apparently good and no discrepencies in her story were detected. Im- pressibility was faulty but this was ascribed to distractibility. Following this there was a period of dull depression with lack of energy which was soon followed by rapid physical failure with fainting spells and epileptiform seizures. The diagnosis originally made was that of manic- depressive insanity but the absence of any marked activity and the con- tented character of the mood suggested an inadequacy, with the consequence that laboratory tests were made with the following results: Noguchi butyric acid, Nonne-Apelt and reduction tests on the cerebro- spinal fluid all positive. Cell count, 112 per cub. mm. Noguchi-Wassermann test positive on blood serum and cerebro-spinal fluid (4 plus in both). Other cases might be cited to illustrate the value of the serum test in diagnosis in doubtful cases but these will suffice. Conclusions. 1. The Noguchi modification of the Wassermann test gives very useful and reliable results in the diagnosis of syphilitic and parasyphilitic disease of the nervous system. 2. In general paralysis of the insane a negative reaction in the blood serum is very exceptional. (98 per cent positive in the cases here reported and 90 per cent positive in 1,198 cases from the literature.) In the cerebro- spinal fluid a positive reaction occurs in nearly the same numbers. (96.7 per cent in our cases and 81 per cent in 1,076 cases in the literature.) 3. A negative reaction in the cerebro-spinal fluid with a positive in the blood serum occurs more frequently in cerebro-spinal syphilis than in general paralysis. (123 cases in the literature give 80 per cent positive in the blood serum, while 139 cases give only 29 per cent positive in the cerebro-spinal fluid.) / .UNIVERSITY OF ILLINOIS -URBANA N301 12088567901A