V. SOME RESULTS OF TREATMENT (continued 2)

2. Was the failure to obtain results by long years of treatment due to “drug fastness” of the spirochetes? It has been held that the organism of syphilis will develop an immunity after a time to mercury and arsenic preparations. This led Fournier to recommend intermittent treatment as more efficient than continuous treatment. Noguchi has shown that in test tube experiments, the spirochetes develop a tolerance to increasing doses of arsenic. It must be emphasized, however, that this finding has not been established for the conditions in vivo. Another explanation of the failure of treatment in certain instances has been offered by McDonagh, who describes a life cycle of the organism of syphilis under the name of cytorrhyctes luis, of which he believes the spirochete to be merely one form, the other forms not being affected by arsenic or mercury.

382

Some results of systematic intravenous salvarsan therapy in PARETIC NEUROSYPHILIS (“general paresis”) are partial in the sense that with clinical recovery the laboratory tests remain partially or less strongly positive.

Case 117. Annie Martin was a charwoman, 37 years of age. She had applied for relief at a general hospital, to which she was admitted on the suspicion of nephritis; but upon admission she became markedly excited and noisy, and spoke of seeing angels and hearing God speak to her. As the attendants were unable to quiet her, she was promptly transferred to the Psychopathic Hospital. She maintained that she had been sent to the Psychopathic Hospital through the spite of the general hospital doctors, and she claimed that other people were also attempting to work her harm for the purpose of taking her children from her. Visual and auditory hallucinations were marked, as was the patient’s loquacity, irritability, and flight of ideas. However, she seemed entirely oriented and her memory appeared to be intact. She was able to explain somewhat clearly her supposed condition. The voices told her that somebody was after her and that her soul belonged to the devil; that she was to be married but that her soul was to be damned. These voices probably belonged to priests. She was under the impression that she was going to be sent to an electric chair and said, “I think I am coming to the end and I want a pair of rosary beads before the end comes.”

This patient’s pupils were markedly unequal and entirely stiff to light and accommodation. Neurologically, however, there were no other symptoms. There was a slight trace of albumin in the urine and there were no casts.

The psychiatric diagnosis in this case would off-hand undoubtedly be dementia praecox. Yet the stiff pupils are almost proof positive of neurosyphilis. If further proof were necessary, it is found in the laboratory tests, which 383showed a positive W. R. of the serum and fluid, with a “paretic” gold sol reaction; there were 22 cells per cmm., there was excess albumin, and a positive globulin reaction.

Under intensive antisyphilitic treatment, there was a slow improvement. After several months, the patient was entirely free from mental symptoms; the spinal fluid tests became entirely negative except that the gold sol reaction has remained strongly positive.

1. Should treatment be continued in the case of Annie Martin in spite of the clinical recovery and the negative tests except the gold sol? We would again emphasize that it is unreasonable to suppose that a long-standing case of syphilis can be cured in a period of a few months of treatment and while the tests may become negative, it would seem foolhardy to stop treatment on this account. We do know that in many cases a Wassermann reaction remaining negative for many months may again become positive, indicating that the negative reaction did not mean cure but rather the absence of the Wassermann bodies in the circulation at the time the test was made.

2. What is the significance of the paretic gold sol reaction when the other tests have become negative? As previously stated, the gold reducing substance in the spinal fluid seems to be different from the substances which give the other pathological reactions. We should feel in this case that the process which was producing these gold reducing bodies had not been stopped, in other words, cure was not complete.

3. Should one make a diagnosis on the “paretic” gold sol reaction alone? The so-called paretic gold sol curve is not always indicative of general paresis or even of syphilis but may occur in non-syphilitic conditions as brain tumor, multiple sclerosis, etc. In our experience we have seen no case of untreated neurosyphilis in which the gold sol alone was positive, that is, in cases in which therapy has not changed the findings in the spinal fluid. In our experience the gold sol reaction has been fortified by one or several of the other tests as the W. R., globulin test, pleocytosis.

384

Some effects of systematic intravenous salvarsan therapy in PARETIC NEUROSYPHILIS (“general paresis”) are limited to the laboratory findings without clinical improvement.

Two examples of such limitation are offered: William Roberts (118) and John Silver (119).

Case 118. A bank teller, William Roberts, 39, was sent to the Psychopathic Hospital for a depression so marked that he had become entirely unable to work or care for himself. The story was that some money had been left him by his uncle, that Roberts could not prove his right to the money, and that depression, insomnia, and occasional periods of confusion had followed during a period of about five months.

On admission, Roberts appeared wholly disoriented and unable even to give his correct age. Attention could not be held, and the patient would slide off into statements like: “Oh, I made a mistake, I fooled a lot of people, I have a terrible disease, they are going to get it, they are going to get me,” etc., etc. There was great difficulty in thinking, and a marked reaction of fear. This cluster of phenomena certainly suggested very strongly the diagnosis of manic-depressive psychosis.

Neurologically, Roberts proved quite negative except that the tendon reflexes were very active and the pupils reacted somewhat sluggishly to light. The blood serum W. R. was negative. No history of syphilis could be obtained; nevertheless, Roberts kept dropping remarks about the terrible disease from which he was suffering. It seemed best to proceed to lumbar puncture, and the spinal fluid disclosed a positive W. R., globulin, increased albumin, pleocytosis, and “paretic” gold sol reaction.

The diagnosis of General Paresis was accordingly made. During the next year and a half, no improvement was made; a slight speech defect was developed, and tremors of the hand and tongue appeared.

385The effect of treatment is particularly instructive. Only after 18 months in the hospital was intensive antisyphilitic treatment instituted; but after a few months of this treatment the W. R. of the spinal fluid had become negative, the cells normal in number, globulin absent, albumin present only in normal amount. Only the gold sol reaction remained positive. It is still of a paretic type. Treatment, however, did not succeed in altering the patient’s mental condition in the slightest. At the end of many months of treatment, we still confront a man showing marked psychic symptoms and a “paretic” gold sol reaction without other laboratory signs.

1. What is the significance of the practically negative tests in this case without clinical improvement? One must believe that the tests became negative as the result of treatment, and that this change in the tests was due to the clearing up of some inflammatory reactions which were present. This may mean that the syphilis had been reduced to inactivity or latency if not cured, or at least that there was no activity sufficient to cause a positive W. R. in the blood serum, whereas whatever activity was present in the brain was in such a region that it did not cause any reacting substances to be cast into the spinal fluid. This would not mean that there would necessarily be any return of function already lost, because this may be considered as a permanent loss which cannot be compensated for. As to these tests, we now feel that the case should remain stationary; that is, that no new symptoms will be added. However, we believe that it is somewhat premature with our present knowledge to make this claim very forcibly, and would rather suggest that this case be considered as demonstrating an interesting fact, the meaning of which can be learned only after a period of years.

2. Why does the gold sol reaction remain strongly positive when all the other tests become negative? As already pointed out, above (Case Martin (117)) there is no known rule about the disappearance of one or other of the abnormal findings in spinal fluid under treatment, and we can at present offer no explanation of this phenomenon. It does, however, illustrate how careful we must be in drawing any conclusions from tests in cases that are being treated.

386

Diminution in the spinal fluid tests may occur in treated cases of neurosyphilis without clinical improvement.

Case 119. John Silver, a man 29 years of age, presented classical symptoms of General Paresis: He had a convulsion shortly before his admission to the Psychopathic Hospital, his memory was poor, he was only partially oriented, he was very euphoric and expansive—thought he had millions, that he was the Czar of Russia, and so on. His tendon reflexes were very much increased and there was a marked speech defect. The W. R. of both blood and spinal fluid were strongly positive; the spinal fluid showed globulin, increased albumin, pleocytosis, and a “paretic” gold sol reaction. There was, therefore, no question about the diagnosis, and the patient was at once put under antisyphilitic treatment. This was continued for five months; slowly the intensity of the reactions in the spinal fluid diminished. At the end of the five months, there was the very slightest possible trace of globulin, with a doubtful increase in albumin, one cell per cmm., and a mild syphilitic gold sol reaction. The W. R.’s in the blood and spinal fluid, however, remained strongly positive. There was no mental improvement coincident with the weakening of the spinal fluid tests, and at the end of the five months, the patient had a series of convulsions in which he died.

This case is given as a contrast to Case Henry (114) in which clinical improvement occurred without diminution in laboratory tests; in the case of John Silver, marked diminution in the intensity of these tests had no prognostic significance. This was in keeping with the condition as shown in Case Roberts (118) where, while the gold sol was the only test to remain positive, the patient did not improve mentally.

1. What is the explanation of the lessening of the pathological elements in the spinal fluid under treatment? We have seen that the various findings may occur independently 387of one another, and we must admit that we do not know definitely what it signifies, or why one may be present or absent. It has been held by Head and Fearnsides that the findings in the spinal fluid represent conditions in the spinal cord and spinal meninges, or at the base of the brain only, and not conditions elsewhere. This is in keeping with our finding that the gold sol reaction in the spinal fluid post mortem very often differs from that in the ventricular fluids or cerebral, subdural, and subpial fluids. And further, we have found that during life the findings in paresis in the spinal fluid may differ markedly from those in the third ventricle, and that the change in the fluid in these two areas under treatment may not occur simultaneously.

388

Systematic intensive treatment of PARETIC NEUROSYPHILIS (“general paresis”), including intraventricular injections of salvarsan, may entirely fail.

Case 120. James McGinnis, aged 39, came to the hospital on a stretcher, semi-conscious, moaning, unable to reply to questions; there were signs of a right hemiplegia.

The next day, McGinnis cleared a little and became able to utter a few words. His wife said that he had been entirely well up to four years ago. At that time he was struck in the eye by the head of a hammer that flew off the handle. Diplopia had developed, but disappeared.

Only two years later did a marked change appear. McGinnis became careless as to personal appearance. Seemed absent-minded, apathetic and drowsy; he would fall asleep in his chair or while at work. He lost his position and became apprehensive, making not very strenuous efforts to find work, and finally consulted a physician. The physician told him that he had a sluggish liver and gave him calomel.

Six months later, McGinnis was restored to his position as foreman, and his work remained satisfactory for some six months. Then (about six months before coming to hospital), his speech became slow and somewhat unintelligible. He quit work, saying that his speech was going from him and that he might be considered to be drunk. His memory grew rapidly worse. There was improvement after a vacation and he returned to work, but continued to be ataxic, complained of vertigo, and fell down several times, though without loss of consciousness. On the very day of his admission to the hospital, in attempting to get out of bed, he fell, and psychotic symptoms at once appeared. There was slight improvement again with entire disappearance of all paralysis after a few days, a slow clearing up of the speech disturbance, and a certain return of memory.

Physically, there was little to note. Neurologically, the left 389pupil failed to react to light. The tendon reflexes were all very active, and more active on the left side. Other abnormal reflexes were absent. Improvement continued for a number of weeks, but the patient never recovered from his speech defect, and his memory remained impaired. Irritable at times, McGinnis was for the most part very happy and sure he would get well. The W. R. of the blood serum was negative, but the spinal fluid reaction was strongly positive, even down to 0.1 cc. The globulin and albumin amounts were excessive. There was a “paretic” gold sol reaction. There were 7 cells per cmm. The diagnosis of General Paresis was made.

Intravenous injections of salvarsan, arsenobenzol or diarsenol were made, and intramuscular injections of mercury, and potassium iodid by mouth were given. No real improvement occurred after a certain initial betterment; the spinal fluid yielded no changes. Diarsenolized serum according to the Swift-Ellis technique was then injected into the third ventricle. Under this treatment also there was no change for the better over a period of several months. The patient died suddenly after a series of convulsions, apparently from paralysis of respiration.

1. What are the causes of hemiplegia and confusion or unconsciousness? We must consider epilepsy, brain tumor, cerebral thrombosis, cerebral hemorrhage, multiple sclerosis, cerebral spinal syphilis, and general paresis.

390

MILD TREATMENT, often thought “adequate,” MAY FAIL, WHEN INTENSIVE TREATMENT PROVES SUCCESSFUL.

Case 121. Arthur Bright, a printer, had acquired syphilis in his 49th year, some six months before examination. He had been treated during these six months by three injections of salvarsan, injections of mercury, and mercury by mouth. He had been apparently cured until about a month before admission. He had fallen without warning from his chair in a convulsion accompanied by unconsciousness, which lasted about two hours. The patient had since been feeling rather peculiar. For instance, time seemed to flow too rapidly. Sometimes the patient had had difficulty in talking.

Physically, nothing abnormal could be found either in general condition or neurologically. The patient was, however, incontinent. Mentally, he was apathetic and unalert, even paying no attention to his outside physician when he came to visit him.

The diagnosis of cerebrospinal syphilis already suggested by his history was confirmed by the laboratory tests, which showed a positive serum and spinal fluid W. R., paretic gold sol reaction, 41 cells per cmm., an excess of albumin, and a positive globulin test.

1. What is the prognosis in cerebrospinal syphilis in the early secondary stage? The prognosis appears very good provided that intensive treatment be given and provided that no vascular insult or other focal destructive lesion occurs before treatment has had time to do its work.

2. Why did not the “effective” (?) treatment for the syphilis, dating from the primary lesion, succeed in staving off the cerebrospinal syphilis? It remains a question whether the treatment by three injections of salvarsan was efficient in this particular case. Of course, it may prove true that no treatment whatever in the present stage of knowledge will stave off cerebrospinal symptoms in certain cases.

391Treatment: Bright was given intravenous injections of diarsenol twice a week, with occasional injections of mercury salicylate. After two weeks, the patient seemed markedly improved, and continued to improve rapidly. He was symptomatically well at six weeks. The spinal fluid had then become negative, although the serum W. R. had remained positive.

After discharge from the hospital, Bright returned to his work, but continued to take the diarsenol treatment weekly, and two months later the serum W. R. became negative.

Small injections of diarsenol at intervals of a month were continued, and Bright remained perfectly well for four months, when a peculiar seizure developed and lasted for several hours. This seizure consisted in a sort of somnambulism in which Bright stood up at a table, making marks on paper, and could not be persuaded to desist. After this seizure, Bright re-entered the hospital, again showed no mental or physical symptoms and no abnormalities of blood or spinal fluid.

3. What is the explanation of this seizure? It is possibly due to a small vascular insult, for which potassium iodid may be suggested with precautions as to hygiene and continued observation. He has since remained entirely well.

392

Another example where MILD MEASURES (though conceived to be “adequate”) SEEMED TO BE LEADING TO FAILURE; INTENSIVE THERAPY SUCCESSFUL.

Case 122. Levi Morovitz, a waiter, 39 years of age, came to the hospital with evidences of an old left hemiplegia, including the left side of the face (there was a left-sided Babinski, Gordon, and Oppenheim, and all the reflexes were fairly active; sluggish pupil reactions, Rombergism, and speech defect). Morovitz was much depressed, very slow in thinking processes, had a marked memory disturbance in general and apparently much deterioration mentally.

A history was obtained to the effect that Morovitz had acquired syphilis at about 33, but that he had received practically continuous treatment ever since at a dispensary. He had, in fact, received four injections of salvarsan a year before coming to the hospital. Of late, Morovitz had become much more cheerful and talkative, imagining he could do great things if he had money. He had begun to eat very rapidly and to be very nervous. His feet had begun to drag; a distinct speech defect developed, but from this he had recovered. About six weeks before entrance, Morovitz had a shock, which left him with the left hemiplegia above mentioned and with considerable headache.

Even while the preliminary examination was being performed, Morovitz developed a minor seizure without loss of consciousness. First came severe pain over the frontal region, which grew in severity so that the patient held his head in his hands. A bit later, twitching movements began in the thumb and in the fingers of the left hand, and the small muscles of the extensor group of the thumb and third finger showed contractions. These contractions grew more general and the excursions of the fingers greater, until finally every finger of the left hand became involved, whereupon movements of the same sort, though of smaller amplitude, 393began in the other hand. Finally the left arm began to jerk with alternate contractions of the biceps and triceps. The whole seizure lasted more than five minutes. During the seizure there was dizziness and pain in the head, chiefly on the right side.

Diagnosis: The attention is at once arrested by the data of the seizures described. It appeared that we had to assume an irritation of the right side of the brain, possibly due to vascular disease, or to brain tumor, or perhaps to syphilis. The shock with residual hemiplegia would be consistent enough with any of these diagnoses. However, the history seemed somewhat long for brain tumor. Nor were there any definite symptoms of intracranial pressure. “Adequate” treatment unfortunately does not rule out syphilis. The comparatively early age (39) of the patient makes it difficult to explain the vascular disease except on the basis of syphilis. Add to the hemiplegia the euphoria and grandiose ideas of a year’s duration, and we arrive at a diagnosis of neurosyphilis, probably Paretic Neurosyphilis.

The laboratory tests showed the W. R. of the serum and spinal fluid positive, 80 cells per cmm. in the fluid, large amounts of globulin and albumin, and a “paretic” type of gold sol reaction.

To be sure the Jacksonian seizure is not especially characteristic of paretic neurosyphilis, and even suggests a local irritation in the motor area, such as a localized meningitis, possibly of a diffuse gummatous nature.

This patient was put on intensive antisyphilitic treatment, namely, salvarsan twice a week and injections of mercury. He recovered rapidly. After a few months he left the hospital, and after treatment had continued for a year, he resumed his work by which time both blood and spinal fluid had become negative.

It must be recalled that this patient had from the time of his infection what has been considered good antisyphilitic therapy, in spite of which he developed after a period of years, the symptoms and signs of neurosyphilis in its most dangerous form. The conclusion must be drawn that however good such treatment is for the majority of cases, it 394was insufficient for Morovitz. That the early failure to cure was not due to any “drug fastness” of the spirochete or to any peculiarity of strain is proved by the result of more vigorous antisyphilitic treatment which caused an apparent if not a real cure. With our modern methods of treatment checked by Wassermann reactions and spinal fluid examinations, treatment is given according to the needs of the individual patient rather than according to general preconceptions. We have reason to believe that under these conditions there will be fewer cases developing late symptoms on account of insufficient treatment given even to patients who are willing to co-operate to the last degree.

The fact that Morovitz had no apparent symptoms for several years led to rather desultory treatment chiefly in the form of mercury by mouth. Previous to the time when the W. R. and lumbar puncture were available, the physician had no exact means of determining cure except the non-appearance of symptoms. But a period of years of quiescence before the outbreak of symptoms referable to the involvement of the nervous system is characteristic of syphilis. With this knowledge in mind it is evident that today the care of a syphilitic patient must be guided, in part at least, by examinations of the spinal fluid and W. R.

395

Salvarsan treatment may even occasionally be of value in simple FEEBLEMINDEDNESS due to congenital syphilis.

Case 123. The somewhat unattractive Robert Matthews was brought, at 5 years of age, to the hospital for backwardness of mind. It appears that the patient was born at term, with instruments, that he began to talk at a year, and to walk at 13 months, but that in point of fact, he had not talked intelligibly to date. Robert had never played with other children and is regarded by his parents as backward. In fact, Robert’s sister—a year his junior—is much brighter. Robert had had scarlet fever but without sequelae.

Examination by the Binet scale showed that, although he is actually 5½ years, he graded by the Binet scale at 4 and was regarded as feebleminded.

The physical examination showed a general adenopathy and prominent frontal bosses. In the study of the family history in the search for an etiology for the evident feeblemindedness, little or none could be found. There were no miscarriages or stillbirths; the parents were living and well. There was only the one sister above-mentioned, who is brighter than Robert.

The advantage of a routine W. R. is here well shown, for the W. R. in the serum was positive.

1. What is the prognosis of cases of syphilitic feeblemindedness? It would appear that every case is an individual problem.

2. What is the effect of treatment? Robert Matthews was given mercury protoiodid ⅛ gr., three times a day, by mouth, for three months. The protoiodid was followed by ten injections of salvarsan, average: 0.15 gram, during six months. At the end of this period, the W. R. in the blood had become negative. A re-examination by the Binet scale, when Robert was 65 12 years of age, showed him to grade at 5⅖, so that one might conclude that Robert had shown more mental progress in a year than he had previously.

396Note: The patient’s sister, 4 years of age, is attractive and bright, measuring beyond her actual age according to the intelligence tests. However, the girl was found to have a positive W. R. It may be that Robert and his sister illustrate the hypothesis of Mott: that the syphilitic virus becomes less potent as the years go on, and that the younger children in the family are less affected than the older. However, in our series, there are a number of instances in which this hypothesis is not substantiated.

3. What is the share of syphilis in the production of feeblemindedness? The percentage of syphilitic cases found in institutions is not high. A variety of cases have been proved to be congenitally syphilitic in the absence of a positive serum W. R.

Fernald^[19] has charted a comparison of cases diagnosticated “moron” (that is, feeblemindedness proper, in the narrower English sense) and “imbecile.” Fernald says that the morons have, as a group, many more bad family histories than have the imbeciles, to quote—“Only 70% of the [imbecile] group have bad family histories. This at first seems surprising, but when we consider that more of our syphilitic, traumatic, and sporadic cases tend toward the lower end of the feebleminded group, and when we remember that with such cases there is often a seemingly normal family tree, the drop in the curve appears logical.”

The situation with the idiots, of whom only 38 came into Fernald’s study, was similar; 12 out of 38, or 32%, of idiots, had good family histories. On these figures, how unfortunate it would be to dub feeblemindedness hereditary! It is true, however, that 68–70% of the idiots and imbeciles, judging by W. E. Fernald’s intensive study, do have bad family histories.

Goddard^[20] states that of all the causes of feeblemindedness, 397there is perhaps none for which there is less evidence than syphilis. Goddard found syphilis in 27 of his intensively charted cases of feeblemindedness, that is, in 9% of all his charts. He finds the majority of the syphilis cases occurring in relatives of the feebleminded to be in the hereditary group; for example, of 164 charts in the hereditary group, 17, or 10%, showed syphilis. In 34 charts in a group termed “probably hereditary” 3, or 9%, showed syphilis. Of 37 charts in the group termed “neuropathic” 4, or 11%, showed syphilis, whereas in 57 “accident” and 8 “no cause” groups, there were but 2 (4%), and one, or 13%, showing syphilis. However, Goddard concedes that much more careful studies are necessary if we are to give an exact evaluation of syphilogenic feeblemindedness.

The first ten of the Waverley Anatomical Series are shortly to be described in a forthcoming publication.^[21] Of these ten cases, four showed some slight evidence of chronic inflammatory changes, indicating the possibility of a syphilitic or similar infectious condition. These cases, be it remembered, were not cases of juvenile paresis, but cases of what, for the lack of a better name, may be called “ordinary” feeblemindedness.

If all or any of these processes are syphilitic, the syphilis is virtually extinct. The cases had not been treated for syphilis and were not regarded as syphilitic, though several of them showed a few stigmata somewhat suggestive of syphilis. The anatomical conclusion at this time is still doubtful.

As in the text case, the hypothesis of syphilis as a direct cause for simple feeblemindedness must be entertained for a few cases. In any event, it would not seem logical to let any institution for the feebleminded run without a Wassermann analysis of the population. In addition to the Wassermann data from the blood serum, osteological data from the X-ray have proved of occasional value for syphilis diagnosis in this as in other groups.

398

“Within the gates of Hell sat Sin and Death.”

Paradise Lost, Book X, Line 230.

399