Part 30
Treatment in this case consisted of intravenous injections of salvarsan, diarsenol, or arsenobenzol, whichever drug was most easily obtainable, given twice a week in doses of 0.6 gram each. In addition, he was given occasional injections of mercury salicylate as well as potassium iodid by mouth. Once or twice a week, 40 to 60 cc. of spinal fluid were withdrawn. Under this treatment for a period of three months, the patient showed no improvement whatsoever, either in his mental condition or in the laboratory findings. However, treatment was faithfully persevered in, and shortly after the three months, improvement began to be noticed. At first, the patient began to admit that possibly he may have slept a few winks some time during the previous six months, for he said he realized it was not possible for a man to live without sleep for that period. Then he began to admit that he might have slept a few hours during the night, and later that he was sleeping pretty fairly. His memory also showed improvement. His general attitude showed alertness, and he began to interest himself in his surroundings and in the events of the world, and finally he gained complete insight into his condition.
In the meantime, that is after three months of treatment, the laboratory findings began to grow weaker. The gold sol reaction was the first to decrease in strength, and after four months of treatment, it vacillated between negative and a mildly positive “syphilitic” reaction. Then the globulin and albumin became less in amount, and the W. R. began dropping off in the 0.1 and 0.3 cc. dilutions. As is usually true in those cases of neurosyphilis that receive adequate treatment, the cell count early dropped to normal. The W. R. in the blood serum, however, remained positive.
As the patient’s condition seemed so much better, he was allowed to leave the hospital at the end of five months. He took things easily for the following seven months, and then, after being out of employment for the period of a year, as his health continued good, he decided to return to work. Before doing so, he entered the hospital again for a lumbar puncture. At this time, it was found that the cell count was normal, there was a very faint trace of globulin, possibly a slight increase above normal albumin content, and a very mild gold reaction. The W. R. in the spinal fluid was negative including the 1.0 cc. dilution; the blood serum remained positive.
The patient then returned to his old position and has done satisfactorily for the past six months. During this entire time, he has been coming to the hospital for treatment: during the major portion of the time, about once in two weeks; of late, once in four weeks.
The significant point in this case is that improvement did not show itself until after more than three months of intensive treatment, and then the improvement was synchronous with a weakening of the spinal fluid tests.
It is further significant that his mental and physical condition was good before the tests had reached anything like normal; and that under treatment, these tests continued to grow weaker and weaker, until at the end of a year, they were practically negative.
The case further illustrates the enormous number of injections of salvarsan preparations that may be given to a patient without causing any appreciable damage to the general health or to the kidney function. Mr. Ryan has had more than 60 injections.
1. How soon after treatment is instituted does improvement usually occur in paretic neurosyphilis? In our experience improvement usually shows itself in from two or three months of treatment. Occasionally the improvement may be very marked shortly after treatment is commenced, that is, after three or four injections of salvarsan. This is not, however, the rule and as in the case of Ryan, it may be only after more than three months that improvement is seen. This means that in the treatment of these cases patience must be exercised and much work done.
2. What is the point of withdrawing large amounts of spinal fluid as in the case of Henry Ryan? It has been stated that the withdrawal of 40 or more cc., of spinal fluid while the patient is under treatment has the effect of reducing the intraspinous and intracranial pressure and thereby allowing the drug to diffuse into the nervous tissue better than it would do under ordinary conditions. How much truth there is in this contention it is difficult to say and there is as yet no experimental evidence to confirm this contention. As a matter of fact, the spinal fluid in cases of paresis is usually under increased pressure and it is at least plausible to conceive that a reduction of this pressure may give some symptomatic relief.
=Evidence of the activity of syphilis outside the central nervous system may be seen in cases of neurosyphilis despite intensive treatment.=
=Case 116.= William Rosetti was a speculator, 43 years of age, when he was brought to the Psychopathic Hospital on account of an outbreak in which he smashed a showcase at the store where his sweetheart was employed; he caused so much commotion that he was arrested.
On admission, he was very excited, talking loudly and at length. For some days it was very difficult to manage him, he was so active. At any moment, he would insist upon undressing and taking physical culture exercises. He was very euphoric and expansive, and had no insight into his condition.
=Physically=, he was a powerfully-built man and in very good physical condition except for an iritis and moderate thickening of the peripheral arteries. The =neurological signs= of importance were Argyll-Robertson pupils, and absent knee-jerks and ankle-jerks. With these findings in mind, a tentative diagnosis of GENERAL PARESIS was made, and this was substantiated by the laboratory tests, which gave positive W. R.’s in blood and spinal fluid, globulin, excessive albumin, slight pleocytosis, and a “paretic” gold sol reaction.
When the patient’s mental condition was somewhat better, he gave a history of syphilitic infection 15 years before, for which he had had almost continuous treatment. As a matter of fact, treatment had been pretty strenuous because he had recurring skin lesions and iritis. It was practically impossible to get the skin lesions to heal with mercury, and it was not until salvarsan was introduced that a good result was obtained in this respect. After one or two injections of this drug, the skin lesion disappeared and has never returned. However, at least once a year, he has had attacks of iritis, and for this reason was still being treated for syphilis at the outbreak of his psychosis.
He was at once placed on more strenuous antisyphilitic treatment in the form of diarsenol, semi-weekly, aided by mercury injections. After a few months of this treatment, his mental condition improved so much that he seemed to be entirely normal. Treatment was continued, however, without any abatement, and it was of great interest to note at the end of five months of such treatment that, although mentally he seemed entirely well, he had an attack of iritis, which was considered as a sign of active syphilis. This would appear to indicate the great difficulty of getting results in certain cases of syphilis with any drugs at our command at present, as in the iritis we are dealing with a condition which as a rule reacts fairly readily to antisyphilitic remedies.
1. Are there different strains of spirochetes showing various degrees of malignancy? This question has been discussed at length in the literature but there is no satisfactory answer at the present time. We must always consider the reaction of the organism and the host; and it is true in syphilis, as in every other disease, that in some individuals it is more difficult to get any therapeutic results than in others.
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.
=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 showed 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.
=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.
The 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.
=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 of 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.
=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 pupil 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.
=MILD TREATMENT, often thought “adequate,” MAY FAIL, WHEN INTENSIVE TREATMENT PROVES SUCCESSFUL.=