Section Vi, Neurosyphilis and the War.

=Traumatic exacerbation(?) in PARETIC NEUROSYPHILIS (“general paresis”).=

=Case 92.= The case of Joseph Larkin was of note from the point of view of the Industrial Accident Board. This Irish teamster was said to have been injured in his head two or three months before coming up for examination at the age of 45. For a week Larkin had had frontal headaches, had been sleeping poorly, and had been somewhat worried. In fact, he had stopped work. The W. R. of the serum was positive and a diagnosis of PARESIS could be made. The case did not come up for consideration by the Industrial Board until two years after his initial appearance.

The =physical examination= showed irregular pupils, sluggish pupillary reactions, Achilles absent, swaying in the Romberg position, enlargement of the heart to the left, positive W. R. of the blood and of the spinal fluid.

=Mentally=, the patient’s orientation for place was poor and his memory defective. Emotionally he was depressed or apathetic and was apprehensive. His flow of thought was slow, and his insight into his condition poor.

It is interesting that a variety of causes have been assigned in this case for the condition: such as, his work, anemia, unhygienic surroundings, and arteriosclerosis.

This case is not a sharply-defined case of post-traumatic general paresis, since there had undoubtedly been a variety of mental changes before the accident. Accordingly, recovery of damages to a full amount could hardly be expected as in certain cases in which the phenomena of paresis appear only after the trauma.

Post-traumatic cranial gumma—developing 13 months after local injury of skull. ]

=Trauma: syphilitic lesion of skull at site of injury.=

=Case 93.= The medicolegal interest of Richard Marshall is extreme, as may be seen from the following brief report by the Psychopathic Hospital to the Industrial Board.

“As to the case of Richard Marshall, a patient under the provisions of the temporary care act from December 1 to December 10, inclusive, this case has proved unusually interesting in that the patient has proved to be syphilitic by the Wassermann reaction of the blood. There is no evidence of syphilis in the examination of the cerebrospinal fluid. The X-ray examination of the skull, taken in connection with the Wassermann reaction of the blood, warrants the diagnosis of syphilitic osteitis of the skull at the site of the old injury. We regard his present condition as shown by the X-ray as a syphilitic bone condition predisposed to by the injury. We do not find that the patient has any features of traumatic neurosis.

“Mentally, having an actual age of 30, patient grades at 11.2 years. It may be that patient has always been a moron. He has earned about $8.30 a week.

“We regard the patient as deserving treatment and feel that responsible parties in the case would do well to have such treatment instituted.”

The principal symptom of which Marshall complained was headache chiefly felt in the region of the osteitis. There was marked sensitiveness to percussion in this area. It is of course difficult to decide whether the headache was entirely due to the gummatous lesions or whether the trauma had caused contusions of the brain as well. It is also possible that the dura underlying this area was involved.

=OCCUPATION-NEUROSIS in a granite-cutter: SYPHILITIC NEURITIS?=

=Case 94.= David Fitzpatrick was a case referred to the Psychopathic Hospital by the Industrial Accident Board. He was a granite-cutter of 52 years of age, and had begun to complain of pain in the forearm, extending back from the elbow, about six months before admission. It seems that the patient had been growing progressively worse and had thought he would have to quit work because of difficulty in grasping the hammer. A physician had told him that he must stop his work at granite-cutting or else he would entirely lose the use of his arm. He was in point of fact laid off because of slackness of work and had been unable to get work again. The pain in the arm, however, had continued and at times was very severe. Sometimes the pain and the worry led to insomnia. Fitzpatrick wanted the insurance company to pay certain accumulated bills, and maintained that he would be able to do work at $15 a week if work could be found for him. The general situation in this case can be gathered from the following abstract from the report to the Industrial Accident Board.

“Secretary Industrial Accident Board, “Dear Sir: “In re David Fitzpatrick

referred to us with a copy of an impartial report filed by the Massachusetts General Hospital,—we concur with said impartial report that there is now no evidence of paralysis of the arm. We do not find that the positive Wassermann reaction, although it indicates a history of syphilis, has affected the patient other than possibly to have reduced his general mental capacity. Our special tests yielded a percentage of 62% of what a patient of his age and station should possess. There seems, however, to be no connection between this reduction of mental capacity and the difficulty with the arm. We cannot connect the history of alcoholism with the arm trouble.

“There is some evidence that other stone workers have at times shown such effects.

“The patient’s fairly circumstantial account of his difficulty seems to point to a degree of myalgia or muscular pain in the region of the forearm when held in a certain position and a feeling of numbness in the third and fourth fingers. Whether these phenomena are due to local pressure upon nerves in the upper part of the forearm due to neuritis, or whether we are dealing with a functional neuralgic phenomenon is a question.

“We have applied some special tests for faradic sensibility to all the fingers of both hands and have found that the fingers of the right hand are still less sensitive than those of the left, particularly the thumb and the little finger. This test has not yet been applied in a sufficiently large number of cases to prove any difficult point, nevertheless the findings are in line with the patient’s own circumstantial account of former feelings of numbness in the third and fourth fingers of the right hand.

“Obviously, then, our opinion is that there is still to be found some effect of the disease, whatever it was, which caused the patient to knock off work. If we had more experience with such cases and more data with the new test which we have applied, we should perhaps be inclined to admit the diagnosis of occupation neuritis and to suppose structural alterations in the nerve trunks corresponding with the location of the muscular pain and the anesthesia of fingers and the dulling of electric sense, but in the present stage of our experience, it is probably wiser to call the case one of occupation neurosis.”

It is clear that the W. R. in this case was of peculiar value in at least partially clearing up the findings, yet it must be remembered that it is a principle of the modern administration of industrial accident boards and similar organizations that it is the employer’s lookout whether the employee has syphilis. Recovery can be made as if the injury were due wholly to an accident. It was not possible however definitely to prove or disprove a relation of syphilis in the form of a syphilitic neuritis to the condition in this case.

The special tests above referred to are the electric sensory threshold tests of E. G. Martin.

=Character change: neurosyphilis.=

=Case 95.= Joseph Wilson offered a very serious social problem. He was the father of two children, and his wife was pregnant at the time of his admission to the Psychopathic Hospital. He was a husky-looking man of 33 years of age, but for the past four years he had been deteriorating in his work; he had been drinking heavily, and finally had stolen to obtain money for liquor. It was on account of his alcoholism and delinquency, which were taken as an indication of change of character, that he was sent to the hospital.

Examination on his arrival disclosed at once that there was more to the case than alcoholism, for the =neurological examination= showed that the pupils were irregular, the right being larger than the left, both reacting sluggishly to light, and there was an inequality in the reaction of the two eyes, the left being better than the right. The tendon reflexes were exaggerated, with ankle clonus on both sides, more marked on the right. There was also a marked speech defect. Otherwise the =physical examination= showed nothing of importance.

The W. R. of the blood and spinal fluid was strongly positive. The globulin test was strongly positive, the albumin was markedly increased, there were 74 cells per cmm., and a gold sol reaction of the “paretic” type.

A formal =mental examination= did not show very much of consequence; his memory showed no marked impairment, he was not deluded or hallucinated, and he had a pretty good insight into his failings. However, he was somewhat childish, and his irritability was quite marked. Were one to rely upon the mental signs alone, it is probable that a diagnosis of chronic alcoholism with deterioration would be made; but in the presence of the physical findings and the laboratory tests, the diagnosis of neurosyphilis had to be given. It is obvious that, while the patient was suffering from a progressive brain disease, and while he did show mental symptoms, there was not sufficient ground on which to commit him, and therefore he had to be turned out into the community. As a matter of fact, he was not prosecuted on account of his theft, because, although legally responsible, it was felt that his disease was at the basis of the character change which had led him into difficulties. Further developments of his relations with society had to be considered, however. It was possible to get him to discontinue the use of alcohol altogether, and for nearly a year he has taken no alcoholic liquor and has been self-supporting. However, his irritability has been very great, making it very difficult for his wife to live with him, and causing his sister to break off all relations with him.

Here, then, is a man with a marked CHARACTER CHANGE as the result of neurosyphilis, so that it is difficult for him to maintain the usual social relations. It does not seem possible to remove him from the community.

1. May one speak of general paresis without mental symptoms? If one considers general paresis a mental disease, of course it cannot exist without mental symptoms. However, if one considers the disease as a chronic syphilitic meningoencephalitis characterized by its pathological anatomy, then one may readily speak of general paresis although no real evidence of mental symptoms can be discovered. It would seem that we must take this attitude with our present conception of brain localization, for it is easy to conceive of a general paretic process affecting areas which do not definitely relate to psychic function. And further, such a process may exist but not be of such a grade as to cause mental symptoms.

=The neurosyphilitic’s family should not be forgotten in diagnosis and treatment.=

=Case 96.= The Bornstein family is remarkable. Let us hang the story on Becky, the mother, an Austrian woman of 43 years, who appears to have been perfectly well up to within a year. About a year ago, Mrs. Bornstein began to suffer from severe headaches, which were treated with apparent success by an osteopath: at all events, Mrs. Bornstein recovered therefrom in about six months. However, two months later, she had a convulsion, with foaming at the mouth, blueness of face, and general muscular stiffening. The convulsion lasted for several minutes. Again, a fortnight before admission, the patient had five convulsions of an identical nature in a single night.

Moreover, since the first convulsion, Mrs. Bornstein’s =mental condition= has altered and become variable, so that at times she is excited, at times depressed. She would assert inaccurately that there was some one in the house, and that she had at different times committed crimes of a heinous nature. Now and then she would seem to see moving pictures. Her memory was poor and she seemed to believe that events of five or six years ago had just happened.

The pupils were sluggish, the knee-jerks and ankle-jerks were absent, there was slight ataxia, and there was speech defect. The suspicion of neurosyphilis was so strong that it seemed surprising that the W. R. of the blood serum, even after repeated tests and after the provocative injection of salvarsan, proved negative. However, the spinal fluid yielded a positive W. R., and a gold sol reaction of the “paretic” type, together with 12 cells per cmm., and a marked increase of albumin, with positive globulin. It would seem warrantable to make a diagnosis at least of syphilis of the nervous system in this case, but it is a question whether we should be warranted in making the diagnosis general paresis.

That the diagnosis is doubtful may perhaps be seen from the variety of diagnoses in the rest of the family. In the first place, Mrs. Bornstein’s husband admits syphilitic infection many years before. He states also that his wife after marriage showed signs of syphilis and received some treatment, although limited. It is stated also that the husband himself at this time has a positive W. R. and has stiff pupils and petit mal attacks. The oldest son, 22 years of age, is confined in an institution with juvenile paresis. The second son has recently died at the age of 20 years, receiving a diagnosis of rupture of the aorta. A third son, 19 years of age, has the appearance of having achondroplasia, although the proportions of his limbs do not quite correspond with those of an achondroplast. The fourth son, 17 years of age, is suffering from caries of the spine. A fifth son, 14 years old, is neurotic and has the so-called Olympic forehead. The sixth and last son died shortly after birth of unknown cause.

=Neurosyphilitic’s normal-looking family proved syphilitic.=

=Case 97.= Walter Heinmas was a draughtsman 33 years of age when he was brought to the Psychopathic Hospital suffering from mental disease. This was diagnosed as general paresis, both on account of the clinical symptomatology and on account of the laboratory findings. In fact, it was a case of the classical type with marked euphoria and grandiosity.

As is the routine procedure at the Psychopathic Hospital, in the case of all syphilitic patients, the family was sent for. This consisted of the wife and two daughters, aged 9 and 7 respectively. The patient denied any knowledge of a syphilitic infection. The wife, also, gave no history of any primary, secondary, or tertiary symptoms; there had been no abortions, miscarriages, or stillbirths; both children had been born at term and had been entirely healthy. Examination showed that the mother had no signs referable to syphilis, and that both the children were mentally well endowed, with good physique and showing no stigmata of congenital syphilis. Still the W. R. of all three (the mother and the two children) was positive in the blood serum. These tests were repeated several times on the children, with and without injections of salvarsan, and they remained consistently positive.

1. Are these children to be considered congenital syphilitics despite the absence of stigmata or symptoms? We must consider these children as congenital syphilitics and candidates for the group frequently spoken of as syphilitis hereditaria tarda.

2. What is the frequency of syphilitic involvement in the mate and children of paretics? In our series, we have found that about 15% of the marriages where one member develops paresis, result in sterility; that in 18% abortions, miscarriages and stillbirths occur; and that in 15% positive W. R. is obtained. We have adopted the motto: “=The families of paretics are the families of syphilitics.=”

=Neurosyphilis: question of marriage.=

=Case 98.= Mr. Jacobs’ wife was admitted to the hospital with a diagnosis of general paresis. A few weeks after her admission, she died as a result of her disease. According to our routine, her husband and the children were examined for evidences of syphilis.

Mr. Jacobs’ blood serum was found on repeated tests to be positive. He resolutely denied any knowledge of a syphilitic involvement, but it was later learned from his brother that about two years before his marriage—that is, more than 25 years before we saw him—he had acquired syphilis and had had a very small amount of treatment.

Mr. Jacobs was put upon antisyphilitic treatment in the form of injections of .3 gram of salvarsan every two weeks with occasional intramuscular injections of mercury salicylate. After seven months of treatment, the blood serum still remained positive. At about this time, the patient came to us to ask about getting married again. He said that he was living with his sister, who kept telling him that he was the cause of his wife’s death, and this was so unpleasant that he desired to start a home for himself again!

1. What advice should be given? It is a general opinion that the longer the period after the initial infection, the less the chances of infecting a partner. This chance is further reduced under antisyphilitic treatment, of which a considerable amount had been given in the case of Mr. Jacobs. However, when one considers the trickiness of syphilis and the fact that there is some chance of infection, which we would apparently overlook if we gave him permission to marry at this time, the only possible course was to tell the patient that he should not consider marriage until his Wassermann had become negative and remained so for some time. The children in this case were negative.

2. What is the physician’s duty to the family of a syphilitic patient? It is our firm conviction that it is the duty of every physician to his syphilitic patient, to the patient’s family, and to the community, to examine the mate and the children for evidence of syphilis acquired or congenital and to offer treatment if it is found to be needed. This is one of the chief means at our disposal today to prevent the late disasters of syphilis, acquired or congenital, for by such examinations the syphilitic condition is discovered before lesions have occurred which are irreparable. We know that the mate and children of a syphilitic patient have been exposed to syphilitic involvement, and it is our duty as physicians in possession of such knowledge, and as guardians of the public health, to investigate such cases, so that if they be found to have syphilis, steps may be taken to treat them early.

3. How much danger is there of causing unhappiness and breaking up families by this procedure? This question offers a chance for many theoretical answers. The facts are, however, that in doing this as a routine for nearly three years and examining several hundred families, there has been no instance to our knowledge in which a family has been broken up or grave difficulties have been encountered by this procedure.

4. In what percentage are the mates or children of neurosyphilitics found to show definite symptoms of syphilis? It is our opinion that the situation in regard to neurosyphilitics is the same as for syphilitics in general: That the same laws of attenuation of virus, and of chance occur here as elsewhere.

Just as this book is going to press, we have learned that the distraught Mr. Jacobs, still desirous of starting a home for himself and feeling entirely well, consulted a physician. This physician took a sample of blood and had it tested at a competent laboratory, which reported the blood negative.

On the strength of this test, the physician felt himself warranted in recommending, or at least not advising against, Mr. Jacobs’ marriage, which has probably now taken place.

Although there is some doubt what ethical relation a state institution shall maintain with physicians in private practice, we took occasion to call the attention of our patient’s new counsellor to the fact of the patient’s neurosyphilis. We noted that the man’s serum had been constantly positive (Massachusetts State Board of Health findings) in a score or more of observations. We called attention to the fact that lumbar puncture had shown positive signs of neurosyphilis, including a positive W. R., globulin, excess albumin, pleocytosis, and positive gold sol. These facts, according to a letter received from the private practitioner in question, have not altered his opinion in the slightest to the effect that our patient is completely normal and entirely suitable for marriage. It is clear that he regards the patient as not a victim of General Paresis.

5. What is the significance o the negative observation eventually obtained in Jacobs’ serum? One’s first thought is to impugn the accuracy of the laboratory work, but against this suspicion is the excellent reputation of the laboratory in question, and the agreement in the majority of its findings with those of the State Board of Health. It is more likely, as we assured the private practitioner at whose request the observation was made, that this negative test was an exceptional and isolated observation such as is not infrequent in long series of observations, particularly those made under therapeutic conditions. In so important a matter, we are inclined to feel that the physician in question should have resorted to two more observations at intervals before running counter to the position taken by the hospital.

——many a hard assay Of dangers, and adversities, and pains.

Paradise Regained, Book IV, lines 478–479.

V. SOME RESULTS OF TREATMENT

Cases 99–103 show the Variety of Structural Lesions that Treatment has to face.

=SPASTIC HEMIPLEGIA in PARETIC NEUROSYPHILIS (“general paresis”), showing marked degenerative changes, a condition in which therapy could be theoretically of very little avail. Autopsy.=

=Case 99.= James McDevitt arrived at the Danvers Hospital, July 20, 1906 (saying that he came to be “thawed out”), and died less than six months later: January 12, 1907. He was 34 years of age. He had been a shoe-worker after leaving school, had worked eight years with the General Electric Co., and had then become a bartender. He had, however, stopped work in September, 1905, and we may safely say that mental symptoms had begun insidiously at about that time. His symptoms, if there were any, had been masked by a heavy alcoholism, but an obvious change had appeared in November, 1905. The patient lost ambition, smoked and loafed about his room, and developed speech disorder. He denied venereal disease, nor was there any superficial evidence of such.

=Physically=, the patient showed little or no disorder except acne of the trunk, patches of eczema on the left lower chest, and numerous brownish scars along both tibiae.

=Neurologically=, the Romberg position was maintained, but the gait was very unsteady on attempts to walk a straight line; fingers, tongue, and face were tremulous, and finer movements were performed with marked incoördination. No direct or consensual light reactions could be obtained in the pupils, which were dilated and irregular.

The condition of the reflexes is important on account of the autopsy findings. The abdominal and cremasteric reflexes were prompt, and the knee-jerks equal and very lively. Achilles and normal plantar reactions were present; there was no clonus; the arm reflexes were very brisk.

=COMMON THERAPEUTIC CONCEPTION=

VP = TYPICAL PARESIS

MV = TYPICAL CEREBROSPINAL SYPHILIS

V = TYPICAL SYPHILITIC ARTERIOSCLEROSIS

(M = Membranes, V = Vessels, P = Parenchyma, [] = not involved)

CHART 21

The =mental symptoms= need not detain us. Consciousness was clear; orientation for time, place, and to some extent for persons, was imperfect. Arithmetic had been largely forgotten. Handwriting was irregular and scrawling, and in places unintelligible. Although the patient claimed that his memory was intact, it was decidedly imperfect. He remarked that John D. Rockefeller, a Chicago king, was President; the General Electric Works had almost 50,000 people at work; and in fact Lynn was one of the largest cities in the state, having over 12,000 people. The height of patient’s room was estimated at 25 feet. There was a slight euphoria. There was never any doubt of the =diagnosis= of PARETIC NEUROSYPHILIS (“general paresis”).

Five months after admission, slight convulsions developed, after which the patient was more dull and demented; he became bedridden. More convulsions followed, leaving the right arm and hand useless. There were clonic spasms of the muscles of both lower legs. Decubitus developed and death occurred.

We may set the total duration of symptoms in the case of James McDevitt at a little over a year; nor is there any evidence of previous or prodromal symptoms beyond a total period of about 15 months, unless we may regard his leaving the General Electric Works to become a bartender some nine years before death, as a symptomatic change of character. In any event, it is of note that the =autopsy= showed singularly few lesions. Death was due doubtless to complications following decubitus, and there was a slight acute splenitis. The kidneys showed some parenchymal change. The aorta showed many patches of sclerosis, with calcification or ulceration throughout its length. These changes were not characteristic of syphilitic disease. There was considerable coronary arteriosclerosis and a slight mitral valvular sclerosis. There was a brown atrophy of the heart muscle, somewhat surprising in a man of 34 years. The =brain= was practically normal, weighed 1200 grams, and showed convolutions normal in size, relation, and arrangement. There was no sclerosis grossly evident in the blood vessels. The pia mater appeared to contain a considerable excess of clear fluid. The calvarium was of normal thickness and showed diploë and the dura mater failed to show adhesions. There were no macroscopic signs of lesion in the spinal cord.

=Microscopically=, the lymphocytosis, plasmocytosis, and phagocytosis of the perivascular spaces, (relative?) increase in blood vessels, the gliosis, and evidence of nerve cell destruction, taken together warranted the diagnosis of PARETIC NEUROSYPHILIS. It was plain that the nerve cell destruction was best marked in the inner layers of the cortex. The microscopic study of the spinal cord showed that there was very possibly a slight sclerosis of the posterior columns in the lumbar region, but this was so slight that it could hardly be noted in the myelin sheath stains (Weigert). Very sharply marked, on the other hand, were the bilateral pyramidal tract lesions in the lumbar and thoracic regions, less marked at the cervical levels.

Without attempting to analyze carefully all these findings, it is interesting to note in this case a foil to the usual spinal cord picture of paretic neurosyphilis. The spinal cord, ordinarily normal, or perhaps more usually affected by a degree of posterior column sclerosis, in this case showed such well marked pyramidal tract sclerosis that we may perhaps place the case in a subordinate group of SPASTIC PARETIC cases of NEUROSYPHILIS. The source of the pyramidal tract disease lodges, however, in the cortex cerebri itself, being part and parcel of the lesions mentioned above as affecting more directly the inner layers of the cortex. Many of the so-called giant, or Betz, cells had undergone a complete destruction. It will be remembered that clonic spasms of the muscles of the legs appeared in the fortnight preceding death, and that there had been convulsions for about six weeks before death. There was no evidence at the autopsy why the right arm and hand should have become useless, whereas the left upper extremity remained normal. This case, then, forms an exception to the ordinary paretic neurosyphilis group in that the brunt of the microscopic process was borne by the inner layers of the cortex. The cells of origin of the pyramidal tract fibres had been cut in this lesion, and had become subject to partial or complete destruction. Note, however, that the lesion remained a microscopic one and that the marked convulsions were not related to gross lesions, thereby following the rule for paretic seizures.

Bilateral pyramidal tract sclerosis, secondary to destruction of large motor (Betz) cells of motor (precentral) cerebral cortex—paretic neurosyphilis. ]

From the standpoint of possible treatment, it is of course true that few organs of the body showed grave lesions save in the calcified and ulcerated aorta, which conceivably might have become quiescent under appropriate treatment. But, although the brain was almost if not quite normal in the gross, and although its membranes showed practically no lesion, treatment would not have been very promising. To be sure, the exudate might have been cleared away if the spirochetes responsible therefor had been destroyed by treatment. Yet the destruction of the giant cells of origin of the pyramidal tract fibres to such an extent as in this case could hardly have been compensated for by any known process. So far as we are aware, the destruction of considerable numbers of the smaller association elements of the brain is subject to the compensation of other elements of the nervous system, which conceivably might be re-educated or newly educated to perform certain processes. The histological picture in a case like that of McDevitt accordingly leads to the hypothesis that so well marked a spastic paresis, even in the presence of otherwise favorable signs, would be of especially baneful portent therapeutically.

=NEUROSYPHILIS with total duration of symptoms twenty-two days. The comparatively MILD BRAIN LESIONS, INFLAMMATORY AND NOT DEGENERATIVE in type, suggest the possibility that therapy might have been successful. Autopsy.=

=Case 100.= Jacob Methuen, 35, was a carpenter from Newfoundland. He was working upon a certain Thursday with his brother, who noticed that Jacob was lifting the tools about in an unusual manner and talking strangely to his fellow workmen. He fell asleep, going home in the street car, and said afterward that he felt dazed and peculiar. He talked all kinds of nonsense to his wife upon arrival. Methuen remained in bed next day, fancying he was going to die, calling his family together, and saying good-bye to them. He remained in bed all through the next day, but on Sunday appeared better,—more active, and in fact quite natural. He slept only an hour Sunday night, calling to his wife that it was time to get up. On Monday he began to be irritable to his wife, and accused her of flirting with his brother and intending to elope with him. He struck his wife several times, and when two brothers came to watch him, accused them both of trying to steal his wife, and struck them. Tuesday he remained in bed until late at night, when he arose and tried to assault the family.

It seems that another brother of the patient had died but eleven days before his admission to the hospital and five days before the onset of Jacob’s symptoms. Since his brother’s death he had been dwelling upon religious matters, and in fact the day after his brother’s death, he waked up during the night, saying that he was too happy to sleep, that he heard the Master’s voice, and at times the devil’s voice; that there was to be a modern miracle and his spiritual life from now on would be different.

Eleven days after admission to the hospital, Methuen died, making a total duration of symptoms, beginning at his brother’s death, of 22 days.

=NEUROSYPHILITIC LESIONS=

=LESIONS OF THE SECONDARY PERIOD=

(1) INTERSTITIAL ENCEPHALITIS OR MYELITIS (“meningitis”) (2) PARENCHYMATOUS ENCEPHALITIS OR MYELITIS (“encephalitis,” “myelitis”)

=LESIONS OF THE TERTIARY PERIOD=

(1) CHRONIC INTERSTITIAL ENCEPHALITIS OR MYELITIS (“gummatous meningitis”) (2) CHRONIC PARENCHYMATOUS ENCEPHALITIS (“dementia paralytica”) (3) CHRONIC PARENCHYMATOUS MYELITIS (“tabes dorsalis”)

“We have shown that the central nervous system is affected by syphilis at the same periods and in the same manner as are other internal organs. In addition the ‘parasyphilitic’ lesions are also of a typically syphilitic nature, being directly comparable to the parenchymatous affections found elsewhere in the body. They are ‘tertiary’ lesions differing only from the so-called ‘gummatous’ processes in the central nervous system in that their localization is in the parenchyma while that of the latter is in the interstitial tissues.”

McIntosh and Fildes, 1914

CHART 22

=Physical examination= showed a man 5′ 9″ tall, weighing 149 pounds, rather pale and poorly nourished, with a somewhat enlarged heart and no evidence of venereal disease.

=Neurologically= there was a slight facial and digital tremor, but otherwise no symptom or reflex disorder except that the tendon reflexes were generally increased; the knee-jerks especially were very vigorous. There was no speech defect. His handwriting was fairly legible.

The patient was very noisy and uncontrollable, tearing clothing and biting, striking the attendants, refusing food, talking rapidly, loudly, and incoherently. His manner suggested auditory hallucinations but no positive evidence of these was obtained. His clothes could not be kept on him. The following is a sample of his reactions: As the examiner entered, the patient stood stark naked and glaring. He started to talk as follows: “Methuen,—I, Saviour, come to life and ought to die—— Now I lay me—— Now I die—— The heart beats—— No, I ain’t going to die—— I am going out soon. I want my clothes—— You can’t hold me; I am strong.” (Struggles violently with the attendants.) “I am God. God. I know you, you can’t fool me.——I am here——I can do you all. How many doctors are there here?” (Struggles violently. Looks at examiner.) “He is writing something. Sir, you can’t fool me in a million years. Do you understand that, doctor? You can’t fool me. Write all the prescriptions you want to. Ten thousand years; you hear that, doctor? Ten thousand years. You can’t fool me; ten thousand years. Ten thousand years are but a day for the spirit of the Lord,” etc., etc.

The excitement continued unabated. The patient became entirely disoriented, and finally almost unable to move. He lay in bed trying to talk and muttering broken gibberish, still attempting to struggle to the extent of his limited strength.

The =autopsy= showed no sign of lesion (brain weight 1380 grams), unless, perhaps, the occipital regions were slightly firmer than the rest of the brain. Death was apparently due to a bilateral pneumonia, bronchial type. There was an acute splenitis. The only chronic lesions of the body were a bilateral chronic adhesive pleuritis and a slight sclerosis of the arch of the aorta.

Paretic neurosyphilis (“general paresis”) macroscopically normal, microscopically characteristic. Treatment does not have to face massive destructive processes already complete. ]

=Microscopically= there was a distinct though mild degree of lymphocytosis of the perivascular spaces in many regions. Somewhat extended search failed to reveal plasma cells, and it is certain that if plasma cells existed, they must have occurred in very small numbers.

Here, then, was a case of DIFFUSE NEUROSYPHILIS (with brain picture consistent) with symptoms lasting but 22 days and with an appearance of acute mania. It is to be noted that this case arrived at the hospital on the eleventh day of his symptoms. The case occurred long before the development of the temporary care system in Massachusetts. It is probable, or at any rate possible, that he would have been brought to the hospital far earlier, say, upon the sixth day, had the modern temporary care system been installed at that time. The routine W. R. examination would then have been made. With more effective hydrotherapy, it is possible that the patient’s life might have been prolonged and that treatment might have been effective. So far as we can see, the case would have been a singularly good one for treatment despite the practical unmanageability of the case under ordinary home treatment, and even under hospital conditions where modern hydrotherapeutic appliances are not available.

=PARETIC NEUROSYPHILIS showing very MARKED MENINGITIS, suggesting that therapy might have produced improvement. Autopsy.=

=Case 101.= We report the case of John Baxter, a boat tender of 48 years, because this particular victim of PARETIC NEUROSYPHILIS seems to have had the most markedly thickened and altered meninges in our whole series. Of course, the therapeutic theory upon which we now proceed in the treatment of non-paretic and possibly even of paretic neurosyphilis is that, other things being equal, the meningitis can be removed by treatment, or in the course of treatment, so that the degree of ultimate recovery rather depends upon the condition of the brain substance itself than upon the condition of the meninges. Here, at all events, is an example of the most highly meningitic neurosyphilis that we have seen.

Curiously enough, two of Baxter’s brothers were also patients at the hospital at which Baxter died, and a number of the other members of the family are reported as “nervous.” It seems that at 35 Baxter began to drink heavily and had never given over the habit of alcoholism.

Upon admission to the hospital, in fact, he showed a sufficiently typical picture of delirium tremens. His consciousness was clouded, he had vivid visual hallucinations and was very apprehensive.

His heart was enlarged to the left; the pulse, 120, was of increased tension and irregular; there was peripheral arteriosclerosis; the teeth were poor; the tongue coated; and the mouth foul. The urine showed a trace of albumin and rare hyalin casts.

=Neurologically=, the gait was somewhat unsteady, there was an extreme tremor of the whole body, including the tongue and fingers. The Romberg sign was negative although there was marked swaying. The pupils were equal and reacted normally; the knee-jerks were markedly exaggerated, the arm reflexes somewhat exaggerated. The remainder of the reflexes upon systematic examination were negative.

A high degree of chronic leptomeningitis. Pia mater thick, opaque, concealing brain. In paretic neurosyphilis (“general paresis”). ]

Upon arrival, Baxter was put to bed, but he barricaded his door and fought with the attendants. The tremor increased, the hallucinations were both visual and auditory. After a few days, Baxter became so weak that he could not move. He refused to eat for a period of two days, explaining in whispers that he did not wish to be poisoned; a voice had told him the food was to be poisoned. The voice was of agreeable tones, probably belonging to a lady; it did not speak, but sang to him. The clouding of consciousness failed to clear up, as in delirium tremens, so that, though patient was admitted March 3d, it was hardly possible to speak freely with him until more than a month later, April 9th. A good-natured conversation would run as follows:

“What is your name?” “Baxter.” “First name?” After long pause, “Don’t know.” “John?” Pause of 7 seconds, “Yes, I think it is.” “How old are you?” “There are legs——there is a body——up to here——” “Say the alphabet.” Term not understood. “Say the a, b, “Oh yes; a, b, c, d (long pause), e, f; I cannot c.” say it, I did not have much education; I am not intelligent.” (In point of fact, the patient had a good grammar-school education, and had long worked as a clerk in a grocery store, with good wages.) There was some speech defect.

Soon the hallucinatory phase passed, and the patient remained in a cloudy and disoriented state, inaccessible, rarely speaking, and gradually failing physically. Death occurred about three months after admission (pulmonary symptoms).

In estimating the duration of the process in John Baxter, we must take into account that he left the grocery business and became a hard-working but poorly-paid boat tender at about 35 years, at the same time that the alcoholic habit began.

The =autopsy= showed that death was due to bronchopneumonia with pleurisy. There were in the body a variety of chronic lesions, such as gastritis, colitis, epididymitis, splenitis, parietal and valvular endocarditis, prostatitis, chronic appendicitis, and some mesenteric lymphnoditis. The heart was somewhat hypertrophied. There was a slight diffuse nephritis with cysts, emaciation, and decubitus. The calvarium was thick and somewhat dense. The dura was thickened and adherent, and the pia mater,—as above stated, the most thickened and altered pia mater in our series,—is described as everywhere thickened, of a brownish gray and white color, especially over the vascular lines, and as showing small white areas of deeper thickening scattered over the surface, but most markedly over the sulci, and not as a rule over the crowns of the gyri. There were also yellowish brown spots with a suggestion of fibrin over the lateral aspects of both hemispheres. The vessels at the base were not remarkable in the gross. The brain weighed 1220 grams, and appeared to be of darker color than usual.

=Some cases of PARETIC NEUROSYPHILIS (“general paresis”) have so much BRAIN ATROPHY that it is not possible to expect much improvement through antisyphilitic therapy.=

=Case 102.= Theodosia Jewett, dead at 58 years, showed the most remarkably wasted brain in a long series of victims of paretic neurosyphilis. We present her case to emphasize what therapy must face in certain instances, but would recall the fact that exceedingly few such wasted brains have come to our attention in cases dying in the institutions of Massachusetts.

Mrs. Jewett, a housewife, whose parents died of shock, and one of whose two brothers also died of shock, was a normal child and schoolgirl, and worked as dressmaker until she was married, at 24, to a grocer, by whom she had two children. At the age of 46, Mrs. Jewett began to suffer from so-called “nervous prostration.” The attack lasted some two years, but there were no psychotic symptoms beyond worry and insomnia. The menopause occurred at 52, at which time the first signs of psychosis appeared, namely, a forgetfulness concerning familiar matters, such as sewing, cooking, and the like. At 55, this amnesia had become so marked that Mrs. Jewett could neither write nor tell time. She, however, was a perfectly quiet and easily manageable patient, often subject to drowsiness in the day.

Six months before her admission to the hospital, she began to suffer from insomnia, failed to recognize her surroundings, and had a number of crying spells. Restlessness had begun a month before admission; auditory hallucinations developed in the form of imaginary conversations with dead persons. A certain loquacity set in, and for a week before admission, Mrs. Jewett became somewhat resistive.

=Physically=, the patient was sallow, poorly nourished, with pale mucous membranes, peripheral arteriosclerosis, no teeth, muscular feebleness, tremor of hands and tongue, and active knee-jerks. =Mentally=, the patient was depressed, talked to herself, assumed a supplicating position, suddenly altered her attitude, and was very tremulous. Her talk was low, mumbling, and incoherent, for the most part composed of answers to her own questions. Sometimes there was a curious difficulty in speaking, such that the lips moved but no sound emerged; but for the most part there was no difficulty in uttering words. The patient either could or would not write. Only when the attention was secured by speaking to her sharply was she apparently able to understand questions, and the answers to these sharp questions came spasmodically and as if interrupting her own thoughts. Nor was it ever possible to obtain a repetition of the same answer.

The patient died in exhaustion, with pulmonary symptoms three weeks after admission.

The =autopsy= which was performed 3½ hours after death showed the following points of interest:

The heart weighed 210 grams. There was marked thickening of the aortic valve. The coronaries were slightly thickened.

The lungs were slightly adherent to the chest wall at the apices and posteriorly. The right lung was consolidated in the lower two lobes posteriorly and the bronchi exuded pus; the left lung was not remarkable. There was a chronic splenitis.

The liver showed fibrous changes, was a brownish-red in color, mottled with yellow.

Combined weight of the kidneys 195 grams. The capsules were adherent, tearing the cortex when stripped.

The diploë were well marked. The dura was not adherent. The pia was slightly thickened and raised from the cortex by a large amount of subpial fluid (showing atrophy of the cortex). The pial vessels were injected, more markedly so on the left side. The arachnoid villi were reported as moderately developed, especially along the longitudinal fissure.

The brain was rather soft in all regions. The weight was 1045 grams. According to Tigges’ formula the weight of the brain should be approximately 8 times the body length in centimeters. The length in this case was 158 cm., therefore, according to this formula the weight of the brain should have been 1464 grams. The difference of more than 400 grams is evidently a loss to be accounted for by atrophy, a very heavy loss.

Perivascular exudate (low power) in atrophic cortex from case of general paresis. ]

Markedly atrophic cortex, but without local perivascular exudate. ]

1. Was the “nervous prostration” at 46 of syphilitic origin? One cannot give a categorical answer to this question. The high incidence of shock in the family suggests poor stock in which a psychoneurosis is not an unusual phenomenon. The presence of syphilis might act as a debilitating factor or agent provocateur, if it were not to cause any demonstrable brain lesion. As pointed out in the case of Harrison (9), however, it is not unusual in neurosyphilis to find a history of symptoms occurring years before the final breakdown and symptoms frequently not recognized as of neurosyphilitic nature.

2. Does the fairly long duration of the psychosis (at least 3 years) explain the marked atrophy? Cases having symptoms even much longer than three years at times show relatively very little atrophy, so that this factor in itself cannot be said to explain the tremendous destruction of tissue.

=The THERAPY OF NEUROSYPHILIS has to face not merely variations in the degree of brain wasting and in the degree of meningitis, but also variations in the topographical distribution of lesions. Autopsy.=

=Case 103.= To bring out this point we may instance the case of Alfred Weed, a victim of PARETIC NEUROSYPHILIS, dying at the age of 48 years after a course of about seven years. The following is an abstract of the clinical history:

A. W. suffered from lues some 24 years before his death at Danvers Insane Hospital in 1907. There is no account of insanity in his family. The patient had been undergoing mental changes for six years before death. At the age of 42 began to take interest in socialism and spiritualism. Would become excited at times and was observed to talk to himself. At times it seemed that he was reacting to visual hallucinations. After eight months he became depressed and apprehensive and developed delusions of poisoning.

On admission to the Danvers Insane Hospital in June, 1902, the subject was found to be ataxic, falling in the Romberg position. Pupils were equal but of pin-point size. There was tremor of the facial muscles. The knee-jerks were absent. Speech was ataxic. Memory defective. Depressed. Thought he was to be punished. Refused to eat.

Later in the year of admission, patient became more negativistic. He refused to have his clothes brushed. His answers were slow. Mental arithmetic was correctly but slowly done. During January, 1903, the patient was apt to be active and talkative for a time, and then his attitude would suddenly change to one of silence, resistivement and untidiness. From time to time he would be querulous and sulky. In August, 1903, the patient became weaker and could walk with assistance only. Paralysis developed in the left facialis region and in the left external rectus. Pupils were still small, but the left had become smaller than the right. Light reaction tests unsatisfactory. Knee-jerks could not be obtained.

In December, 1903, the patient was untidy and helpless, lying with his thighs and legs flexed. The limbs were spastic on passive motion. In 1905, the pain sense of the legs was found lost and the pupils were small and stiff. The protruded tongue was deflected to the right. The right labial fold was more prominent than the left. Knee-jerks remained absent. Ataxia was extreme.

The =Neurological Findings= may be summed up as follows:

1. Ataxia of the legs.

2. (Probable) Diminished sensibility in the legs.

3. Pupils small and stiff. Left smaller than the right.

4. Paralysis of left facialis.

5. Paralysis of left external rectus.

6. Tongue protruded to right.

7. Right elbow jerk greater than left.

8. Knee-jerks absent.

The cause of death was bronchopneumonia. The walls and valves of the heart showed a few chronic changes. There was a marked splenitis and an atrophy of the liver. The kidneys showed numerous depressed scars. The arch of the aorta was somewhat sclerotic. The following is a full description of the head findings which we present by way of comparison with other cases. Note especially the cerebellar, dentate, and olivary changes. Note also the fact that palpable sclerosis is demonstrable over a far larger area than atrophy, so that we may almost safely conclude that the process of induration sometimes precedes that of atrophy. One gets the impression from the extent of visible atrophy and tangible induration in this case, that a possible therapy would have not merely to clear the perivascular spaces of cells and spirochetes, but would also need to arrest the indurating and wasting process. Nor could any therapy deal effectively with the superior frontal and upper central atrophy of the cerebrum of this case, or with the olivary and cerebellar lesions.

=Head=: Hair thin at vertex. Scalp normal. Calvarium thin and dense. Dura mater slightly adherent to calvarium at vertex. Sinuses normal. Arachnoidal villi well developed. Pia mater of anterior and central regions contains an excess of fluid. The pial veins well injected.

The =pia mater= exhibits one unusual lesion: Faintly yellowish brown spots of miliary and slightly larger size are scattered irregularly in clusters over the vertex. These miliary pial macules are observed especially over the posterior third of the left superior frontal gyrus (a group of twelve or more). Two are seen in the pia mater of the right superior frontal gyrus. One is seen in the upper part of the left post central gyrus. The upper end of the right postcentral gyrus contains three macules.

Besides these brownish macules, the pia mater also shows focal white thickenings which resemble the more frequent appearances of chronic fibrous leptomeningitis. The white thickenings are of irregular size but are, as a rule, larger than the macules above mentioned. They occur, as a rule, over the sulcal veins and are most frequent in the anterior region.

The vessels at the base are normal. There is no evidence of pial thickening at the base of the brain. =Brain= weight, 1265 grams. There is visible atrophy of both superior frontal gyri and of the upper two-thirds of both central gyri. The extent of palpable sclerosis surpasses that of visible atrophy. Palpable increase of consistence is shown by the prefrontal, orbital (more marked on left side), frontal, central, hippocampal and occipital regions. The temporal cortex is of normal or slightly reduced consistence.

Section of the cerebral cortex shows everywhere preservation of the cortical markings. The sclerosed areas show a diminution in depth of the cortex, which is more marked in the left prefrontal region. The white matter of the centrum semiovale of the prefrontal and occipital regions on both sides shows an increase of consistence. The cerebellar cortex also shows variations in consistence. The clivus and lobus cacuminis and the posterior half of the inferior surfaces of both cerebellar hemispheres are firmer than normal. The laminæ of the left clivus are a trifle narrower than those of the right. There is visible extensive atrophy of the laminæ on both sides of a fissure in the middle of the left lobus cacuminis. In the coördinate portion of the right cacumen there is a similar process which is less marked. The dentate nuclei are firm. The olives show an increase of consistence, equal on both sides. The left olive shows on section a crowding together of its folds in the middle part of the upper limb.

Spinal cord was not remarkable.

=Summary=:

Adhesive pachymeningitis Chronic fibrous leptomeningitis Miliary pial macules Cerebral atrophy Cerebral sclerosis Cerebellar atrophy and sclerosis Bronchopneumonia Chronic splenitis Nephritis Aortitis

=It is generally recognized that DIFFUSE NEUROSYPHILIS (“cerebrospinal syphilis”) frequently is cured through antisyphilitic therapy. Example. Mental improvement, in one month; recovery from paralysis, ten months.=

=Case 104.= John Edwards, a man of 28 years, well developed and nourished, with general enlargement of glands and skin lesions, came to the hospital in a stuporous condition, with evidences of a complete hemiplegia.

According to the wife, Edwards had had a chancre of the lip about a year before, for which he had been treated with an intravenous injection, presumably of salvarsan, and also presumably with mercury. The lip lesion had then disappeared. For a month before admission, Edwards had had headache and dizziness, for which he was given pills and drugs. There had also been difficulty with speech and numbness of the left arm as far up as the elbow, but this paresthesia had quickly disappeared. The hemiplegia was of only a few days’ duration. After a feeling of nausea and vomiting, the patient had fallen with left-sided paralysis. Afterwards, he had shown mental peculiarities, eventually becoming noisy, hard to manage, and appropriate for hospital care.

The =physical examination= showed a variety of increased reflexes, including ankle clonus on the left side.

The question might arise whether this case was one of hemorrhage or thrombosis, and the facts about the onset of the hemiplegia are inadequate for a decision. However, at so early an age, the probability of syphilis is large and the history of labial chancre was quite suggestive. If we may conclude neurosyphilis, the diagnosis of thrombosis rather than rupture of blood vessel is likely. The laboratory tests bore out the diagnosis since the W. R. of serum and fluid both proved positive; the gold sol reaction was syphilitic; there were 176 cells per cmm.; there was excess albumin, and a positive globulin reaction.

=NON-PARETIC NEUROSYPHILIS=

=DIFFUSE NEUROSYPHILIS, MENINGOVASCULAR PARENCHYMATOUS, CEREBROSPINAL SYPHILIS=

CASES SYSTEMATICALLY TREATED 13 CLINICAL RECOVERY, C.S.F. NEGATIVE 11 UNIMPROVED 1 UNIMPROVED, BUT C.S.F. NEGATIVE 1

MASSACHUSETTS COMMISSION ON MENTAL DISEASES, November, 1916

CHART 23

The outcome in such a case is dubious. If death does not occur soon, recovery is not impossible under treatment. At all events, a considerable improvement is likely.

Edwards was given bi-weekly injections of salvarsan, intramuscular injections of mercury salicylate, and doses of potassium iodid, averaging 100 grains, three times a day. Under this treatment, he slowly recovered and became mentally clear after a few weeks. The paralysis seemed complete and permanent. Even after three or four months, there was absolutely no change in the condition, and Edwards was quite unable to move either arm or leg. Meanwhile, the spinal fluid had become practically negative to all tests.

Treatment was somewhat optimistically continued and was rewarded at the end of ten months with marked improvement such that the patient was able to stand on the paralyzed leg and move the arm to a certain degree. This improvement is still continuing. The spinal fluid and the serum have remained negative to laboratory tests.

Note: A period of six months is commonly regarded as that period in which improvement in paralysis is to occur if there is to be any improvement. There was certainly not the slightest improvement in the paralysis of this case before eight or nine months of treatment had elapsed, and it took ten months to secure the marked improvement mentioned.

1. What is the significance of the prodromal symptoms? The headache and dizziness should have been viewed with great gravity. They are characteristic in MENINGOVASCULAR NEUROSYPHILIS.

Moreover in this case there had also been difficulties with speech and other transient symptoms which should have called attention far earlier to the possibility of neurosyphilis.

2. What is the significance of the high cell count: 176 per cubic millimeter? Such high cell counts are frequent enough in diffuse neurosyphilis, but low cell counts are frequent also. But although the high cell count taken alone is of lesser significance, the fact that the high cell count in this case is associated with a “syphilitic” gold sol reaction is of far greater significance for diagnosis. These associated findings are characteristic of meningovascular neurosyphilis.

3. What kind of recovery may be expected in successful examples of treatment in meningovascular cases? Recovery with defect. It will be noted that ten months elapsed before any marked improvement occurred on the paralyzed side. We could not expect a complete recovery from this paralysis.

4. Was inadequacy of treatment following the chancre responsible for the early cerebrospinal involvement? In this connection one must remember that such neural involvements occur occasionally even during active treatment (neurorecidives). The discontinuance of treatment after a short period, in this case less than a year, is always a risk to say the least. And this is true even though the W. R. becomes negative, for trouble of a neurosyphilitic nature may occur later; this when both blood and spinal fluid have previously been found negative. The old rule of following and treating a syphilitic for several years despite the disappearance of symptoms is still a good rule.

=The results of systematic, intensive, intravenous salvarsan therapy in atypical neurosyphilis (cases not certainly paretic, tabetic or the common types of meningovascular neurosyphilis) may be in our experience as good as the results of treatment in common meningovascular cases: example.=

=Case 105.= Henri Lepère, a machinist, 48 years of age, came voluntarily to the Psychopathic Hospital for a gradually failing memory and inability to work. He had had indigestion for four years (epigastric distress, nausea, no vomiting). He was still suffering from epigastric distress and from headaches. At times he had had difficulty in walking.

=Physically=, Lepère looked older than he was; he was very poorly developed and nourished, and seemed very weak. There was a slight visceroptosis.

=Neurologically=, there was considerable speech defect, particularly well marked in test phrases. The pupils were contracted and gave the Argyll-Robertson reaction. Neurologically there were no other signs.

=Mentally=, there was a depression with worry; but it was a question whether these phenomena were not entirely natural. The special complaint was of failing memory.

The Argyll-Robertson pupil also prima facie signifies neurosyphilis. Lepère, in fact, admitted syphilitic infection at 23. The gastric symptoms at once suggested tabes. The knee-jerks and ankle-jerks were, to be sure, preserved; however, this is not very unusual in tabes. The amnesia and aphasia naturally suggested paresis. Without resort to laboratory findings, accordingly, the diagnosis of taboparetic neurosyphilis (“taboparesis”) was suggested.

=EFFECT OF EARLY TREATMENT ON THE DEVELOPMENT OF NEUROSYPHILIS=

TOTAL CASES 4134 DEVELOPED GENERAL PARESIS 198 = 4.8% DEVELOPED TABES DORSALIS 113 = 2.7% DEVELOPED CEREBROSPINAL SYPHILIS 132 = 3.2% ——————————— 443 = 10.5%

=EFFECT OF TREATMENT= Repeated None 1 course energetic NUMBER OF CASES 100 134 924 DEVELOPED G.P. 25 = 25% 31 = 23.1% 30 = 3.2% DEVELOPED TABES 11 = 11% 16 = 11.9% 25 = 2.7% DEVELOPED C.S.S. 3 = 3% 21 = 15.6% 71 = 7.6%

Poorly Better treated treated 1880–84 1895–99 NUMBER OF CASES 617 1139 DEVELOPED G.P. 60 = 9.7% 37 = 3.2% DEVELOPED TABES 22 = 3.5% 16 = 1.4% DEVELOPED C.S.S. 15 = 2.4% 28 = 2.4%

MATTAUSCHEK AND PILCZ

CHART 24

The serum W. R. proved positive, but the spinal fluid W. R. very slightly so (yielding only moderate reaction with 1 cc., 0.7 and 0.5 cc., and a negative reaction with 0.3 and 0.1 cc.). Globulin was moderate, and albumin was found in only moderate excess. There were 21 cells per cmm. in the spinal fluid. The gold sol reaction was that which we regard as typical of syphilis or tabes. If we were to rely upon the weakness of the fluid W. R. and the nature of the gold sol reaction, we should be inclined to favor the diagnosis of DIFFUSE NEUROSYPHILIS (“cerebrospinal syphilis”) rather than resort to the diagnosis of paretic neurosyphilis.

Salvarsan treatment was attended by the rapid disappearance of headaches and gastric symptoms and by a rapid gain in weight and feeling of well-being. Salvarsan was continued twice a week for two months, whereupon Lepère returned to work. He has been successfully at work now for seven months without return of symptoms. Four months after beginning of treatment, the spinal fluid was examined and found entirely negative. Nevertheless, the serum W. R. has remained positive despite eight months of salvarsan treatment.

1. What is the meaning of the titrations in the spinal fluid Wassermann reaction? When Plaut originally applied the Wassermann reaction to spinal fluids, he used 0.2 of a cc. of spinal fluid. With this amount of fluid he found that cases of general paresis gave a positive reaction in about 100% of the cases while this positive reaction was only given by 40 to 60% of the cases of cerebrospinal syphilis and tabes dorsalis, hence he promulgated a differential point that a negative reaction in spinal fluid indicated that the case was not general paresis. Hauptmann later showed that if 1 cc. of spinal fluid were used, a positive reaction would occur in practically 100% of the cases of general paresis, cerebrospinal syphilis and tabes. Therefore, at present, we use the different titers of spinal fluid from which we draw the following conclusions: If the reaction in the untreated case is negative with 0.1 and 0.3 of a cc. and positive with the 0.5, 0.7 and 1 cc. dilutions as in the case of Lepère, we are probably dealing with non-paretic neurosyphilis. With this method of titration we are also better able to watch the progress of treatment as the dilutions of 0.1 and 0.3 cc. become negative first.

2. How soon can one expect improvement after commencement of salvarsan therapy in cases of diffuse neurosyphilis? The time relation of results in treatment varies with each individual case. In the case of Lepère gastric symptoms that had been present for a number of months disappeared as if by magic after the first injection of salvarsan. As a rule, it is true that the more acute the symptoms the quicker their disappearance but this does not hold for all cases, as in this particular instance the long-standing symptoms disappeared very rapidly. The symptoms often disappear very much more rapidly than the laboratory, tests change.

3. How can the mental symptoms (depression and failing memory) of which patient complained be explained? In the first place, as has been stated, it is doubtful if these are more than subjective and the result of the patient’s feeling of discomfort and pain. However, it is also possible that there may be intracranial involvement of the meninges or of the brain itself. And, if such were the case, the improvement might be the result of the treatment.

=The Argyll-Robertson pupil should not be used as a basis for a necessarily bad prognosis if treatment can be given.=

=Case 106.= Frederick Stone was a business man of large interests. He had been in the hands of physicians for several years for a variety of disorders such as renal, respiratory, cardiovascular, and so on. No suspicion of syphilis had apparently been uttered by the physicians despite the fact that Mr. Stone readily stated that he had had a chancre thirty years before, and that he had received several years’ treatment of mercury and potassium iodid by mouth.

It appeared that a few years ago he had begun to have trouble with his nose, which was cauterized and operatively interfered with without satisfactory results. This nasal condition had later been diagnosticated as gummatous, and had improved considerably under a mild antisyphilitic treatment. However, this nasal condition had been considered and treated quite separately from the remainder of Mr. Stone’s troubles.

What brought him to attention was a sudden diplopia with ptosis. There was a paralysis of the external rectus of the left eye, as well as a drooping of the lid on this side. The left eye was much inflamed. The diplopia greatly bothered the patient, and there was also considerable pain in the left frontal region, confined chiefly to the distribution of the first division of the trigeminal nerve. According to the patient this headache was periodic. There was considerable tenderness to pinprick over the area and a diminution of sensory discrimination of fine touch. Both the pupils failed to react to light.

The remainder of the neurological symptomatic examination was surprisingly clear of disorder, nor was there anything in the history suggestive of tabes. There was ozena as well as evidence of the operative work upon nares and throat. Possibly the arteries were slightly hardened; blood pressure was 165 systolic. There was a large trace of albumin, and there were numerous hyalin casts in the urine.

=PARETIC NEUROSYPHILIS=

=(GENERAL PARESIS)=

Cases systematically treated 50

CLINICAL REMISSIONS 34 68% C.S.F. ALTERED TO NEGATIVE 4 8% C.S.F. ALTERED TO WEAKER 16 32% C.S.F. UNALTERED 14 28%

CLINICALLY UNIMPROVED 16 32% C.S.F. WEAKER 7 14% C.S.F. UNALTERED 9 18%

MASSACHUSETTS COMMISSION ON MENTAL DISEASES NOVEMBER, 1916

CHART 25

=Mentally=, there was a degree of depression and worry hardly out of keeping with the general situation. Despite the preservation of memory, Mr. Stone failed to do rather simple arithmetical calculations; this was the more remarkable as in his business he had to handle figures a great deal and had been doing so until recently. There was a slight tremor in his writing, as well as a certain difficulty in enunciating test phrases. Insomnia, irritability, and a feeling of nervousness and of being tired out, completed the picture.

A suggestion for diagnosis would be classically offered by the Argyll-Robertson pupils. Should not a patient with the Argyll-Robertson pupils have either tabes or paresis? However, in favor of tabes, besides the pupil, are to be counted merely the troubles with the eyes. In the direction of paresis we have to consider speech defect, to say nothing of less definite symptoms such as insomnia and increased irritability.

We are inclined to think, however, that the disease in this case is meningovascular. This diagnosis is suggested by the cranial nerve palsies and by the headache. Headache is much more rarely a phenomenon in the paretic type of neurosyphilis than in the meningovascular type.

In point of fact, the spinal fluid phenomena bore out the diagnosis of MENINGOVASCULAR NEUROSYPHILIS inasmuch as the globulin, albumin, cellular content, gold sol, and W. R.’s were all weakly positive.

1. How far can we regard the cardiorenal defects as syphilitic? Perhaps we may do so on the general principle of parsimony in scientific interpretation.

The diagnostic lumbar puncture led to an extremely severe exacerbation of the pains on the left side of the head. In fact, these pains could not be held in check by the exhibition of pyramidon. Mr. Stone regarded the pain as due to the lumbar puncture. However, there was no improvement in the pain in the prone position,—a feature characteristic of lumbar puncture pains. Upon administration of salvarsan, this local pain rapidly disappeared. In fact, there was a startling improvement; the ocular palsies disappeared in a few weeks, although these palsies had been present for several months before the administration of salvarsan. The blood pressure was reduced; the urine became negative. Perhaps the most startling feature of all (although of this we are not sure) was that the patient states he was accepted by a life insurance company although he had been twice refused previously.

=Note= in this case the 30–year interval between infection and generalized neurosyphilitic involvement. Note also the amenability of the process despite this duration. We are perhaps entitled also to note that a neurological examination careful enough to detect an Argyll-Robertson pupil should have been made by a number of examiners long before the particular crisis which we have sketched. It is also permissible to note that the rhinological work should not have been carried out independently of all other medical work.

2. What are the untoward results of lumbar puncture? It is true that there is always a possibility of setting up a septic meningitis by lumbar puncture, but this is a very remote possibility and with any reasonable care it is not to be considered. Lumbar puncture also has a considerable danger in cases of increased intracranial pressure. In cases of brain tumor where the tumor is located in the posterior fossa, sudden death may occur from withdrawal of spinal fluid. This is supposed to be due to the medulla being pressed down into the foramen magnum and causing paralysis of respiration. Therefore lumbar puncture should never be performed except with the greatest caution in a case in which brain tumor is suspected.

However, aside from these remote serious consequences which play very little rôle in the ordinary procedure of lumbar puncture, certain unpleasant symptoms do frequently arise. These symptoms are chiefly headache and nausea, but, however, may go as far as vomiting. These symptoms occur almost entirely in the cases in which there is no abnormal condition producing increased spinal fluid pressure. Such unpleasant symptoms may last as long as four or five days; as a rule, however, last only for a period of a day or two.

3. What is the treatment of discomfort following lumbar puncture? It is a rule well worth observing that the patient after lumbar puncture should remain flat on his back without a pillow for 24 hours in order to avoid any unpleasant symptoms. If any symptoms do occur, it will be almost certainly when the patient arises, and in nearly every instance they will be overcome if the patient again assumes the prone position. Raising the foot of the bed so as to lower the head also helps. Veronal or bromides may be given but as a rule are not very satisfactory.

4. How permanent is the improvement obtained in the case of Mr. Stone likely to be? As a matter of fact, the patient discontinued treatment as soon as he felt well again, but after two months the pain returned to be again quickly dispelled by salvarsan. This improvement must be considered as only temporary. Under continued treatment there may be no further relapse. There is, however, evidence that much damage has been done to the body by the spirochetes, much of which is irreparable. It is even possible that further disintegration might occur even while undergoing treatment. Still treatment offers much in such a case and is to be highly recommended.

=In DIFFUSE NEUROSYPHILIS, rendering the spinal fluid negative by treatment may mean neither cure nor disappearance of symptoms.=

=Case 107.= Greta Meyer, a widow, 51 years of age, came voluntarily to the hospital, seeking medical aid for a marked depression. She was also suffering from a right hemiplegia. It appeared, according to Mrs. Meyer, that she was married at 16, and lived with her husband until 29, whereupon she left him on account of his alcoholism, his abuse of her, and the discovery through his physician that he was suffering from venereal disease. She had had two healthy children and there never had been miscarriages or stillbirths. Six years after the separation, namely at 35 years of age, and 16 years before resort to the Psychopathic Hospital, Mrs. Meyer developed certain red areas on her hand, and learned at a hospital that these were due to syphilis. She kept up treatment for these lesions for a year, until she seemed perfectly well.

She had, in fact, remained perfectly well for some 14 years, until at 49, a small tumor had appeared on the right side of the forehead, near the hair line. This tumor was firm and not sore. Medical treatment reduced it, leaving, however, a depression in the bone. One day, about a month after the appearance of the tumor, the patient lay down for a nap, and upon awaking found she could only with difficulty move her right arm and leg. Her face was not affected; she was not in pain; and there was no disorder of speech. In a few days she got much better and she had been improving for some time past through the administration of further medicine.

However, since the onset of the hemiplegia Mrs. Meyer had been very despondent. There had been ups and downs but she had rarely felt well. The depression was a mild one and in point of fact may perhaps be regarded as non-psychopathic, since at her age with her disability, there might well be a degree of sadness and unhappiness concerning the future. =Mentally=, there was no other disorder of note, and in particular no disorder of memory.

=METHODS OF TREATMENT=

I. BY MOUTH. 1. MERCURY 2. IODIDES 3. ARSENIC

II. INTRAMUSCULAR INJECTIONS 1. MERCURY 2. SALVARSAN, NEOSALVARSAN, OTHER ARSENIC PREPARATIONS 3. SODIUM NUCLEINATE 4. ANTIMONY

III. INTRAVENOUS 1. MERCURY 2. MERCURIALIZED SERUM 3. SALVARSAN, NEOSALVARSAN, ARSENIC 4. IODIDES

IV. SPINAL INTRADURAL 1. SALVARSANIZED SERUM (IN VIVO—SWIFT-ELLIS) 2. SALVARSANIZED SERUM (IN VITRO—MARINESCO-OGILVIE) 3. MERCURIALIZED SERUM (BYRNES)

V. CEREBRAL SUBDURAL AND INTRAVENTRICULAR 1. SALVARSANIZED SERUM (IN VIVO) 2. SALVARSANIZED SERUM (IN VITRO) 3. MERCURIALIZED SERUM

CHART 26

=Physically=, the patient showed a right-sided hemiplegia with excessive right knee-jerk, but without Babinski or other abnormal reflex phenomena. The extraocular movements were somewhat restricted in range but there was neither strabismus nor nystagmus.

The question arose whether the hemiplegia was of hemorrhagic or thrombotic origin. After all, at 51 years, hemiplegia is rather unlikely to be of a non-syphilitic arteriosclerotic origin; moreover, we had a clear history of syphilis. The serum W. R. proved positive as well as the spinal fluid W. R. The finding of 77 cells per cmm., excess albumin, and positive globulin test, taken in connection with the entire picture seems to warrant a diagnosis of CEREBROSPINAL SYPHILIS. If we proceed on statistical grounds, it might be regarded as more probable that the hemiplegia is THROMBOTIC in origin rather than hemorrhagic. It appears that syphilitic cerebral thrombosis rather characteristically occurs without preliminary symptoms, despite the fact that many cases do show headache, dizziness, and restlessness as prodromal symptoms.

1. What is the treatment indicated in the case of Mrs. Meyer?

It would appear that little or nothing can be done for the hemiplegia unless the claims of Franz with respect to reëstablishment of a degree of function in certain hemiplegics are substantiated. However, the indication of meningitic process as shown by the spinal fluid, suggests that the case is not a purely vascular one but may be regarded as meningovascular. (Possibly, also, we should regard the left frontal depression and scar as indicative of a non-parenchymatous and non-vascular process.) Accordingly, antisyphilitic treatment should be theoretically of some value.

In point of fact, the patient was given injections of mercury salicylate, mercury by mouth, and potassium iodid. Her psychopathic depression under this treatment, supported by proper hygiene and rest, diminished. However, six months later, the patient slipped on a wet floor and fell. Though the impact seemed hardly sufficient to cause a fracture, the pelvis was somewhat severely fractured. Very probably there was a syphilitic rarefaction of the bone. Six months later the patient’s depression was still in evidence, though somewhat less than upon admission. The blood serum remained positive but the spinal fluid had become entirely negative, both in respect to the W. R. and in respect to the other findings.

2. How may one explain the continuance of the depression after the spinal fluid had become entirely negative under treatment? It may be that while the active process had been stopped, as seems probable from the negative spinal fluid, that a permanent destruction of brain tissue may account for the depression. We recognize this readily in instances of vascular disturbance where (as also in this case) the active process being stopped, a residual defect remains.

3. Should treatment have been discontinued on reduction of the gumma? It cannot be too often emphasized that the disappearance of symptoms in cases of syphilis can not be considered as evidence of cure. The neurologist and psychiatrist see only too often cases of neurosyphilis occurring in patients who have been declared cured at some time previous because the symptoms then present had cleared up and remain in abeyance for years.

=Contrary to various warnings, arteriosclerosis by no means absolutely contraindicates intensive salvarsan therapy.=

=Case 108.= Victor Friedberg, 42 years of age, gave the following history. He acquired syphilis at 22 years. He had “adequate” medical treatment for two years with inunctions of mercury and mercury by mouth and potassium iodid. The only secondary symptoms were skin lesions of the legs; these disappeared upon treatment. Married, Friedberg has one child, apparently normal. There had been no miscarriages or stillbirths.

At about 34 years, there began to be shooting pains in the legs, occurring at first about once in three months, but later much more frequently. These pains were severe, lightning in character, lasting several days at a time, at which period his head would feel heavy; but there were no disturbances, crises, or difficulty in locomotion.

At 36 years of age, Friedberg waked up with pain one night, and found he was unable to move his left leg or hand, and he felt his mouth drawn to the left. Upon trying to get out of bed, he fell to the floor. In five hours, however, he was entirely recovered, able to get up and walk about, and to use his left arm quite normally. He went to sleep, but upon waking up after an hour, discovered that his left side was again paralyzed. After two weeks in a hospital, he was able to walk with a crutch. The arm remained helpless for about a year. Both arm and leg improved slowly for two years, after which time his condition had remained stationary. For four years past, there had been no more pain, but at 42—about two years before admission—the pains returned in his legs, back, and side. At that time he received four injections of salvarsan, mercury tablets, and potassium iodid. Three weeks before admission to the hospital, Friedberg again began having headaches, very much worse than formerly. At first these headaches were frontal, then occipital, and there was a feeling as if something were growling inside of the head. There was a feeling of pressure in front on the head and at the base of the nose.

=Physically=, Friedberg appeared somewhat older than his assigned age. There was a degree of general peripheral arteriosclerosis, but in general the physical examination was negative. Neurologically, there was a left hemiplegia with appropriate increase of the reflexes on that side, spasticity, Babinski reflex, and an Oppenheim; the pupils reacted properly; there was no Romberg reaction.

Mentally, Friedberg was entirely negative.

The W. R. of the blood serum was doubtful, as was that of the spinal fluid. There were but two cells per cmm. and there was neither globulin nor excess albumin in the spinal fluid.

The =differential diagnosis= might lie between cerebral hemorrhage and syphilitic thrombosis. Thrombosis is much more common as a result of syphilis than is hemorrhage. The occurrence of the thrombosis during sleep without premonitory symptoms is also characteristic in syphilis. Possibly there was a low-grade spinal meningitis at the bottom of the lancinating pains. Whether the headache is an arteriosclerotic effect or due to a meningitis not shown in the cerebrospinal fluid is doubtful. However, the absence of inflammatory products in the cerebrospinal fluid rather indicates that the headache is of arteriosclerotic origin. Autopsies, however, warn us that we may have a localized meningitis in various parts of the cranial cavity without the determination of any inflammatory products in the spinal fluid.

1. How shall we explain the doubtful (slightly positive) W. R. in the spinal fluid if the case is one of VASCULAR BRAIN SYPHILIS? The finding is not unusual in these cases. The W. R. producing body is recognized to be of a separate nature from the globulin and albumin bodies, and is probably also separate from the gold sol reaction producing bodies.

Treatment: The theory of treatment is that any spirochetes that may be still active in the body should be destroyed. Accordingly, although salvarsan can certainly have no effect in reproducing nerve tissue, it nevertheless seems indicated. It is frequently stated, however, that salvarsan is dangerous in cases of this group. We have not found this statement correct. In this case, there was a symptomatic improvement, as far as pain and discomfort went, under salvarsan and iodids.

2. What precautions should be taken in intensive salvarsan treatment of syphilitic arteriosclerosis? Treatment should be begun with very small doses of salvarsan, that is, about 0.1 of a gram and then the amount slowly increased. The injection should be given slowly so as not to put too great a load upon the cardiovascular system.

3. What rôle does the mental attitude of the patient play in a case like that of Friedberg? It was quite evident that Friedberg was neurotic and that he had a syphilophobia. Consequently some of the symptomatic improvement may have been more results of assurances offered by the physician and knowledge that he was being treated, than results of salvarsan. In some cases mental anguish suffered by the patient is of more importance than the actual symptoms of the disease and this point must be always borne in mind in handling syphilitic patients.

=Symptoms of intracranial pressure cured by antisyphilitic treatment.=

=Case 109.= Mrs. Annie Rivers, a housewife 36 years of age, sought advice and treatment for severe convulsions which she had had during a period of several weeks. She left the hospital before being properly examined, and had several more convulsions, after which she was brought back in a state of marked confusion. The confusion shortly disappeared almost completely, and a good history was obtained.

It appears that the patient led a normal life and had had six children, the last of whom was born about four months before her coming to the hospital. The first symptoms appeared about a month after the birth of the child, when, one afternoon, Mrs. Rivers suddenly fell unconscious while ironing. She remained unconscious for nearly three hours. During this attack there were no convulsive movements or tongue-biting; and after the spell, she felt neither lame nor sore, but merely tired. This was Mrs. Rivers’ statement; but her daughter stated that the patient really did have convulsive movements. A week later came a second convulsion, followed by daze and stupor. This second attack lasted two hours.

About a week before entrance, the patient had remained in bed on account of dull grinding pain in the left side of the head, below the ear, and upon this day the patient vomited twice. In addition to the dull grinding pain, there were pains referred to the ear itself and to the left side of the head, especially over the left eye; there were no pains on the right side of the head. The next day the patient was better, but the day thereafter again remained in bed. The only other symptoms were cold feelings at times and bright spots in the field of vision.

No =mental symptoms= were observed in Mrs. Rivers except a bit of depression after her hasty retreat from the hospital the first time. Upon her second admission, however, after a week or ten days’ residence, apathy developed together with considerable amnesia for the same facts she had quite readily remembered a few days previously. Along with the apathy and amnesia developed considerable headache; and there were attacks of vomiting.

=UNTOWARD SYMPTOMS OF THERAPEUTIC AGENTS=

=A. SALVARSAN=

CYANOSIS MALAISE RAPID PULSE PERSPIRATION RESPIRATORY DIFFICULTIES FEVER NAUSEA, VOMITING, DIARRHOEA DERMATOSES EDEMA KIDNEY IRRITATION LIVER IRRITATION INTENSIFICATION OF SYMPTOMS COLLAPSE

=B. MERCURY=

SALIVATION FETID BREATH EXCESS FLOW OF SALIVA TENDERNESS OF TEETH—LOOSENING AND FALLING OUT SPONGY GUMS—EROSION METALLIC TASTE NECROSIS OF BONES OF JAW SORENESS OF PARETIC AND MAXILLARY GLANDS SWELLING AND EROSION OF TONGUE AND MUCOUS MEMBRANES GASTRO-INTESTINAL SYMPTOMS ANEMIA PAIN IN JOINTS NEPHRITIS

=C. IODINE=

SKIN LESIONS METALLIC TASTE SALIVATION CORYZA URTICARIA (EVEN TO GRADE OF ANGIONEUROTIC EDEMA) PAINS CONSTIPATION INVOLVEMENT OF JOINTS FEVER SOFTENING AND BLEEDING OF GUMS EROSION OF MUCOUS MEMBRANES GASTRO-INTESTINAL SYMPTOMS ANOREXIA WEAKNESS

CHART 27

On the =physical= side, it is interesting to note that the ophthalmoscopic examination upon Mrs. Rivers’ first admission to the hospital was entirely negative, whereas a week later, pronounced difficulty with vision appeared so that in a few days she was able to make out only very large type. The fundi now showed hazy and indistinct disc outlines, with small yellowish areas of fatty degeneration above the disc, reduction of arterial calibre, and dilated and somewhat tortuous veins (no projection of papillæ), so that the ophthalmological diagnosis was chronic neuritis.

The physical examination otherwise was mostly negative. The skin presented irregular areas covered with silvery scales over the arms and chest, back, abdomen, and legs (the patient had had psoriasis several years before). Both pupils reacted to light and distance, though the right was slightly larger than the left and somewhat irregular. There was a slight tremor of the tongue and extended fingers. The reflexes were active, especially the knee-jerks; no abdominal reflexes could be obtained. The serum W. R. was positive, but the spinal fluid W. R. was negative. The spinal fluid showed but 3 cells per cmm., but there was a positive globulin test and an excess of albumin.

=Diagnosis=: After the symptoms had fully developed, it became clear from the optic neuritis, headaches, and vomiting that a condition of intracranial pressure existed. In view of the positive serum W. R., it is natural to conceive that the agent producing the intracranial pressure was a gumma.

It is, of course, possible that a marked degree of meningitis might be so localized as to produce the same symptoms. The diagnostician would crave a pleocytosis of the spinal fluid if a diagnosis of meningitis is to be made; and there was no such pleocytosis. On the whole, we do not feel that it is possible to make a diagnosis either of MENINGITIS or of GUMMA.

=Treatment=: Treatment, however, caused a disappearance of all symptoms. The treatment consisted of but one injection of 0.3 gram of salvarsan, followed by a few injections of mercury; whereupon Mrs. Rivers became much brighter, recovered her vision, lost her headaches, ceased to have convulsions or vomiting spells.

1. Is salvarsan contraindicated in cases with involvement of the optic or auditory nerves? Such a contraindication exists according to prevailing opinion. In this particular case, a hemorrhagic retinitis occurred after the injection of salvarsan, but this retinitis disappeared along with the other symptoms. On the whole we believe that in many cases of optic or auditory nerve involvement salvarsan should be used. However, one should never lose sight of the possibility of untoward results and should advise such treatment only when other treatment seems inefficient.

=TABETIC NEUROSYPHILIS (“tabes dorsalis”) may show very marked improvement as a result of intraspinous therapy.=

=Case 110.= Mr. McKenzie was a retired merchant of 42 years whose complaint was that he tired very easily, could not make his legs go where he wished, was unsteady and felt a numbness in his legs. These symptoms had been in progress for a few months only when the examination was made. This disclosed Argyll-Robertson pupils, absent knee-jerks and ankle-jerks, Romberg sign, unsteady gait, moderate ataxia and dysmetria. The W. R. was negative in the blood serum but positive in the spinal fluid with 0.2 cc., and there were 107 cells per cmm. With the symptoms and signs it was therefore easy to make the diagnosis of TABETIC NEUROSYPHILIS (“tabes dorsalis”).

The patient was given five intraspinous injections of mercuric chloride in blood serum (mercurialized serum) according to the method of Byrnes. The dose was 0.001 gm. of mercury. Two weeks after the first injection the cell count was 58 cells per cmm., the Wassermann was positive only with 0.4 cc. After the fourth injection there were but 18 cells and the Wassermann reaction was negative even with 1½ cc. of spinal fluids. The symptoms had improved to such a degree that the patient had no complaint whatsoever and considered himself cured.

1. What are the unpleasant results of intraspinous therapy? Frequently there is an exacerbation of symptoms and pain may be quite severe after intraspinous injections. This, however, lasts only a short period, that is, as a rule less than 24 hours. There may be other symptoms of cord irritation as retention of urine or lack of sphincter control. A rise of temperature is not unusual.

=Treatment may alter the W. R. to negative in blood and spinal fluid in TABES DORSALIS.=

=Case 111.= Ivan Rokicki was a baker, 43 years of age, who came complaining of exceedingly severe attacks of abdominal pain with vomiting. He described these attacks as having occurred periodically for a number of years, lasting sometimes as long as a week, during which time Rokicki could not eat or get relief short of large doses of morphine.

Upon his arrival, Rokicki was seen in one of his attacks; he was curled up with excruciating pain, and the abdomen was rigid, though it was impossible to produce additional pain by external pressure. There was spasmodic vomiting, frequently followed by slight relief from the pain, which however shortly recurred and caused the patient to cry out in his suffering. The condition was controlled by opiates but lasted a full week. The leucocytes remained normal and there was no rise of temperature. The attack ceased spontaneously.

Save for the pain, Rokicki’s =mental examination= proved entirely negative. =Physically=, Rokicki was fairly well developed and nourished. His pupils were slightly irregular: the left markedly larger than the right; both pupils failed to react to light, and the left pupil also failed to react in accommodation. There were no other reflex disorders evident to systematic examination, nor was there sensory disturbance or speech defect. The heart seemed somewhat enlarged but there were no murmurs; blood pressure: systolic 150; diastolic 110.

The correct symptomatic diagnosis in Rokicki’s case proved to be gastric crises, and this diagnosis must perforce be the first to entertain in view of the chronicity, the periodicity, the non-relation to diet, and the spontaneous cessation of the seizures. The observation of Argyll-Robertson pupils was naturally held to substantiate the diagnosis of TABES DORSALIS.

The possibility of abdominal inflammation could be shortly dismissed on account of the absence of tenderness (the rigidity in this case was not accompanied by tenderness), fever, and other characteristic signs. There was no diarrhoea, such as is found in lead colic, and there was no other sign of plumbism. Jaundice was absent and there was no special radiation of pain from the abdomen. One had to think of gastric ulcer and hyperchlorhydria, and possibly malaria or gastroenteritis.

The pupillary reactions pointed to a syphilitic condition despite the fact that the lack of reaction to accommodation (over and above the Argyll-Robertson phenomenon) in the right pupil is not entirely typical. Accordingly, although there was no areflexia, Romberg sign, or ataxia, resort was had to the W. R. This however proved negative, in blood and spinal fluid; nor was there any globulin or excess albumin; there were 5 cells to the cmm., in the spinal fluid.

We are left, accordingly, with characteristic gastric crises; Argyll-Robertson pupils, slightly irregular; and a somewhat enlarged heart.

Upon investigation, it appeared, however, that a year before the attack above described, the patient had been examined and both blood and spinal fluid found positive to the W. R. At that time, treatment, consisting of intravenous injections of salvarsan and intraspinous injections of salvarsanized serum (Swift-Ellis), had been instituted. Whereupon the laboratory tests had become negative, as above stated, and there had been no alleviation of the symptoms.

1. How can Rokicki’s normal deep leg reflexes be explained? The abolition of the deep reflexes is of course due to lesions properly localized. It is probable that this particular case of tabes dorsalis is more truly “dorsal” than most cases; for most cases exhibit lesions involving regions lower than the dorsal. Both in these dorsal cases and in certain rare cases of cervical tabes, the deep leg reflexes are preserved. (See cases Green (30) and Halleck (31).)

2. What is the mechanism by which a characteristic gastric crisis is produced? The mechanism is unknown. Some endeavors have been made to meet gastric crises by surgery of the posterior roots, on the assumption that the irritation causing the pain was located either in the posterior ganglion or in the passage of the nerve through the meninges. In only a few instances, however, has the result been what was desired. In many instances the gastric crises and pain continued uninterrupted and in addition came discomfort due to the lack of sensation in the part supplied by the severed nerve. At present this treatment is seldom carried out.

3. Should antisyphilitic treatment be continued in such a case? As far as our present knowledge of syphilis goes one would hesitate to suggest further antisyphilitic treatment, feeling that the active process had been entirely stopped as suggested by the absence of any positive findings either in the blood serum or in the spinal fluid. We should perhaps conclude that there was no more activity in this case and that the crises were due to the changes that had already taken place in the nerve tissue and which could no longer be changed.

=The literature is in doubt concerning (in fact is preponderantly against) the success of treatment in PARETIC NEUROSYPHILIS (“general paresis”). Our experience has yielded a number of apparently successful results through systematic intensive intravenous salvarsan therapy. Example.=

=Case 112.= Albert Forest had always been a successful salesman, but in the middle of March, in his 46th year, he was arrested for grabbing a purse from a woman in front of a theatre and running down the street with it. In court, Forest acted strangely and he was sent to the Psychopathic Hospital for observation. Upon investigation, it appeared that his wife thought he had been showing mental changes for about a year. For example, he would embrace his wife on a street car, or refuse to pay her fare. He once attempted to hit his son on the head with a red-hot poker. Now and then he would become sleepy and stupid. He looked rather older than his age and had a coarse tremor of the hands. Otherwise, no change could be detected in the physical examination, either neurologically or otherwise. As for the manual tremor, Forest’s wife gave a history of considerable alcoholic indulgence on his part.

For several days, nothing abnormal could be detected in the man; and in particular, his memory for both remote and recent events was very good and his knowledge of current events was good. Simple arithmetic was easy to him.

One evening his temperature was found to be 104° F. and no cause could be discerned for this. The next morning, Forest was discovered in a stupor, with a complete right hemiplegia. The Babinski reflex, the Oppenheim reflex, and ankle clonus had appeared on the right side, and the right arm was spastic.

However, all symptoms of this paralysis had disappeared by four o’clock in the afternoon, and the paralytic phenomena were replaced with violence. The patient fought with the attendants and for some time remained extremely difficult to manage, being confused and subject to outbreaks of violence with destruction of furniture and other property about the ward.

=Diagnosis.= At first we were naturally inclined to dismiss the case with a diagnosis of alcoholism. The transient hemiplegia at once raised a considerable question of brain syphilis or of brain tumor.

The W. R. of the serum was doubtful. The spinal fluid yielded, besides marked excess of albumin and much globulin, also a “paretic” gold sol reaction and 75 cells per cmm. The W. R. was positive.

=Treatment.= The patient was given injections of salvarsan, 0.6 gram, twice a week, with potassium iodid. After a few weeks improvement followed, and after several months all the laboratory tests became negative, the patient was apparently perfectly normal mentally and was discharged from the hospital, and has remained well for 18 months without further treatment. The serum W. R. has continued to be negative.

1. What is the significance of the so-called “doubtful” W. R.? Where there is not a complete uniformity the results of the strong and weak antigens (see appendix on technique of Wassermann reaction) the result is reported as doubtful. In the majority of instances repetitions will give a strong positive reaction.

2. Is the case of Forest to be regarded as one of general paresis? Sometimes such cases are termed in the literature syphilitic pseudoparesis (see case Burkhardt (58)). The differential diagnosis of this group is entirely therapeutic. There are, unhappily, no laboratory tests which will suffice in the present stage of knowledge to differentiate a case of so-called pseudoparesis from general paresis. We are inclined to term the case one of GENERAL PARESIS, with recovery, or, at all events, with remission.

=The literature is in doubt concerning (in fact is preponderantly against) the success of treatment in PARETIC NEUROSYPHILIS (“general paresis”). Our experience has yielded a number of apparently successful results through systematic intensive intravenous salvarsan therapy. Example.=

=Case 113.= We present the case of Gussie Silverman, a housewife, 35 years of age, among other reasons, for its social interest. The case is, on the whole, sufficiently typical of GENERAL PARESIS. =Physically=, for example, the pupils failed to react to light and accommodation and were unequal, the right being larger than the left. The knee-jerks were sluggish though equal. The ankle-jerks could not be obtained. The abdominal reflexes were not obtained. Otherwise, there was no reflex disorder.

From the =laboratory= point of view, the W. R. was positive in the blood and in the spinal fluid. There were 80 cells per cmm. and there were an appropriate globulin and albumin reactions. Mrs. Silverman was rather poorly nourished and had a slight edema of the ankles.

=Mentally=, she was found on admission to be markedly depressed. It appeared that during a recent pregnancy, terminated by the birth of a 7–months child, she had fainted several times a day, that since the confinement she had been very nervous, that she had been asking her husband not to send her away, that she had refused to leave the house, that she had become excited even to the point of injuring herself, especially at night, and that she would go so far as to scratch her husband, shortly afterward being very sorry for her performances. Before this last pregnancy there had been four others and the resulting children were all apparently in good health. Except for the fainting spells during the pregnancy, it would not appear that the story just told is at all characteristic of paresis.

However, in the hospital Mrs. Silverman could hardly be got to answer questions, continually saying, “You know what it is; I don’t have to tell you.” She claimed so marked a degree of confusion as not to know where she was and what she was doing. She would beg despondently that something be done for her, and iterate and re-iterate these claims. There appeared to be a marked degree of amnesia. Some one, she felt, had controlled her thoughts and made her do things she did not want to do and say things she did not want to say, things she did not know she was about to say. She said, “I feel like jumping around. I couldn’t believe myself as if I am me. Some one is making me jump around. I used to hear him talking. I don’t know who it is. I used to keep my eyes open and I couldn’t move. I feel only I would like to talk, and talk, and talk, and talk all the time. It seems to me that some one talks in me. I couldn’t sleep for five minutes. My God, I wish I could sleep! I used to feel something in my heart. I used to faint. It seems to me I used to see a funny thing. What it was I can’t tell. It used to talk to me, make me get out of bed, throw me about, make me do things. O, I don’t know what it was.”

These not entirely characteristic mental symptoms, together with the suggestive physical signs and the laboratory examination, caused treatment to be instituted; under which treatment (intravenous injections of salvarsan) she improved rapidly. Mental symptoms disappeared under the administration of 12 injections of salvarsan within two months. Moreover, the spinal fluid became entirely negative. Two and a half years have now elapsed since her discharge and she has shown no return of symptoms. The serum W. R. has always remained negative although there has been no treatment since leaving the hospital. There has, however, been no change in the reflexes, which remain as on admission. The 7–months baby has continued to be perfectly healthy. Its W. R. is negative, as are the W. R.’s of the husband and the other three children. It must seem surprising that a healthy child could have been born from a mother with generalized syphilis as in this case. However, perhaps there are more instances than we imagine like the case of baby Silverman.

1. May a patient be considered permanently cured although there has been no recurrence of symptoms for 2½ years and although the Wassermann has remained negative? One would hesitate to give a definite statement that the patient was cured until more time had elapsed. It is quite possible that spirochetes may be lurking in some portion of the body without causing the production of symptoms or Wassermann bodies and yet ready to break out at any time. This hypothesis has added weight from the recent work of Warthin already quoted. We advise examination of this patient at intervals of not longer than six months for a good many years.

2. Should the course under treatment cause us to change the diagnosis? It has often been stated that a differential point between cerebrospinal syphilis and general paresis is the reaction to treatment, that is, that a case which recovers could not be general paresis. Head and Fearnsides state that if six months after beginning of treatment the spinal fluid has become negative, the case should be considered as one of cerebrospinal syphilis and not general paresis. We do not feel ready to concur in this view as we know of no similar logic in medicine. We have many cases in which a spinal fluid has remained positive for six months and later become negative, so that where the symptoms shown are those of paretic neurosyphilis, we are inclined to consider the case such until such time as more definite evidence checked by post mortem examination causes us to change this point of view.

3. Do the reflexes change under treatment? The signs of spasticity often do disappear under treatment and also when there is no treatment. A few instances have been reported in the literature where Argyll-Robertson pupils are said to have altered to normal. It has never been our good fortune to see such a change nor have we seen an absent knee-jerk become normal, as has also been reported, except where it is the result of pyramidal tract disease superimposed upon the posterior column sclerosis causing a return of reflex. This, of course, is not to be considered as a return of the normal. (See Case 1.)

=Some RESULTS of systematic intravenous salvarsan therapy are PARTIAL (e.g., clinical recovery and persistence of positive laboratory tests).=

=Case 114.= Walter Henry was an undertaker in a small town. He was married and the father of two healthy children. In May, 1914, he began to lose his appetite. He felt restless and seemed to be losing his grip, and in August he repaired to a sanatorium, where he remained for two months. Shortly after leaving the sanatorium, he fainted one day, while digging a grave, during a spell of great heat. Since that time there had been numerous “weak spells,” with headaches and general debility, insomnia, and loss of weight.

In February, 1916, Mr. Henry came to the hospital for advice, but the trip from a distant part of the state was apparently such a strain for him that shortly after admission he collapsed. There were no convulsive movements in this collapse, but the patient was confused and his breathing was rapid and stertorous. The semi-stupor lasted for about 48 hours. Upon recovery from the stupor, Henry was found entirely disoriented, much confused, and laboring under the belief that he was digging a grave. After a time he again fell into a stupor and his temperature rose to 103° F.

The emaciation of this man was striking and unusual, but systematic =physical examination= showed no special disease. =Neurologically=, there were marked tremors, and there were purposeless movements of the arms. There was a marked speech defect. The pupils were dilated, regular, and equal, and reacted, though slightly, to light. Nothing abnormal was noted upon systematic examination of the reflexes.

The W. R. was strongly positive in the blood and in the spinal fluid; the gold sol reaction was typically “paretic”; there were 16 cells per cmm., globulin was present, and albumin was greatly increased.

The =diagnosis= GENERAL PARESIS was accordingly made, and treatment instituted. Intravenous injections of arsenobenzol, at first, and later of diarsenol, were given, as a rule twice a week (usual dose, 0.6 of a gram). Mercurial injections and potassium iodid were also given. This treatment was continued as the patient began to improve. The improvement was of such a degree that at the end of four months, Mr. Henry returned to his home and his work. He had had 30 intravenous injections of salvarsan substitutes. Despite the treatment and the clinical improvement, the laboratory tests remained essentially unchanged. The W. R.’s of the blood and spinal fluid remained strongly positive, as well as also the globulin and albumin; the gold sol reaction was still “paretic”; the cells stood at one per cmm. The patient has continued antisyphilitic treatment since leaving the hospital, and has remained apparently well, with good insight into his condition.

1. What is the significance of a temperature of 103° in a paretic without signs of infection and a normal leucocyte count? Temperatures of this type are not infrequent in the course of general paresis. They are usually spoken of as “paretic temperatures.” Their meaning is not understood, but they are often stated to be due to a disturbance of the heat-regulating mechanism. Such temperatures may remain elevated for a considerable period of time, but the elevation may be very transitory. At times they vary, like septic temperatures.

2. What can be argued from the fact that the cell count became normal? If thorough antisyphilitic treatment is vigorously given, it will be found that in the vast majority of cases of neurosyphilis the cell count will return to normal. It matters not whether the treatment be intravenous or subdural. It is very difficult, however, to obtain this result in general paresis by the use of mercury alone. It cannot, however, be urged that this finding has any great prognostic significance as it occurs in the cases which do poorly as well as in those which recover symptomatically.

3. Is it safe to give large doses of salvarsan to a patient in a stupor? It is not a good plan to give a large dose to such a patient on account of the danger of sudden death. This is probably due as much to the strain put on the heart as it is to any effect on the nervous system, or specific arsenic effect. In this particular instance, a dose of 0.15 gm. was the initial injection and this was increased five centigrams per injection.

=IMPROVEMENT IN PARETIC NEUROSYPHILIS (“general paresis”) may become evident only after several months of intensive treatment.=

=Case 115.= Henry Ryan was a shipping clerk, 54 years of age, who was brought to the hospital following a convulsion. For a few months preceding this period, Mr. Ryan had been failing in his abilities. He had been very forgetful, showed no energy, and had become very irritable. He also complained of insomnia and of feeling nervous.

On admission to the hospital, the most striking feature in the mental situation was that he claimed that he had not slept a wink for three months, and each day he would solemnly affirm that he had not slept at all the preceding night, although the records might show that he had slept eight hours. Argument was of no avail against this conviction. In addition, his memory was very poor; he showed little knowledge of current events, and had no ability with arithmetical problems.

=Neurologically= viewed, the points of chief significance were contracted immobile pupils and a speech defect, especially noticeable on the repetition of test phrases. The whole picture was suggestive of general paresis, and this diagnosis was confirmed by the laboratory findings. It was found that the W. R. was positive in the blood and spinal fluid, that there was a pleocytosis, positive globulin reaction, excess of albumin, and a “paretic” gold sol reaction. Consequently, the diagnosis of GENERAL PARESIS seemed justified, although the patient denied any knowledge of a syphilitic infection.

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.=

=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.

=Treatment=: 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.

=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, began 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 was 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.

=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 6–5⁄12 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.

Note: 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 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 states that of all the causes of feeblemindedness, there 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. 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.

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

Paradise Lost, Book X, Line 230.

VI. NEUROSYPHILIS AND THE WAR

Although the American toll of war syphilis has not yet begun and although the crop of neurosyphilis due to war infections may not arrive until the mid or late twenties of the century (witness German experience in the eighties of the last century), it seems proper here to give a number of abstracts re neurosyphilis as it has developed in the war. Available reports from English, French, and German sources have been levied upon for the years 1914–16.

It is clear that all the armies have had their share of neurosyphilitics, some clearly diseased before enlistment, some developing symptoms as a result of training, stress, or shock, others hastened or made worse by war conditions.

There are important questions of pension, retirement, and compensation for neurosyphilitics. No previous war has had the benefit of the Wassermann reaction and other exact tests bearing upon the nature, progress, and curability of neurosyphilis.

That we shall have our fill of pension and other problems can already be seen from continental reports. Thibierge, for example, states that syphilis has become a real epidemic among the French soldiers and mobilized munition workers.

Hecht of Austria claims that no less than an equivalent of 60 army divisions have been temporarily withdrawn from fighting on the Teutonic side for venereal diseases. He commends Neisser’s idea that salvarsan and mercury should be given in the trenches. While hundreds or thousands of Austrians are sick with syphilis, sound and healthy men are being shot down in their stead. The diagnosis of syphilis, according to Hecht, ought to be a signal for sending the men to the front. He makes even the somewhat bizarre suggestion that special companies of syphilitics should be formed, for convenience of treatment, on the firing line.

Not only is the syphilis problem in the army of importance to the military authorities, but also to the civil population, and perhaps to them a greater problem. With the great increase of venereal disease that is the result of the conditions of army life in war time, there will be a considerable percentage of cases developing neurosyphilis a number of years after discharge from the army, but caused by the infection acquired during service. In addition many men will bring the disease back to America in an infectious stage and spread it. We would advocate that the names of all soldiers who had acquired syphilis and were not considered cured at time of discharge should be given to health organizations in their home states that they may be given further care.

These practical and several theoretical questions are raised by the following fourteen cases which we have condensed from their sources.

=A tabetic lieutenant “shell-shocked” into paresis? Case from Donath of Vienna.=

=Case A.= An apparently competent German professor in an intermediate school, a lieutenant of infantry reserves, 33 years old, on the 17th August, 1914, was stunned for a while by the shock of a cannon-firing 25 feet away. Urination became difficult. Headaches and limb pains ensued, with paralysis of fingers, gastric troubles, forgetfulness especially for names, insomnia, and general scattering of mental faculties.

=Neurologically=, the pupils were irregular, left larger than right; Argyll-Robertson reaction. Right knee-jerk livelier than left. Achilles reactions absent. Slow and dissociated pain reactions in feet, lower thighs and lower quarter of upper thighs, with hypalgesia or analgesia. Station good; gait steady. Mentally depressed, slow of thought. Speech poor and of indistinct construction (mild dementia). Calculation ability poor. No pleasure in work.

Wassermann reaction of serum weakly positive.

It seems that for a year the patient had been subject to spells of anger. He was irritated by his wife who had been nervous since an earthquake.

On the occasion of the earthquake, 1911, the patient himself had had a spell of difficulty with urination. The spell had lasted two or three months. The patient had had a chancre in 1902, “cured” in four or five weeks with xeroform. In 1908, when about to marry, he had had six mercurial inunctions.

1. Is this a case of traumatic paresis? From the somewhat meagre account it would appear that Donath’s lieutenant should rather be termed “shell-shock paresis,” in the sense of a paretic neurosyphilis liberated by shell-shock (using shell-shock in the sense of a shock without direct brain injury).

2. What compensation is due such a man as Donath’s lieutenant? The ordinary principles applicable to traumatic paresis are not here in point, since no symptoms pointing to trauma of brain ever supervened. See discussion under Case G.

3. How frequent is paresis in armies? R. L. Richards in White and Jelliffe’s Treatment of Nervous and Mental Diseases writes as follows (of course concerning peace times):

“The French estimate that paresis cases are 7 per cent of all their military cases. The German estimate is 6.6 per cent. In our own army at the Government Hospital for the Insane, of 490 cases of mental diseases among officers and enlisted men, 37, or 7 per cent, were paresis. During the Russo-Japanese War, in the Russian Psychiatric Hospital at Harbin, the percentage of paresis was 5.6 per cent among the cases developing at the front.”

=A French soldier “shell-shocked” (also burial) into incipient tabes dorsalis? Case from Duco and Blum of Paris.=

=Case B.= A French soldier was buried by effects of shell explosion September 8th, 1914. He sustained no wound or fracture.

Incontinence of urine developed. Anesthesia of penis and scrotum. Reflexes absent; pupils sluggish. Wassermann reactions suspicious.

The diagnosis =tabes dorsalis incipiens= was made (hematomyelia of conus terminalis eliminated).

The patient was estimated to be “40% incapacitated,” according to the French “échelle de gravité” of conditions. A full pension would not be justified in the opinion of the French authors.

1. Is there evidence of an increase or exacerbation of tabes dorsalis in the war? Birnbaum, reviewing German war neurology, quotes Weygandt as believing that the war has probably had to do with the production of both tabes and paresis in many instances. Other cases, however, have merely been made worse by the war stress. Thirdly, there are cases in which the war stress has done no harm whatever. Westphal has seen both tabes and paresis develop in men who had never before shown any mental or physical symptoms whatever, and accordingly, Westphal must be counted among those who regard war stress as a liberating factor for these diseases. Redlich and Donath are cited in the same connection. (The case of Donath is the case presented above as Case A.)

A very interesting claim was made by Cimbal to the effect that he found many examples of paresis developing in the early period of the war, particularly in November and December, 1914. Later, according to Cimbal, cerebrospinal syphilis and tabes became more prevalent.

=Neurosyphilis in a German recruit, possibly AGGRAVATED ON military SERVICE. Pension not allowable. Case from Weygandt.=

=Case C.= A German, long alcoholic and thought to be weakminded, volunteered, but shortly had to be released from service. He began to be forgetful and obstinate, cried, and even appeared to be subject to hallucinations. The pupils were unequal and sluggish. The uvula hung to the right. The left knee-jerk was lively, right weak. Fine tremors of hands. Hypalgesia of backs of hands. Stumbling speech. Attention poor.

It appeared that he had been infected with syphilis in 1881 and in 1903 had had an ulcer of the left leg.

The military commission denied that his service had brought about the disease. In the phrase of the Canadian Pension Board the German commission would probably have rendered a report “aggravated on service,” not “by service.” (See Canadian cases D, E, and F.)

1. Has paresis increased in the war? Both French and German figures controvert the claim. Marie, for example, found not a single paretic amongst the skull injury cases at the Salpétrière. Most authors are found demonstrating cases which they clearly regard as in some way produced or unfavorably influenced by the war. There seems, therefore, to be a little inconsistency between the general statement that paresis has not increased in the war and the somewhat frequent cases described as occurring in and modified by the war. However, Bonhoeffer, on the basis of nine months’ war experience, also holds it to be probable that paresis is no more frequent in the field than in the home population.

2. Is the old syphilitic especially liable to break down under war conditions? According to Richards, Shaikewicz says that in the Russo-Japanese war paresis was noted especially among the officers and non-commissioned officers, and that it was undoubtedly hastened in its development by war conditions. Steida says that while ordinarily we find paresis developing twelve to twenty years after the primary sore of syphilis, in these cases it developed in five to ten years after the primary sore. Some of the cases progressed with unusual rapidity. It was also noticed that among soldiers from the front, under treatment, evidences of syphilis were present in 20%, while among the other soldiers under treatment, evidences of syphilis were present in 1.6%. Undoubtedly the old syphilitic is especially liable to break down under war conditions.

But, on the whole, the German authors in this war find no evidence favoring Steida’s claim of the hastened post-infective outbreak.

3. How did it come about that the efficient German system permitted this alcoholic and weakminded syphilitic to enter the army? As will be seen, he was a volunteer. In general, the German system has been supplied with army surgeons who have been trained, not by brief and “brush-up” courses, but by longer periods, sometimes two years in duration.

=Syphilis contracted before enlistment, “AGGRAVATED BY SERVICE.” Canadian case, courtesy of Dr. J. L. Todd, Canadian Board of Pension Commissioners.=

=Case D.= A laboring man, 42, who always strenuously denied syphilitic infection, proceeded to France eight months after enlistment. He had not been in France three weeks when he dropped unconscious. He regained consciousness, but remained stupid, dull in expression, and with memory impaired. His speech was also impaired. There was dizziness and a right-sided hemiplegia.

He was confined to bed four months and was then “boarded” for discharge.

=Physically=, his heart was slightly enlarged both right and left; sounds irregular; extra systoles; aortic systolic murmur transmitted to neck; blood pressure 140:40. Precordial pain, dyspnea.

=Neurologically=, there was a partial spastic paralysis of the right thigh which could be abducted, could be flexed to 120°, and showed some power in the quadriceps. There was also a spastic paralysis of the right arm, but the shoulder girdle movements were not impaired. There was a slight weakness on the right side of the face. There was no anesthesia anywhere.

The deep reflexes were increased on the right side, Babinski on right, flexor contractures of right hand, extensor contractures of right leg, abdominal and epigastric reflexes absent, pupils active, tongue protruded in straight line.

Fluid: slight increase in protein. W. R.+++

The Board of Pension Commissioners ruled that the condition had been aggravated by service. (See Case E, “aggravated on service.”)

1. In view of the fact that the majority of the cases here abstracted happen to be in common soldiers, is there any evidence bearing on relative incidence in officers and men? Quoting R. L. Richards:

“The percentage of paresis cases among officers alone is variously estimated from 50 per cent in the German army (Stier) to 58.9 per cent in the Austrian army (Drastich). Since paresis is a disease of more advanced life, it is but natural that the percentage of paresis among officers, non-commissioned officers, and older soldiers should be higher than among the whole military body, where the average age is, as we have seen, well below thirty years. Hence the above figures do not mean a greater prevalence of syphilis among those classes, but that we have no means of knowing how many of the others develop paresis. If anything it shows that these ‘soldiers by calling,’ have a more stable mental make-up, since they succumb chiefly to an exogenous toxin.”

Rayneau at the 19th Congress of French Alienists and Neurologists at Nantes in 1909, discussing the insane of the army from a medicolegal point of view, states that the most frequent mental disease amongst officers and soldiers is general paresis. At least, this disease is the most frequent basis of invaliding, retirement, or placing in the inactive list. He states that French and foreign statistics are at one upon this matter, quoting Christian as finding 32% among the soldiers interned at Charenton; Gamier at Dijon, 59%; Meilhon at Quimper, 42% and Talon at Marseilles, 33.8%. Grilli found 31 of 40 officers interned in Florence, Sienna and Milan victims of general paresis. Stier’s German statistics indicate about 50%. Rayneau himself found 16 of 20 officers paretic and 17 out of 27 subalterns and gendarmes.

The Neurological Society of Paris held a conference December 15, 1916, with the chiefs of the neurological and psychiatric military centres of France, and discussed a variety of questions concerning invaliding, incapacity, and compensation in neuroses and psychoses of war. Dupré dealt especially with the psychoses of war as caused by trauma, strain, infection, and intoxication. General paresis is regarded by Dupré as the most important of the dementias found in the army. The medicolegal point of view is, of course, that general paresis is necessarily related to an old syphilis, but its late development leads to misinterpretations as to its probable cause, both by the family and friends and even by magistrates. The war acts in the French nomenclature as an agent revélateur or as an agent accélérateur. Although its cause is prior and exterior to the war, general paresis in a majority of cases is brought out (revélé) by the lack of adaptability of the general paretic to the novelty and difficulties of his surroundings and duties in war. Trauma, strain, and alcohol in a certain number of cases accelerate the progress of a general paresis. The aggravation of paresis is produced by these same factors, but especially by violent cerebral trauma. According to Dupré, the Val-de-Grace statistics show that the number of paretics has not been increased by the war. Medicolegally, the victim of general paresis, like the victim of traumatic or infectious chronic mental disorder, may be assigned an incapacity of from 50 to 100%, and these patients are invalided under Réforme No. 1,—a permanent invaliding.

Lépine of Lyons also discusses the compensation question in general paresis. Lépine thinks that, although syphilis is indispensable in paresis, yet the truth is that syphilis plus something else unknown to us is responsible for general paresis. This something else is neither a special kind of virus nor is it a particular kind of prepared soil alone. Trauma, physical, intellectual, and moral strain, and insomnia are the factors to which he calls special attention as adjuncts in the production of general paresis. As to the responsibility of the State for the production of general paresis, according to Lépine, the maximal responsibility should be 40% on account of the very considerable predisposition to paresis created by pre-existent syphilis.

Marie remarked that, although there had been thousands of head cases at the Salpétrière, there had not been a single case of general paresis. Dupré agreed with Marie that trauma was not a frequent etiological factor; strain and alcohol were more important. The Society agreed that in exceptional cases, where an encephalic trauma could be regarded as accelerating or aggravating the disease, the degree of incapacity might be set at from 10 to 30 per cent.

=Syphilis contracted before enlistment, “AGGRAVATED ON SERVICE.” Canadian case, courtesy of Dr. J. L. Todd, Canadian Board of Pension Commissioners.=

=Case E.= A laboring man, 44, acquired syphilis at a time unknown. Ten months after enlistment this man developed symptoms on the firing line. He was inattentive, irrational, incoherent. The diagnosis was then “mania.”

There were, however, scars at angle of mouth and on lower lip. Occipital glands were palpable, fine tremor of hands. The W. R. was +++.

Later the patient became violent, destructive, untidy, disoriented. Auditory hallucinations are recorded.

He was “boarded” for discharge five months after the first symptoms. The board agreed that these symptoms would have appeared in civil life. In view of a difference of opinion as to the part played by stress of service, his condition was set down as “aggravated on service” (not, it will be noted, by service, see Case D).

1. Under what conditions should pensions be awarded for disability resulting from venereal diseases? According to a personal communication from Dr. J. L. Todd, Chairman of the Board of Pension Commissioners for Canada, pensions are awarded for all disabilities appearing during service, unless they can be shown certainly to be due to the men’s own fault and negligence. It would appear that during service covers both aggravations by and on service. There remains some doubt as to whether contraction of venereal disease constitutes negligence.

2. What have been conditions in the small inactive American army of the past? Richards has made a study of statistics at the Government Hospital for the Insane, Washington.

“The leading features of this mental disease were well exemplified in our cases the past year. They formed 7.5 per cent of the total number. They averaged forty years of age, and Ziehen says 80 per cent of all cases are in the fourth or fifth decade of life. They averaged ten and a half years’ service, which would indicate that the military life was their calling. Only one had any serious hereditary defect. Stigmata of degeneration were infrequent, averaging only two for each case. 66 per cent had good schooling, considering their opportunities. Physical signs were frequent in each case. Only one showed normal light reaction. Ziehen says the light reaction is retained in only 20 per cent of the cases. Patellar reflex was absent in one case and normal or exaggerated in five. The speech defect was slight in four cases. Other physical signs were present in the usual proportions. Memory defects existed in all the cases. In four the onset was with excitement. One began with a character change as the most marked feature. In only two were the transfer diagnoses correct. One, beginning as a quiet dementia, was diagnosticated paralysis agitans, because of a marked tremor. One was excited and euphoric and was called a manic-depressive psychosis. One with an obscure onset was diagnosticated as a neurasthenic. The other one was first observed in this hospital. The physical signs should have led to a correct diagnosis in each of these cases.”

=Duration of neurosyphilitic process important re compensation. Canadian case, courtesy of Dr. C. B. Farrar, Psychiatrist, Military Hospitals Commission.=

=Case F.= A Canadian of 36 enlisted in 1915, served in England, and was returned to Canada in February, 1917, clearly suffering from some form of neurosyphilis (W. R. positive in serum and fluid, globulin, pleocytosis 108).

There is no record of any disability or symptom of nervous or mental disease at enlistment. The first symptoms were noted by the patient in May, 1916, six months or more after enlistment. The case was reviewed at a Canadian Special Hospital, October 11, 1916, by a board of examiners. This board reported that:

“The condition could only come from syphilitic infection of three years’ standing” (a decision bearing on compensation); but the general diagnosis remained:

“Cerebrospinal lues, =aggravated by service=.”

The picture which the medical board regarded as of at least three years’ standing was as follows:

History of incontinence, shooting pains, attacks of syncope, general weakness, facial tremor, exaggerated knee-jerks, pupils react with small excursion. Speech and writing disorder, perception dull, lapses of attention, memory defect, defective insight into nature of disorder, emotional apathy.

1. Was the conclusion “aggravated by service” sound? On humanitarian grounds the victim is naturally conceded the benefit of the doubt. But it is questionable how scientifically sound the conclusion really was.

2. Could the condition come only from syphilitic infection of at least three years’ standing? Hardly any single symptom in this case need be of so long a standing; yet the combination of symptoms seems by very weight of numbers to justify the conclusion of the medical board.

=Can PARETIC NEUROSYPHILIS (“general paresis”) be lighted up by the stress of military service without injury or disease? A possible example from P. Marie, Chatelin and Patrikios of Paris.=

=Case G.= In apparently good health a French soldier repaired to the colors, in August, 1914, being then 23 years old.

Two years later, August, 1916, symptoms appeared: speech disorder with stammering, change of character (had become easily excitable), stumbling gait. He became more and more preoccupied with his own affairs, grew worse, and was sent to hospital in October, 1916.

He was then foolish and overhappy, especially when interviewed. There was marked rapid tremor of face and tongue. Speech hesitant, monotonous, and stammering to the point of unintelligibility. His memory, at first preserved, became impaired so that half of a test phrase was forgotten. Simple addition was impossible and fantastic sums would be given instead of right answers; handwriting tremulous, letters often missed, others irregular, unequal, and misshapen.

Excitable from onset, the patient now became at times suddenly violent, striking his wife without provocation. After visit at home, he would forget to return to hospital. Often he would leave hospital without permission (of course the more surprising in a disciplined soldier).

No delusions were found.

The serum and fluid W. R. were positive, albumin in fluid, lymphocytosis.

=Neurological examination.= Unequal pupils, slight right-side mydriasis, pupils stiff to light, weakly responsive in accommodation, reflexes lively, fingers tremulous on extension of arms.

The patient had, December 5, 1916, an epileptiform attack with head rotation, limb-contractions and clonic movements.

1. Should this soldier recover for disability obtained in service? Marie was inclined to think military service in part responsible for the development of the paresis. Laignel-Lavastine thought so also, but that the amount assigned should be 5%–10% of the maximum assignable.

2. What is the duty of the military authorities relative to so called traumatic paresis? Medicolegally speaking, Froissart, quoted by Rayneau, states that a victim of traumatic paresis may or may not have presented mental disorders before the accident, that is, that the paretic symptoms may develop out of a clear sky as a result of the accident. The accident itself must be of a serious nature. The accident must be followed by phenomena pointing to brain injury of traumatic nature. These phenomena need not be characteristic symptoms of general paresis at the outset. The period elapsing between the trauma and the supervening condition of paresis must be occupied without notable interruption, at first by phenomena of a purely traumatic nature, later by signs indicating the onset and evolution of general paresis.

The French invaliding process called Réforme No. 1 with pension is granted according to the governmental instructions only to officers, subalterns, and soldiers whose disease is due to trauma. In view of this governmental regulation, the military surgeon must write out certificates describing every cranial trauma, however slight, which might have a bearing on the development of paresis. However, he should not too readily admit trauma as a cause of paresis. If a long period of quietude, a period in which the trauma itself seems to have undergone a complete recovery, supervenes, then general paresis should not be reported by the surgeon.

Lépine has recently noted the following features as desirable in board reports concerning paretics: nature of trauma, length of service, fatigue endured, insomnia, date of infection, treatment, W. R.

=Can “gassing” light up a paresis? Example from de Massary of Issy-les-Moulineaux.=

=Case H.= A soldier, 35, was sent to the Centre Neurologique with a hospital ticket reading:

“Neurasthenia, general weakness following intoxication by gas.”

The soldier was thought at first to be a neurasthenic. But he soon showed signs of more pronounced mental trouble. The voice was suspicious. There was a slight irregularity of pupils.

An epileptiform attack occurred, followed by aggravation of symptoms.

Lumbar puncture showed pleocytosis. The W. R. of the serum proved positive.

Yet the evident =neurosyphilis=, possibly =paretic= (de Massary’s diagnosis), was preceded by a neurasthenia and the neurasthenia was preceded by “gassing.”

De Massary believes the patient and his family would perhaps be justified in believing the condition produced by the injury. De Massary is not clear as to the financial deserts of the patient. It is not a manifest case of aggravation of antebellum symptoms, even if it be neuropathologically an instance of acquired loss of resistance to pre-existent spirochetes in body or brain.

1. What adjuvant factors have been recognized in military paresis? Aside from syphilis, Rayneau finds that alcoholism, malaria, sunstroke and various intoxications serve as causes for paresis. Rayneau points out that the apparent integrity of the mind in general paresis may be such that they last in the army some time and have their oddities ascribed to misconduct or breaches of discipline. In fact the Legrande du Saulle called this early period in general paresis the medicolegal period, showing, as it so often does, thefts, outrages against decency, frauds, assaults, exhibitionism and the like. To be sure these acts are absurd and infantile and not difficult to recognize as of psychotic origin.

=Syphilis may bring out epilepsy in a subject having taint. Case from Bonhoeffer, 1915.=

=Case I.= A man of 35 in the Landwehr acquired syphilis some time in the summer of 1914. He was a good soldier, passed through several clashes, and was promoted to Unteroffizier.

To understand what followed it must be stated that he had been a bed-wetter to 11, had been practically a teetotaler (Bonhoeffer’s point is perhaps that otherwise epilepsy might have developed sooner?), and, when he did drink, vomited almost at once, and had amnesia for the period of drunkenness. His father had been somewhat of a drinker. His sister had suffered from convulsions as a child.

February, 1915, the Unteroffizier lost appetite, got headaches, and went to hospital for a time. Upon getting better, he was sent on service to Berlin. In a Berlin hotel he had his first convulsions and unconsciousness, biting his tongue. He was confused for several days, and, when he had become clear, had a pronounced retrograde amnesia together with a tendency to fabricate a filling for the lost period.

This retrograde amnesia is uncommon in epilepsy and suggests organic disease. No sign of organic disease was found on neurological examination. The patient had no signs of the epileptic make-up. The serum W. R. was negative. On the whole, Bonhoeffer regards the epilepsy as “reactive” to the syphilis, as a syphilogenic epilepsy.

As to the amnesia, it is of interest that alcohol should long before have been able to cause amnesia in this man in the same way as does now the syphilitic epilepsy.

1. In view of the fact that this Landwehr man appears to have acquired syphilis while on campaign, what is the responsibility of the government for treatment? The Canadian authorities, as stated under Case E, are in doubt whether contraction of venereal disease constitutes negligence on the part of the soldier. It would appear to us that where a government does not take suitable steps to prevent the acquisition of syphilis by the soldiers, the government must assume a measure of responsibility for the syphilis incurred. The government’s responsibility would be still greater in equity, it would appear, if commercial opportunities for the acquisition of syphilis are maintained under more or less close government supervision or (even as has been claimed for certain encampments on our own Mexican border) if shelter for illicit sex relations is afforded within the limits of a military camp. In a certain community, “E,” for example, it is claimed by Exner, the district for prostitutes was “situated within the lines of military camps and protected and ‘regulated’ by the military authorities.”

But even if the government has no legal responsibility in this regard, it would be well to consider the ultimate results of the syphilis that will probably be acquired by great numbers of soldiers under campaign conditions. Aside from the ravages of syphilis outside the nervous system, it is well known, as Weygandt intimates for German conditions, that the aftermath of war will be a high proportion of cases of neurosyphilis.

Weygandt remarks in his review of the influence of the war upon psychiatry, that the opportunity for syphilitic infection in the campaign is considerable. In the war of 1870, the conditions in this regard were extremely unfavorable, and writing in 1915, Weygandt remarks that at present there should be a prophylaxis against syphilitic infection by the soldiers, which prophylaxis should be the most energetic possible. Continence on the part of the soldiers and the isolation of infected women, with examination by specialists, have been advocated by Neisser and by Mendel. In the ’80’s a great number of cases of locomotor ataxia developed in Germany, which were due to syphilis acquired by the soldiers and officers in the war of 1870.

=Syphilis in a psychopathic subject. Convulsions 5 days after Dixmude. Case from Bonhoeffer, 1915.=

=Case J.= A soldier in the reserves, 23, was, subsequently to his being brought to hospital, described by his wife as a rather over-sensitive fellow, who could hardly look at blood and was meticulous about the household. He had always been subject to headaches, especially after hard work. However, he had passed through his military training well in 1910, not even having been bestraft.

He began service in October and fought at Dixmude on the 19th. On the 24th in the trench and while being carried back, he had several spells of pallor, falling stiff, and then having convulsions. Brought finally to the Charité in Berlin, he had more spells of sudden pallor, collapse with brief convulsions, tossings in bed, and absences, post-convulsive headaches, and mild bad humor.

There were numerous attacks several days apart in the first seven weeks. The patient was not of an “epileptic” disposition, though he was rather readily dissatisfied. Headaches also occurred without relation to convulsions.

The serum W. R. was positive. Treatment by mercurial inunctions. No further convulsions. Prognosis as to the possibility of a constitutional epilepsy unknown.

=SYPHILITIC ROOT-SCIATICA (lumbosacral radiculitis) in a fireworks man with a French artillery regiment. Case presented from Dejerine’s clinic by Long.=

=Case K.= No direct relation of this example of root-sciatica to the war is claimed nor was there a question of financial reparation.

There was no prior injury. At the end of March, 1915, the workman was taken with acute pains in lumbar region and thighs, and with urgent but retarded micturition.

Unfit for work, he remained, however, five months with the regiment, and was then retired for two months to a hospital behind the lines. He reached the Salpétrière October 12, 1915, with “double sciatica, intractable.”

There was no demonstrable paralysis but the legs seemed to have “melted away,” fondu, as the patient said. Pains were spontaneously felt in the lumbar plexus and sciatic nerve regions, not passing, however, beyond the thighs. These pains were more intense with movements of legs; but coughing did not intensify the pains. Neuralgic points could be demonstrated by the finger in lumbar and gluteal regions and above and below the iliac crests (corresponding with rami of first lumbar nerves). The inguinal region was involved and the painful zone reached the sciatic notch and the upper part of the posterior surface of the thigh.

The sensory disorder had another distribution objectively tested. The sacral and perineal regions were free. Anesthesia of inner surfaces of thighs, hypesthesia of the anterior surfaces of thighs and lower legs. The anesthesia grew more and more marked lower down and was maximal in the feet, which were practically insensible to all tests, including those for bone sensation. There was a longitudinal strip of skin of lower leg which retained sensation.

Position sense of toes, except great toes, was poor. There was a slight ataxia attributable to the sensory disorder—reflexes of upper extremities, abdominal, and cremasteric preserved, knee-jerks, Achilles and plantar reactions absent.

The vesical sphincter shortly regained its function, though its disorder had been an initial symptom.

Pupils normal.

The “sciatica” here affects the lumbosacral plexus. Signs of disorder at one time or other affected the first lumbar distribution of the third lumbar and first and second sacral nerves.

As to the syphilitic nature of this affection, there had been at eighteen (22 years before) a colorless small induration of the penis, lasting about three weeks. There was now evident a small oval pigmented scar. The patient had married at 20 and has had three healthy children.

The lumbar puncture fluid yielded pleocytosis (120 per cmm.). Mercurial treatment was instituted.

The treatment has not reduced the pains. Long thinks it was undertaken too long (six months) after onset. The warning for early diagnosis is manifest. There was somehow a delay under the medical conditions of the army.

=Can the “lighting up” of NEUROSYPHILIS IN CIVIL LIFE be induced by the domestic stress of war? A possible example from Dr. R. Percy Smith, London.=

=Case L.= A German Jew in London passed into the PARETIC form of NEUROSYPHILIS shortly after the outbreak of war under conditions suggesting that the stress of emotions directly or indirectly lighted up the neural process.

The man was a bank-officer, 52 years old, and married. He had lived many years in England and was in fact a naturalized citizen. He had been under treatment for syphilis by Sir Jonathan Hutchinson, 29 years before, namely, at the age of 23. Subsequently, Sir John had given him permission to marry.

It proved that for years the man had had fixed pupils, absent knee-jerks, and a perforated ulcer of the foot. However, there had been no other mental or nervous symptoms preventing bank-officer’s work.

At the outbreak of war the man was discharged from the bank. He grew worried and sleepless. He began to charge himself with sex irregularity. He went down to the city and burned trust documents belonging to others.

From worry and self-accusation he passed into depression and agitation. He developed a belief that not only he but also his German wife were to be executed. He thought he was a criminal and was to be hanged.

The depression then altered to a condition of hilarity and loquacity.

In addition to the fixed pupils and absent knee-jerks, a speech disorder shortly developed.

The patient was placed under care, but quickly (a few months?) passed into an advanced stage of paretic neurosyphilis and died.

=SHELL-SHOCK PSEUDOPARESIS (non-syphilitic). Recovery. Case from Pitres and Marchand of Bordeaux.=

=Case M.= June 19, 1915, a shell exploded some distance from Lieutenant R. He remembers the gaseous smell, the bursting of several shells nearby and a sensation of being lifted into the air. When he recovered consciousness, he was in hospital at Paris-Plage, covered with bruises and scratches. They told him he had been delirious and had vomited and spat blood.

June 24, his wife came to see him, but this visit he could not remember. Nor could his wife at first recognize him, he was so thin. He roused a few moments and recognized his wife, but relapsed into torpor again. Speech was difficult and ideas confused.

A few days later he was able to rise; but his mental status grew worse, especially as to speech and writing; the latter quite illegible. There was insomnia, or, if he slept, war dreams.

August 7, he began a period of five months’ convalescence passed with his family, depressed, given to spells of weeping, confined to bed or couch, unable to “find words,” conscious of his state and troubled about it, speaking of nothing but the war, and afraid to go out for fear of ambuscade. There was at first a slight lameness of the right leg. Although he could walk, he felt pain in the knee on flexing the right leg on the thigh. He walked holding this leg in extension.

On going back to the colors, he was immediately evacuated to the Centre Neurologique at Bordeaux, January 20, 1916.

Examination found a bored, impatient, irritated man, vexed that a man who was not sick should be sent up “comme fou.”

Omitting negative details, =neurological examination= showed slight lameness as above, body stiff and movements jerky; difficult, unsteady gait. The lieutenant could stand for some time on either leg, tongue and face tremulous during speech. Limbs moderately tremulous, especially in the performance of test movements.

Knee-jerks and Achilles jerks absent. Other reflexes, including pupillary, normal. Segmentary hypalgesia of right leg, especially about knee. Tremulous speech and writing. Patient would stop short in speaking for lack of words.

Malnutrition. Appetite good, but a bursting feeling after meals.

Skin dry, scaly on legs, fissured on fingers.

Serum W. R. negative. Fluid not examined.

=Mental examination.= Conscious and complaining of his troubles, Lieutenant R. claimed persistently that he was not sick. Memory for recent events was in general poor. Errands easily forgotten. Lost in the street. Complaint of corpse odors round him. Everybody is looking at him and making fun of him. He was apt to insult bystanders. He was afraid of German spies. Things in shops angered him as they seemed to him to be of German manufacture.

There were frequent periods of depression, with pallor and no spontaneous speech for some hours to a half-day. Headaches coming on and stopping suddenly.

As to diagnosis, the first impression, say Pitres and Marchand, was that of general paresis. The progress of symptoms after the shock was consistent with this diagnosis. The mental state and the physical findings seemed consistent, although the pupils were normal. His partial insight into his symptoms was not inconsistent with the diagnosis. He had a characteristic self-confidence. There had been four stillbirths (two twins) two children are alive, 11 and 13. Typhoid fever at 30. Syphilis denied. No mental disease in the family.

The patient had never done military duty, having been invalided for “right apex.” But he had volunteered and been accepted in September, 1914.

1. Was this diagnosis, general paresis, at any time justified? The spinal fluid should of course have been examined. The peculiar lameness of the right leg was certainly not characteristic of general paresis, and was perhaps hysterical. (There was no limitation of visual fields or any other definite sign of hysteria.) Presumably some quality of speech defect, the amnesia, and the euphoria, together with absent knee-jerks, led to the diagnosis general paresis. By the 20th of March, 1916, the knee-jerks had become lively; the Achilles jerks normal. At this time the patient had gained in weight, could walk though stiffly, had headache (especially right frontal) and a feeling of lead in head, less tremor, lack of desire to undertake anything. He still wanted to go back into service. He still saw spies about. Dreams terrible; devoured by spiders, leggins instruments of torture. Skin still atrophic. June 4 there was no more tremor of speech or face. Symptoms largely disappeared except a few ideas of persecution. Recovery October, 1916.

2. How was Lieutenant R. cured? Apparently by rest in the Centre Neurologique. Pitres and Marchand do not speak of the subtle relation between mental state and the idea of non-return to military service. This motive might still work even if Lieutenant R. kept protesting quite sincerely that he wanted to go back into military service.

=SHELL-SHOCK PSEUDOTABES (non-syphilitic, serum W. R. positive). Improvement. Case from Pitres and Marchand of Bordeaux.=

=Case N.= Innkeeper B., 36, a shell-shock and burial victim June 20, 1915, was looked on by a number of physicians as a case of genuine tabes.

Even eight months after the episode, he still showed (when observed by Pitres and Marchand, February 3, 1916) absence of knee-jerks and Achilles jerks, a slight swaying in the Romberg position, pupils sluggish to light, incoordination, delayed sensations. There was also a history of pains in the legs, compared by the patient to those of sciatica. These pains came in crises, the longest of which had lasted 30 hours.

It seems that this soldier’s troubles began the day after his shock with a feeling of swollen feet and of cotton wool under them. He stayed on service, however, walking with increasing difficulty.

At the time of his evacuation, July 10, he could walk with great difficulty. “Strips of lead were between his legs.” He could hardly control movements in the dark, or descend stairs. Often his legs would bend under him. Vesical function sluggish.

After a few months the patient could walk better. On February, 1916, he walked thrusting his legs forward trembling, and dragging toes a little. He could not support himself on either leg. Jerkiness and incoordination in extension or flexion of leg on thigh.

The muscular weakness was decidedly against tabes or at all events a pure tabes. The incoordination proved to be due, not to loss of position sense (which was intact) but to unsteady muscular contractions. Deep sensibility was intact.

There were no mental symptoms. There was a slight hesitation in speech and doubling of syllables, but nothing demonstrable with test phrases.

The serum W. R. was positive. Syphilis denied.

1. What is the cause of these phenomena? Pitres and Marchand lean to the hypothesis of slight internal traumatism. They believe that there is either (a) slight internal hemorrhage in the nervous system, or possibly (b) what they call “nerve cell contusion,” or perhaps (c) caisson-disease-like phenomena from aerial decompression. Some authors incriminate (d) the gases. It has been reported by certain French authors that shortly after shell-shock injury or burial there is a pleocytosis in the spinal fluid as well as evidence of hemorrhage. The pleocytosis is said to last only a short time; hence when patient arrives at a base hospital lumbar puncture usually discloses nothing.

Baalim and Ashtaroth

Paradise Lost, Book I, line 422.

VII. SUMMARY AND KEY

No more important human problem now exists than syphilis. Syphilis of the nervous system or, briefly, neurosyphilis is a highly important fraction of the total problem. The few outstanding dates and items which we present on the following page give but a faint idea of the amount of observation and thinking which the medical aspects of neurosyphilis alone have required. The present work deals with but a small fraction of the results of this work, nor can we more than glance at the scientific history of syphilis and neurosyphilis—a history that would form an epoch in itself.

It is only in the most recent years that syphilology and the narrower science of neurosyphilology have threatened to become separate disciplines boasting full time specialized workers. Up to recent years the contributions to the theory of syphilis have been largely by-products of work in larger sciences and arts. Thus, the cellular pathology of syphilis as worked out by Virchow and the more special vascular features as worked out by Heubner were incidental in the progress of pathological anatomy and histology. The bold procedure of Quincke in proposing lumbar puncture also had its more general ground in the extension of clinical medicine,—an interpretation likewise true of the French achievements in the cyto-diagnosis and chemical diagnosis of the lumbar puncture fluids. The careful histological definitions of the Nissl-Alzheimer group were incidental to the application of approved and classical pathological methods to neurological and psychiatric material.

Again, the work of Schaudinn, as well as that of Metchnikoff and Roux, was ingenious work with the methods of parasitology and experimental pathology. The great work of Schaudinn in establishing the constancy of the spirocheta pallida in syphilis may be said to have started syphilology as something approaching a special discipline. The ideas of one of the greatest of immunologists, Bordet, were almost immediately applied to the serum diagnosis of syphilis by Wassermann and the further application of this method to the problems of neurosyphilis was almost immediate, with the spirocheta pallida as an object of attack. The commanding intelligence of Ehrlich could at once seek application of long incubated ideas of chemotherapy with the startling outcome, salvarsan.

=DATES, NEUROSYPHILIS=

VIRCHOW PATHOLOGY 1858 HEUBNER ENDARTERITIS 1874 QUINCKE LUMBAR PUNCTURE 1891 RAVAUT, SICARD, NAGEOTTI, WIDAL CYTODIAGNOSIS, C.S.F. 1901 WIDAL, SICARD, RAVAUT ALBUMIN, C.S.F. 1903 METCHNIKOFF AND ROUX TRANSMISSION TO APES 1903 ALZHEIMER HISTOPATHOLOGY, BRAIN SYPHILIS 1904 SCHAUDINN AND HOFFMANN SPIROCHETA PALLIDA 1905 WASSERMANN, NEISSER AND BRUCK SERUM DIAGNOSIS 1906 PLAUT WASSERMANN REACTION, C.S.F. 1908 EHRLICH SALVARSAN 1909 SWIFT AND ELLIS SALVARSANIZED SERUM 1912 NOGUCHI AND MOORE SPIROCHETES, BRAIN TISSUE, 1913 PARESIS LANGE GOLD SOL TEST 1913

CHART 28

The history of syphilis and neurosyphilis was now to be thickly sown with ideas and results growing from the achievements of Schaudinn and Ehrlich. The positive reactions in the blood and spinal fluid in the most striking of mental diseases, general paresis, led to the impression that general paresis itself might at last be proved to be what Mœbius had suspected, namely, 100% syphilitic. We know how difficult is the technical proof of spirochetosis in the brains of general paretics both post mortem and ante mortem, but no one doubts the certainty of the syphilitic hypothesis concerning the origin of general paresis.

The data of the gold sol reaction ultimately obtained from the ideas of Thomas Graham concerning colloids, as developed by Szigmondi and effectively applied by Lange, have broadened and solidified the whole plane of attack.

The ingenious suggestions of Swift and Ellis (salvarsanized serum) and the notable work of Noguchi and Moore (spirochetosis in paretic brains) indicate to us as Americans what the establishment of scientific institutes may do to permit the rapid application of new ideas to branches of inquiry that are opened out. Scientific institutes do not manufacture a Virchow, a Metchnikoff, a Schaudinn, a Bordet or an Ehrlich but they directly permit such men to work and indirectly stimulate the development of more.

The series of 137 cases here at least presented does not touch systematically the problems of the neuropathology of syphilis, which would themselves require a textbook of respectable size. We have, however, presented in Part I, cases 1 to 8, some indication of the protean nature of the material and from time to time in the remainder of the book somewhat fuller accounts of the pathological anatomy and histology have been presented than are strictly necessary in the demonstration of the principles of modern systematic diagnosis and treatment.

Our work may be said to represent psychopathic hospital practice as available to us in our official capacities at the Psychopathic Department of the Boston State Hospital. A word is necessary concerning the nature of this practice. The dispensary and ward practice of a modern state psychopathic hospital, such as the Boston institution (founded in 1912) and the Ann Arbor institution (founded in 1906), is to be sharply distinguished from asylum practice. Those who have not followed the evolution of the modern psychopathic hospital with the lowering of bars to the admission of patients and the extension of its benefits to a group of sick persons far removed from the medicolegal concept “insanity” may not soon grasp the general nature of psychopathic hospital material. Psychopathic hospital practice stands, in fact, almost midway between asylum practice in the classical sense and private practice. This has come about through the great extension of the so-called voluntary relation under which hundreds of patients now resort to the beds and out-patient rooms of a psychopathic hospital, who would formerly have remained untreated or inadequately treated. Moreover, the broadening of the concept of mental diseases as a whole has permitted in some parts of the world the establishment of laws under which psychopathic and psychotic patients may be brought to psychopathic hospitals and even to asylums under the easiest possible conditions and restrictions, omitting court procedure altogether. The operation of the voluntary and temporary care provisions of law has accordingly yielded us, in the Boston institution, a great group of cases formerly not at all accessible to hospital diagnosis and treatment. Needless to say, as always under such conditions, we have been able to show not merely that hospital diagnosis or treatment is of importance to a new group of cases, but also that home treatment, especially home treatment under supervision, is possible and even ideal for a large group of cases about which utter darkness or profound misgivings ruled in the not very distant past.

Accordingly, we are fain to insist that our material is of importance in new programs of community organization for the stamping out of disease. The work in psychopathic hospitals upon neurosyphilis in particular is essentially a part of the public health program, although our special work will not soon be taken over by the public health officers, so complicated are the ramifications of medical and social diagnosis and treatment in the neurosyphilis group.

We have tried in Part IV (medicolegal and social cases) to give a few examples to illustrate the part played by neurosyphilis in society; but we regard this part of our work as the least satisfactory and the least representative in the total work. Our colleagues in social service, in mental hygiene, in psychopathology and in criminology will easily in the next few years provide a far more adequate basis for a full account of the public and social aspects of neurosyphilis. One point we should emphasize here. The psychopathic hospital worker, whether physician or social worker, must shortly decide upon and consolidate a program with relation to the families of neurosyphilitics.

The syphilographers of the dermatological and special syphilis clinics have their identical problems with the families of syphilitics; but the dispensaries for mental cases and in particular the psychopathic hospital and asylum out-patient departments tap another reservoir of syphilitic families at a stage when the memory of the initial horrors of syphilitic infection is dimmed or erased. Any program for the diagnosis and treatment of syphilis of the innocent must take into account not only the skin, syphilis, and internal medicine clinics but also the clinics for mental and nervous diseases wherein neurosyphilitics are not infrequent. Whether the ultimate percentage will stand at 10, 15 or 20% for the neurosyphilitics in mental clinics, is of no importance to the principle. There are enough neurosyphilitics having economical importance and humanly precious families to warrant definite steps.

The Massachusetts Commission for Mental Diseases has in the last few years employed the services of two medical workers whose time has been largely devoted to the applications of our recent knowledge in neurosyphilis and has gone so far as to establish a neurosyphilis ward in one of the district state institutions (Summer Street, Worcester, under the Grafton Hospital Board). Special social workers in the field of neurosyphilis have also been available from time to time. These social workers are enabled with the support of the medical profession to do a great deal of good, for example, with the slogan THE CHILD OF A PARETIC IS THE CHILD OF A SYPHILITIC.

The nature of the intake of patients into psychopathic hospital wards and out-patient clinics is such that great numbers of non-mental syphilitics arrive for diagnosis and possible treatment. Moreover, the existence of syphilis in non-suspects is a fact picked up by the way in routine Wassermann serum diagnosis.

The mental clinic in the modern sense with the medicolegal bars lowered or well nigh removed, turns rapidly into a clinic for neurological cases as well. The German models for mental and nerve clinics are rapidly being imitated. The result of this administrative novelty in our hospital procedure has incidentally yielded us many representative cases of entirely non-psychotic and even non-psychopathic neurosyphilis. Our impression grows and deepens that the neurosyphilitic is seldom merely a spinal syphilitic. The neurosyphilitic is nearly always the victim not merely of spinal disease but also of intracranial disease. Per contra, the victim of intracranial neurosyphilis is almost always more or less importantly affected by spinal neurosyphilis.

The net result of the modern work on neurosyphilis has been to bring the neurologist and the psychiatrist together upon one platform in diagnosis and more and more upon one platform in treatment. But aside from the clinical evidence that the neurosyphilitic is apt to be a victim of both brain syphilis and cord syphilis, the autopsy evidence is stronger still. Even the victim of tabetic neurosyphilis (“tabes dorsalis”) himself is rarely found at autopsy without more or less evidence of significant encephalic disease of a chronic inflammatory or degenerative nature. Aside from tabes dorsalis and Erb’s paraplegia, the rule is almost universal that neurosyphilis is a matter of the entire nervous system.

In view of the generalization of neurosyphilitic process, one might question the advantage of any topical grouping of neurosyphilitic disease. Practically speaking, however, as we have shown in Chart 5, it seems advisable to separate the neurosyphilitic diseases into six roughly distinguishable groups. First, there is the great group that we have chosen to term =diffuse neurosyphilis=, including many of the cases of so-called cerebral or cerebrospinal syphilis of the neurological clinics and the group of cases that have been treated in private practice by internists and neurologists without recourse to institutions. These cases have lived at home and have not been socially hard to manage until the late phases of their disease when the victims, if poor, are sent to almshouses and infirmaries under municipal or state care. These are the cases which have been in the past regarded as most amenable to the classical iodid and mercurial treatment. Indeed there is record of numerous therapeutic successes in the group.

Whereas the lesions in diffuse neurosyphilis are chiefly chronic inflammatory and degenerative changes of a diffuse nature (with vascular changes incidental or subordinate to the inflammation and the degeneration), there is an important and large group of cases that we have termed =vascular neurosyphilis= in which the factors of inflammation and degeneration are subordinate to vascular insults. These are cases of syphilitic arteriosclerosis and the best examples are victims of cerebral thrombosis. The clinical symptoms of the immediate attacks (of apoplectiform, epileptiform or other acute nature) are not in themselves distinguishable from the immediate effects of non-syphilitic vascular disease; nevertheless the establishment of their syphilitic etiology is of the utmost importance on account of the possibilities of treatment of the underlying syphilis. For, as the neuropathologist must always insist, the immediate effects of vascular insults whether syphilitic or non-syphilitic are much more extensive than the ultimate paralytic or residual irritative effects; and by consequence a greater optimism is justifiable in the confronting of these cases than the nihilistic observer is likely to entertain.

Physicians dealing with chronic disease in general are apt to be somewhat nihilistic, but this nihilism is increased a hundred fold in disease of the nervous system. How important then is any work which shall demonstrate partial or even complete recovery from serious looking apoplectic and other seizures, besides all of which the point of syphilitic treatment naturally lies in the prevention of future insults of the same sort. Therapeutic experience in this vascular group has almost as good a toll of successes as in the diffuse neurosyphilis group above mentioned, that is to say, the modern systematic treatment and even the old pre-salvarsan treatments have succeeded fairly well in removing the products of inflammation from the membranes of the nervous system and in abolishing vascular disease.

The old principle that the dead neurone in the central nervous system cannot be regenerated remains a perfectly firm principle; but there are any number of neurones and even neurone systems that are not essential to life or to the pursuit of happiness. We accordingly have just as good a theoretical therapeutic outlook in many instances of chronic neurosyphilis as we have in chronic diseases of many other organs. Add to this the fact that a great number of the most sharply-defined and grave symptoms are probably not due to destruction of neurones but to irritation and functional disability of neurones, and the conclusion is compelled that, as hinted above, an entirely unjustifiable pessimism and nihilism have prevailed in some quarters. Of course, the recoil from such pessimism with the onset of salvarsan treatment led various enthusiasts to an undue optimism.

Another great group distinguished by the existence of spinal cord disease is the group we have termed =tabetic neurosyphilis=, which group contains the classical tabes dorsalis or locomotor ataxia and its congeners.

The question of therapeutic optimism comes up most forcibly in the field of tabes. It is hard, however, at this time to give a proper and scientifically founded estimate of the therapeutic outcome in tabetic neurosyphilis with modern methods. So much can be said: namely, that the alleviation of pain and the palliation of other symptoms can be successfully claimed as a result of the renewed interest in the treatment of this affection. What was said above concerning the finality of the death process in a dead neurone is very strikingly true, of course, of some of the neurones of the posterior columns in tabes dorsalis. Still only portions of these neurones (namely, those which run an intradural course) are strikingly altered in a great many cases. Now and again one is greatly astonished to observe the restoration of the lost knee-jerk in cases of neurosyphilis (see for instance the case of Alice Morton (1), with discussion). In short, the relation of several tabetic symptoms to irritative conditions and functional disability of neurones may be considered established. Naturally, moreover, if therapy can stop the upward course of the affection as it passes from lower to higher nerve roots (according to reasonably well-established ideas of the genesis and progress of this affection), we are entitled to a further degree of optimism.

The question of therapeutic optimism versus pessimism is forced upon attention in the fourth great group of neurosyphilitic diseases which we have chosen to distinguish, namely, the group of =paretic neurosyphilis= including the disease formerly known as general paresis, paralytic dementia, softening of the brain and the like.

Of course, no one can gainsay there is a group of cases having in the natural course of events a prognosis of fatality within a term of years, say three to five years, and we have cases in our series which go to show that even with the modern intensive treatment the characteristic down-grade symptomatic progress and ultimate fatality occur. Still, we have other cases diagnostically on all fours with the fatal cases that have seemed to get either entirely well with the laboratory tests returning to normal and without further mental symptoms, or else lose mental symptoms on the one hand or laboratory signs on the other. We should strongly object to any account of paretic neurosyphilis which should insist that its necessary outcome is fatality within a term of years. Of course, viewing our knowledge of the affection in the past, we should be compelled to object to the generalization “paresis fatal” on the evidences of the universally recognized remissions. If nature can stop a paretic process, why cannot man do as much? Can it be alleged that our own apparent therapeutic successes and those of others are merely curious examples of coincidences, namely, that remissions have chosen to occur precisely when therapy was systematically applied? The percentage of therapeutic successes with modern intensive treatment, wherever it may ultimately stand, is already too high for this hypothesis of fortuitous remissions.

Moreover, we believe that the details of the clinical progress of some of the reported cases are convincing on this point. What, however, is the distinguishing feature of paretic neurosyphilis? It is in one sense a particular kind of diffuse neurosyphilis. The tissues are apt to show not only encephalic but also spinal changes. There is apt to be a more or less well-defined meningitis, but the characteristic feature, without which the diagnosis of paretic neurosyphilis would hardly be rendered, is the existence of disease of the cerebral cortex. This disease is parenchymatous in the sense of showing nerve cell destruction. There is also an interstitial reaction in the shape of a neuroglia overgrowth, but the striking and pathognomonic feature is the infiltration of the sheaths of the small vessels in the cortex, giving evidence of an inflammation very intimately affecting the cellular mechanisms of the nervous system. It is striking how often a smaller or larger share of the cells found in the vessel sheaths are plasma cells. It does not appear, however, that the diagnosis of paretic neurosyphilis as against diffuse non-paretic neurosyphilis can be made in the stained sections with complete safety on the basis of plasmocytosis in the former and lymphocytosis in the latter. Whatever the results of careful histological differentiation by future neuropathologists may yield, it is at all events true that we cannot yet make an important differentiation clinically on the basis of the differential count of plasma cells and lymphocytes in the puncture fluids. However this may be, there is an important distinction between diffuse neurosyphilis of the non-paretic type and paretic neurosyphilis in that paretic neurosyphilis rarely if ever fails to show important degrees of intracortical perivascular inflammation with larger or smaller numbers of plasma cells.

What has the therapeutist to face in this matter? The answer, as elsewhere, depends somewhat upon what the future may decide as to the habitat and toxic or antitoxic activities of the spirocheta pallida. The early claims that the spirocheta pallida was extravascular and lay for the most part in the parenchyma and not in the vessel sheaths were perhaps overbold, since other workers have found the spirochete in the vessel sheaths also (Mott).

Aside from the spirochete and its accessibility to spirochetocidal drugs, there seems to be no reason for supposing that the perivascular sheaths cannot be cleansed of their inflammatory contents. There is, again, no reason why the phagocytic cells should not continue to perform their scavenger function until such time as the degenerative process in the parenchyma (a process not necessarily progressive in the absence of the spirochete or its products) ceases. There is every reason to suppose that a great many of the clinical phenomena are not necessarily due to permanent destruction of neurones and neuronic organs (dendrites, axis-cylinders, nets and the like) but are due to various microphysical conditions of pressure, intoxication and the like.

The inflammatory conditions in the spinal cord of poliomyelitis, which conditions are precisely as striking as those of the paretic cortex, are beyond a question cleared away in the progress of the affection. Reference to the paradigm case (1) will show the type of our argument. There is no manner of doubt that in this paradigm case almost every portion of the nervous system had been sometime swept by spirochetosis and many of its small vessel sheaths stuffed with chronic inflammatory products. As for paretic neurosyphilis itself, a great many of its most striking clinical phenomena, such as loss of memory and disorientation, as well as great degrees of apparent dementia, are found virtually as often in cases with very slight anatomical changes as in cases with marked cortical devastation. The inference is plain, that these phenomena are to a degree functional rather than structural.

In brief, we conclude not only from therapeutic experience but also on a priori grounds that the histological conditions in paretic neurosyphilis are not entirely hopeless, and certainly not more hopeless than conditions in many chronic diseases outside the nervous system. Accordingly, we plead for a temperate optimism as to therapeutic results in general paresis.

A fifth group of neurosyphilitic cases bulking rather largely in textbooks of pathology is the group of the =gummata=. For a variety of reasons (therapeutic and otherwise) the actual number of gummata of the nervous system available for clinical or even for anatomical study is much smaller than the books might lead one to infer.

The sixth and last of the main groups of neurosyphilitic diseases is that of the =juvenile forms=, among which we find not only diffuse forms without a special and well-defined course, but also characteristic examples of paretic and tabetic neurosyphilis. The distinction of a juvenile or congenital group of neurosyphilitics is, on theoretical grounds, perhaps hardly defensible. On practical grounds, however, the juvenile neurosyphilitics do form a group having special relations to feeblemindedness, epilepsy and the like.

We must be clearly understood as to the rough, six-unit classification just given. It is practical merely. For comparison we have given in other charts more expanded lists of the diagnostic entities in neurosyphilis among which that of Head and Fearnsides is of special interest, see Chart 2, page 21.

We shall now proceed to a brief analysis of the findings in our chosen series of 137 cases. We shall not reproduce the case headings of these cases, but expand their statements where necessary and tie them together so far as possible into a reasonable and systematic statement of the situation in neurosyphilis. The footnotes will contain references to other cases in which identical points are illustrated as in the leading cases. The leading cases will in all instances be placed first in the footnotes.

The paradigm shows meningeal, vascular and parenchymatous lesions and thus illustrates our definition of the term DIFFUSE which means precisely meningeal, vascular and parenchymatous. The meningeal lesions gave rise to two prominent sets of lesions, first, the marked tabetic lesions of the spinal cord (due to the spinal root neuritis incidental to the spinal meningeal inflammation), secondly, the characteristic asymmetrical and focal atrophy of cranial nerves incidental to a now largely extinct meningeal process at the base of the brain. The vascular lesions are responsible for another important and characteristic factor in the case, namely, the bilateral pyramidal tract sclerosis; the bilateral cysts of softening of the corpora striata are characteristic effects of old syphilitic cerebral thromboses. The parenchymatous disease in our paradigm is everywhere obvious, less so perhaps in the cortex itself than elsewhere, although here also evident in the shape of lesions suggesting an early phase of tissue atrophy.

The paradigm is of interest in demonstrating what in broad lines must be taken as an ascending disease proceeding not only from spinal cord to encephalon but also traceable as proceeding from lower parts of the spinal cord to upper parts thereof and from the lower encephalon to the higher structures of the cerebral cortex itself.

The paradigm insistently calls attention to the advantage of persistent therapy not only in its display of remarkable successive recoveries from permanent looking symptoms but also histologically from the remnants of inflammatory process to be found in an otherwise almost wholly dismantled nervous system with extinct lesions.

TABETIC NEUROSYPHILIS (“tabes dorsalis”), of course, often proceeds to death without special complications of syphilitic nature. We have chosen a case, however, to demonstrate a terminal complication with vascular insult. Incidentally the case shows another complication inasmuch as the cause of death was rupture of aortic aneurysm. It is important to bear in mind these complications in tabes dorsalis which go to prove that the spirochetosis of tabetic neurosyphilis is not limited to the region of the spinal roots or to the spinal region in general. Tabetic neurosyphilis is apt to be only a part of a total picture of neurosyphilis just as neurosyphilis itself is only a part of the general syphilitic process.

Our case of PARETIC NEUROSYPHILIS (“general paresis”) is a characteristic one in duration (three years and three months). The aortic sclerosis almost constantly found in neurosyphilis and especially in paretic neurosyphilis is here also shown. The spinal cord showed lesions which are also almost always found in paretic neurosyphilis. The characteristic frontal emphasis of the atrophic and indurative lesions is shown. There is also a display of gross changes in the pia mater. The characteristic so-called granular ependymitis or sanding of the ventricular surface is shown. The case is distinguishable from the paradigm in not showing the effects of vascular insults in the shape of cysts of softening. The cerebellar sclerosis of the case is fairly characteristic of paretic cases. There is even a suggestion of atrophy in the temporal region suggesting the so-called Lissauer’s paresis. Clinically the case belongs in the classical grandiose group of paretics (“O. K. No. 1 superfine”).

VASCULAR NEUROSYPHILIS is illustrated in a fourth autopsied case. It may be noted that the pia mater in this case is practically normal. The tissues outside the area of softening due to the syphilitic thrombosis of nutrient vessels are practically normal. The case was one of almost complete sensory aphasia with word-deafness. The clinical picture is accordingly quite distinct from those of the paradigm (1) and of the case of general paresis (3) just discussed.

JUVENILE PARESIS is illustrated by a case with exceedingly extensive lesions, largely meningeal and parenchymatous. The cerebral lesions are atypical since in places they suggest the tuberous sclerosis of Bourneville. The brain atrophy is extreme (965 grams) and it is possible that this apparent brain atrophy was in part hypoplasia, since the spirochetosis of this case was doubtless congenital. However, clinically the patient was fairly normal up to the age of 18.

A case of so-called SYPHILITIC EXTRAOCULAR PALSY demonstrates a characteristic meningeal process more extensive than the clinical symptoms would have indicated. In fact, focal clinical nerve palsies are as a rule, if not constantly, partial phenomena of a far more extensive process of neurosyphilis. They are far more limited clinically than anatomically and histologically. It seems at first sight improper to term them cases of diffuse neurosyphilis in view of their clinical focality, yet they are best described as partial cases of diffuse neurosyphilis.

A case of GUMMA of the left HEMISPHERE is presented which appears to have led to death in about four years from onset. This case, like many others, is not an example of purely focalized syphilitic process inasmuch as cysts of softening indicating slight vascular insults are present elsewhere (pons). There is also a degree of leptomeningitis, particularly basal.

Our discussion of the nature and forms of neurosyphilis is completed by a rare case probably belonging in the so-called cervical hypertrophic meningitis of Charcot but actually due to a GUMMA OF THE SPINAL MENINGES. The importance of therapeutic optimism is emphasized in this case as in the paradigm. Theoretically the meningeal inflammation of neurosyphilis ought to be almost entirely if not entirely removed by therapy, and these two cases, like several others in the series, seem to illustrate this possibility.

Neurosyphilis sometimes receives the clinical diagnosis neurasthenia simply through omission to apply proved diagnostic methods. An instance is given in which the PARETIC form of NEUROSYPHILIS (“general paresis”) received the diagnosis neurasthenia for a period of five years, at any time during which period it would doubtless have been possible to render the correct diagnosis and apply treatment.

Neurosyphilis may imitate not only the psychoneuroses but also the psychoses themselves. We present a case of an architect, which looked almost precisely like manic-depressive psychosis and had a history of attacks, but in which the positive serum W. R. led (in accordance with hospital rules) to an examination of the spinal fluid. The spinal fluid tests proved the case to be one of PARETIC NEUROSYPHILIS.

However, a positive serum W. R., even when associated with mental symptoms, and when those mental symptoms include grandiosity, does not prove the existence of neurosyphilis either in its paretic or non-paretic form. Our instance seems to be one of MANIC-DEPRESSIVE PSYCHOSIS. The spinal fluid tests were entirely negative. The course of the disease was also that of manic-depressive psychosis. In the absence of positive spinal fluid tests, the diagnosis neurosyphilis was excluded.

Neurosyphilis and even PARETIC NEUROSYPHILIS may result in symptoms that would ordinarily lead to the diagnosis dementia praecox.

It is important not to rule out neurosyphilis on the ground of a negative serum W. R. The fluid W. R. may turn out positive. We present a case (of a salesman) in which the serum W. R. was repeatedly negative (even salvarsan did not act provocatively) yet the spinal fluid W. R. proved positive. The case was clinically one of classical PARETIC NEUROSYPHILIS (“general paresis”). It is a good rule to proceed to lumbar puncture, even when the serum W. R. is negative, if there are suspicious symptoms (e.g., speech defect and memory impairment, grandiosity) or signs (e.g., marked reflex disorder, especially pupillary disorder).

DIFFUSE NEUROSYPHILIS was above defined as “meningovasculoparenchymatous.” This disease is typically associated with six positive tests (positive serum W. R., positive fluid W. R., pleocytosis, gold sol reaction, positive globulin reaction and excess albumin). One or more and frequently several of these six tests are likely to run mild in diffuse neurosyphilis; that is to say, these tests are apt to run milder than the identical tests in paretic neurosyphilis (“general paresis”). The clinical course of the diffuse, and especially the meningovascular cases, is likely to be protracted. The prognosis as to life is good, barring fatal vascular insults. The illustrative case was a case with slow course. There was a series of attacks followed by a paralytic stroke, a finding highly typical of the diffuse form of neurosyphilis. The spinal fluid reactions were mild, suitable to the general principle above stated.

These tests are likely to run stronger, as above stated, in paretic neurosyphilis (“general paresis”), than in the diffuse form. In particular, the gold sol reaction is likely to be shown in what is termed “paretic” form rather than in what is termed “syphilitic” form. The clinical course of PARETIC NEUROSYPHILIS is likely to be brief. A characteristic case with very heavy globulin and albumin tests is presented.

TABOPARETIC NEUROSYPHILIS (“taboparesis”) is clinically a combination of the symptoms of tabetic (“tabes dorsalis”) and those of paretic neurosyphilis (“general paresis”). First comes the tabes dorsalis lasting often for many years. Afterward follows a characteristic general paresis. The ultimate paretic picture is likely to retain, however, various characteristics of tabes. The laboratory tests in the paretic phase of taboparesis are characteristic of general paresis and not of tabes dorsalis. The prognosis after the paretic phase has arrived is that of general paresis.

The diagnosis of the neurosyphilitic forms would be easy if these principles were always carried out to the letter. The important fact is as follows: diffuse (that is, meningovasculoparenchymatous neurosyphilis) may look like paretic neurosyphilis (“general paresis”) at certain periods of the clinical and laboratory examination. This fact is of obvious importance. The general prognosis of diffuse neurosyphilis is regarded as good quoad vitam. The general prognosis of paresis is bad. If, however, the differential diagnosis cannot be rendered at particular phases of a given case, then no safe prognosis can be offered in the individual case. In particular no prognosis affecting the administration or non-administration of modern systematic treatment can or should be offered in these doubtful phases.

It is not always safe to exclude neurosyphilis even when the fluid W. R. is negative. Particularly in vascular neurosyphilis the fluid W. R. and even all the other laboratory signs in the spinal fluid may sometimes be negative. A positive serum W. R. yields the correct pointer to diagnosis. Of course, also in many cases of vascular neurosyphilis one or more of the laboratory signs may be suggestive even when the fluid W. R. is negative. Theoretically there may be cases in which all the six tests are negative and yet the diagnosis neurosyphilis be the correct one.

A clinically important sign in neurosyphilis is the so-called seizures. These occur both in DIFFUSE NON-PARETIC NEUROSYPHILIS and in PARETIC NEUROSYPHILIS.

Aphasia is likewise a symptom in both these forms of neurosyphilis, namely, in the DIFFUSE non-paretic and in the PARETIC form.

The literature contains reference not only to seizures and aphasia as characteristically paretic but also to remissions. Remissions like seizures and aphasia are found in both the PARETIC and NON-PARETIC forms of neurosyphilis. They have important bearings on prognosis in all forms of neurosyphilis and are of especial significance in the evaluation of treatment. (Remissions coincident with apparent cure.)

So far we have been dealing with cases of neurosyphilis in which there was no doubt of the existence of mental symptoms. There are cases, however, in which although the laboratory signs of neurosyphilis exist, proving beyond doubt the existence of a chronic inflammatory reaction and allied pathological conditions in the cerebrospinal axis, there are no mental symptoms of neurosyphilis. We have called some of these cases PARESIS SINE PARESI and present examples.

To illustrate complications we give a case of PARETIC NEUROSYPHILIS with autopsy in which there were ante mortem signs of HERPES ZOSTER or, at all events, of a skin eruption limited to the area of a thoracic nerve.

A case of GUMMA of the brain in which decompression was warranted and performed is presented. The fluid W. R., as in many such cases, was negative; serum positive.

A case of CRANIAL NEUROSYPHILIS (extraocular palsy without mental symptoms) showed a positive Wassermann serum test and a negative spinal fluid.

The laboratory reactions in TABETIC NEUROSYPHILIS (“tabes dorsalis”) run somewhat like those of diffuse non-paretic neurosyphilis and are accordingly milder than those of paretic neurosyphilis. The fluid W. R. and the gold sol reaction in particular are apt to run mild. The clinical course of tabes dorsalis is well known to be protracted and the prognosis quoad vitam is good except that we must always bear in mind the possibility of vascular insults and complications of a syphilitic origin in the rest of the body.

It is important to remember that TABETIC NEUROSYPHILIS is often quite atypical clinically and may even show no single symptom warranting the old clinical name locomotor ataxia.

There are even cases in which the name tabes dorsalis is not warranted in view of the fact that the lesions are not low in the cord but are higher up (TABES CERVICALIS).

A rare form of neurosyphilis is ERB’S SYPHILITIC SPASTIC PARAPLEGIA against which one needs to consider a number of non-syphilitic spinal cord diseases. Our case showed a weakly positive serum W. R., a negative fluid W. R., and the other tests of the spinal fluid were moderately positive.

SYPHILITIC MUSCULAR ATROPHY is classified by Head and Fearnsides both in their meningovascular group and in their group of the so-called syphilis centralis. Our case affecting in large part the small muscles of the hands in a teamster, may be due either to spinal parenchymal lesions or to root neuritis or to both.

It is a little extraordinary and very important that the laboratory signs are apt to be positive even in the SECONDARY period of SYPHILIS. Perhaps a third of all cases of syphilis in the secondaries would, if tested, yield positives precisely like those of full-blown paretic or diffuse neurosyphilis. Strangely enough, these signs may occur without clinical symptoms. The illustrative case, a mechanic, yielded various mental symptoms. The cases of secondary syphilis with laboratory signs of neurosyphilis but without clinical symptoms are of the greatest theoretical importance in relation to the problem above mentioned of paresis sine paresi. It may well be inquired whether in some instances the neurosyphilis of the secondaries does not persist until the exhibition of mental or physical symptoms of neurosyphilis years later. It must be remembered that this conception is hardly more than a hypothesis at the present time. That such signs of chronic inflammation could exist without symptoms is not so surprising when one thinks of the startling immediate improvement seen after treatment or even in remissions without treatment. One is reminded of the crisis in pneumonia wherein clinical improvement takes place entirely independent of the mechanical conditions in the lung which just after the crisis remain as suppurative as before.

The diagnosis of JUVENILE NEUROSYPHILIS is made upon the same lines as that of neurosyphilis in the adult. We present two cases, one with optic atrophy and the other with signs of congenital syphilis antedating the symptoms of paresis.

Congenital syphilis is also apparently capable of producing a simple form of FEEBLEMINDEDNESS, that is to say, a form of disease non-paretic, non-tabetic, and without special tendency to vascular insults.

We present a case of JUVENILE TABETIC NEUROSYPHILIS (“juvenile tabes”). The tests were all positive.

The line of separation between typical and atypical cases of neurosyphilis is vague and indistinct and some of the cases classified by us amongst puzzles perhaps belong under systematic diagnosis and vice versa. The section on PUZZLES AND ERRORS in the diagnosis of neurosyphilis is introduced by six cases of error in the diagnosis of the paretic form of neurosyphilis. These errors were made known by autopsy. Aside from the sixth case, whose etiology must remain in doubt and which was a unique case of PERIVASCULAR GLIOSIS, there is ground for the belief that the other five cases in this Danvers Hospital study of diagnostic errors were perhaps actually syphilitic though not of the paretic form of neurosyphilis. At all events, the brain tissues in these cases failed to show the plasma cell deposits which are characteristic in the sheaths of the intracortical vessels in paretic neurosyphilis.

A case illustrates the complication of TABES by arteriosclerotic symptoms, in which case the arteriosclerosis may naturally have been of syphilitic origin. Two cases especially illustrate the possibility of confusing the ataxia of general paresis with CEREBELLAR ATAXIA. These cases showed lesions of the cerebellar structures, notably of the dentate nucleus. No one can read these cases or any of the autopsied cases in our series, without perceiving how fundamental and even critical is the demand for autopsies in fatal cases of neurosyphilis. The practitioner who can secure an autopsy in a fatal case of neurosyphilis and have the tissues worked up by approved neuropathological methods is almost bound to add his bit to neurological theory. Even cases of classical tabes dorsalis are often signally important to the theorist on account of the relations of the neural to the non-neural complications.

We then proceed to a group of cases without special order in which a variety of diagnostic questions arose.

A case of questionable neurosyphilis in the secondary stage of syphilis brings up the problems of syphilitic neurasthenia.

Syphilis may act as agent provocateur of HYSTERIA as Charcot insisted.

A case illustrative of difficulties in diagnosis between neurosyphilis and manic-depressive psychosis follows.

A case for diagnosis is given which shows that errors in the diagnosis of neurosyphilis are entirely possible even when abundant clinical and laboratory data are available. A case with a weakly positive Wassermann reaction in the spinal fluid finally turned out to be one of BRAIN TUMOR.

Some questions as to the diagnosis of NEUROSYPHILIS versus Idiopathic Epilepsy are brought up by a case in which phenomena of paresis seemed to have occurred very early, about two years after the initial syphilitic infection.

A case of PARETIC NEUROSYPHILIS is offered in which hemiplegia and hemitremor strongly suggested vascular lesions; but the autopsy showed no coarse lesions and merely confirmed the diagnosis paresis microscopically.

An autopsied case of PARETIC NEUROSYPHILIS is given, in which the pupils persisted in reacting normally. Herpes zoster-like lesions in life yielded no special signs at autopsy (all root-ganglia looked alike above and below zone of “shingles.”)

An example of NEUROSYPHILIS, probably PARETIC, yielded symptoms highly suggestive of manic-depressive psychosis. An interesting feature in this case was the birth of a healthy child nine months after the onset of the psychotic attack.

An example of exophthalmic goitre following the acquisition of SYPHILIS showed at autopsy a heavy scarring of the optic thalamus and unilaterally atrophic process in the cerebral cortex.

We come to some questions concerning the Argyll-Robertson pupil. It is agreed on all hands that the Argyll-Robertson pupil is characteristic of the paretic and tabetic forms, but the sign occurs also in other neurosyphilitic conditions; in fact the sign does not necessarily indicate neurosyphilis as an instance of PINEAL TUMOR demonstrates.

The question raised above as to the possibility that neurosyphilis may exist in the absence of positive findings in the spinal fluid is illustrated in a man, a mechanic, who claimed syphilitic infection and showed an Argyll-Robertson pupil on one side. The serum W. R. was positive; the fluid tests were negative.

An extraordinary case is given in some detail in which NEUROSYPHILIS in the form termed DISSEMINATED ENCEPHALITIS proved fatal within seven months of the initial infection.

We have frequently mentioned the classical assumption that paretic neurosyphilis (“general paresis”) is a fatal disease. Some have suggested that there is another form clinically almost identical with general paresis except that it pursues a long course and the suggestion has been made that these cases be termed pseudoparesis. We are of the opinion that this term should be dropped and advocate the use of the word pseudoparesis only for non-syphilitic disease looking like paresis, such as alcoholic pseudoparesis and the like.

The question whether there is a form of mental disease SYPHILITIC PARANOIA is raised by a case with auditory hallucinations, ideas of persecution and attacks of excitement. The diagnosis of alcoholic hallucinosis was actually made although there is no proof that the patient ever drank alcohol.

Alcohol may cause symptoms identical with those of paretic neurosyphilis, including seizures, Argyll-Robertson pupils, speech defect and mental symptoms. The differentiation is readily made by the negative laboratory findings. An illustration is given in our case of the alcoholic teamster. Cases such as this bear the name ALCOHOLIC PSEUDOPARESIS.

However, when the clinical picture is the same as in the case of our teamster, the alcohol may only be a complicating factor in neurosyphilis, as shown by our next case of the alcoholic steamfitter who in fact was shown to have NEUROSYPHILIS.

Sometimes cases of apparently frank alcoholism, even with apparently characteristic delirium tremens and neuritis, prove to be essentially neurosyphilitic. On the other hand, true combinations of ALCOHOLISM and NEUROSYPHILIS occur which it would be proper to classify under either heading and in which therapy must take serious account of both conditions.

As above stated, we elect to use the term pseudoparesis only for non-syphilitic cases. There are other forms of pseudoparesis than alcoholic pseudoparesis. The question of Diabetic Pseudoparesis is raised by an exceedingly complicated case of which our best interpretation is that the patient, a proved syphilitic (with syphilitic osteomyelitis (?)), a huge doorkeeper, was perhaps suffering from an old SYPHILITIC scarring of the PITUITARY body. Neither this case nor a second case, one of PARETIC NEUROSYPHILIS with glycosuria is actually entitled to the diagnosis diabetic pseudoparesis. The second case of paretic neurosyphilis with glycosuria brings up some unanswerable questions as to the pancreatic or basal meningitic or other origin for the glycosuria.

Isolated symptoms are often presented by neurosyphilitics (e.g., hemianopsia); but we tend to regard these cases as due to focal lesions that are merely part and parcel of DIFFUSE LESIONS.

A neurosyphilitic case (a steward) with the rather unusual complication (for our northern region) of severe MALARIA producing cerebral thrombosis is reported.

The diagnosis Dementia Praecox was actually made in the case of a young school-teacher in whom the laboratory findings proved conclusively that the condition was one of NEUROSYPHILIS. The gold sol reaction in this case was mild. The chief lesion at autopsy was a fresh looking, gelatinous pial exudate over the spinal cord which turned out to contain an almost pure display of very numerous plasma cells.

The question of LUES MALIGNA is brought up in a rectifier of spirits in whom the characteristic tremendous destruction of tissue, toxemia and failure to react to antisyphilitic treatment were illustrated. Moreover, this case had a trauma (cautery) to the tonsil, as in other cases of lues maligna.

A case somewhat suggestive of brain tumor, of neurosyphilis and of multiple sclerosis turned out to be MULTIPLE SCLEROSIS (the fluid showed a pleocytosis and a moderate amount of globulin with a paretic type of gold sol reaction).

As a foil to this case that we regard as multiple sclerosis, we present a second case with nystagmus, optic atrophy and spasticity in which the suspicion of multiple sclerosis might well be raised but which the tests demonstrated to be NEUROSYPHILITIC.

An even stranger imitation of well-defined non-syphilitic entities was presented by a case apparently of Huntington’s chorea (except for absence of the hereditary taint) which case, however, proved to the surprise of all diagnosticians to be one of NEUROSYPHILIS.

Frequent errors of diagnosis must occur in the field of the senile psychoses. We present a case that would at first blush warrant the diagnosis of senile arteriosclerotic psychosis in a sea captain of 75 years (wife dead 15 years before of general paresis) who turned out to be a characteristic case from the laboratory standpoint of NEUROSYPHILIS.

The Protean nature of the symptomatology of neurosyphilis is sufficiently established. Still, a case that might fit into textbooks concerning DISSOCIATION OF PERSONALITY is certainly a clinical oddity, as illustrated by a fugacious musician.

A case with strong suspicions of neurosyphilis of tabetic type turned out to be more probably one of neural complications in PERNICIOUS ANEMIA.

NEUROSYPHILIS IN JUVENILES presents puzzling conditions.

One case was marked clinically by attacks of excitement. It is impossible to place this case among the main groups of juvenile neurosyphilis.

Another case of FEEBLEMINDEDNESS, also NEUROSYPHILITIC in origin, presented physical symptoms and laboratory signs of paretic neurosyphilis; yet this case had been considered one of simple feeblemindedness.

A case apparently of JUVENILE PARETIC NEUROSYPHILIS in a 15 year old boy presented the rather unusual complication of shocks with quadriplegia, a vascular complication not usually expected in the paretic type of neurosyphilis in adults.

Epileptic phenomena are rare as the effect of JUVENILE NEUROSYPHILIS, but occur as demonstrated in a case which slipshod methods of diagnosis might well have regarded as one of idiopathic epilepsy.

A case of JUVENILE PARETIC NEUROSYPHILIS with the complication of ADDISON’S DISEASE is given (autopsy confirmation).

The puzzle in diagnosis offered by syphilis in the secondary stage is illustrated by a case which showed the characteristic NEUROSYPHILITIC complications of the SECONDARY STAGE of syphilis. This patient may well have been a moron at the outset and exhibited some reactions (refusal to talk) explicable on the basis of feeblemindedness. She was a neurosyphilitic only in the sense of the neural complication that we find in the secondary stage of syphilis. As stated above, we do not yet know what the fate of these neural complications of secondary syphilis is to be. The frequency of this finding in secondary syphilis is probably too great to warrant the hypothesis that it must always go on to a chronic neurosyphilis; but we certainly are warranted in regarding these cases as potential chronic neurosyphilitics.

A case of TABOPARETIC NEUROSYPHILIS in which the heavy exudate characteristic of paresis became a soil for a growth of the typhoid bacillus is presented with autopsy. This fatality with TYPHOID MENINGITIS is merely a concrete example of the many complications which syphilitics and especially neurosyphilitics have to sustain.

The case series then goes on to illustrate, though quite inadequately, a variety of MEDICOLEGAL AND SOCIAL complications of neurosyphilis. It is well known that many social complications with grave moral, economic and even political difficulties occur.

Our series starts with a “public character” whose eloquence and reformatory efforts led to a considerable notoriety. The autopsy in this case showed singularly few lesions despite the fact that the case was microscopically one of wholly characteristic PARETIC NEUROSYPHILIS. The question might arise how far we are entitled to correlate the reformatory efforts of this always eccentric character with syphilis. The man himself a physician, was aware of the doubt which his Argyll-Robertson pupils threw upon his medical situation. He explained them on the basis of an old smallpox! We are inclined to think that the whole of this man’s life, from his giving up of medical practice to live as a kind of literary and political hack, was due to subtle changes of neurosyphilitic origin. The fact that there was a certain delinquent streak in the man is not inconsistent with this idea. Interestingly enough, a fall on the ice in the man’s 61st year actually started up the fatal process, a condition of affairs amply illustrated in cases of neurosyphilis, brought out by trauma that come to the attention of the Industrial Accident Board in connection with claims for compensation.

A case of sudden grandiosity illustrates an episode of NEUROSYPHILITIC origin. Such a person might well be regarded by the lay newspaper reader as a crank or a grafter but the neurosyphilitic possibility should always be entertained in cases of this order.

As against the social difficulties that look in the direction of the classical paretic grandeur, we present a case of apparent suicidal attempt by gas, which attempt was followed by a period of amnesia that, taking into account the laboratory findings, was probably NEUROSYPHILITIC.

Vistas of extraordinary interest are opened out by studies of the relation of neurosyphilis to delinquency. The case of the psychopathic reformer (Case 83) above mentioned was one in which the delinquency may possibly have been related to acquired syphilis. We present also a case of juvenile neurosyphilis, a young man of reform school type in which JUVENILE PARETIC NEUROSYPHILIS was established. This patient, in fact, deteriorated very rapidly to a condition of considerable dementia a few months after the diagnosis was established.

A striking case of so-called DEFECTIVE DELINQUENCY is presented, an alcoholic prostitute of the reformatory group. The NEUROSYPHILIS in this case was a complication rather than an original factor in the delinquency.

One case of PARESIS SINE PARESI was that of an habitual criminal and forger who, without showing mental or physical symptoms of neurosyphilis, yielded the laboratory signs of paretic neurosyphilis. Again, as in the case of the prostitute just mentioned, the CRIMINALITY seems to have antedated the neurosyphilis and even to have been hereditary.

By way of introducing the next group of Industrial Accident Board cases, we present a case of JUVENILE PARESIS with initial TRAUM.

The Industrial Board group is of note in that the signs of the traumatic form of paretic neurosyphilis do not occur immediately upon the accident. Some time elapses in which the physical, chemical or parasitological changes have time to work themselves out in the injured tissues. Many hypotheses may be raised as to the reason why a trauma lights up a syphilitic process. Of course, =false claims= =may be made for compensation by neurosyphilitics= in whom the symptoms were already in existence before the accident and in whom they may not even be markedly exacerbated by the accident. The false claimants can probably not readily frame a story which the expert psychiatrist cannot discredit if he is allowed to perform laboratory tests and give the patient the benefit of thorough examination. However, some cases of established PARETIC NEUROSYPHILIS are perhaps truly subject to exacerbations of the clinical process and it may well be held that such exacerbations warrant partial compensation.

The fact that a trauma may light up a syphilitic process is illustrated in a case that came to the Psychopathic Hospital, in which a SYPHILITIC LESION developed in the skull AT THE SITE OF SKULL INJURY.

A case of OCCUPATION-NEUROSIS that might be interpreted as a syphilitic neuritis is presented. The case is still in doubt as to its scientific evaluation.

The workmen’s compensation group of syphilitic cases is of extraordinary general interest since it indicates that employers may well be on the lookout not to employ known syphilitics unless fortified by special insurance arrangements. Whether in future employers may desire =to employ only W. R. negative workmen= is one of the highly complicated questions re workmen’s compensation and health insurance.

But the problems of neurosyphilis are not merely medicolegal and broadly public or social. The most appealing difficulties lodge within the bosom of the family. Now and then a case of INCOMPATIBILITY OF TEMPERAMENT, perhaps complicated by alcoholism, occurs which tests prove to be NEUROSYPHILITIC.

Special attention should be drawn to a certain NEUROSYPHILITIC FAMILY in which both parents and five children showed a variety of syphilitic diseases, including syphilis without apparent neural complications, paretic neurosyphilis, juvenile paresis, aortic aneurysm, achondroplasia and caries of the spine, and an as yet indefinite neurosis. There was a sixth child that died shortly after birth, as well as three stillborn.

One =cannot conclude= from the normal look of a neurosyphilitic’s family =that the normal-looking members are not syphilitic=, as illustrated by the family of our draughtsman.

The most =intricate social complications= may arise. We present a case of a syphilitic man (a well-to-do merchant) who was apparently being goaded into a second marriage because he was continually being charged with having caused his first wife’s death. This he had actually done in a certain sense because his wife had died of general paresis, having contracted syphilis from him.

In the fifth section on THERAPY, we have attempted to outline some of the principles and problems that arise in the treatment of neurosyphilis. Enough has probably been said concerning the attitude of optimism or pessimistic nihilism that may be adopted toward the whole subject. It must be borne in mind, however, that a great deal of the work on treatment of neurosyphilis is still in the experimental stage. As a rule, each case must be considered separately and individually and the prognosis can be made satisfactorily only after treatment has been given. This section contains a group of cases that have been treated rather intensively and the results of this treatment are indicated. The section is introduced by five untreated cases, the brains and cords of which have been studied post mortem. These illustrate the pathological conditions which we have to meet, and from these examples we can draw the theoretical conclusion that some cases are beyond the aid of therapy on account of the brain destruction. Others, in which the symptomatology bespeaks just as grave a situation, turn out on autopsy to have very little actual damage to the brain tissues and therefore should theoretically at any rate be amenable to antisyphilitic therapy.

In order to get any adequate conception of the possibilities of therapeutic results in cases of neurosyphilis, one must consider the pathological changes that occur and how far these changes are reparable. In cases in which the destruction of tissue is marked, it is, of course, out of the question to expect to get any marked clinical improvement. A case of spastic hemiplegia in paretic neurosyphilis is given with the autopsy findings as an illustration of irreparable damage that may occur to the parenchymatous structure, thus precluding any chance of functional recovery.

On the other hand, there is a group of cases in which the symptoms may be exceedingly severe and yet the actual destruction of tissue be almost nil. This point is illustrated by a case in which total duration of symptoms terminating in death was only 22 days. At autopsy there was very little in the way of macroscopical lesions, and microscopically there was no marked evidence of destruction in the parenchymatous tissue. The lesions were represented chiefly by perivascular infiltration. According to all our modern ideas, this type of reaction is resolvable under antisyphilitic treatment. Though this case was one of very short duration, similar pathological pictures may be obtained in cases of considerably longer standing. It is also of great importance to remember that symptomatically such a case may be in no way distinguished from a case with marked atrophy.

Another autopsied case is given which shows an exceedingly =marked meningitis=. The meningitic processes according to the literature and experience react very readily to antisyphilitic treatment in the form either of mercury and iodid or in combination with salvarsan. The lesion here present would probably have improved had intensive treatment been given. Clinically the diagnosis of general paresis was made and, as has been the rule in the past, treatment was not given on the ground that it had no value in paresis. While this is an extreme case of meningitis, it is to be remembered that the vast majority of cases of paretic neurosyphilis show some degree of meningitis. Just as in the marked meningitis of the diffuse neurosyphilis, so with the meningitis of the paretic form, improvement is expected under treatment. As a part or even the whole of the symptomatology in a given case may be due to this meningitic process, we have reason occasionally to expect marked improvement as the result of antisyphilitic treatment.

As a contrast to this case with marked meningitis, another case of =marked atrophy= is given. Here the atrophy was very perceptible on macroscopical examination and the mere view of the brain at once indicated that in such a case important results from treatment were not to be expected.

The =topographical variation= of the lesions in neurosyphilis must be remembered when treatment is to be instituted. Thus very marked lesions may exist in portions of the brain which do not give any very definite localizing symptoms. As a result, one may be led to believe from clinical evidence that the case is a very mild one though the lesions may really be very extensive. The topographical distribution must, therefore, be taken into consideration in trying to estimate the damage done. This point of topographical distribution of the lesions is illustrated by a case.

It has been generally recognized that =clinical improvement=, if not cure, may be =readily obtained in the group of diffuse neurosyphilis=, i.e., so-called cerebral and cerebrospinal forms of syphilis. These are cases in which the parenchyma is very slightly, if at all, affected and in which the lesion is chiefly in the meninges and blood vessels, irritative rather than degenerative. A case is given to illustrate this point. In our experience systematic intravenous salvarsan therapy associated with mercury and iodid gives remarkably good results in the vast majority of this group of cases.

It is generally conceded that antisyphilitic treatment, particularly salvarsan, has a very satisfactory result applied to diffuse neurosyphilis. But the same good results may be obtained in cases which are not so typically of the diffuse type. An illustration is given in the case of a machinist in which the diagnosis was in doubt between paretic, tabetic or diffuse neurosyphilis. The result of treatment was as satisfactory as could be expected in any type of neurosyphilis and this in a case of several years’ duration with Argyll-Robertson pupils.

As a rule, the Argyll-Robertson pupil is taken as a grave omen for treatment, an idea based upon a conception that the Argyll-Robertson pupil so frequently represents the old so-called “parasyphilitic” cases, which, in the past were taught as being incapable of improvement by the ordinary antisyphilitic methods.

A second case with Argyll-Robertson pupil shows again that the =prognosis may be very good despite the Argyll-Robertson sign=.

But even in the diffuse neurosyphilis, the symptomatic results of treatment may not be entirely happy. Under treatment it may be possible to reduce the spinal fluid tests to negative without, however, as in the case of our hemiplegic lady, making the physical or mental symptoms disappear. In other words, it may be possible to stop the active progress of the disease without removing the symptoms.

One is always warned of the danger of intravenous salvarsan therapy in hemiplegic cases due to arteriosclerotic conditions. While this warning is well justified, it does not mean that the most intensive treatment is contraindicated, as shown in the case of our hemiplegic machinist. Such may be given over long periods of time with the most satisfactory results.

A case is given which illustrates the value of antisyphilitic treatment in cases showing symptoms of intracranial pressure due to syphilitic disease. In the case of the woman which we cite, we believe that the symptoms of intracranial pressure were probably due to a gummatous new growth, although it is possible that they were due to a marked meningitic process. However, the results of a limited amount of antisyphilitic treatment in this case were very brilliant. Similar results may often be obtained in gumma of the brain. This is not always true, however, and it may become necessary to use surgical procedure in order rapidly to overcome the effects of intracranial pressure.

While it has always been conceded that treatment would greatly help cases of diffuse and vascular neurosyphilis, the utmost pessimism has existed concerning the results to be obtained by treatment in cases of tabetic and paretic neurosyphilis. Only in the last five or six years, due to the stimulus of Ehrlich’s discovery of salvarsan and the introduction of the intraspinous methods of therapy, have intensive work and study been given to the treatment of these cases. And though it has been by no means settled in the minds of the various workers in this field, as to what the ultimate results of such treatment will be and though some do not believe that there is any good to be expected from our present methods, still the majority of men who are treating these cases systematically feel very much encouraged.

=At times very brilliant results= are to be obtained by intraspinous treatment =in tabetic neurosyphilis= (“tabes dorsalis”). A very striking illustration is given of a case of this sort in which the symptoms dated only a few months but which had all the classical symptoms, signs and laboratory tests. Five intraspinous injections of mercurialized serum were sufficient to cause the disappearance of the subjective symptoms and to reduce the spinal fluid test to negative.

It must be emphasized that the best results in cases of tabetic neurosyphilis are usually to be expected in cases in which the symptoms are of short standing. Where the process is of long duration and much destruction of spinal cord tissue has occurred, the best one can expect is that the activity and progress may be halted. This is illustrated by our case of a baker, 43 years of age, who had been suffering from the symptoms of tabes for some years. Under treatment it was possible to get an entirely negative serology of the blood and spinal fluid. Despite this evidence that the activity of syphilis had ceased, the symptoms continued unabated. We are ready to believe, however, that much good was accomplished. For the patient should not have any further untoward developments or the appearance of any new symptoms. These, without such treatment, might well be expected. At times excellent clinical results are obtained in long-standing cases.

The results of treatment in paretic neurosyphilis (“general paresis”) have been considered even less hopeful than in tabetic neurosyphilis (“tabes dorsalis”); indeed, it has often been stated that the patients are made worse by treatment. Recent work, however, supports a much more optimistic viewpoint. We feel that =intensive treatment has been of the greatest value in a number of cases of paretic neurosyphilis=. Two cases are given which show the most satisfactory and brilliant results of intensive intravenous salvarsan therapy in cases diagnosed as general paresis. The first case, an excellent salesman, 46 years of age, with most aggravated mental symptoms, recovered symptomatically and all his tests were rendered negative. He has now remained entirely well and economically efficient for about two years without further treatment. The other case, a housewife, also with very marked symptoms suggestive in all ways of general paresis, also recovered rapidly under treatment and her tests became negative. Her remission has now lasted for nearly three years without further treatment.

At times it is not possible to get the spinal fluid tests to become negative in cases of paretic neurosyphilis under the most intensive salvarsan therapy. In spite of this, the clinical condition of the patient may improve so greatly that the patient can be considered =clinically recovered=. An illustration is given of an undertaker who was brought from a condition of the greatest cachexia and mental confusion to a condition of robust appearance and mental efficiency under intravenous salvarsan therapy, in spite of the fact that his tests were very slightly if at all reduced in intensity. He has been able to resume his former occupation and his former life with great satisfaction to himself and his family.

Improvement in paretic neurosyphilis under treatment is not to be expected very early. =Two or three months of active treatment= may elapse before one sees signs of improvement. Indeed, as illustrated by our case of the shipping clerk, this improvement may begin to make its appearance only after more than four months of intensive treatment consisting of two injections of salvarsan per week. In spite of the long delay in this case, complete clinical recovery occurred and the tests became almost negative at the end of a year of treatment.

It is not only in the central nervous system that the syphilitic process may resist the most intensive treatment. In the case of the speculator, a victim of paretic neurosyphilis, which we cite, a perennially recurrent iritis appeared after several months of the most intensive salvarsan treatment which was apparently sufficient to reduce the symptoms of the paretic neurosyphilis, but not of non-neural syphilis.

We give the case of a charwoman having the diagnosis of paretic neurosyphilis, who, under intensive treatment, made a symptomatic recovery. The interesting point in her findings is that all the tests in the spinal fluid became negative except the gold sol reaction which remained of the “paretic” type. There is no general rule as to the reaction of the spinal fluid tests under treatment. At times one test is the first to disappear under treatment; again it is another. We have seen many cases in which the gold sol was the first test to become negative and others, as the case given, in which it is the last to show any change. As in our undertaker, symptomatic clinical improvement may be practically complete without any change in the spinal fluid tests.

One must remember that it is the condition of the patient that is of first importance; not so much the laboratory tests. Having shown the clinical recoveries with the tests remaining positive, we now have to report two cases in which there was =improvement= as shown =by the tests but no clinical improvement=. The first patient, a bank teller of 39 years, with a diagnosis of paretic neurosyphilis, received intensive intravenous salvarsan for several months. Under this treatment all the tests became negative except the gold sol which remained of the paretic type. In spite of this, there was not the slightest improvement in his mental condition.

The second case, a young man of 29 years in whom the symptoms of neurosyphilis had recently appeared, under treatment showed a marked diminution in the intensity of the spinal fluid tests, notwithstanding which the patient became more and more demented and died after a series of convulsions.

Of course, good results indicated above in some of our cases of paretic neurosyphilis are not to be expected in every case no matter how intensive the treatment. We give a case of paretic neurosyphilis in which the most intensive intravenous salvarsan therapy gave no satisfactory results. This was followed by several intraventricular injections of salvarsanized serum. The results of this combined treatment, however, were still not satisfactory, and the patient died.

In order to emphasize as strongly as possible what we believe is a great =advantage of systematic intensive treatment= for neurosyphilis, we offer two cases in different time periods of neurosyphilis. The first is a printer with the symptoms of diffuse neurosyphilis six months after the appearance of his chancre. These symptoms appeared despite three injections of salvarsan, injections of mercury and mercury by mouth. Under intensive treatment (meaning injections of salvarsan twice a week and continued injections of mercury), complete recovery occurred in a few weeks.

The second case is that of a waiter with signs and symptoms of neurosyphilis in whom the diagnosis lay between the diffuse and paretic forms. This patient developed his symptoms in spite of continuous antisyphilitic treatment during the six years since his infection. This treatment had been comparatively mild, consisting in great part of mercury by mouth. However, he had had courses of injections of mercury and several injections of salvarsan. Under a systematic course of intravenous injections of salvarsan twice a week for a number of months, all symptoms disappeared and the spinal fluid tests became negative as well as the W. R. in the blood serum.

A final case is offered which indicates that antisyphilitic treatment may occasionally be of service in improving the mentality of a FEEBLEMINDED CONGENITAL SYPHILITIC.

No attempt has been made in this section to give a per cent evaluation of the results of treatment in any one group of neurosyphilis. Two charts (charts 25 and 26), however, are appended which give an indication of some of our results. It seems to us, however, that it is too early to make any definite statements as to how far treatment will take us in the groups of neurosyphilis. We do feel decidedly, however, that many patients, in whatever group of neurosyphilis the diagnosis may place them, will respond to intensive systematic antisyphilitic treatment. =It is unfair to give an entirely grave prognosis in any case of neurosyphilis until the effect of treatment has been tried.=

In a separate section, entitled NEUROSYPHILIS AND THE WAR, we have presented fourteen cases selected from British, French and German writers in the war literature of 1914–16. Most of these cases were naturally somewhat inadequately reported under the critical conditions of literature made in the war. We present the cases for what they are worth: at all events they draw attention to the extraordinary interest of the neurosyphilis problem in relation to the war.

Such cases as A, one of tabes dorsalis apparently developing paresis by a process akin to shell-shock, is of value in the interpretation of the development of paresis in civil life. By “shell-shock” we commonly refer to a condition in which there is no actual traumatic injury of the brain. The hypothesis must be then that the explosion in some way indirectly caused an alteration of living conditions of the spirochetes, permitting the development of paresis.

Case B similarly seems to be a case in which a latent syphilis has turned shell-shock into tabes dorsalis.

Cases C, D, E bring up the question of aggravation of neurosyphilis by service and on service, respectively.

Case F likewise shows how, in the determination of amount of pension, the probable duration of the neurosyphilitic process is important.

Case G seems to show that war stress alone, without the emotional or physical effects of shell-shock, may kindle a latent syphilis into paretic neurosyphilis.

Case H similarly suggests that the “gassing” process may effect the same result.

Case I seems to show that the neuropathically tainted person may have latent epilepsy brought out through syphilis, the syphilis in this case having been acquired during the first summer of the war.

Case J was an interesting case of a syphilitic who, after the stress of the Battle of Dixmude, became an epileptic.

Syphilitic root-sciatica was developed in Case K at work in the war zone.

Case L is one of a civilian who apparently would not have developed paresis at precisely the moment when he did, if he had not been discharged as a German Jew from his long-held bank position in London.

Two cases, M and N, are cases of shell-shock, non-syphilitic; yet the picture of paresis in the one case and of tabes in the other was for a long time almost convincing to the examiners. They are better termed cases of pseudoparesis and pseudotabes, using the prefix “pseudo”, as usual, to signify a non-syphilitic imitation of the disease in question.

To sum up in the most general way the lessons of this book, we may emphasize again (1) the unity-in-variety of the phenomena of neurosyphilis, (2) the value of a hopeful approach to the therapy of all cases of neurosyphilis, even the paretic form, and (3) the value of applying syphilis tests to every case of neurosis or psychosis.

(1) RE unity-in-variety of neurosyphilitic phenomena.

The unity of these phenomena is confirmed, theoretically, by the common factor of spirochetosis: practically, by the Wassermann reaction, positive in serum or spinal fluid! Almost at this point the unity of phenomena ceases. Neither chronicity, nor evidence of mononuclear cell deposits, nor evidence of serious structural damage to the nervous system, nor presence of other positive tests than the W. R., nor existence of mental or nervous symptoms or signs, is a common feature of neurosyphilis. Sometimes the nervous system appears to harbor spirochetes in the most cordial manner as guest-friends (paresis sine paresi.) Again, perhaps as an expression of elaborate processes of immunity, the spirochetes take effect in relatively huge gummata. Sometimes the neurosyphilitic process rises as if by a regular process of siege from spinal nerve-root to spinal nerve-root (tabes dorsalis and diffuse neurosyphilis). Again, the nervous system is taken by storm, as it were (disseminated encephalitis). Very frequently the neurosyphilis is simply an indirect effect of blood-vessel disease, and huge masses of tissue are scooped out in necrosis with dependent secondary degenerations; and later the extinct lesions of vascular origin may or may not betray evidence of their syphilitic origin. Sometimes diffuse processes run on, apparently, with perfect fatalism to a mortal issue in a few years both with and without treatment. Again treatment appears to accomplish much (see fuller discussion under 2). The laws governing the preference of processes to lodge in membranes, vessels, and parenchyma, and in all combinations of these, have not been worked out. Hardly a case of neurosyphilis, properly studied ante mortem and post mortem, but would throw important light on our medical approach to one of the great problems of civilization, the problem of syphilis as a whole.

(2) RE value of a hopeful approach to the therapy of neurosyphilis.

The prognosis of neurosyphilis is not worse than that of the chronic diseases in general. In fact, the prognosis of neurosyphilis quoad vitam is either good or dubious, certainly not bad. The surprising reversals of form which the spirochete shows in certain remissions are always to be awaited. Treatment of neurosyphilis has certainly effected amazing results, not so much by way of Ehrlich’s therapia sterilisans magna as by means of systematic intensive treatment. Even paretic neurosyphilis (general paresis) seems to have been cured. Preparetic phases are theoretically hopeful. Nor is it so certain that paretic neurosyphilis will ultimately prove a perfectly distinct species of neurosyphilis. General paresis seems to us at least to be more closely related to diffuse neurosyphilis than is tabes dorsalis to diffuse neurosyphilis. In any particular case, moreover, =during a good part of the early months or years=, =it is difficult or impossible to tell the paretic from the non-paretic forms of diffuse neurosyphilis by any combination of clinical observations and tests=. In the instance of more protracted neurosyphilis, e.g., tabetic, the outlook for vascular complications is such that antisyphilitic treatment directed at prevention of these complications is scientifically warrantable, even if the tabetic process itself proves unassailable. The old distinction of syphilis and parasyphilis, so striking and apparently satisfactory when introduced by Fournier, seems to be a false distinction which should be dropped. Therapeutically, we should approach all cases of neurosyphilis without bias or nihilistic prejudgments.

(3) RE universal applicability of syphilis tests in nervous and mental cases.

The importance of putting every neurosis or psychosis through syphilis tests is not based alone on the frequency of neurosyphilis, though neurosyphilis is surely frequent enough. The importance of universally applying these tests is established by the experience of lingering doubts both in the physician’s mind and (nowadays increasingly) in the patient’s and friends’ minds, so long as these tests are not applied. Nor should the positive serum Wassermann reaction fail to be followed by lumbar puncture and appropriate tests. The general practitioner confronting neuroses or psychoses—and what practitioner does not?—must not expect valuable results from consultation with neurologists and psychiatrists when he does not carry to these specialists the results of at least the serum W. R. in his patient. Not only are practitioners, specialists, and patients subject to discomfiture on the eventual and delayed proof of syphilis or neurosyphilis, but valuable time has been lost to treatment. How often the physician of yore (and really not so long since) had to be regarded as an eccentric virtuoso if he tested urine as routine! Well, for routine use in nervous and mental diseases, the Wassermann serum reaction is at least as important as urinalysis. Nor would we cease our homily with the general practitioner. We know neurologists and psychiatrists who use the Wassermann test only when it is likely to be positive! But they are dying out.

APPENDIX A

In appendix A a brief outline is given of the six tests (W. R. on blood serum and spinal fluid, cell count, globulin test, albumin test, gold sol test). This is not intended as a complete working manual but rather as indicating the methods used in diagnosis in the cases presented herein. For more complete details the reader may be referred to textbooks on the subject of serology, among which may be mentioned Kaplan: “Serology of the Nervous System”; Plaut, Rehm and Schottmüller: “Leitfaden zur Untersuchungen der Zerebrospinalflüssigkeit”; Kolmer: “Infection, Immunity and Specific Therapy,” and, for the Wassermann technique, an article by Dr. W. A. Hinton in M. J. Rosenau’s “Preventive Medicine and Hygiene.”

Our own W. R’s. have been performed at the Wassermann laboratory of the Massachusetts State Board of Health (formerly the Neuropathological Testing Laboratory, Harvard Medical School), under the supervision of Dr. W. A. Hinton. The other tests are performed at the Psychopathic Hospital. It is very important that a close relationship should exist between the clinician and the Wassermann laboratory if the most is to be obtained from the reactions. This relationship has been effectively close between the authors and the above-mentioned laboratory; and has enabled us to get very much clearer ideas about certain cases than could otherwise have been obtained.

=Cell Count.= In order to obtain the number of cells per cmm., the examination should be made of the fresh fluid as soon as possible after this is withdrawn. The most convenient counting chamber for this purpose is the so-called Fuchs-Rosenthal counting chamber, the ruled spaces of which contain slightly over 3 cmm. (an ordinary blood cell counting chamber may be used). According to the method used by us the cells are stained in a pipette with Unna’s polychrome methylene blue. Using a white-counting pipette, stain is drawn up to the first or second marking and the remainder of the pipette filled with spinal fluid. This makes no change in the dilution for practical purposes. After two or three minutes the staining is satisfactory and the counting may be done. With this stain a differential count may be made. Plasma cells stain a lavender as contrasted to the blue of the lymphocytes. The characteristic halo surrounding the eccentric nucleus is visible. The blood cells do not assume color with this stain; hence it is unnecessary to add any acetic acid.

For permanent preparations, and more accurate differential counts of the spinal fluid, the Alzheimer method may be used. The technique is given in a paper by H. A. Cotton and J. B. Ayer as follows:

1. Lumbar puncture in the usual manner.

2. 96% alcohol, in proportion to twice the amount of cerebrospinal fluid, is added drop by drop and well mixed.

3. Centrifuge the mixture for one hour at high speed in a glass tube with conical end. (An ordinary electric urinary centrifuge apparatus can be employed, the tube to be well stoppered to prevent evaporation.)

4. The supernatant fluid is poured off, leaving a small coagulum in the bottom of the tube.

5. Add absolute alcohol—alcohol and ether—ether, each separately for one hour, to dehydrate and harden coagulum.

6. The coagulum can now be gently loosened from the bottom of the tube by a long needle. The tube is then inverted, and the coagulum allowed to fall into the hand by a quick tap on the end of the tube. Care must be taken not to squeeze or handle the coagulum. The hand is placed over a small homeopathic vial, containing thin celloidin, and the coagulum allowed to drop into the celloidin, where it remains over night (twelve hours usually).

7. Coagulum is placed in thick celloidin which is allowed to evaporate slowly. It is then mounted on blocks and sections cut 14µ in thickness.

8. The sections are stained and mounted according to the following procedure:

(a) Remove celloidin by absolute alcohol and ether.

(b) 80% alcohol.

(c) Water.

(d) Sections are carried on glass or platinum needle into a dish of Pappenheim’s pyronin-methyl green stain and kept in a water bath at 40° C. five to seven minutes.

(e) Quickly cool dish in running water.

(f) Wash off superfluous stain in plain water.

(g) Absolute alcohol to differentiate—until no more stain comes away from section.

(h) Clear in Bergamot oil.

(i) Mount in balsam.

The normal cell count may be stated as being up to 6 cells per cmm.; from 6 to 12 cells may be considered as suggestive of pathological condition and more than 12 cells per cmm. as definitely pathological. The type of cell in syphilitic diseases is preponderantly the small lymphocyte. A low percentage, that is, very rarely over 20%, of large lymphocytes, endothelial phagocytic cells, polymorphonuclear leucocytes and plasma cells may also be found. The finding of plasma cells in any number in the spinal fluid is suggestive although not conclusive evidence for the diagnosis of paretic neurosyphilis.

=Globulin= is an albumin which is precipitated by half saturation with a salt. A very simple and satisfactory test is known as the Nonne-Appelt test, which has been modified by Ross-Jones. Into a test tube of small diameter, run 1 cc. of spinal fluid. Place under this fluid with a pipette, 1 cc. of a saturated solution of ammonium sulphate ((NH{4}){2}SO_{4}). If any globulin is present a white, sharply-defined ring will form at the junction of the two fluids. According to our readings, a ring that is just visible with the aid of a black background is called 1+, a ring that is just visible without the black background, 2+; a ring easily perceptible, 3+ and a relatively very heavy ring, 4+. On shaking the tube, if globulin is present, the fluid will show turbescence.

Another simple globulin test used in our laboratory as a check on the Nonne-Appelt test is the Pandy test. A few cc. of a clarified 10% solution of phenol are placed in a watch glass. One drop of spinal fluid is run into this solution. A milky turbescence indicates globulin.

The presence of globulin in the spinal fluid is always an indication of abnormality of the cerebrospinal axis. There is nothing differential in this finding as it occurs in all inflammatory processes. However, it is characteristically present in most cases of neurosyphilis (exception to the rule: the pure vascular type does not show globulin in a very high per cent).

=Albumin Test.= Albumin in small quantities is present in all spinal fluids. Increase over the normal amount occurs in pathological conditions such as most cases of neurosyphilis, especially in those in which globulin is found. Any albumin precipitant may be used for rough clinical calculation, comparing the amount of precipitate with that from the normal fluid. Our method is to place 1 cc. of spinal fluid in a small test tube of about 5 mm. diameter and to precipitate the albumin by the addition of 3 drops of 33⅓% of trichloracetic acid. This test has its chief value as confirmatory of the globulin test, since in the vast majority of instances where globulin is found there will also be found an increase in albumin.

The =Gold Sol Reaction= is an empirical test discovered by Carl Lange in the utilization of the work of Zsigmondi with solutions of colloidal gold and albumins. Briefly the details of the test are as follows:

Ten tubes are set up in a rack. To the first tube 1.8 cc. of a 0.4% of salt solution is added and to each of the following tubes 1 cc. of this solution. Then to the first tube containing 1.8 cc. of salt solution one adds 0.2 cc. of the spinal fluid to be tested. This gives a dilution of 1 to 10. From this tube 1 cc. is pipetted into the second tube and this process continued through the ten tubes. This gives dilutions of spinal fluid of 1 to 10, 1 to 20, 1 to 40, etc., to 1 to 5120 in the last tube. Then 5 cc. of colloidal gold solution is added to each tube. A positive reaction is indicated by the precipitation or throwing down of the colloidal gold into its metallic form. This produces a change in color. This precipitation may be partial or complete and the amount of precipitation is indicated by the color and is read as follows:

The unchanged fluid is called 0; a slight change giving a red-blue as 1; a further change giving a blue-red as 2; a straight blue as 3; a lavender or violet as 4; and the colorless fluid representing complete precipitation as 5. The numbers are placed in a row, indicating the tube in which the color occurs. The fluid from a case of paretic neurosyphilis will give a complete precipitation beginning in the first tube and running through a number of tubes and then grading off. It may be indicated 5 5 5 5 4 3 1 0 0 0. The characteristic reaction of fluids from tabetic and diffuse neurosyphilis is less strong than from the paretic. The greater part of the reaction will take place, however, in the first five tubes, but as a rule it will not begin very strongly in the first two. A characteristic reaction is 1 2 3 3 2 1 0 0 0 0. Another reaction that may be considered characteristic of the tabetic or diffuse form is 3 3 3 2 1 0 0 0 0 0. Fluids from non-syphilitic cases as a rule give a reaction having its greatest intensity beyond the fifth tube, that is, in the high dilutions.

A reaction characteristic of brain tumor or tuberculous meningitis is 0 0 0 0 1 3 3 2 1 0.

The conclusions that may be drawn from the gold sol reaction have been summarized by one of the authors as follows:

1. Fluids from cases of general paresis will give a strong and fairly characteristic reaction, especially if more than one sample is tested, in the vast majority of cases.

2. Very rarely a general paresis fluid will give a reaction weaker than the characteristic one.

3. Fluids from cases of syphilitic involvement of the central nervous system other than general paresis often give a weaker reaction than the paretic, but in a fairly high percentage of cases give the same reaction as the paretics.

4. Non-syphilitic cases may give the same reaction as the paretics; these cases are usually chronic inflammatory conditions of the central nervous system.

5. When a syphilitic fluid does not give the strong “paretic reaction,” it is good presumptive evidence that the case is not general paresis; and this test offers a very valuable differential diagnostic aid between general paresis, tabes and cerebrospinal syphilis.

6. The term “syphilitic zone” is a misnomer, as non-syphilitic as well as syphilitic cases give reactions in this zone; but no fluid of a case with syphilitic central nervous system disease has given a reaction out of this zone (test thus valuable negatively). Any fluid giving a reaction outside of this zone may be considered non-syphilitic.

7. Light reactions may occur without any evident significance, while a reaction of no greater strength may mean marked inflammatory reaction.

8. Tuberculous meningitis, brain tumor and purulent meningitis fluids characteristically, though not invariably, give reactions in higher dilutions than syphilitic fluids.

9. The unsupplemented gold sol test is insufficient evidence on which to make any diagnosis, but used in conjunction with the Wassermann reaction, chemical and cytological examinations, it offers much information looking toward the differential diagnosis of general paresis, cerebrospinal syphilis, tabes dorsalis, brain tumor, tuberculous meningitis, purulent meningitis.

10. We believe that no cerebrospinal fluid examination is complete for clinical purposes without the gold sol test.

The =Wassermann reaction= as carried out in the Wassermann Laboratory is based on the principles of the original method—the only essential modification consists in the employment of cholesterinized alcoholic extracts of human hearts as antigen instead of aqueous extracts of foetal livers from cases of congenital syphilis. Experience has shown that properly standardized antigens made from human hearts are much more sensitive in the detection of true cases of syphilis.

=Antigens.= Three antigens are used, each being an alcoholic extract of human heart which is saturated at room temperature with cholesterin. These antigens differ slightly in their sensitiveness. Before the test is made each antigen is diluted with 0.85% salt solution in the proportion of four parts of the cholesterinized antigen extract to sixteen parts of 0.85% salt solution. The amount to be used, the dosage, is carefully determined by testing each antigen against a large number of known positive and known negative specimens of blood. The dosage of the antigens employed is less than one-half the amount which inhibits hemolysis when the antigen is incubated for one hour with the hemolytic system which consists of complement, amboceptor and cells in the proper proportions. These antigens are designated as A, B, and C. Antigen A is the most sensitive. B and C are very similar to each other quantitatively and qualitatively.

=Specimens to be tested.= The serum which separates from the clot is withdrawn, centrifugalized if necessary, and then heated at 55 degrees for thirty minutes. 0.1 cc. of serum is used in the test and 0.2 cc. of each specimen is used as a control to exclude the presence of anti-complementary substances. Spinal fluids are tested in two ways. As a routine 0.5 cc. of the spinal fluid is used in the test and 1.0 cc. is used in the control; or when especially requested spinal fluids are titrated by using respectively 1.0, 0.7, 0.5, 0.3, and 0.1 cc. of the spinal fluid for each test and 1.0 cc. of spinal fluid for the control. Spinal fluids are not inactivated.

=Complement.= The complement is obtained from the serum of guinea pig’s blood. No complement is used when older than eighteen hours. A 10% solution and 0.85% salt solution is used in the test. The amount used is twice the minimum quantity necessary to hemolyze the sensitized cells.

=Sheep’s Corpuscles.= A 5% suspension of sheep’s corpuscles in 0.85% salt solution is prepared from defibrinated sheep’s blood. The corpuscles are washed three times and for each washing four to five times as much 0.85% salt solution is used as the original volume of the defibrinated blood.

=Amboceptor.= The amboceptor is prepared by injecting sheep’s corpuscles into a rabbit. The serum of this rabbit which contains amboceptor is diluted with 0.85% salt solution so that 0.25 cc. will hemolyze 0.5 cc. of a 5% suspension of sheep’s corpuscles. In the test twice the quantity or 0.5 cc. of amboceptor is used.

=Sensitized Cells.= The sensitized cells consist of equal parts of washed sheep’s corpuscles and diluted amboceptor. This mixture is incubated in a water bath at 37° C. for a half hour to effect the sensitization of the cells.

=Technique of the Wassermann Test.= One-tenth cubic centimeter of each inactivated specimen of serum and 0.5 cc. of each uninactivated specimen of spinal fluid is pipetted into a separate tube. A mixture is freshly prepared in salt solution, each cubic centimeter of which contains the proper amount of antigen A (the most sensitive antigen), and two units of a 10% solution of guinea pig serum (complement). One cubic centimeter of this mixture is pipetted into each test tube. These tubes are then incubated for forty minutes in a water bath at 37° C. At the end of this period, sensitized cells are added, and the tubes are again incubated in a water bath at 37° C. for one hour. Each specimen which shows any degree of inhibition of hemolysis is retested in the afternoon. For this second test antigen A is again used and in addition antigens B and C. A control is also made for each specimen retested to eliminate any possibility of the inhibition of hemolysis being due to anti-complementary substances in the serum or spinal fluid tested. The technique of the second test differs in no wise from that of the first, except for the use of a control in each retested specimen and the employment of three antigens instead of one. The degree of positiveness is noted for each retested specimen and compared with the degree of positiveness obtained for the corresponding specimen with the same antigen-complement-salt solution mixture in the morning’s test. The specimen is retested on the next day when discrepancies occur between the morning reading for antigen A and the afternoon reading for antigen A. From the above description it will be noted that the negative specimens have but a single test with one antigen only, while the positive specimens are retested, thus permitting a confirmation of any positive reaction. In this way attention is focalized on the positive specimens.

=Interpretation of Results.= Antigen C (the weakest of the three antigens) is used entirely for diagnostic purposes and any specimen showing the slightest degree of inhibition with this antigen and stronger degrees of inhibition with the other antigens is reported as positive. The specimens which are strongly or moderately positive with antigens A and B and negative with antigen C are reported as doubtful. In testing spinal fluids by the titration method, antigen C is used and the readings are based upon the degree of inhibition of hemolysis noted. The intensity of this inhibition is indicated by Arabic numerals: “5” indicates complete inhibition, while “1” means a faint cloudiness, hence a weak reaction. Intermediate numbers show relative intensity varying between complete inhibition “5” (strong positive) and slight inhibition “1” (weak positive); “—” equals no inhibition (negative).

Although it is commonly believed that the recent administration of antisyphilitic treatment will affect the reaction by making it negative, this is not our experience, and it is, therefore, not necessary that treatment be withdrawn for a short period before the specimen is submitted for examination.

The reaction as carried out in this laboratory has the following diagnostic significance: =Positive indicates syphilis=, except very rarely in acute febrile conditions such as malaria and pneumonia. =Negative does not exclude syphilis.= In obscure conditions a series of less than three negatives has little diagnostic significance. =Doubtful suggests syphilis.= It is therefore advisable to submit three or more specimens in such a case, and interpret a persistently or predominatingly doubtful reaction as indicative of syphilitic infection.

=Bruck Test.= A new serum test for syphilis has recently been described by C. Bruck. Following are recent results in our laboratory with this test.

This new test for the diagnosis of syphilis by C. Bruck has aroused much interest. The scientific standing of Bruck and the simplicity of the technique led us to overcome our prejudice, that has been the offspring of the numerous tests that have been offered of late. Bruck states that since the discovery of the complement fixation test for syphilis by Wassermann, Neisser and himself in 1906, he has been trying to find a simple chemical reaction that would take the place of the complicated technique of the Wassermann reaction. This method, as he has published it, was worked out and is being used at the front, in the present war, where complete laboratory equipment is not available.

Commencing our experiments with a great deal of scepticism, we were much surprised at the results obtained, which are given below. Whatever may be the final status of the test in the determination of syphilis, we feel that there is a great deal of interest in the fact that this simple chemical reaction does pick out certain differences in the composition of blood sera and that apparently a large number of syphilitic sera differ in their chemical composition percentage from the majority of non-syphilitic sera.

The technique, while exceedingly simple, offers many chances for errors and individual variations so that we have thought it well to give directions and cautions at some length.

Bruck’s technique is described as follows: “The test is made with 0.5 cc. clear serum in a test tube, to which is added 2 cc. of distilled water, and the whole shaken. Then, with a precision pipette, 0.3 cc. of the ac. nitr. purum of the German pharmacopeia is added and the whole thoroughly shaken and then set aside at room temperature for ten minutes. Then 16 cc. of distilled water at room temperature is added, and closing the tube with the finger, it is shaken up and down three times carefully, not vigorously enough to make it foam. This is repeated ten minutes later, and the tube is then set aside for half an hour. By this time the precipitate is entirely dissolved in the tube with the normal serum, while the syphilitic serum shows a distinct, flocculent turbidity. In two or three hours, or better still, in twelve hours, the gelatinous and characteristic precipitate is piled up on the floor of the test tube.”

The acid is prepared by diluting the Acidum nitricum of the U. S. P. (Sp. gr. 1.403) with distilled water until the hydrometer shows the specific gravity 1.149, which corresponds to the nitric acid of the German pharmacopeia, but since this requires a special hydrometer, a simpler method is to make a 25 per cent solution of the Acidum nitricum, which will give about the proper specific gravity.

The serum is obtained by allowing 10 cc. of blood to stand at room temperature for an hour, and then centrifuging. Serum that has stood for some time may be used as well as the fresh, and even bloody serum does not seem to confuse the results to any great degree. The serum gives the same results with or without inactivation. Post mortem blood gave results as constant as that obtained during life, in the few cases that we had in this series. But the reaction may be influenced markedly by the size of the test tubes. We have found that the 13×1.9 cm. is the most favorable size.

When one first thinks of this test it appears very simple and probably somewhat crude as a chemical reaction, but there are certain precautions that must be observed, and several hundred normal and syphilitic sera should be tried before the investigator can feel that he has a refined routine technique. There is the personal equation which must be watched, for here is probably the greatest source of error, and readily explains why two different persons get widely varying results with the same sera if they have done only a few dozen tests. We must take it for granted that the reaction is a quantitative one, where some positive reactions may differ only slightly from the normal non-syphilitic, and, furthermore, any normal serum may be made to give a positive reaction, and almost any positive serum be made to give a negative by improper manipulation at some point in the test. There are as many places for error to creep in as there are steps in the process. Bruck has omitted many details in his publication, which allow personal variations, and so we have tried to develop a routine process that will eliminate as many of these as possible.

We shall here attempt to explain the methods which we have found most satisfactory and at the same time indicate the places where error is likely to occur. The 0.5 cc. of serum is added to 2 cc. of distilled water, and shaken thoroughly. Now add slowly exactly 0.3 cc. of acid from a precision pipette, care being taken it does not flow down the side of the tube. The tube should be shaken gently while the acid is being added, for this prevents the formation of a flocculent precipitate in normal serum which is difficult to dissolve later. After the acid is added shake each tube gently to make sure that these flakes do not persist. It is difficult to shake each tube in exactly the same manner, as must be done if we expect uniform results.

The first 250 tests of this series were made by allowing the tubes to stand for ten minutes as Bruck advocates. Then we found that practically all sera gave a positive reaction if allowed to stand 15–20 minutes, and so in the other tests of the series an attempt was made to make the reaction more sensitive by allowing the tubes to stand only 6–7 minutes. During this time the tubes should be shaken gently once or twice. The manner in which the 16 cc. of water is added also influences the reaction. If allowed to flow freely in upon the precipitate, the positive may be forced into solution as well as the negative. Both pipette and tube should be slanted and the water allowed to flow down the side of the tube without disturbing the precipitate. If all has gone well up to this point, we may see a marked difference between the normal and syphilitic precipitates, in that the normal will begin to go into solution at once, thus clouding the water, while a positive precipitate will be composed of large flakes which show little or no tendency to go into solution or cloud the water above. It must be remembered that the most flocculent positive precipitate will go into solution if the fluid is splashed or shaken too hard while the tube is being inverted. If any doubt as to the character of the precipitate now exists, it may be allowed to stand ten minutes longer, and again inverted as before, or even repeated several times during the next hour or two. We see no reason why the tubes should be left to stand over night, for during this time a precipitate usually settles in the normal tubes. This, however, differs from the syphilitic precipitate in that it is still finely granular and goes back into solution readily when the tubes are inverted.

In view of these possible grounds for error, it is only logical to run controls of known positive and known negative sera along with each group of unknown bloods, and even then certain tubes will seem doubtful, in which event the test should be repeated with added precaution to see if a definite positive or negative reaction may be obtained.

In the last tests of this series we seemed to aid the reaction by rendering the serum-water solution alkaline by one or two drops of 10 per cent potassium hydroxide before the acid was added. The positive sera have a larger precipitate, while the normal seem to dissolve more readily.

TABLE I

Syphilis: nervous system involved.

General Paresis Wassermann and Bruck agree positively 47 Wassermann and Bruck agree negatively 7 Wassermann and Bruck at variance 10

Tabes Dorsalis Wassermann and Bruck agree positively 3

Cerebrospinal Wassermann and Bruck agree positively 8 Wassermann and Bruck agree negatively 3

Juvenile Paresis Wassermann and Bruck agree positively 1

Summary: Wassermann and Bruck agree positively 59 Wassermann and Bruck agree negatively 10 Wassermann and Bruck at variance 10

TABLE II

Syphilis: nervous system not involved.

Syphilis Wassermann and Bruck agree positively 12 Wassermann and Bruck at variance 5

Congenital Syph. Wassermann and Bruck agree positively 3 Wassermann and Bruck agree negatively 2

Summary: Wassermann and Bruck agree positively 15 Wassermann and Bruck agree negatively 2 Wassermann and Bruck at variance 5

TABLE III

Non-syphilitic: Wassermann reaction negative. Doubtful or positive Bruck 86 Bruck test negative 216

Total for three groups: Wassermann and Bruck agree positively 74 Wassermann and Bruck agree negatively 230 Wassermann and Bruck at variance 101

The tests here reported were made on blood sera obtained from patients admitted to the Psychopathic Hospital and its Out-Patient Department. As a routine Wassermann test is made on each patient who enters the hospital, it was only necessary to take another tube of blood from each patient, and check the results in each instance with the Wassermann reaction. As it takes several days to get the report from the Wassermann laboratory of the State Board of Health, there was no chance of being prejudiced by a previous knowledge of the Wassermann reaction. The cases for the most part were those of mental disease; the majority in good general physical health.

A comparison of the total number with the Wassermann reaction shows that there was a general agreement of 304 of the 405 cases tested, or a percentage agreement of practically 75%. In considering the cases of syphilis of the central nervous system in a group by themselves, we find that the agreement is closer, since 69 of the 79 cases tested, or 87% agreed without any question of doubt. It will be noted that in several cases of general paresis, the Wassermann reaction, which was repeated at intervals, was negative, and in most of these cases the Bruck test was negative also. Our few cases of congenital and latent syphilis also checked very closely with the Wassermann test. In the various groups of mental cases in this series, no factor of interference was discovered. It is also of interest that in the cases where the blood was obtained post mortem, the Bruck test agreed with the Wassermann result obtained on ante mortem blood serum. Further work on post mortem sera will be reported. Some of the patients not included in the syphilitic groups that have a negative Wassermann and no clinical signs of syphilis, give a history of previous infection at some time, which might partly account for the variations in the two tests.

CONCLUSIONS

1. We present results of the Bruck sero-chemical test in 405 cases. In 101 of these cases there were definite clinical manifestations of syphilis, in which the Wassermann and Bruck tests agreed positively in 74 or 75%. The two tests agreed negatively in 12 instances, and were at variance in 15.

2. In the group which showed syphilis of the nervous system we had 64 cases of clinically certain general paresis, of which the Wassermann and Bruck tests agreed in 54 instances, or practically 85%. In other forms of central nervous system involvement the agreement was 100% in the 15 cases tested.

3. In the cases with no apparent involvement of the nervous system the agreement was somewhat less, being 76%. This may be in keeping with the fact that the Wassermann test was not so strongly positive in these cases.

4. The advantages of the test are: (1) the short time required to do the test; (2) the limited amount of apparatus necessary, and (3) the simplicity of the technique.

5. The disadvantages of the test seem, for the most part, to be bound up in the personal variations that are apt to occur.

6. We are here dealing, most probably, with a quantitative chemical difference in the protein content of syphilitic and non-syphilitic sera, the nature of which is not understood by us. It is our hope that this may be brought to light in the near future in the field of chemistry.

APPENDIX B COMMON METHODS OF TREATMENT USED IN CASES OF NEUROSYPHILIS

The =treatment for neurosyphilis= according to the viewpoint of the authors =is treatment for syphilis=. It is necessary in order to cure a case of neurosyphilis to cure the syphilis in the patient. Accordingly, the methods of treatment best adapted for the cure of syphilis are indicated in the treatment of neurosyphilis. As experience shows that it is often more difficult to cure the neurosyphilitic cases, treatment will have to be pushed with greater intensity than in some non-nervous system syphilis. In general, then, the methods that have been applied by the syphilologist will be used in the treatment of cases of neurosyphilis. In addition, methods attempting to bring the drug into local contact with the central nervous system have been devised. The methods of treatment have been in part indicated in Chart 27.

The method chiefly used in treatment of the cases of this book is what we have called =intensive systematic intravenous treatment=. The treatment consists of intravenous injections of salvarsan (or a substitute for salvarsan, as arsenobenzol and diarsenol) given in a dose of about 0.6 gram and repeated twice a week over a period of a number of months. In addition, injections of mercury salicylate averaging 0.065 gram once a week are given and potassium iodid by mouth. As indicated, the important point is to keep up treatment for a long period of time. This method has produced practically no untoward results, certainly no more untoward results than are to be expected with salvarsan in smaller quantities and it has seemed to us that the therapeutic results have been as satisfactory as in any other form of treatment.

Specialized forms of treatment intended to place the drug in contact with the central nervous system may be described under the headings of =spinal intradural treatment= and =cerebral subdural= and =intraventricular treatment=.

Three main therapeutic agents have been largely used. These are (1) salvarsanized serum according to the =method of Swift-Ellis= (=in vivo=). The serum according to this method is prepared as follows: An intravenous injection of salvarsan is given to a patient and blood withdrawn at the end of one-half hour. This is allowed to clot. The serum is removed and after inactivation at 56° C. for one-half hour it is ready for use. The average dose is 15 to 30 cc. of serum. As a matter of fact, it is not necessary to use the blood serum from the same patient to whom the intraspinous injection is to be given. (2) The salvarsanized serum according to the =method of Ogilvie= (=in vitro=). Blood serum is prepared from any patient and to it is added salvarsan in such a strength that the amount to be injected, 10 to 30 cc. of serum, will contain 0.0001 to 0.001 gm. (3) Mercurialized serum according to the =method of Byrnes=. Mercury bichloride is added to blood serum in such proportion that the amount of serum to be injected will contain from 0.00065 gram to 0.0026 gram.

The method of intraspinous injection is to perform lumbar puncture, withdraw an amount of fluid approximately equivalent to the amount to be injected; then allow the serum to be injected to run in by gravity.

For the =cerebral=, =subdural and intraventricular= injections, the same sera may be used as for the intraspinous. Five or six times as much salvarsan may be given, but a smaller amount of serum may be advisable, that is, 10 to 15 cc. To perform injections a trephine opening is made in the calvarium about the size of a dime. The location of choice for the opening is slightly back of the longitudinal prominence just to the right of the median line, to avoid the frontal sinus. For subdural injections a curved needle is thrust between the dura and the brain and the serum allowed to flow in slowly by gravity. For the intraventricular injections a blunted spinal puncture needle is thrust through the brain substance into the 3rd ventricle. When the 3rd ventricle is reached the clear cerebral fluid will flow out; then after withdrawing a sufficient amount, the serum may be introduced by gravity. The trephining may be done under local anesthesia but as a rule it is better to induce general anesthesia. The subsequent injections can be made without recourse to any anesthesia whatsoever, as they are practically painless.

All procedures both in the injections and in the preparation of sera are naturally to be performed under aseptic conditions.

INDEX

Abscess, tonsillar, associated with neurosyphilis, 250.

Addison’s disease in juvenile paretic, 279.

Agraphia, 101.

Albumin test, 474.

Allbutt, Clifford, 257.

Alcoholism, chronic, 227.

Alcoholic dementia, 237. epilepsy, 229. hallucinosis, 225. pseudoparesis, 222, 223, 451.

Allergie, 129, 204.

Alzheimer, 428. method, 472.

Amboceptor, 477.

Amnesia, 195.

Anaphylaxis, 129.

Anatomical formulae, 25.

Antigens, 476.

Aortic aneurysm, 35, 439.

—— sclerosis, 41, 46, 135.

Aphasia, 31, 43, 101, 262, 445.

Apoplexy, 197.

Argyll-Robertson pupil, 209, 212, 217, 291, 450. as isolated symptom, 217. in alcoholism, 214, 229.

Arndt, Junius and, 249.

Arsenobenzol, 375, 377, 389, 486.

Arteriosclerosis, cerebral, 101. not a contraindication to intensive salvarsan therapy, 359. radial, 68.

Ascending lesion, 23.

Asymmetrical lesions, 19.

Ataxia, 31, 223.

Atheromatous degeneration, 35.

Atrophy, cerebellar, 39. cerebral, 47, 134, 205. parenchymal, 41. pontine, 39.

Atypical case congenital neurosyphilis, 270.

Ayer, J. B., 472.

Ballet, 72.

Barrett, A. M., 54, 175, 187, 212, 218, 219.

Bechterew, 219.

Binet and Simon, 304.

Binet scale, 277.

Birnbaum, 403.

Blood pressure, high, 70, 262, 124.

Bly, 252.

Bonhoeffer, 404, 415, 417.

Bordet, 427.

Bratz, 278.

Bruck test, 479.

Bruck, C., 479.

Bumke, 214.

Canavan, 256. and Southard, 70.

Cell count, 471.

Cerebral syphilis, see diffuse neurosyphilis.

Cerebrospinal syphilis, see diffuse neurosyphilis.

Cervical hypertrophic meningitis of Charcot, 56, 441.

Chancre, extragenital, 75, 342.

Character change, neurosyphilis, 314.

Charcot, 60, 186.

Choroiditis, 242.

Christian, 407.

Cimbal, 403.

Civilization and syphilis, 76.

Clinical evidences of syphilis, 131.

Clouston, 158.

Collins, Joseph, 145.

Compensation in neurosyphilis, 309, 402, 456.

Complement, 477.

Conduct disorder, 38.

Congenital syphilis, absence of stigmata, 318. as cause of feeblemindedness, 159, 447. involvement of nervous system in, 274.

Congenital neurosyphilis, 270, 395. resembling feeblemindedness, 272.

Conjugal neurosyphilis, 263.

Convulsions, 43, 101, 248, 362. cause of in paretic neurosyphilis, 232. in psychopathic subject with syphilis, 417.

Corneal opacity, syphilitic, 234.

Cotard, 73.

Cotton, H. A., 472.

Craig, C. B., 152, 196.

Cramer, 125.

Cranial neurosyphilis, 140. tenderness, 139.

Crises, gastric, 367.

Cysts, ependymal, 59. of softening, 27, 36, 54.

Cytorrhyctes luis, 381.

Dana, Charles L., 65, 77, 78.

Dazed states, 264.

Deafness, 63.

Decompression, 138.

Defective delinquent—diffuse neurosyphilis, 300, 455.

Dejerine-Tinel, 61.

Delinquency and juvenile neurosyphilis, 298.

Delirium tremens, 332.

Dementia, 137.

Dementia paralytica, see paretic neurosyphilis.

Dementia praecox, 74, 185, 247.

Depression, 95, 126.

Depressive drugs, 189.

Diabetes, and neurosyphilis, 240. insipidus, 190.

Diabetic pseudoparesis, 238.

Diarsenol, 377, 389, 391, 486.

Differential diagnosis, alcoholism and neurosyphilis, 227, 231, 234, 236. brain tumor, diabetic pseudoparesis and neurosyphilis, 238. diffuse and paretic neurosyphilis, 165, 193, 247. manic-depressive psychosis and neurosyphilis, 69. multiple sclerosis and neurosyphilis, 253, 255. neurasthenia and neurosyphilis, 65, 183. senile arteriosclerotic psychosis and neurosyphilis, 262.

Diffuse neurosyphilis, cerebrospinal syphilis, cerebral syphilis, spinal syphilis, 17, 80, 85, 97, 103, 122, 140, 183, 193, 300, 331, 342, 359, 433, 439, 443. premonitory symptoms, 342. prognosis, 80, 103, 124, 433, 443. spinal fluid findings in, 348. symptoms, 99. treatment, 98, 103, 184, 302, 390. treatment, results, 343.

Diplopia, 50, 184, 253, 356. causes, 140.

Donath, 401, 403.

Drastich, 407.

Duco and Blum, 403.

Dupré, 407.

Dysdiadochokinesis, 231.

Ehrlich, 184, 428, 429.

Encephalitis, 27, 248. disseminated, 218.

Endarteritis, 220.

Ependymal cysts, 59.

Ependymitis, 40, 47, 49, 134.

Epilepsy, 192. alcoholic, 229. brought out by syphilis, 415. Jacksonian, 103. parasyphilitic, 194. relation to juvenile neurosyphilis, 277. syphilitic, 103, 194. syphilogenic, 415.

Epileptic neurosis, 195.

Erb’s syphilitic spastic paraplegia, 147. treatment of, 148.

Euphoria, 73.

Excited states, 95.

Exner, M. J., 416.

Exophthalmic goitre, syphilitic (?), 205.

Extraocular palsy, 140, 441.

Eye changes in neurosyphilis, 257.

Eye muscles, paresis of, 17, 50.

Facial paralysis, 53.

Families of neurosyphilitics, 275, 316, 318, 320, 373, 431, 457.

Family of neurosyphilitic, normal-looking, but syphilitic, 318.

Familial syphilis, 299, 306.

Farrar, C. B., 411.

Fearnsides, Head and, 21, 140, 150, 193, 217, 374, 378.

Feeblemindedness, 395. and congenital syphilis, 159.

Fernald, W. E., 159, 273, 396.

Fildes, McIntosh and, 129, 329.

Focal changes, 221. meningitis, 50. softenings, pontine, 54.

Fournier, 142, 222, 186, 194, 381.

Franz, 357.

Froissart, 413.

Fugue, hysterical, 264.

Garnier, 407.

General paresis, see paretic neurosyphilis.

Glands, 270.

Gliosis, 39, 47, 49, 136, 180.

Globulin, 229. tests, 473.

Glycosuria, 238, 241.

Goddard, 397.

Gold sol reaction, 247, 474. in brain tumor, 100. paretic, 85, 98. paretic, other tests negative, 383, 385. in purulent meningitis, 100. syphilitic, 85, 98, 345.

Graham, Thomas, 429.

Grandiosity, 72, 295, 455.

Graves, W. W., 157.

Grilli, 407.

Gross, 257.

Gumma, see gummatous neurosyphilis.

Gumma of tonsil, 250.

Gummatous neurosyphilis, 53, 56, 137, 138, 140, 221, 362, 438.

Hallucinations, 53. in paretic neurosyphilis, 249.

Hauptmann, 348.

Head and Fearnsides, 21, 140, 150, 193, 210, 217, 374, 387.

Headache, 53, 63, 122, 247, 352. causes of, 209.

Hecht, 399.

Hemianopsia in neurosyphilis, 242.

Hemiplegia, 31, 45, 80, 122, 262, 360. causes of, 389.

Hemitremor, 197.

Heredity, neuropathic, 84.

Herxheimer reaction, 152.

Heubner, 427, 428.

Hinton, W. A., 471.

Huntington’s chorea, 258.

Hutchinsonian teeth, 45.

Hydrocephalus, 134, 306.

Hyperreflexia, explanation of, 233.

Hypochondriacal ideas, 133.

Hysteria, 185, 301.

Hysterical symptoms, 18.

Incontinence, vesical in tabetic neurosyphilis, 144. rectal, 56.

Incubation period of neurosyphilis, 152.

Infectiousness of neurosyphilis, 95.

Insight, 95.

Insomnia, 63.

Intracranial pressure, 139, 362.

Intraspinal lesions, 95.

Intraspinous therapy, 122, 366, 486. unpleasant results of, 366.

Intraventricular injections, 389, 487.

Involution-melancholia, 187.

Iodine, untoward results, of, 363.

Iritis, 17.

Järisch-Herxheimer reaction, 72.

Joffroy, 214. and Mignot, 64.

Junius and Arndt, 249.

Juvenile neurosyphilis, 438, 447. relation to epilepsy, 277.

Juvenile paresis, see juvenile paretic neurosyphilis.

Juvenile paretic neurosyphilis, juvenile paresis, 45, 154, 157, 272, 275, 298, 306, 440. age of onset, 158. and Addison’s disease, 279. and delinquency, 298. prognosis, 156, 158, 162, 273, 275. treatment, 154, 161, 278, 299.

Juvenile paretic neurosyphilis, with initial trauma, 306. congenital amputation of toes in, 158.

Juvenile tabetic neurosyphilis, 161, 447.

Kaplan, 255, 471.

Kéraval, 257.

Key, 427.

Knee-jerks, absence of, 223. lively, 75. return of, 24.

Koefod, Solomon and, 243.

Kolmer, 471.

Kraepelin, 65, 66, 69, 88, 91, 95, 187, 225, 249.

Krafft-Ebing, 84.

Laignel-Lavastine, 413.

Lange, C., 428, 429, 474.

Lancinating pains, 92, 141.

Lépine, 408, 413.

Leptomeningitis, 47, 54, 135.

Lewandowski, 210.

Liability of paretic, 295.

Lissauer’s paralysis, 38.

Locomotor ataxia, see tabetic neurosyphilis.

Long, 418.

Lucke, Baldwin, 93, 144.

Lues maligna, 250, 452.

Lumbar puncture, untoward effects, 352. treatment of, 354.

Lüth, 278.

Lymphocytosis, 23, 30, 40, 49.

McDonagh, 381.

McIntosh, Fildes and, 129, 329.

Malaria, cerebral, simulation of paretic neurosyphilis, 245.

Mallory and Wright, 472.

Manic-depressive psychosis, 68, 71, 77, 187, 202, 291, 384, 442.

Marie, Chatelin and Patrikios, 412.

Marie, 408, 414.

Martin, E. G., 313.

Massary, de, 414.

Mattauschek and Pilcz, 347.

Medicolegal and Social, 454. period of paretic neurosyphilis, 414.

Meilhon, 407.

Memory, failing, 63.

Meningitis hypertrophica cervicalis of Charcot, 56. sympathica, 19. syphilitic, 103.

Mercurialization, 98.

Mercury, 58, 83, 85, 98, 148, 193, 235, 376, 377, 389, 391, 395, 486. untoward results of, 363.

Metasyphilis, 89.

Metchnikoff and Roux, 427, 428.

Microgyria, occipital, 47.

Mignot, Joffroy and, 64, 66.

Migraine, 19.

Mitchell, H. W., 218.

Mœbius, 429.

Mott, F. W., 158, 257, 308, 396, 437.

Multiple sclerosis, 253, 256. relation of syphilis to, 254. spinal fluid findings in, 254.

Muscular atrophy, 149, 446. syphilitic relation to amyotrophic lateral sclerosis, 150.

Muscular weakness, 279.

Myerson, A., 196.

Nageotti, 428.

Nausea, 63.

Neisser, 399.

Nerve trunk tenderness, 148, 234.

Nervousness, 63.

Nervous indigestion, 63.

Neurasthenia, 63, 183.

Neuritis, cranial, 51. optic, 365. root, 235. syphilitic, 235.

Neurorecidive, 152, 153, 184, 196, 235.

Neuroses, relation of syphilis to, 186.

Neurosyphilis, 187, 238, 240, 242. aggravated on military service, 404. atypical, 258, 346. atypical case resembling hysterical fugue, 264. dates, 428. forms of, 20, 21, 28, 29, 95. galloping, 328. history of, 427. incubation period, 152. infectiousness of, 95. laboratory findings in, 82. latent, 142, 203. lesions, 303. lighted up by stress of military service, 412. and marriage, 319. prevention, 320. onset, 64. in primary stage, 186. in secondary stage, 185, 283, 390. in secondary stage, prognosis, 390. in secondary stage, treatment, 153. spinal, 23. and the war, 399, 466.

Nissl-Alzheimer method, 427.

Noguchi, 381. and Moore, 428, 429.

Nonne, 82, 125, 152, 186, 195, 196, 214, 216, 235, 254, 265. -Apelt test, 473.

Numbness, 56.

Nystagmus, 45, 253, 256, 279.

Obersteiner, 249.

Occupation-neurosis, 312.

Ogilvie method, 487.

Operation for gumma, 139.

Optic atrophy, 256. in juvenile paretic neurosyphilis, 154.

Optic thalamus, syphilitic lesion of, 205.

Osteitis, syphilitic, 311.

Ozena, 350.

Pains, 31.

Pandy test, 474.

Paralysis, 123. recovery from, 342. of respiration, 248.

Paranoia, syphilitic, 225.

Paraphasia, 19, 43.

Paraplegia, 26, 30.

Parasyphilis, 89.

Paresis sine paresi, 126, 186, 204, 303, 445.

Paresis, see paretic neurosyphilis.

Paretic neurosyphilis, dementia paralytica, general paresis, softening of the brain, 37, 63, 68, 74, 78, 80, 85, 97, 131, 188, 192, 197, 199, 202, 227, 241, 262, 289, 295, 309, 314, 323, 338, 372, 375, 377, 382, 384, 386, 388, 392, 435, 440, 442. adjuvant causes of, 414. causing social complications, 289. causes of death in, 197. course, 85. duration, 88. forms, 95. improvement, 377. incidence among officers, 407. incidence among soldiers, 402. lesions of, 131. “lighted up” by domestic stress in civil life, 420. “lighted up” by “gassing,” 414. mortality from, 89. nomenclature, 88. onset, 192. pathology of, 436. prognosis, 435, 444. symptoms, 90, 131. symptoms, mental, 87. symptoms, physical, 86. versus diffuse neurosyphilis, 165. versus vascular neurosyphilis, 169, 172. with very marked meningitis, 332. with very marked brain atrophy, 335. without mental symptoms, 315. traumatic exacerbation, 310. traumatic form, 308, 413. traumatic, shell-shock, 401. treatment of, 85, 370, 372, 377, 382, 384, 386, 388, 392. treatment, results of, 351.

Pensions for disabilities resulting from venereal disease, 409.

Pensions for neurosyphilis, 411.

Peripheral neurosyphilis, 19.

Perivascular infiltration, 41.

Pernicious anemia with spinal symptoms, 267.

Petit mal attacks, 195.

Pförringer, 61.

Phobia, 67.

Pilcz, Mattauschek and, 347.

Pitres and Marchand, 421, 424.

Plaut, 249, 348, 428.

Plaut, Rehm and Schottmüller, 471.

Plasmocytosis, 40, 49, 55.

Pleocytosis, 23, 220, 247, 344. effect of antisyphilitic treatment on, 244, 376. in remissions, 243. significance of, 243. spinal fluid otherwise negative, 270.

Polydipsia, 190.

Polyuria, 190.

Pontine hemorrhage, 219. softening, 54.

Posey and Spiller, 257.

Potassium iodid, 58, 85, 98, 193, 222, 376, 377, 389, 486.

Preparesis, 65, 77, 78.

Prince, Morton, 195.

Psammoma, 213.

Pseudoneurasthenia, 66.

Pseudoparesis, 449. alcoholic, 222, 229, 451. diabetic, 238. senile, 263. shell-shock, 421. syphilitic, 223, 371.

Pseudoparetic neurosyphilis, 222.

Pseudotabes, shell-shock, 424.

Psychogenic neurosyphilis, 189.

Psychographic disturbance, 228.

Psychopathic personality, 302.

Ptosis, 350.

Pupillary reaction, changes in, 261. signs, 69.

Pupils, Argyll-Robertson, see Argyll-Robertson pupils. irregular, 79, 201. normally reacting in paretic neurosyphilis, 199. sluggish reaction to light, 188. stiff as isolated symptom, 265.

Purkinje cells, binucleate, 48.

Putnam, James J., 19, 56.

Pyramidal tract lesion, bilateral, 326. sclerosis, 44.

Quadriplegia in juvenile paretic neurosyphilis, 275.

Quincke, 427, 428.

Randsklerose, 24.

Ravaut, 428.

Ravaut, Sicard, Nageotti, Widal, 428.

Rayneau, 407, 413, 414.

Recovery, 77.

Recurrences, 70.

Redlich, 403.

Régis, 73.

Remissions, 122, 435, 445.

Retardation, 187.

Retention of urine, 56.

Retinitis, hemorrhages, 365.

Richards, R. L., 402, 404, 406, 409.

Robertson, A. R., 59.

Rod cells, 226, 297.

Romberg sign, 141, 216, 279.

Root-sciatica, syphilitic, 418.

Rosenau, 471.

Ross-Jones test, 473.

“Rum fit,” 229.

Ryder, Charles T., 42.

Saddle-shaped nose, 210.

Salivation, 98.

Salmon, Thomas W., 89.

Salvarsan, 75, 83, 85, 193, 222, 377, 389, 486. provocative, 78, 79. untoward results of, 363.

Salvarsanized serum, 75.

Schaudinn, 427, 429.

Sciatic pain in neurosyphilis, 149.

Seizures, 31, 64, 83, 103, 444. causes of in paretic neurosyphilis, 194. Jacksonian, 392. minor, 392.

Senile arteriosclerotic psychosis, 262.

Sensitized cells, 478.

Sérieux and Ducaste, 96.

Shaikewicz, 404.

Shanahan, 278.

Sheep’s corpuscles, 477.

Shock, 42, 81.

Sicard, 428.

Six tests, 80, 85. in tabetic neurosyphilis, 141.

Smith and Solomon, 479.

Social cases, 454. service, 232.

Solomon, 142, 255. and Koefod, 243. Smith and, 479. Southard and, 202, 303.

Somnolence, 45.

Southard, E. E., 48, 134, 212. and Canavan, 70. and Solomon, 202, 303. and Taft, 397.

Spasms, clonic, 326.

Spastic hemiplegia in paretic neurosyphilis, 323.

Spastic paraplegia, Erb’s, 147, 306.

Spasticity, 18, 256.

Speech defect, 69, 133.

Spiller, 150. Posey and, 257.

Spinal fluid findings in secondary stage of syphilis, 151, 185, 283. in juvenile paretic neurosyphilis, 275. negative in diffuse neurosyphilis, 140. negative in gummatous neurosyphilis, 138. negative in neurosyphilis, 216. negative in tabetic neurosyphilis, 269. in tabetic neurosyphilis, 141.

Spinal fluid, withdrawal for therapeutic purposes, 377, 379.

Spinal syphilis, see diffuse neurosyphilis.

Spirochetes, “drug fastness,” 381, 394. strains, 76, 263, 276, 381, 394.

Steida, 405.

Sterility in tabetic neurosyphilis, 144.

Stier, 407.

Stokes, Wile and, 186.

Suicide, 92, 126, 240, 296, 301.

Summary, 427.

Syphilis aggravated by service, 406, 411. on service, 409.

Syphilis as cause of diabetes, 241. as cause of feeblemindedness, 396. hereditaria tarda, 160, 318. history of, 427. lesions in, 329. of lung, 211. from Mongolian, 76. primary, 65. secondary, 65. tertiary, lesions in, 329.

Syphilitic feeblemindedness, pathology of, 160. neuritis, 312. psychosis, 91.

Syphilophobia, 67, 361.

Syphilotoxins, 72.

Swift, 129, 212.

Swift and Ellis, 428, 429. method, 428, 487.

Tabes dorsalis, see tabetic neurosyphilis.

Tabetic neurosyphilis, tabes dorsalis, locomotor ataxia, 30, 31, 141, 146, 366, 367, 434, 446. associated with cerebral symptoms, 177. atypical, 143. cervical, 146. course, 141. with negative spinal fluid findings, 269. prognosis, 94. shell-shock, 403. “shell-shocked” into paretic neurosyphilis, 401. symptoms, 93. symptoms in order of frequency, 145. treatment, 145, 366, 367. plus vascular neurosyphilis, 175. with vascular insult, 30, 439. versus pernicious anemia, 267.

Taboparesis, see Taboparetic neurosyphilis.

Taboparetic neurosyphilis, taboparesis, 92, 135, 195, 284, 443. course, 92. nomenclature, 94. prognosis, 92, 443. and typhoid meningitis, 284.

Taft, A. E., Southard, E. E., and,

Talon, 407.

Taylor, E. W., 50.

Temperature, paretic, 376.

Tests, changes under treatment, 102. changed to negative in paretic neurosyphilis without clinical improvement, 385. changed to less strongly positive in paretic neurosyphilis without clinical improvement, 386.

Therapeutic conception, 324.

Thibierge, 399.

Thierry, 158.

Throbbing in head, 63.

Thrombosis, cerebral, 36, 42, 342, 357, 360, 124.

Thymus, persistent, 282.

Tibial exostoses, 100.

Tigges’ formula, 248.

Todd, J. L., 406, 409.

Transient deafness, 18. blindness, 18. paralysis, 124. paralysis, condition in which occurs, 123.

Trauma and juvenile neurosyphilis, 278, 306. neurosyphilis, 456. paretic neurosyphilis, 199, 308, 310. syphilitic osteitis, 311.

Treatment of neurosyphilis, 67, 75, 83, 124, 148, 184, 222, 235, 299, 328, 332, 335, 342, 346, 350, 351, 355, 384, 390, 392, 395, 419, 439, 457. case in which theoretically of no avail, 323. methods, 356, 486.

Treatment of syphilis, effect on development of neurosyphilis, 142, 347.

Tremor, 197. intention, 256

Tubercle, 80.

Tuberous sclerosis of Bourneville, 47.

Tumor, cerebral, 53, 191, 238, 253. pineal, 213.

Unconsciousness, 53. causes of, 389.

Vascular changes, 220.

Vascular neurosyphilis, 31, 42, 72, 296, 359, 433, 440. plus tabetic neurosyphilis, 175. prognosis, 433. versus paretic neurosyphilis, 169, 172.

Veeder, B. S., 274.

Vertigo, 122.

Viet, 278.

Virchow, 427, 428.

Vomiting, 53, 63.

Warthin, 241.

Wassermann reaction, 191. and alcoholism, 230. in congenital syphilis, 160, 271. meaning of “doubtful,” 360. negative in diffuse neurosyphilis, 184. negative in juvenile paretic neurosyphilis, 298. negative in spinal fluid in spinal syphilis, 148. negative in spinal fluid in neurosyphilis, 101. negative in neurosyphilis, 252. negative in paretic neurosyphilis, 77. technique, 476. titrations in spinal fluid, 348.

Wassermann, Neisser and Bruck, 428.

Weiler, 214.

Weygandt, 403, 404.

Widal, Sicard, Ravaut, 428.

Wiles and Stokes, 186.

Word-deafness, 35, 43.

X-ray diagnosis of bone conditions, 136.

Yerkes-Bridges, 304.

Ziehen, 409.

Zsigmondi, 429, 474.

-----

Footnote 1:

The cases chosen to illustrate the propositions of the boxed headings always illustrate several other points. See the footnotes of Section VI for lists of cases illustrating special points. The names assigned to the cases are fictitious and chosen to suggest race or descent.

Footnote 2:

Notes of Dr. James J. Putnam.

Footnote 3:

M = meningeal V = vascular P = parenchymatous

Footnote 4:

E. E. Southard: Lesions of the granule layer of the human cerebellum; Journal of Medical Research, XVI, 1907.

Footnote 5:

Proof of marked parenchymatous lesions must hang on post mortem data; the inference here as to the presence of parenchymatous lesions is a clinical inference.

Footnote 6:

Reprinted from an article by Southard & Solomon: “Latent neurosyphilis and the question of Paresis sine paresi.” Boston Medical & Surgical Journal, XXIV, 1.

Footnote 7:

Solomon: “How Shall Latent Syphilis be Treated? The Prophylaxis of Syphilis of the Central Nervous System.” Interstate Medical Journal, XXIII, 8.

Footnote 8:

Joseph Collins: Syphilis of the Brain, Journal American Medical Association, July 10, 1915, Vol. LXV, pp. 139–144.

Footnote 9:

A. M. Barrett has recently discussed this subject in a paper in the Journal of the American Medical Association, Vol. LXVII, Dec. 2, 1916.

Footnote 10:

Reprinted from an article by Southard & Solomon: “Latent neurosyphilis and the Question of Paresis sine paresi.” Boston Medical and Surgical Journal, XXIV, 1.

Footnote 11:

E. E. Southard. A case of glioma of the pineal region, Am. Jour. of Ins., Vol. LXI, 1905.

Footnote 12:

Since this was written Collins has had further difficulties related to his neurosyphilis, improving under treatment.

Footnote 13:

Warthin: “Persistence of active lesions and spirochetes in the tissues of clinically inactive or ‘cured’ syphilitics,” American Journal of Medical Sciences, CLII, 1916.

Footnote 14:

“The Significance of Changes in Cellular Content of Cerebrospinal Fluid in Neurosyphilis,” Boston Medical and Surgical Journal, CLXXIII, 27.

Footnote 15:

Plaut: Ueber Halluzinosen der Syphilitiker, Berlin, 1913.

Footnote 16:

Borden S. Veeder: Hereditary Syphilis in the Light of Recent Clinical Studies; Am. Jour. of Med. Sc., CLII, 1916.

Footnote 17:

Reprinted from article by Southard and Solomon: “Latent Neurosyphilis, the Question of Paresis sine paresi,” Boston Medical and Surgical Journal, XXIV, 1.

Footnote 18:

(This case was furnished by Dr. D. A. Haller from the Peter Bent Brigham Hospital series.)

Footnote 19:

Fernald, W. E. Standardized Fields of Inquiry for Clinical Studies of Borderline Defectives. Mental Hygiene, Vol. 1, No. 2, April, 1917.

Footnote 20:

Goddard, H. H., Feeblemindedness, its Causes and Consequences, 1914.

Footnote 21:

W. E. Fernald and E. E. Southard. Waverley Research Series in the Pathology of the Feebleminded. Proceedings of the American Academy of Arts and Sciences, 1917.

Footnote 22:

Thibierge. La Syphilis dans l’armée, 1917.

Footnote 23:

Hecht. Wien. klin. Woch., xxix, 51.

Footnote 24:

Donath. Beiträge zu den Kriegsverletzungen und -er-krankungen des Nervensystems. Wiener klin. Wehnschr., No. 27–8, 1915.

Footnote 25:

Duco et Blum. Guide pratique du Médecin dans les Expertises médicolégales militaires. Paris, 1917.

Footnote 26:

Birnbaum. Kriegsneurosen und -psychosen auf Grund der gegenwärtigen Kriegsbeobachtungen: Sammelbericht. Z. f. d. ges. Neurol. u. Psychiat., Bd. XII, H. 1, 1915.

Footnote 27:

Weygandt. Kriegseinflüsse und Psychiatrie. Jahreskurse f. ärztl. Fortbildung, Maiheft, 1915.

Footnote 28:

Bonhoeffer. Erfahrungen über Epilepsie und Verwandtes im Feldzuge. Monatschr. f. Psychiat u. Neurol., Bd. 38, H. 1–2, 1915.

Footnote 29:

Exner, M. J., Prostitution in its relation to the army on the Mexican Border, Social Hygiene, Vol. 3, 2, April, 1917.

Footnote 30:

Bonhoeffer, loc. cit.

Footnote 31:

We have recently reviewed the outcome in 300 untreated cases of paretic neurosyphilis (Psychopathic Hospital material, strictly comparable with treated cases) finding but 5 now capable of self-support and 10 more in normal-looking remission. This percentage is far lower than that in treated cases (at present, July, 1917, 50 in 200 capable of self-support).

Footnote 32:

Alice Morton (1).

Footnote 33:

Francis Garfield (2).

Footnote 34:

John Dixon (3).

Footnote 35:

James Pierce (4).

Footnote 36:

John Lawrence (5).

Footnote 37:

Flora Black (6).

Footnote 38:

Mrs. Lecompte (7).

Footnote 39:

John Wyman (8).

Footnote 40:

Greeley Harrison (9). Also Albert Robinson (45), Alice Caperson (46), Abel Bachmann (74).

Footnote 41:

Lyman Agnew (10). Also Ethel Hunter (47), Bessie Vogel (52), Isaac Thompson (83), Juliette Lachine (11).

Footnote 42:

Juliette Lachine (11). Also Lyman Agnew (10), Ethel Hunter (47), Bessie Vogel (52), Isaac Thompson (83).

Footnote 43:

Henry Philipps (12). Also Bridget Curley (59), Margaret O’Brien (68), Annie Martin (117).

Footnote 44:

William Twist (13). Also Lester Crane (20), Thomas Donovan (23).

Footnote 45:

John Jackson (14). Also Martha Bartlett (21), Paolo Marini (28), Margaret O’Brien (68).

Footnote 46:

Pietro Martiro (15). Also Meyer Levenson (22), Achilles Akropovlos (50).

Footnote 47:

Joseph Sullivan (16).

Footnote 48:

Gregorian Petrofski (17). Also Richard Lawlor (25), John Bennett (34), Julius Kantor (54), Albert Forest (112).

Footnote 49:

Frederick Wescott (18). Also Martha Bartlett (21), James Burns (56), Victor Friedburg (108).

Footnote 50:

Agnes O’Neil (19). Also Michael O’Donnell (24). John Edwards (104). Arthur Bright (121).

Footnote 51:

Lester Crane (20). Also Greeley Harrison (9). David Borofski (49). David Collins (61).

Footnote 52:

Martha Bartlett (21). Also Agnes O’Neil (19), Vivian Walker (87).

Footnote 53:

Meyer Levenson (22). Also Albert Forest (112).

Footnote 54:

Thomas Donovan (23). Also William Twist (13), Bessie Vogel (52), David Collins (61).

Footnote 55:

Michael O’Donnell (24). Also Alice Morton (1).

Footnote 56:

Richard Lawlor (25). Also Bessie Vogel (52), —— —— (88).

Footnote 57:

John Morrill (26).

Footnote 58:

David Tannenbaum (27). Also Mrs. LeCompte (7), Annie Rivers (109).

Footnote 59:

Paolo Marini (28). Also Flora Black (6).

Footnote 60:

Mario Sanzi (29). Also Stephen Green (30), Paul Halleck (31).

Footnote 61:

Stephen Green (30). Also Paul Halleck (31), Henri Lepère (105), Ivan Rokicki (111).

Footnote 62:

Paul Halleck (31).

Footnote 63:

Margaret Neal (32).

Footnote 64:

Joseph Graham (33).

Footnote 65:

John Bennett (34). Also Alice Caperson (46), Florence Fitzgerald (81), Vivian Walker (87), Arthur Bright (121).

Footnote 66:

Mary Coughlin (35).

Footnote 67:

Theresa Mullen (36). Also John Lawrence (5), John Friedreich (77), Gridley Ringer (78), James Arnold (80).

Footnote 68:

Isaac Goldstein (37).

Footnote 69:

Archibald Sherry (38).

Footnote 70:

Caroline Davis (39). H. F. (40). Samuel North (41). Elizabeth Brown (42). Robert Allen (43). John Hughes (44).

Footnote 71:

Albert Robinson (45). Also Greeley Harrison (9).

Footnote 72:

Alice Caperson (46). Also Florence Fitzgerald (81).

Footnote 73:

Ethel Hunter (47). Also Lyman Agnew (10), Bessie Vogel (52), Juliette Lachine (11).

Footnote 74:

Milton Safsky (48). Also Daniel Falvey (55).

Footnote 75:

David Borofski (49). Also Lester Crane (20).

Footnote 76:

Achilles Akropovlos (50).

Footnote 77:

Daniel Wheelwright (51).

Footnote 78:

Bessie Vogel (52). Also Lyman Agnew (10), Juliette Lachine (11), Ethel Hunter (47).

Footnote 79:

Carrie Pearson (53).

Footnote 80:

Julius Kantor (54). Cf. James Burns (56). Henri Lepère (105). Frederick Stone (106).

Footnote 81:

Daniel Falvey (55). Cf. Francis Murphy (60).

Footnote 82:

James Burns (56). Also Frederick Wescott (18), Martha Bartlett (21), Victor Friedburg (108).

Footnote 83:

John Summers (57).

Footnote 84:

Peter Burkhardt (58).

Footnote 85:

Bridget Curley (59).

Footnote 86:

Francis Murphy (60).

Footnote 87:

David Collins (61).

Footnote 88:

Joseph Buck (62).

Footnote 89:

Albert Fielding (63).

Footnote 90:

Calvin Hall (64).

Footnote 91:

Donald Barrie (65).

Footnote 92:

Lawrence Washington (66).

Footnote 93:

Joseph Temple (67).

Footnote 94:

Margaret O’Brien (68). Also Henry Phillips (12). Bridget Curley (59). Annie Martin (117).

Footnote 95:

Frank Mason (69).

Footnote 96:

Annie Kelly (70). James Lauder (71).

Footnote 97:

James Lauder (71).

Footnote 98:

Margaret Green (72).

Footnote 99:

Marcus Chatterton (73).

Footnote 100:

Abel Bachmann (74).

Footnote 101:

Mrs. Brown (75).

Footnote 102:

James Seabrook (76).

Footnote 103:

John Friedreich (77). Cf. Isaac Goldstein (37).

Footnote 104:

Gridley Ringer (78).

Footnote 105:

John Doran (79).

Footnote 106:

James Arnold (80).

Footnote 107:

Florence Fitzgerald (81). Also John Bennett (34), Alice Caperson (46), Vivian Walker (87), Arthur Bright (121).

Footnote 108:

Frederick Estabrook (82).

Footnote 109:

Maj. Isaac Thompson, M.D. (83).

Footnote 110:

Lester Smith (84).

Footnote 111:

Annie Marks (85).

Footnote 112:

Frank Johnson (86).

Footnote 113:

Vivian Walker (87).

Footnote 114:

—— —— (88). Cf. Richard Lawlor (25). Bessie Vogel (52).

Footnote 115:

Margaret Tennyson (89). John Lawrence (5). Mary Coughlin (35). Theresa Mullen (36). John Friedreich (77). Gridley Ringer (78). James Arnold (80).

Footnote 116:

Joseph O’Hearn (90).

Footnote 117:

Levi Sussman (91).

Footnote 118:

Joseph Larkin (92).

Footnote 119:

Richard Marshall (93).

Footnote 120:

David Fitzpatrick (94).

Footnote 121:

Joseph Wilson (95).

Footnote 122:

Becky Bornstein (96). Walter Heinmas (97). Mr. Jacobs (98).

Footnote 123:

Walter Heinmas (97).

Footnote 124:

Mr. Jacobs (98).

Footnote 125:

James McDevitt (99).

Footnote 126:

Jacob Methuen (100).

Footnote 127:

John Baxter (101).

Footnote 128:

Theodosia Jewett (102).

Footnote 129:

A. W. (103).

Footnote 130:

John Edwards (104). Cf. Henri Lepère (105), Frederick Stone (106), Arthur Bright (121), Agnes O’Neil (19), Paolo Marini (28).

Footnote 131:

Henri Lepère (105). Cf. Julius Kantor (54).

Footnote 132:

Frederick Stone (106).

Footnote 133:

Greta Meyer (107). Cf. John Jackson (14).

Footnote 134:

Victor Friedburg (108).

Footnote 135:

Annie Rivers (109).

Footnote 136:

Mr. McKenzie (110). Cf. Ivan Rokicki (111).

Footnote 137:

Ivan Rokicki (111).

Footnote 138:

Albert Forest (112). Cf. Gussie Silverman (113), Walter Henry (114), William Rosetti (116), Annie Martin (117), Levi Morovitz (122), Peter Burkhardt (58).

Footnote 139:

Gussie Silverman (113).

Footnote 140:

Walter Henry (114).

Footnote 141:

Henry Ryan (115).

Footnote 142:

William Rosetti (116).

Footnote 143:

Annie Martin (117). Cf. William Roberts (118).

Footnote 144:

William Roberts (118). John Silver (119).

Footnote 145:

John Silver (119).

Footnote 146:

James McGinnis (120).

Footnote 147:

Arthur Bright (121). Cf. Levi Morovitz (122), John Bennett (34).

Footnote 148:

Levi Morovitz (122).

Footnote 149:

Robert Matthews (23). Cf. Isaac Goldstein (37).

Footnote 150:

For cases in which, without autopsy we have risked the diagnosis neurosyphilis in the absence of W. R. in serum or fluid, see William Twist (13), Frederick Wescott (18), Martha Bartlett (21), Thomas Donovan (23), Paolo Marini (28), Margaret Neal (32), Bridget Curley (59), Victor Friedburg (108), Ivan Rokicki (111).

Footnote 151:

From Mallory and Wright: Manual of Laboratory Technique.

Footnote 152:

Bruck. Münch. med. Wochen. Jan. 22, 1917.

Footnote 153:

Smith and Solomon. Boston Medical and Surgical Jour.

Footnote 154:

Bruck: Journal of American Medical Association, Vol. lviii, No. 12, March 24, 1917, p. 944.

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TRANSCRIBER’S NOTES

1. Pg. 456, added footnote anchor for footnote A. 2. Silently corrected typographical errors and variations in spelling. 3. Archaic, non-standard, and uncertain spellings retained as printed. 4. Footnotes were re-indexed using numbers and collected together at the end of the last chapter. 5. Enclosed italics font in underscores. 6. Enclosed bold font in =equals=. 7. Subscripts are denoted by an underscore before a series of subscripted characters enclosed in curly braces, e.g. H_{2}O.