Chapter XVI: Introduction (8)

=Differential diagnosis between NEUROSYPHILIS, DIABETIC
PSEUDOPARESIS and BRAIN TUMOR.=

=Case 64.= A large and imposing person, Calvin Hall, 55, had been employed as a doorkeeper and guard, in which position he was on duty for 12 to 14 hours daily. Eventually, however, he had begun to have a good deal of pain in the legs and a few months before observation, one day, his legs gave way and he fell to the floor. There was, however, no loss of consciousness, and he was carried to a general hospital. The result of an examination there was that his family was informed that he had some nervous trouble.

Hall now began to be melancholy and wept a good deal. His appetite and sleep remained intact. He felt too weak to walk. At the end of about a year, he began to improve and again became able to do a little light work. About a month before coming to the Psychopathic Hospital, about two years after the onset of symptoms, Hall suddenly began to talk excessively, in a rambling and rather senseless way. A fortnight later, he began to suffer from insomnia and restlessness.

Some medical facts were available: It seems that at 25 years this patient had become infected with syphilis though there had never been any secondary signs. He was married four years later but there had not been any children. Moreover, for four years past, the patient had been treated for glycosuria.

Upon admission, the patient’s sensorium was clear, but his orientation was only partial. He could give a fair account of his life, but it appeared that his memory was somewhat impaired. There were auditory hallucinations (voices of relatives). He often mistook the identity of persons about him. He talked in a grandiose fashion of his great strength and especially of a God-given power to read minds. His flow of thought was rapid, rambling, circumstantial, and with traces of irrelevance. He was rather continuously busy and at times restive. There was a good deal of emotional agitation and apprehensiveness, and again the patient would become suspicious and tearful.

=Physically=, there was a discharging sinus connected with the right humerus, close to the elbow. The pupils, though equal and regular, were sluggish in reaction to light. The knee-jerks and ankle-jerks were absent. There was no Romberg sign but there was some swaying in the Romberg position. There was a moderate ataxia in walking. Glycosuria to a moderate degree was determined. There were no casts or albumin in the urine. The W. R. of the blood and of the spinal fluid was negative. The albumin of the fluid, however, was considerably increased. X-ray examination of the skull yielded a suggestion of absorption of the posterior clinoid processes of the sella turcica. The X-ray examination of the arm in the region of the sinus showed a chronic osteomyelitis, possibly syphilitic (or diabetic?).

The diagnostic problems in the case of Calvin Hall are extremely intricate. There are clinical suggestions of general paresis, not confirmed by the laboratory findings.

1. Are we dealing with a case of diabetic pseudoparesis? Is the pain
in the legs of like origin, and has a neuritic process led to the
absence of the knee-jerks? The Allen treatment appears to have had
no beneficial result in this case.

2. Is there a tumor of the sella region, which could account for the
mental symptoms and the glycosuria? The spinal fluid albumin might
be regarded as consistent with a variety of psychoses, including
that of brain tumor. We have to remember the definite history of
infection, the sterile marriage and the possibly syphilitic
osteomyelitis.

=DIABETES AND NEUROSYPHILIS, relations?=

=Case 65.= Donald Barrie, a man of 61, diabetic for several years, had begun to worry about the diabetes, feeling that he was about to die, and had gone so far as to make several threats of suicide. Hence he was brought to the Psychopathic Hospital for observation.

Barrie was rather well developed and nourished, although he looked far older than he was. There was a marked arcus senilis; the skin was dry and rough; the radial and other accessible vessels were markedly sclerosed; abdomen obese; right testicle very low with thickened and hard epididymis.

=Neurologically= there was little abnormal to discover. The pupils were irregular; both reacted fairly well to light. There was a slight tremor of the extended hands, and still less of the tongue. The voice was slightly thick and the patient stumbled somewhat on test phrases. Urine: specific gravity, 1029; sugar; no acetone; no diacetic acid. Sugar 2 to 11 grams for 24 hours on ordinary diet. It proved impossible to get the patient sugar-free, either by cutting down the carbohydrates or by using the Allen method.

=Mentally=, the depression with reiteration of wrong-doing and self-accusation because of the contraction of syphilis, were the striking features. There was, to be sure, a slight imperfection of memory for remote events; memory for recent events and knowledge of current events was very poor. Barrie claimed that his condition was entirely hopeless, that his memory was exceedingly bad, and that he was no longer capable of supporting his family.

1. What shall be said as to diagnosis in a man of 61 with
glycosuria, depression, amnesia, sluggish pupil, slight tremor,
slight speech defect, and a history of syphilis? The W. R. of the
serum proved positive, and also the W. R. of the spinal fluid. The
gold sol reaction of the fluid was of the syphilitic type. There
were 112 cells per cmm., there was an excess of albumin, and a
large amount of globulin. Accordingly, the diagnosis of PARETIC
NEUROSYPHILIS (“general paresis”), especially in view of the
laboratory findings, seems necessary.

2. What is the cause of the glycosuria? First: possibly it has no
relation with the syphilis; secondly: it may possibly be due to a
syphilitic involvement of the pancreas; thirdly: it is barely
possible that it is due to syphilitic disease of the fourth
ventricle or of the base of the brain, involving the pituitary
region. Perhaps our case is too complex for analysis. At all
events, the case brings up the possibility of a syphilitic
glycosuria.

3. Can the diabetes in the case of Barrie be explained as
syphilitic? Warthin of Ann Arbor has recently described somewhat
remarkable spirochete findings in his autopsy material. The order
of organic infection according to frequency is: aorta, heart,
testis, adrenal, pancreas, nervous system, liver, and spleen.
Warthin has called attention to the relation of pancreatitis and
spirochetosis to diabetes in a recent review[13] of findings in 41
autopsied cases from the University Hospital in Michigan. Warthin
found active luetic lesions in the pancreas in 6 cases.

=Hemianopsia in a case of neurosyphilis.=

=Case 66.= Lawrence Washington, a colored cabman, 58 years of age, began to forget addresses given him by his fares. Moreover, he could no longer see as well as before, especially on looking toward the right side. He himself states that the visual trouble dated back as long ago as his 39th year, at which time he had a terrific pain in both temples, leading back from the eyes. Washington thought that his vision had been getting slowly but steadily worse ever since.

We got the impression that the amnesia claimed by Washington was more or less subjective and he was found to be well informed. This association of amnesia and impairment of vision naturally suggests syphilis. The patient himself stated that he had had a chancre at the age of 18.

We found the W. R. of the serum to be appropriately positive. The W. R. of the spinal fluid was also positive though weakly so. There was an excess of albumin; globulin appeared in large amount; the gold sol reaction was of the syphilitic type; there were 186 cells in the spinal fluid.

Is this case one of paresis or of some other form of cerebrospinal syphilis? Let us consider the data of the =physical examination=. On the whole, the patient was well preserved. There was a slight radial arteriosclerosis, but on the whole the cardiovascular system was almost negative. The blood pressure was 100 systolic, 65 diastolic. =Neurologically= the visual field of the left eye was somewhat limited, and there was a temporal hemianopsia of the right eye. The ophthalmoscopic examination showed a disseminated choroiditis on both sides. The right pupil failed to react to light. The left pupil reacted slowly. Both pupils reacted properly to accommodation.

The knee-jerks could be obtained only on reinforcement, and when obtained, the right was apparently more active than the left. The left Achilles was absent; the right present. There were no other abnormal reflexes.

The motility of the facial muscles was somewhat impaired. Finger-to-finger and finger-to-nose tests were rather poorly done. The muscle sense was good; there was no swaying in Romberg position; and there was no speech defect.

We are unable to decide whether the case is one of the =parenchymatous= type (paretic) or of the =meningovascular= type of =neurosyphilis=. It is certainly rather unusual to find hemianopsia in a paretic.

We have been unable to get definite results from the treatment of this case, since the patient would not return for months after getting an injection or two of salvarsan, on the ground that he was improved enough and did not require further treatment.

1. What conclusion can be drawn from the 186 cells per cmm. in the
spinal fluid? Ordinarily this finding would indicate an active
process. Some writers have claimed that a cell count running above
100 per cmm. was an indicator of diffuse non-paretic
neurosyphilis. It does not appear that this claim has been
substantiated. It is remarkable that this case shows an interval
of 40 years between infection and the occurrence of definite
clinical symptoms. With respect to the cell count, both in
untreated and in treated cases, the following conclusions from a
recent article (Solomon and Koefod)[14] are in point:

1. The number of cells found in the fluid of untreated cases
offers no definite information of prognostic value.

2. One is not justified in drawing any conclusions as to whether
the case is cerebrospinal syphilis or general paresis, nor the
time the process has been active, nor the severity of it, from the
cell count.

3. The cell count may vary greatly from month to month, or when
the interval is but several days, while at other times it may
remain very nearly the same after an interval of months.

4. Cases showing natural remissions may show no reduction in the
cell count, or other spinal fluid findings.

5. Cases treated with salvarsan, either intraspinously or
intravenously, tend to show a more or less rapid fall in the cell
count. This count will, as a rule, remain low during treatment,
but is likely to rise when treatment has been discontinued, but
may rise during treatment after having first fallen.

6. Cases may show remissions during treatment and still have a
pleocytosis.

7. Treated cases having the cell count fall to normal may at the
same time become very much worse and develop more marked paralytic
symptoms.

8. In general paresis the cell count in no way parallels the other
spinal fluid findings.

9. In cases in which the other tests show an improvement, for
instance cerebrospinal syphilis, the cell count also readily and
early drops to normal. At times it may drop to normal before other
spinal fluid tests become negative; again it may be last to reach
normal.

10. The change in cell count seen in syphilitic disease untreated
is also found in non-syphilitic diseases, as brain tumor.

11. The cell count offers nothing of prognostic importance in
syphilis of the nervous system unless accompanied by improvement
of the other laboratory signs.

12. The cell count is not an index to the predominance of
irritative or degenerative changes.

=Case of CEREBRAL MALARIA and SYPHILIS: simulation of PARETIC
NEUROSYPHILIS (“general paresis”).=

=Case 67.= Joseph Temple, 45, who had been a sea-going steamboat steward, was brought to the hospital in a semi-stupor. He was entirely uncoöperative, often resistive, attempting to bite the physician’s fingers, and for the most part lying curled up. He was incontinent and tube-fed. This phase, it seems, had begun the night before entrance to the hospital. Twenty-four hours later, an extraordinary change was noted. Temple became alert and attended to his wants, began to eat well, and began to behave as normally as probably he ever behaved.

He was now able to give a coherent history. It was now January. In the previous September, he had left for Mexico; he was returning when he suddenly fell to the deck, unconscious. After this fall, he had not been well, having had chills and fever. At the Marine Hospital, he had been diagnosed as suffering from malaria, and was given quinine. He had been delirious a short time in the hospital, not being able to recognize his wife, who called. He shortly improved so that his wife was able to take him home. Nevertheless, headache, gastric distress, and intermittent vomiting continued. A spell of confusion took place, two days before admission. The patient tossed about, moaned, and failed to recognize anyone. Malaria of the æstivo-autumnal type was demonstrated in the hospital. The temperature always remained at normal. He was somewhat emaciated and pale. The pupils were small, somewhat unequal, and reacted though poorly to light and distance. The tendon reflexes were lively.

The W. R. of the serum was positive, and information from the patient’s physician runs to the effect that there was a syphilitic infection some seven or eight years ago, followed by secondary symptoms, but the patient had refused to take any protracted treatment. The spinal fluid examination was practically negative.

=Mentally=, the patient was euphoric, expansive, boastful, and showed a marked emotional instability and considerable memory defect.

1. Can the diagnosis of general paresis be made in Joseph Temple?
Certainly the acute confusion and the syncope are consistent
enough with the diagnosis, yet the severe malaria makes it seem
likely that the phenomena were due to a cerebral attack of
malaria, and such occurrences are found in the æstivo-autumnal
form of malaria. Yet malaria would hardly explain the euphoria,
memory defect, and the pupillary findings, to say nothing of the
irritability and the active tendon reflexes. Even if we regard the
active tendon reflexes and the irritability as malarial, the other
phenomena remain outstanding as exceedingly suspicious of paresis.

On the other hand, if we try to support forcibly the diagnosis of
general paresis, we are hardly able to explain the negative
findings in the spinal fluid.

In point of fact, a study of the patient’s past life revealed a
story that the mental traits of euphoria, irritability, and memory
defect had been characteristic of the patient for many years. In
fact, there is some question whether the patient is not really to
be regarded as a moron of high grade.

Upon this basis, if we regard the confusional phenomena as
malarial and the persistent mental phenomena as characteristic of
a moron and somewhat exaggerated by the disease, we have merely to
explain the suggestive pupils. As to these, it must be remembered
that though they reacted poorly to light, still they reacted
somewhat, so it is not a question of explaining an
Argyll-Robertson pupil, but only an impaired pupillary reaction.
Of course, some workers are of the opinion that pupillary changes,
perhaps even the Argyll-Robertson pupils, may occur in syphilitic
cases that are not neurosyphilitic, or at all events are not
victims of central neurosyphilis. Finally, we must remember that
there are cases of neurosyphilis of a vascular type which yield
negative spinal fluids. The case leaves many questions unanswered.

=Can paretic and non-paretic neurosyphilis be differentiated by
means of the gold sol reaction? The gold sol reaction in this case
was an extremely mild one and would not at all have warranted the
diagnosis GENERAL PARESIS, yet the discovery of a heavy meningeal
exudate including an unusually heavy deposit of plasma cells even in
the spinal pia mater will perhaps warrant us in making a final
retrospective diagnosis of paretic neurosyphilis. Autopsy.=

=Case 68.= We would like to give the full effect of our surprise at the outcome of the case of Margaret O’Brien, a school-teacher, 26 years of age. To be sure, Miss O’Brien developed symptoms at 22 or 23 which we can now explain consistently with the outcome of the case; for at that time, she began to complain of severe pain in the head, especially in the forehead and temples, and also became nervous, unable to remain quiet, and given to insomnia. She was markedly depressed at the time and would refuse to talk at times. However, only the headache in this prodromal period could be regarded as particularly suggestive of syphilis, and headache in an over-worked school-teacher is not uncommon.

In fact, the picture presented by the patient was one of catatonic dementia praecox. The patient was admitted to the hospital after a sudden onset of excitement. At first she was very restless, continually looking about and getting up and walking away from the examiner, giving the impression of understanding all questions but preserving an air of indifference. A few days later, the patient was gotten to answer more coöperatively. She remarked that the hospital was heaven although in Boston; that it was summer time (correct) and that her memory was greatly impaired. The physician was a messenger of God (delusion later corrected). The patient had not done God’s will; her breath was leaving her; God’s voice was heard from time to time, and Miss O’Brien had heard it for a long time. God tells her to do His will. However, as Miss O’Brien remarked, “I must think all this nonsense, turning against God.”

The patient frequently attitudinized and would remain in an apparently catatonic condition for many minutes. For the most part, she was resistive and mute and non-coöperative as to examination. From time to time, she made impulsive suicidal attempts. So far as a somewhat inadequate =physical examination= was concerned, nothing abnormal could be made out; in particular, the pupils reacted normally to light and were otherwise normal. The routine W. R. of the blood serum, however, returned positive, and in accordance with the policy of the Psychopathic Hospital, the patient was subjected to a lumbar puncture. The lumbar puncture yielded a positive W. R., 109 cells per cmm., a positive globulin and a considerable excess of albumin, and an exceedingly mild gold reaction—syphilitic type.

Ten days after admission, the patient had a convulsion. She never regained consciousness, continued to have convulsions for a few hours, and died, apparently from paralysis of respiration. The heart continued to beat for a short period after respiration ceased. The =autopsy= was consistent with the diagnosis which had been rendered after the surprising results of the W. R. in the blood and the laboratory findings in the spinal fluid had been learned. There was a generalized encephalitis with congestion of all the smaller cerebral vessels and petechial areas in the meninges and upon the cortical surfaces. We regard the case as one of syphilitic encephalitis.

The brain weighed 1265 grams, indicating a loss of 79 grams by Tigges’ formula (8 times the body length in centimetres). The pia mater was, in the gross, quite normal within the cranium; nor were any cells found in a smear from this pia mater; but the pia mater over the spinal cord was visibly edematous, and a smear from the spinal pia mater showed great numbers of lymphocytes and especially of plasma cells—a finding which was confirmed in stained section, by which a remarkable display of plasma cells was found plastered somewhat generally over the entire pia mater of certain segments. The brain substance was softer than normal, but displayed no differences of consistence. The stripping of the pia mater of the temporal lobes on both sides yielded the so-called “decortication” (that is, the adhesion of small bits of brain substance to the pia mater). The optic nerves were somewhat thinner than normal. No other gross lesions of the brain were found.

The dura mater, although dense and injected, was not otherwise abnormal. There was an early visible sclerosis of the middle meningeal arteries, more marked on the left side.

The cause of death, so far as the autopsy revealed it, was bronchial pneumonia. There was a diffuse nephritis.

1. Are the hallucinations in the case of O’Brien characteristic?
Hallucinations are regarded as playing a minor rôle in general
paresis. In fact, earlier workers sometimes denied that
hallucinations occurred at all, and this denial has been made once
more of late by Plaut,[15] but Kraepelin quotes Obersteiner as
observing hallucinations in 10%, and regards that figure as
approximately corresponding with his own experience. Junius and
Arndt are cited as finding 17% of their cases hallucinated.
Auditory hallucinations are somewhat more frequent than those of
vision (alcoholic psychosis must be considered). The visual
hallucinations of paresis are thought by Kraepelin to be related
with atrophy of the optic nerves, and he states that they occur by
preference in patients having such atrophy. Hallucinations though
not common are more frequent in non-paretic neurosyphilis than in
paretic neurosyphilis.

2. What was the cause of death in Margaret O’Brien? The autopsy, as
above stated, indicated pneumonia. In point of fact, this patient
developed convulsions and ceased respiration, the heart continuing
to beat for some time after respiration had ceased. It may be that
the death should be counted as one of neurosyphilitic seizure.

=Tonsillar abscess associated with neurosyphilis (Lues Maligna?).=

=Case 69.= Frank Mason, 49 years, a rectifier of spirits, was admitted to the Psychopathic Hospital in a tremulous, mentally confused, depressed, and unhappy state. He was particularly concerned because he could not give an accurate account of his past life and because he found that he was continually contradicting himself.

Superficial examination shortly discovered the pupils to be much contracted, irregular, and non-reactive either to light or distance. Although these pupils showed more than the Argyll-Robertson phenomenon, yet the suspicion of syphilis was important.

Throat examination showed a large area of ulceration involving the whole of the right tonsil and extending even to the left side of the median line so that the whole of the faucial pillar was involved. In the midst of this ulcerative area was a mass of purulent necrotic tissue, about which the edges of the ulcer stood out sharply. There was, however, very little acute reaction about the margin of the area.

The association of pupillary changes (especially stiffness to light), what looked like tonsillar gumma, and mental disorder (including memory disturbance) heightened the impression of syphilis.

However, the remainder of the examination was not especially confirmatory of the diagnosis. The man was well developed and obese, with a slightly enlarged heart, with sounds of poor quality and the aortic second sound accentuated. The systolic blood pressure was 130; the diastolic, 90. There was no disorder of reflexes except that the arm reflexes were very lively.

After a time, a few facts concerning the patient’s life became available. Although a rectifier of spirits, Mason could not be found to have over-indulged in alcohol. It appears that some five months before his admission to the hospital, a wisdom tooth had been extracted. About four months before admission, the ulceration of the faucial pillar had begun, and this ulceration was immediately laid to infection from the wisdom tooth cavity. Mason then had to discontinue work and a depression followed. But the account of this depression led us to think that he was a victim more of natural sadness than psychopathic depression. There was much worry and insomnia. To meet the insomnia, large amounts of hypnotics were administered. The sequence of these hypnotics was a tremendous disturbance and continual crying out by the patient. In fact, Mason became so excited that he was removed to the Psychopathic Hospital for temporary care in the condition above mentioned.

We naturally awaited the outcome of the serum W. R. The return was negative. However, the typical position of the ulcerative lesion and the non-reacting pupils,—to say nothing of the mental symptoms and the associated tremors, with incoördination (this incoördination was non-characteristic and apparently due largely to the tremor),—led to lumbar puncture.

The spinal fluid yielded a weakly positive W. R. There was a slight positive albumin, the globulin test was slightly positive, there were 14 cells per cmm., and the gold sol reaction was of the syphilitic type. We were, then, probably entitled to conclude that syphilis was active not only in the body at large but also in the nervous system. Looking back upon the case, we considered that large doses of morphine and hyoscyamus might well have produced the marked mental confusion and possibly the tremors that characterized Mason on his arrival at the hospital.

Improvement followed after a few days of rest; the confusion disappeared and the tremors diminished; the pupils returned to their normal size and reaction; depression persisted, and the patient was very properly much concerned about the tonsillar lesion. However, further improvement did not take place under antisyphilitic treatment and patient died after several weeks from what was believed to be an embolus from the tonsil.

1. What was the true interpretation of Frank Mason’s pupillary
changes? They were probably due to the opiates, despite the fact
that, taken in association with the gummatous lesion of the
faucial pillar, we had regarded them as possibly syphilitic.

2. How shall the negative serum W. R. be explained? Such a reaction
is consistent with the diagnosis _gumma_. It is, however, a little
surprising that with active neurosyphilis and a relatively active
non-nervous syphilitic lesion like that in this case, the serum W.
R. should have been negative. Possibly a repetition of the test at
various times would have shown a positive serum W. R. In any
event, the fluid reaction was positive.

3. Could the tonsillar ulceration be due to dental infection? The
chances are against this on account of the interval (2 months)
between extraction of the wisdom tooth and the ulceration, which
itself seems to be of a tertiary syphilitic nature. In point of
fact, the patient admitted a syphilitic infection 21 years
previously namely, at 28 years of age. At that time he took large
quantities of mercury and potassium iodid by mouth.

4. Relation of the case of Frank Mason to the so-called _lues
maligna_? The case closely resembled the cases reported by Bly.
Frank Mason showed great destruction of tissue, toxemia, failure
to react to antisyphilitic treatment. In both of Bly’s cases, the
tonsil was the starting point of the illness; and in both cases
there was a trauma of the tonsil or peri-tonsillar structures
(tonsillectomy and application of caustic). In our case there not
only had been extraction of a wisdom tooth, but the tonsil had
been cauterized.

=Neurosyphilis versus multiple sclerosis.=

=Case 70.= Annie Kelly is a young Irish woman, 21 years of age, who was perfectly well until three months before her admission to the Psychopathic Hospital, when suddenly one evening she became very dizzy. This was followed by a chill and vomiting. The next day she had a sore throat but was able to be about and do her work. The dizziness, however, continued and she began to feel rather queer. Gradually it became difficult for her to walk on account of staggering.

A little later she noticed a weakness of the left side, involving face, arm, and leg; then she began to find it difficult to talk. Finally the right leg became weak, making walking practically impossible. All these symptoms grew worse and the dizziness increased. At times her vision would be blurred; there were somewhat frequent attacks of diplopia. Finally she had to take to her bed, and at last she lost control of her sphincters.

At no time did she suffer any pain. She was taken to a hospital, and after a time improved somewhat; but she was told she had a brain tumor and had better be in a large city, where she could have surgical aid if this became necessary; consequently, she was brought from Montana to Boston.

On admission to the hospital, the examination disclosed no important symptoms outside of the nervous and locomotor systems. She was unable to walk unless assisted. The pupils were large but reacted well to both light and accommodation, were equal in size, and regular. Slight nystagmus was present; there was no ptosis or strabismus; vision in the left eye was poor. The other cranial nerves showed no involvement. The tendon reflexes were all present and very lively; Babinski, Gordon, and Oppenheim signs were present on either side. The ataxia was marked, especially of the lower arms, and she had some difficulty in the alignment of the fingers. The sense of position of the limbs was very poor. There was some tremor, which was not of the intention type. The writing showed some incoördination. The speech showed nothing abnormal. =Mental examination= disclosed nothing of note objectively, but patient stated she could not think so clearly as she could formerly.

The =diagnosis= would seem to lie between brain tumor,—which had been suggested to the patient by her physician,—multiple sclerosis, and neurosyphilis. The numerous neurological symptoms without any definite evidence of intracranial pressure were sufficient to rule out for the moment the consideration of brain tumor. The syndrome of multiple sclerosis is not complete, but the race, age, and onset, with the increasing and decreasing intensity of symptoms are very suggestive of this diagnosis. The symptoms, of course, are all consistent with neurosyphilis also, and while the patient denied any knowledge of syphilitic involvement, the examination of the blood and spinal fluid was made. The W. R. was negative in both the blood serum and spinal fluid. Further examination of the spinal fluid showed presence of globulin and an increase in the albumin content, 43 cells per cmm. and a “paretic” type of gold sol reaction. With the negative W. R. of both blood serum and spinal fluid, and with so much in favor of MULTIPLE SCLEROSIS, this diagnosis was made.

1. What is the relation of multiple sclerosis to syphilis? There is
no definite relationship between multiple sclerosis and
syphilis,—that is, multiple sclerosis is not a syphilitic disease;
but the complete syndrome of multiple sclerosis is often given by
a syphilitic involvement of the central nervous system (see case
Lauder, 71).

2. Is the spinal fluid finding in this case consistent with multiple
sclerosis? According to Nonne, about 19% of the cases of multiple
sclerosis show globulin and pleocytosis in the spinal fluid. As a
rule, the number of cells ranges between 10 and 20 per cmm. and
the globulin is not present in large amounts. In this case, the
amount of globulin, which was given as 2+, is only a moderate
amount,—less than is usually found in cases of general paresis.
There are not very many cases of multiple sclerosis in the
literature in which a gold sol reaction has been performed, but in
the majority of those tested, the reaction is reported as mild.
However, cases of multiple sclerosis giving a typical paretic
curve have been described by a number of observers, among whom may
be mentioned Kaplan and Solomon.

3. How frequently is it necessary to make a differential diagnosis
between multiple sclerosis and neurosyphilis? Before the days of
the W. R. this differentiation was much more difficult than at
present. But we, however, still have to face a not very rare
difficulty in separating the two conditions. Syphilis is prone to
cause small localized lesions in the nervous system. The changes
in the patient’s condition, with improvements and regressions are
equally characteristic of both diseases. How closely the
symptomatology of neurosyphilis may simulate that of typical
multiple sclerosis is shown in the next case (Lauder, 71). When
the sclerotic area of multiple sclerosis occurs in appropriate
parts of the cerebrum, symptoms of mental disturbances will occur.
In its histological picture multiple sclerosis is at times highly
suggestive of syphilis, even showing mononucleosis and meningitis.

=Optic atrophy; nystagmus; spasticity; intention tremor. Diagnosis:
?=

=Case 71.= James Lauder began to lose his eyesight at 32 years, and was shortly determined to be suffering from primary optic atrophy. In the course of a year, he had become completely blind. No mental symptoms had developed.

=Physically=, Lauder was in very good condition. =Neurologically=, there was a complete optic atrophy with paralysis of the internal rectus muscle, marked nystagmus, and absent pupillary reactions. All the tendon reflexes were exceedingly lively, though the right arm reflexes were more lively than the left, and the left leg reflexes more lively than the right. There was an ankle clonus on both sides. The abdominal and cremasteric reflexes were lively. There was a slight intention tremor. There was, however, no ataxia and no speech defect.

=Diagnosis=: The nystagmus, optic atrophy, and the reflex disorder suggested multiple sclerosis, although the liveliness of the superficial reflexes, especially the abdominal reflexes, was a point somewhat against any advanced degree of multiple sclerosis. It would appear that the absence of pupillary reaction to accommodation is also rather unusual in multiple sclerosis.

The serum and spinal fluid W. R.’s proved positive. There were 25 cells per cmm., albumin was in excess, and there was a positive globulin reaction.

1. What is the significance of optic atrophy and other optic changes
with respect to neurosyphilis? Canavan, from our laboratory, has
reported that she found that 40 of 58 unselected cases of mental
disease exhibited obvious and undeniably important changes in the
optic nerve. She found that optic nerve changes were even more
frequent than chronic spinal cord changes as detectable by the
same method (Weigert myelin sheath method); there were only 34 of
the 58 cases which showed chronic spinal cord changes. Eighteen
cases very probably syphilitic (although the clinical evidence was
not in all cases supported by the W. R.) failed to show optic
nerve changes in but three instances. The 15 syphilitic cases that
did show optic nerve changes showed them in but one eye in three
cases, in both eyes in 12 cases. Canavan incidentally demonstrated
a spirochetosis in the pial sheath of the optic nerve in a case of
neurosyphilis, possibly paretic.

2. What is the frequency of eye changes in neurosyphilis? Posey and
Spiller (“The Eye and the Nervous System,” 1906) quote Kéraval as
finding 42 instances of fundus change in 51 cases of paresis.
Clifford Allbutt found 41 cases of atrophy in 53 of paresis; other
authors have found far fewer. Optic atrophy sufficiently marked to
cause blindness is relatively rare in paresis. Compare table of
eye changes from Joffroy under Case Falvey (55).

As for optic atrophy in tabes, Posey and Spiller record statistics
as so various as to be on the whole unsatisfactory. The highest
percentages found appear to be those of Mott, 80%, and Gross, 88%.
It is evident that the standards for measuring optic atrophy must
differ very much.

=Atypical case of neurosyphilis. Picture of Huntington’s chorea.=

=Case 72.= Margaret Green, 28, was received at Danvers State Hospital in an excited and frightened state. She was very talkative and said that she was being bitten by snakes and serpents. She thought every one approaching her was the devil, and sprinkled what she called “holy water” about her for protection. It was clear that she was hallucinated. She heard her child crying, and she saw a woman carrying it away.

After a few weeks, Mrs. Green grew quiet and more rational except for a few spells of violence and noise; she gave the impression of a rather pleasant and agreeable, though somewhat demented, patient. Physically, beyond a tremor of fingers and tongue and lively knee-jerks and some evidence of enlargement of the heart, there was nothing to be found.

Margaret Green is still in the Danvers Hospital, being now 48 years of age. During the twenty years, she has presented,—besides the mental picture of impairment of memory—occasional spells of confusion, a variety of delusions based, at least in part, upon auditory and vivid visual hallucinations, a certain irritability and psychomotor excitement, and a picture of Huntington’s chorea. The diagnosis of Huntington’s chorea has always been in doubt by reason of the lack of any evidences of hereditary taint; it has, however, not been possible to secure a properly intensive account of her relatives.

It appears that the choreic movements were first observed—in the hospital at least—about 16 years ago. The patient has always been decidedly mixed upon dates. From internal evidence derived from her obviously in part erroneous statements, it may be that the chorea began at the age of 23. It appears that she had been often termed a victim of St. Vitus’ dance, and had had to leave her work in the mill on account of the disease. From one source of information, it would appear that the patient began to have what was called St. Vitus’ dance when she was 14 or 15 years of age; so far as this informant knew, no other member of the family had had the affliction.

The first movements observed in the hospital were irregular, jerking movements, more marked in the left arm but also occurring in the other extremities, as well as in the face, wherein were produced peculiar grimaces. The twitching movements would become decidedly worse during spells of irritability. Observation in the patient’s early thirties left the question in doubt whether the left pupil reacted to light or not. In 1904, when the patient was 36, both pupils failed to react to light either directly or consensually. At this time, the jerky movements continued, especially in the left hand and forearm, the tongue was tremulous, test phrases were poorly pronounced, the knee-jerks were exaggerated (especially the left), and both wrist-jerks were exaggerated. The systematic examination, however, revealed no other neurological disorder. Within a year, slight spurious ankle clonus developed on both sides; the eyes, especially the left, gave the appearance of developing cataracts. A slight consensual light reaction was demonstrable on the right side, but all light reactions were absent in the left eye.

At the age of 42, the patient was still disoriented for time, place, and persons and subject to a deep amnesia; was tidy, tranquil, and of a pleasant demeanor, but many of her muscles were in continual motion. There were chewing movements and both hands and feet were rarely still. There were no longer any spells of irritability or violence; and once when found crying on the piazza, Mrs. Green, on being asked the reason, replied that a gray cat had come and looked at her so hard it made her cry. There were other crying spells at times for equally good reasons, or for no reason.

More recently, the patient has become fairly well oriented for time and place, and has acquired a fairly good insight into her condition and a good memory for past events. She has had occasionally auditory hallucinations, as of water running. In 1914, it was reported that the pupils reacted to light, and the rest of the systematic neurological examination was negative except that the knee-jerks were exaggerated; and a re-examination in 1916 showed the pupils still reacted to light. At present, the patient is disoriented for time, stating that her age is about 25; she is no longer subject to auditory hallucinations; she has a marked difficulty in enunciation, emphasized by the lack of teeth and in part due to continual movements of the tongue; the movements appear to be part of a generalized chorea.

In a systematic review of the Wassermann findings in the hospital population, the blood of Margaret Green was examined and found to be positive. Lumbar puncture forthwith performed showed a positive W. R. in the fluid; there was a positive globulin and an excess of albumin; the gold sol was characteristic of paresis; there were, however, but three cells per cmm.

1. Are the choreiform movements related to the demonstrable syphilis
of the nervous system? Neither the fluid W. R. nor the gold sol
reaction should be regarded as necessarily an indicator of tissue
loss. The fluid W. R. is commonly thought to signify merely that
the fluid contains substances which are somehow due to the
presence of spirochetes in some region pretty closely related with
the fluid. The gold sol reaction, although well established to be
characteristic of neurosyphilis, is perhaps not so strong an
evidence of the existence of spirochetes in the region from which
fluid constituents are derived. There is no pleocytosis. However,
the positive globulin test and the excess of albumin do indicate a
certain amount of destructive process somewhere in the neural
tissues. Are we to suppose that these substances have been
continually found during the course of this disease? This question
cannot be answered with the data in hand, and we can only suspect
that these positive tests for albumin and globulin are an effect
of tissue destruction caused by neurosyphilis. It must be admitted
that the argument here is a little tenuous. The lesson is plain:
that in the present stage of our knowledge the W. R. should not be
omitted even in cases which present a fairly convincing picture of
some well-known entity. Thus, a disease, which looks like
Huntington’s chorea, as well as a disease suggestive of multiple
sclerosis, requires investigation by the methods of the
syphilographer.

2. How shall we explain the changes in pupillary reaction in this
case? They cannot yet be explained. A few observers have reported
changes in pupillary reflexes in the direction of normality. In
our experience such changes have not been noted. It cannot be too
strongly emphasized that it is very easy to make errors in judging
pupillary reaction if care is not used. For instance, if the
patient is accommodating for near vision, light will probably not
cause contraction. A frequent cause of error in testing the light
reflex arises from using a weak electric light. An electric
flash-light is much less efficient than daylight. Probably the
most satisfactory method is to take the patient to a window, ask
him to look at a distant object, shade the eye with the hand,
remove hand, and observe.

3. What is the chief triad of symptoms in Huntington’s chorea? (1)
Choreiform movements associated with (2) progressive mental
enfeeblement, (3) occurring in a patient whose family history
shows a similar condition in a preceding generation.

=Differential diagnosis between NEUROSYPHILIS and SENILE
ARTERIOSCLEROTIC PSYCHOSIS.=

=Case 73.= Marcus Chatterton was a retired sea captain, 75 years of age. At the age of 71, he had had a seizure with a slight right hemiplegia and inability to talk. He had been slightly confused for a short time but had rapidly recovered. During the intervening four years, there had been three similar attacks, and the last one had caused him to come to the hospital. He was, in fact, confused upon admission but had become perfectly clear by the next day. There was a considerable memory defect, which the patient himself did not entirely appreciate. Possibly his judgment had been deteriorating slightly. He had been irritable of late and sometimes sleepless.

=Physical examination= showed a rather well preserved man with but slight senile changes. The pupils were equal and reacted readily to light and accommodation. There was no sensory disorder and no disturbance of coördination. There were no tremors. The systolic blood pressure was 205, the diastolic 135. The arteries were sclerotic upon palpation. A sufficient diagnosis would have seemed to be arteriosclerosis, and the hypothesis of syphilis would hardly have been raised off-hand by most practitioners. The W. R. of the serum was negative. What led to lumbar puncture in this case was the fact that the sea captain’s wife had died 15 years before of general paresis. The lumbar puncture was rewarding since the W. R. was positive. There was an increase of albumin and globulin, a “paretic” type of gold sol reaction, and 56 cells per cmm.

Accordingly, we must regard the condition as one of neurosyphilis. Perhaps the arteriosclerosis was of syphilitic origin. If this is a case of general paresis as we suppose, it is one of very long-standing syphilis.

1. Do delusions of grandeur in the senile period suggest syphilis?
Not necessarily; it appears that there is a small group of senile
cases which might be called cases of senile pseudoparesis in which
extravagant delusions of grandeur are entertained, and in which
frontal atrophy is found although entirely without evidence of
chronic inflammation. It has not been proved that these cases are
of syphilitic origin. It is suggestive that the site of the most
extensive lesion is precisely the site of the most extensive
lesion classically found in paretic neurosyphilis, viz., in the
frontal regions.

2. Is neurosyphilis frequently found in both mates? It can hardly be
said that this is a usual finding. However, it is far from rare,
and it occurs frequently enough to be used in support of the
theory that there is a special strain of spirochete that has a
predilection for nervous tissue. It must be remembered, however,
that the wives of syphilitics are frequently infected without
being aware of it. In such cases they receive no treatment and
consequently have a larger chance of developing neurosyphilis. It
is a good rule to consider the mate of every syphilitic a
candidate for neurosyphilis.

=An atypical case of recurrent dazed states resembling HYSTERICAL
FUGUES. Probably an instance of NEUROSYPHILIS.=

=Case 74.= Abel Bachmann, a man of 40 years, remains doubtful and perhaps belongs to the still unresolved group of mental cases due to syphilis that cannot be placed in any of the well-known categories. Bachmann had been found by the police, working in front of a cowbarn without the consent or even the knowledge of the owner. Bachmann had, in fact, spent the night in the cowbarn and was working with the idea of paying for his night’s lodgings. The situation struck the police as so peculiar, and Bachmann was so confused and irresponsive, that he was brought to the Psychopathic Hospital. The afternoon of his admission, however, he entirely cleared up and was able to give a good account of himself.

His story was that he had been worrying a good deal about a divorce suit, and the morning of his episode he had awakened with peculiar feelings. He walked from Boston to Cambridge, feeling that he was in a strange city. He recognized the places he passed, yet they all seemed to be changed. Upon reaching Harvard Square, he determined to return to Boston and walked and walked, failing to reach Boston. All day he had eaten nothing; when night fell he stole into a field and dug out radishes. A postman stopped and said, “Hello, Bill,” which awakened him as by an electric shock. A barn presented itself, in which he spent the night. In the morning, the barn looked different. In fact, his entire surroundings appeared mysterious. As he felt like working, he went to work in front of the barn.

It seems that in his life there had been two other episodes of a similar nature; in fact, Bachmann had been in a state hospital for six weeks after the first episode. The first episode had lasted a few days only, and followed worry when he learned that the girl with whom he was in love was married. The second attack followed the death of his mother, whereupon he was taken to a state hospital although the total duration of symptoms was only three days. Bachmann had had a chancre or some other form of genital disease at 26, and had at that time been treated with mercury.

Except for irregular and absolutely rigid pupils, reacting neither to light nor to accommodation, Bachmann showed no physical and especially no neurological disease whatever. Moreover, the W. R. in the blood serum was negative.

As to diagnosis, one might consider hysteria, of which, however, there are no visible stigmata. It would not appear that brain tumor would be likely to have lasted so long as eight or nine years, even if we should attempt to make the hypothesis of tumor cover both the non-reacting pupils and the episodes. Bachmann was non-alcoholic, and there was no sign of any other form of intoxication. The spinal fluid showed a negative gold sol reaction, there were no cells in the fluid, there was no globulin; albumin was normal. However, the W. R. was strongly positive.

The situation, then, in this case is that we have somewhat peculiar psychopathic episodes, pupils rigid to light and accommodation, a positive W. R. in the spinal fluid, and extremely little else to permit a diagnosis. We are ignorant as to the course and pathology of such cases. However, we cannot resist the temptation of the diagnosis of neurosyphilis, although further classification is not ventured.

1. What is the significance of stiff pupil as an isolated symptom?
Nonne finds that in the end, after years of observation, the
Argyll-Robertson pupil turns out to be an advance courier of other
more functionally serious signs and symptoms of neurosyphilis. We
can confirm this experience and regard it as an established
clinical proposition that the Argyll-Robertson pupil cannot be
neglected. In this connection, refer to the case of alcoholic
pseudoparesis (Murphy, 60), and also to the case of pineal tumor
(Donald Falvey, 35). Enthusiastic reports have occasionally been
made upon apparent restoration of the true syphilitic
Argyll-Robertson pupil to normal light reaction. The difficulties
in rendering the symptomatic diagnosis of Argyll-Robertson pupil
in a given case are so great, and the chances of complication so
numerous, that we are inclined to attach little significance at
present to these claims.

It may not be amiss to mention a somewhat humorous incident familiar
to some local neurologists. A case was reported by the interne for
a number of months as a victim of a pupil stiff to light and
accommodation, and the entirely adequate cause of this phenomenon
was actually only discovered at autopsy by the triumphant medical
examiner, who demonstrated that the patient in question was
possessed of a =glass eye=.

=TABETIC NEUROSYPHILIS (“tabes dorsalis”) versus PERNICIOUS ANEMIA
with spinal symptoms.=

=Case 75.= Mrs. Brown was a woman of 56, who for the past eight or ten years had been complaining of trouble in her legs. As she described it, at times her legs were so weak she could hardly stand; at other times there was considerable pain and numbness. She has always been considered “high strung”; that is, she had a very bad temper and lost control of herself almost entirely when she became excited. Her legs had been growing progressively worse, and for about a month prior to admission she had been unable to stand or walk. She had also lost control of her bladder. On account of her temper, it had been almost impossible to nurse her; no nurse would stay with her because of her scolding and fault-finding. Recently, she had been having fits of the blues.

Her husband, who was seen before Mrs. Brown, was an old gentleman, over 70, who was chiefly remarkable from the fact that he had unequal, irregular pupils, which reacted neither to light nor accommodation; there was also a speech defect.

The patient herself proved to be extremely irritable, as had been stated,—so much so that at times it seemed almost impossible to do anything for her. She was very querulous, constantly complaining, and not satisfied with anything that was done. Aside from this, her =mental examination= proved to be entirely negative; that is, there were no psychotic symptoms.

The systematic =physical examination= gave the following significant findings: blood pressure, 160 systolic, 90 diastolic; no evidences, however, of peripheral arteriosclerosis. Patient was unable to walk or stand, and had no control over her bladder. The knee-jerks and ankle-jerks absent on both sides; ataxia in the leg movements; loss of sense of localization, with no tenderness over the nerve trunks; no atrophy, paralyses, or muscular asymmetry of the parts. The vibratory sense was maintained. Subjectively, the patient thought that the vibratory sense differed in the legs from that in the arms. Localization, touch, pain, heat, and cold responded to correctly. The arms showed nothing abnormal; there was no incoördination, dysmetria, or dysdiadochokinesis. Her pupils were equal, regular, and both reacted normally to light and accommodation.

=Diagnosis=: The first consideration in the case is naturally tabes dorsalis, especially when one considers that the husband had signs which suggested syphilis of the nervous system. The rapid onset of the acute symptoms in this case, and the absence of the characteristic signs of pain were at least atypical for this diagnosis, as was the absence of any pupillary signs. Further, the W. R. was negative in the blood and spinal fluid; there were no definite signs of inflammatory reaction as shown by the other spinal fluid tests. These findings made a diagnosis of tabes entirely improbable. After tabes, the most frequent cause of the symptoms above enumerated is perhaps to be found in pernicious anemia. Examination of the blood showed that the patient had 2,500,000 erythrocytes per cmm. The hemoglobin by Tallquist scale was 80%. The smear was practically negative; no blasts could be seen. Although this picture is not a typical one for pernicious anemia, at least it is significant in the low number of red cells to be found, and as no causes for anemia were to be found, it seemed probable that we were dealing with a primary anemia. The diagnosis in the case, therefore, is spinal sclerosis of primary anemia. The mental picture was not uncharacteristic of PERNICIOUS ANEMIA.