Chapter XX: Section VI: , Neurosyphilis and the War (2)

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[18] 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.