Part 27

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

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

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

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

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

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

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

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

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

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

1. Ataxia of the legs.

2. (Probable) Diminished sensibility in the legs.

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

4. Paralysis of left facialis.

5. Paralysis of left external rectus.

6. Tongue protruded to right.

7. Right elbow jerk greater than left.

8. Knee-jerks absent.

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

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

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

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

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

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

Spinal cord was not remarkable.

=Summary=:

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

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

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

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

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

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

=NON-PARETIC NEUROSYPHILIS=

=DIFFUSE NEUROSYPHILIS, MENINGOVASCULAR PARENCHYMATOUS, CEREBROSPINAL SYPHILIS=

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

MASSACHUSETTS COMMISSION ON MENTAL DISEASES, _November, 1916_

CHART 23

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

=EFFECT OF EARLY TREATMENT ON THE DEVELOPMENT OF NEUROSYPHILIS=

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

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

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

MATTAUSCHEK AND PILCZ

CHART 24

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

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

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

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

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

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

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

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

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

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

=PARETIC NEUROSYPHILIS=

=(GENERAL PARESIS)=

Cases systematically treated 50

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

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

MASSACHUSETTS COMMISSION ON MENTAL DISEASES NOVEMBER, 1916

CHART 25