Part 14

The =nervous system= showed several unexpected features. The _absence of chronic leptomeningitis_ was striking: the pia mater was everywhere delicate and transparent except that the walls of the cerebellar and chiasmal cisternæ were thickened and that there were slight opacities along the sulcal veins of the convexity. Brain weight 1090 grams. There was a generalized =sclerosis and pigmentation of the cerebral cortex=. The sclerosis varied in degree and was most marked in the prefrontal regions, the anterior halves of the superior frontal gyri, the middle third of the right precentral gyrus, the region of the splenium on the left side, and the sagittal rami. If the _bacillus coli communis_ found in the cerebrospinal fluid had any effect upon the consistence of the brain, obviously hard to prove in a brain of leathery consistence at the outset, it was shown only in the right Rolandic area in the vicinity of the sclerotic part of the precentral gyrus. =Granular ependymitis= of all ventricles. Weight of cerebellum, pons and bulb, 135 grams.

Perhaps the most remarkable feature of all in the case was the occurrence of =cysts of softening= in the posterior part of each =dentate nucleus=. For discussion, see Case 41.

=VASCULAR NEUROSYPHILIS (?) versus PARETIC NEUROSYPHILIS (“general paresis”). Autopsy.=

=Case 41=, like Case 40, was one of arteriosclerotic brain disease with severe cerebellar involvement. Here is another case in which the Danvers staff made a diagnosis of general paresis without dissenting voice. There were some tabetic symptoms, and the spinal cord at autopsy did show a moderate lymphocytic infiltration of the meninges, entirely consistent with the picture in the spinal fluid. In this case, the dentate nuclei of the cerebellum were not destroyed as in Case 40, but were affected by cell atrophies of variable degree in different parts of the nuclei. There was also a severe gliosis of the cerebellar cortex. The left hemisphere of the cerebellum was more severely diseased than the right. The cortex showed far more marked and generalized cell atrophies throughout the layers than did Case 40. The details of this case, which was that of a colored coachman, Samuel North, are as follows:

He was born in 1871. Learned to read and write at school. Stableman and coachman. Alcoholic till 1902. Took much quinine, possibly impairing hearing thereby. Memory impaired and growing worse since 1902. Gait unsteady for a longer but unknown period. August 13, 1907, wandered about, instead of attending boot-black stand, muttered, talked incoherently. In the next few days talked about religion and apparently had hallucinations of hearing. Committed August 16, 1907.

On commitment stoop-shouldered, flat-chested. Gait staggering. Unsteadiness in Romberg’s position. Incoördination of arms and fingers. Coarse tremor of tongue. Tremor of lower jaw. Exaggeration of left knee-jerk and diminution of right. Exaggerated Achilles jerks. Spurious left ankle clonus. Questionable Babinski reaction of left side. Abdominal and epigastric reflexes present but cremasteric absent. Left pupil smaller than right and fails to react to light. Reaction of right pupil sluggish. Moderate defect of hearing of both sides.

During the first week the patient developed hallucinations of sight and hearing, but of no other senses. Disorientation for time, place, and persons. Answers to arithmetical problems given with assurance but as a rule incorrectly (as 17 and 32 are 90; 18 divided by 3 is 88). Handwriting scarcely legible. Memory poor, especially for recent events (recalled a lumbar puncture as an exercise in baptism). Impressibility and attention poor. Euphoria.

Death after gradual failure July 29, 1908.

Lumbar puncture showed: Per Cent. Endothelial cells 9 Lymphocytes 81 Plasma cells 6 Phagocytes 0 Polymorphonuclear cells 4 Unclassified 0 Fibroblasts 0 Cells in 100 fields 700

=Post Mortem Findings.= The cerebrospinal fluid showed a pure culture of _Bacillus coli communis_, and the heart’s blood showed many colonies of an unidentified bacillus. Culture from mesenteric lymph nodes sterile.

The =cause of death= is somewhat in doubt. There was an early pneumonic process with fibrinous pleurisy, and there was an early acute hemorrhagic ileitis with a very slight overlying peritonitis and slight corresponding enlargement of mesenteric lymph nodes. There was an infection of the meninges with _Bacillus coli communis_.

Evidences of =chronic disease outside the nervous system= were: coronary and pulmonary arteriosclerosis, chronic fibrous endocarditis, mitral sclerosis, aortic sclerosis with calcification, chronic splenitis, chronic interstitial nephritis, hepatic atrophy (wt., 900 grams), thickening of cartilaginous portion of right auricle (old trauma), scars of apices of lungs.

The =calvarium= was dense and the =dura mater= everywhere adherent. The =arachnoidal villi= were but slightly developed, but there was one small focus of cortical herniation through the dura mater of the left middle cranial fossa. The =pia mater= was delicate except for slight opacities along sulci. There was some pial thickening over the region of the interparietal sulci on both sides. There was pial pigmentation anteriorly and superiorly.

There is no gross evidence of intracranial arteriosclerosis, except (1) that afforded by the lesions of the dentate nuclei of the cerebellum mentioned below and (2) the swerving to the right of the basilar artery, possibly due not to arteriosclerotic lengthening of the artery but to an unusual shape of the pons (see below).

The =brain= weighed 1245 grams (cerebellum and pons 165 grams). =The anatomical diagnoses of central nervous system= were:

Slight general encephalomalacia (post mortem imbibition of fluid, 31 hours). Slight gliosis of right prefrontal and frontal gyri. Slight gliosis of right optic thalamus. Generalized granular ependymitis, especially near fornix and about foramina of Monro. Anomaly of pons (not gliotic, but possessing far more white matter on the left side than the right). Severe arteriosclerosis confined to the dentate nuclei of the cerebellum.

As we now look over the data in Cases 40 and 41 we are inclined to ask the question, whether modern systematic diagnosis would not have shown these cases to be NEUROSYPHILITIC? One is inclined to answer this question in the affirmative, on the basis that Case 40 showed somewhat questionable Argyll-Robertson pupils, and Case 41 showed unilateral Argyll-Robertson effect. Both cases showed Romberg sign, but the dentate nucleus and other cerebellar disease in each case may in some way have contributed to or imitated this phenomenon. Whether Case 40 was a tabetic must remain a question, but Case 41 must be regarded as a case with spinal and meningeal changes highly characteristic of syphilis.

=VASCULAR NEUROSYPHILIS plus TABETIC NEUROSYPHILIS (“tabes dorsalis”) simulating paretic neurosyphilis (“general paresis”). Autopsy.=

=Case 42.= The case of Elizabeth Brown was at one time carefully studied by Dr. A. M. Barrett in his work on mental diseases associated with cerebral arteriosclerosis and, like Case 43, was one in which tabes dorsalis was a factor. Elizabeth Brown’s maternal grandfather and mother were insane; there had also been insanity in a sister. Mrs. Brown was struck on the head at 44, and was unconscious for an hour, but there were no sequelae to this accident. At 48, there was a shock, or apoplectiform attack, followed by unconsciousness for two hours and by left hemiplegia, right ptosis, and thick speech. Mrs. Brown began to walk again after two weeks, but was found to be forgetful and fabulatory. She seemed at times to be hearing music, and somewhat repeatedly became helpless and unable to walk. She could not remember from day to day, showed incontinence of urine and feces, and was brought to the Danvers Hospital. The physical and mental deterioration was progressive. There were some signs of organic brain disease. The musculature was especially flabby on the left side. The left angle of the mouth drooped, and the left nasolabial fold was smoothed out. The arm movements were ataxic, the tongue protruded to the left, the right pupil reacted but slightly to light (eye blind from cataract), the knee-jerks, Achilles, wrist, and elbow reflexes, were absent. The patient was unable to stand, and there was a marked tremor of the hand, tongue, and lips. There was a zone of anesthesia for pain and tactile stimulation extending round the body, from the 3d to the 6th rib, and there were symmetrical areas of anesthesia on the inner surface of the forearms and the legs.

The =autopsy= showed a =general arteriosclerosis= with =chronic= and =acute meningitis=. The brain weighed 1110 grams; the =pia mater= was moderately thickened; the basal vessels were highly arteriosclerotic. The brain itself, however, normal externally, upon dissection, showed a number of small cysts irregularly scattered in the white substance. The basal ganglia were porous, and there were several small cysts in the pons. =Microscopically=, there was evidence of severe vascular disease, involving not only the arteries but also the veins. It was the superficial rather than the deep arteries that were more often attacked. There was a marked =perivascular gliosis=. Extensive search yielded _no evidence of lymphocyte infiltrations_, either in the brain or in the spinal cord.

The spinal cord showed degenerations in both the lateral and posterior columns, of which the explanation may possibly be like that in our paradigm, Case 1.

Is the case of Elizabeth Brown one of neurosyphilis? We cannot definitely say on account of the non-availability of the modern systematic tests, but it may well be that the case, although certainly not one of paretic neurosyphilis, was one of TABES WITH VASCULAR COMPLICATIONS.

=TABETIC NEUROSYPHILIS (“tabes dorsalis”) with symptoms of cerebral origin producing a picture resembling taboparetic neurosyphilis (“taboparesis”). Autopsy.=

=Case 43.= Robert Allen was the fifth case of error in the diagnosis of general paresis analyzed some years since from the staff meeting records of the Danvers Hospital. The Allen case resembles the case of Elizabeth Brown in that there was a combination of tabetic phenomena with cerebral lesions of a non-paretic character at autopsy. But although there seemed to be an utter absence of inflammatory cells (lymphocytosis) in the case of Elizabeth Brown (42), there were some slight perivascular cell accumulations in the Allen case, with a few mononuclear cells suggestive of lymphocytes. The cerebrum, however, failed to show plasmocytosis. It was seriously diseased, showing a marked neuroglia proliferation about the atrophic nerve cells.

Robert Allen was a printer coming from a long-lived race. The following are the main facts:

Married in 1875 (two children, healthy); again married in 1893 (one child, healthy). Compositor from 1890. In 1898 and 1899 girdle and lancinating pains. Thereafter for several years gait was unsteady. During 1904 and 1905 freedom from pains and improvement in gait but gradually increasing irritability and nervousness. Stopped work on last of March, 1905, owing to sudden increase of irritability, emotionality, boastfulness, expansive schemes, and ataxia.

Habits: no tobacco, very little alcohol at long intervals. No drug habits, no sexual irregularity known.

Committed to Danvers April 3, 1905, with slight muscular development, poor nutrition, acne, irregular, poorly preserved teeth, gingivitis, flat-foot, slight radial arteriosclerosis, slight arcus senilis, a few hyaline casts, leucocytes, epithelial cells, and trace of albumin in the urine, scar in sulcus, and enlarged inguinal lymph nodes.

Ataxic gait, Romberg’s sign, fibrillary twitching of chest, abdominal and facial muscles when standing; right pupil slightly larger than left, pupillary margins irregular, light reactions (electric bulb test) both consensual and direct absent, slight pupillary reaction in accommodation; biceps, triceps and wrist reflexes lively and equal; abdominal, cremasteric and plantar reflexes normal, knee-jerks, Achilles and front taps negative even on reinforcement.

The patient himself stated that his ataxia began in 1904, that he had been under treatment for swelling of legs and feet and pain in limbs since 1903, and that there had been some trouble with limbs since 1895. He had been told that his disease was lead-poisoning. About three weeks before commitment patient said he had had an attack of unconsciousness.

The patient’s speech showed considerable defect. Words were pronounced slowly with slurring and tripping especially of the labials. Orientation perfect. School knowledge well retained. The easier arithmetical problems were accurately performed. Memory imperfect for minor recent events. Estimations of space and time often very imperfect. Variability of mood, sometimes euphoric, sometimes tearful and irritable. Occasional expansive estimates of personal powers (“Can lift three five-hundred pound weights with one finger”). Indistinct expansive financial ideas.

The patient continued oriented, euphoric, expansive, untidy, till October, 1905, but on October 12 developed an infection at the site of a callus on the sole of the foot and died with pyemic symptoms, October 17.

=Post Mortem Findings.= The =cause of death= was streptococcus septicemia with acute ulcerative colitis, acute splenitis, bilateral purulent pleuritis, multiple infarctions of lungs.

There were no signs of =chronic disease outside the nervous system= except a moderate thickening of the mitral valves, and slight dural adhesions.

The brain weighed 1450 grams. The vessels at the base showed a slight degree of sclerosis. There was a slight opacity of the frontal, parietal, and temporal pia overlying slightly atrophied convolutions, whose surfaces showed in a few places slight cuppings. The ependyma over the thalami and the floor of the fourth ventricle was finely roughened. The spinal cord showed a typical TABES DORSALIS.

Although we probably cannot regard either Case 42 or Case 43 as a case of paretic neurosyphilis, and although it must remain doubtful whether they are cases of any form whatever of neurosyphilis (in the absence of the modern tests), yet it seems clear that both these cases may very well have been cases of neurosyphilis on account of the existence of a definite tabetic process in each. The symptoms of these cases, like those of Cases 38 to 41, suggest how difficult it must be _to make a clinical diagnosis of general paresis safely without employing available laboratory tests_. Yet how frequently in the past have neurologists brought data concerning various phenomena in long series of so-called paretics in which the error of diagnosis was certainly between 5 and 15% and frequently still greater. The entire question of the symptomatology of paretic and non-paretic neurosyphilis, therefore, needs re-opening and revision.

=CEREBRAL GLIOSIS (probably non-syphilitic) producing the clinical picture of paretic neurosyphilis (“general paresis”). Autopsy.=

=Case 44.= John Hughes was a hostler, and later assistant with a wholesale drug company, with which he remained for 32 years. He had been moderately but constantly alcoholic all his adult life up to 50 years of age, and at 45 had had an attack of so-called nervous prostration, in which his head had troubled him and he had been seclusive. At 49, he had a serious attack of otitis media, associated with delirium, swelling of the feet, and what was called rheumatism. After this attack of otitis media, Hughes appears to have been not altogether right.

At 53, after a quarrel with his employer, Hughes quit work, began to trade a little in hens and pigs, became forgetful, especially of recent events, and did “a variety of peculiar things.” He was a married man but he had no children. There had been miscarriages but of unknown origin; venereal disease was denied. At 55, a week before admission, Hughes had a spell of unconsciousness for several hours, after which his speech was thick, and restlessness, insomnia, and a wandering tendency set in. Visual hallucinations, fabulation, tremors, “excited-looking” eyes, are described. He would sweep things from the dining-room table, pulled a hot stove into the middle of the floor, attempted to sweep paint off the floor, and cut up a carpet with a knife.

The patient on commitment November 5, 1904, was well developed and nourished. The mucous membranes were rather pale. Bruises and excoriations of limbs. Harsh breathing at the base of each lung. Enlargement of heart; sounds irregular. Accentuation of aortic second sound; tension fair, rate 80. Slight brachial arteriosclerosis. Abdomen slightly distended. The urine contained a faint trace of albumin and many hyaline casts.

Moderate tremor of extended hands. Slight tongue tremor. Romberg’s sign absent (slight swaying). Considerable ataxia of extremities (inability to stand with foot on opposite knee). Vision poor. Hearing could not be tested accurately. Prompt pupil reactions with direct light. Slight consensual reaction in left pupil, absent in right. Deep reflexes equal and lively.

Quiet and orderly at first. Later restless and noisy. Questions were answered at times relevantly, more often irrelevantly. Patient irritable, intractable. Required repeated urging to take nourishment. Consciousness clouded. Orientation imperfect. Attendants are possibly “officers.” Date September, 1995. Slight errors in repeating alphabet. Mistakes in Lord’s Prayer with rhyming tendency. Simple arithmetical tests answered automatically with many mistakes. More complex combinations incorrect. Handwriting tremulous (noted as “typical of general paresis”). Auditory hallucinations (answering invisible persons), “All right, I’m coming.” Amnesia and confabulation. Q. “Have you had breakfast?” A. “No,” (later) “Yes, I had a very light breakfast.” Q. “What did you have?” A. “Anything that came along. A few green peas and beans that were left, bread and butter and pie. I had a good breakfast. Guess feed is very high.” Q. “Give names of your sisters and brothers.” A. “There are three or four I never see. I will have to think them up.” (Later)—“Lillie, Abbie, Julia, George.” On repetition of question, “Elizabeth, Julia, Annie and Lizzie.”

Delusions somewhat doubtful. At no time euphoria.

The patient remained only nine days in the hospital, developing diarrhea a week after admission.

=Post Mortem Findings.= The =cause of death= was bilateral bronchopneumonia of hypostatic distribution, accompanied by bronchitis and acute splenitis. The intestinal tract was normal (despite the diarrhea). No cultures. The heart showed acute myocarditis.

The vessels in general showed no sclerosis, except that the aorta showed a few patches with calcification near bifurcation. There was a moderate degree of mitral sclerosis. The kidneys showed a moderate degree of chronic interstitial nephritis. The heart weighed 530 grams and there was moderate dilatation of all the valves.

There were some evidences of chronic disease outside the nervous system, namely, an obliterative pleuritis on the right side, chronic perisplenitis, and chronic external adhesive pachymeningitis.

The =nervous system= showed a pia mater thin and transparent, with a moderate congestion of larger and smaller vessels. No noteworthy change of the brain substance or of the ventricles was found, except that the cerebral substance was of unusual firmness (autopsy twelve hours after death).

It is clear that the brain was not wholly normal, exhibiting a general induration due in part to subpial gliosis and in part doubtless to perivascular gliosis. =Microscopically= the tissues showed features of great interest, especially multiple focal neuroglia cell proliferations of a perivascular distribution, considerable subpial fibrillar gliosis of an unusually focal type, and a rather general subpial cellular =gliosis=. Histologically, it seemed that this chronic progressive process had started, not so much in relation with dying nerve cells, as in relation with blood vessels. The =perivascular= deposits of neuroglia cells were confined almost exclusively to the infragranular cortex layers. It seems plain that the diagnosis of general paresis was not justified. It is probable that the diagnosis of neurosyphilis is not justified. The explanation may be that now and then cases of cerebral sclerosis may clinically imitate the neurosyphilitic process. It must be borne in mind that the diagnosis in this case was made, like the other cases at head of Part III, without the advantage of modern systematic methods. Clinically speaking, of course, there was no definite Argyll-Robertson pupil, although the consensual reaction, slight on the left side, was absent in the right pupil. The general picture appeared to be one of the so-called demented form of paretic neurosyphilis.

=Differential diagnosis between NEUROSYPHILIS and NEURASTHENIA.=

=Case 45.= Albert Robinson, a man of 28 years, was shipwrecked on one of the Great Lakes. The ship was on the rocks for eight days, and Robinson was under a great strain. Ever after the wreck, Robinson had felt severe pain in the head, neck, and back, and a feeling of great weakness whenever he exerted himself physically or mentally, and seven months after the wreck, he had several attacks of fainting.

For a number of weeks he had worried a good deal about his inability to make money, especially as money was badly needed on account of his wife’s approaching confinement. A few days before entrance, Robinson had become very forgetful, and was unable to recall, the night before entrance, where he had been during the day. On the whole, however, on mental examination no actual evidence of memory defect could be shown to exist.

=Physically=, Robinson was entirely negative, except for some hard glands in each groin. =Mentally=, there was little to show except depression, worry over his financial condition, and his inability to work. The serum W. R. proved negative.

=Diagnosis=: On the whole, the diagnosis of psychoneurosis (see case Harrison (9)) due to the shock at the time of the shipwreck seemed to be proper. To be sure, the patient gave a history of a chancre at 25, treated for two years, after which he was declared cured.

However, following up the clue of admitted syphilis, rigorous questioning elicited the fact that a few months before there had been diplopia, lasting part of a day.

=Lumbar puncture= seemed desirable. The fluid was clear but contained 125 cells per cmm. with appropriately increased amounts of albumin and globulin. The spinal fluid W. R. was positive. The diagnosis of CEREBROSPINAL SYPHILIS seemed established.

The lesson of this case appears to be that perhaps we should never exclude syphilis until we have made an examination of the cerebrospinal fluid. The W. R. of the blood in meningovascular (non-paretic syphilis) is negative in many cases (the figure is sometimes set as high as 40%).

=Treatment=: After a half dozen injections of salvarsan, all symptoms disappeared and Robinson went back to work, claiming to be in a better condition than for some time past.