This part of the case collection, dealing with puzzles and errors, is ushered in by six cases (39–44) drawn from a group of errors in diagnosis made some years since at the Danvers Hospital. These six are autopsied cases. Attention is called to the fact that modern methods of diagnosis might have prevented the errors.

Case 39. Caroline Davis, dead at 49 years, was a case of error in the diagnosis of general paresis. Like Cases 40 to 44, Case 39 was diagnosticated by the full Danvers staff as a case of general paresis; however, it must be added, before the days of the W. R. and the modern methods of systematic diagnosis. As will transpire in the sequel, there is a large question whether Case 39 is not after all really a case of neurosyphilis, possibly not of the paretic group. The details are as follows:

Caroline Davis was a normal school girl till 15, apt in studies, mill worker till marriage at 18; one child, dead (cause unknown). Habits good. Moderate deafness set in in the forties and in 1901 patient became completely deaf in three months’ time. In 1905 she became unable to take care of her house and had a shock in which the right leg was affected.

On commitment patient showed good development and nutrition with slight enlargement of capillaries of cheeks, redness and roughening of skin of right ankle. Teeth absent. Slight radial and brachial arteriosclerosis. Urine negative. Sluggish pupil reactions to light both directly and consensually. Deafness absolute, bone conduction defective. Arm reflexes brisk, knee-jerks equal, brisk. Bilateral Babinski reaction more marked on the right side, tremor of tongue, Romberg’s sign, gait defective. Speech stumbling, writing clear, without tremor.

Communicated by writing only. Consciousness normal, disorientation for day of month, for place (misnames hospital) and for persons (recognizing nurses, not patients).

Patient wrote many letters complaining of pain, headaches and especially of pain in the abdomen and side. The patient was thought to show a slight defect of memory, but her deafness rendered diagnosis difficult. The patient died suddenly on May 23, 1908, shortly after supper, falling backwards, and dying in five minutes with marked respiratory distress.

Post Mortem Findings. The cause of death was not clear. The heart’s blood and cerebrospinal fluid were sterile. There was a small hemorrhage in the anterior part of the right ventricle derived from a small artery of the caudate nucleus. There was about 400 cc. of blood between the dura mater and the pia mater. There was a slight sclerosis of the basal and Sylvian arteries. The brain substance was uniformly softer than normal.

It is possible that the hemorrhage had taken place some time before the patient’s fall and that the brain substance had swollen in consequence. Just before the fall she had a weeping spell.

The anatomical diagnoses were as follows:

Obesity, unequal pupils, fresh wound near left ear, edema of legs, slight focal adhesive pleuritis, hypostatic congestion of lungs, chronic endocarditis, chronic myocarditis, congestion of kidneys, congestion of pancreas, subacute splenitis, chronic adhesive pelvic peritonitis, hematoma and cystic condition of Fallopian tubes, calvarium dense and thick, subdural hemorrhage, slight chronic leptomeningitis, general cerebral atrophy, marked in tips of frontal lobes, old cyst of softening between left corpora albicantia and optic chiasm, small punctures of left ear drum, drums opaque, chronic spinal leptomeningitis; brain weight, 1190 grams.

There were marked firm interadhesions between dura and pia throughout. A lumbar puncture soon after admission in 1907 had shown:

It will be noted that the lumbar puncture yielded no plasma cells and yet showed 30% of lymphocytes. Alzheimer, in 1904, attempted to distinguish the histology of the cerebral syphilitic from that of the general paretic, maintaining that lymphocytosis was the characteristic feature of the ordinary neurosyphilitic, whereas plasma cells were associated with the lymphocytes in the paretic. This case showed lymphocytic deposits. To be sure, they were decidedly subordinate in the cerebral cortex, cerebellum, and basal ganglia, to the marked evidences of nerve cell destruction, although there were perivascular infiltrations about a few of the larger vessels in the white matter of the cerebral cortex.

The spinal cord, however, showed a most severe infiltration, especially in the gray matter, where the infiltration accompanied severe nerve cell changes and arterial changes. The pia mater of the spinal cord was also packed with mononuclear elements, among which, however, no plasma cells could be found.

But although the inflammatory changes in the shape of lymphocytosis were relatively more prominent in the spinal cord than in the cortex, yet the cortex yielded evidence of an exceedingly marked destructive process. Perhaps no layer of any of the areas of the cortex examined failed to show some atrophic alteration. The upper layers of the cortex were everywhere more severely diseased than the lower layers. Here we are dealing with an instance of an active meningomyelitis and subcortical encephalitis. It is, of course, probable that the W. R., had it been performed, would have been positive in this case. On the basis of the histology, we are inclined to regard the clinical picture in this case as belonging among cases of Non-paretic Diffuse Neurosyphilis.

This case, as also the next several, is especially instructive in teaching the difficulty in differentiating paretic and non-paretic neurosyphilis. Not only is this difficulty met in clinical diagnosis, but in pathological diagnosis as well.

The histological diagnosis depends in large part on the work of the Nissl-Alzheimer school, which has received great recognition. At the present time, however, there is beginning to be considerable doubt as to the entire validity of this teaching. At any rate there are many borderline cases in which the differentiation is well nigh impossible. In this case note chronic meningoencephalitis, with cortical degeneration, in the absence of plasmocytosis.

From the clinical standpoint the intensity of the W. R., the character of the gold sol reaction, and the result of therapy have added new points in differentiation. Much more work controlled by autopsies is still needed, however, to put us on sure ground in borderline cases.

Case 40. Case 40 like Case 41 was an error in the diagnosis of general paresis which might be regarded as academic rather than practical. Both were cases of arteriosclerotic brain disease with severe cerebellar involvement. Case 40 had a spinal cord that was not quite normal. There was a tabetiform lesion in the cervical spinal cord (not elsewhere), together with a unilateral degeneration suggesting in some respects a radicular origin. The most striking feature, however, of Case 40 as in Case 41, was a lesion of the cerebellum. In Case 40 the dentate nuclei were in large part destroyed by cysts of softening, although the cerebellar cortex was fairly well preserved on both sides. The details of Case 40 are as follows:

H. F., male, gear maker, born 1850.

Heredity. Maternal grandmother insane. Mother insane at 52, became demented and lost use of limbs, died at 71. Aunt insane.

Personal History. Common school education. Capable workman till within a few months. Early in life alcoholic. Drunk almost every week until 1899 or 1900. Irritable, nervous, selfish, loose in relations with women. Venereal disease denied by wife. Married in 1883. Three frail children. No miscarriages. Neuralgia in 1901 or 1902.

January, 1904, patient left carriage shop on account of mistakes in work, became more pleasant, childish, fearful, talkative, did funny things, later became vagrant, stole from fruit stores, smoked cigarettes picked up in the street, and became restless and irritable.

Committed to Danvers, June 24, 1904, with slightly enlarged heart, somewhat heightened blood pressure, and a slight sediment of epithelial cells in urine.

Romberg’s sign was present, but there was little or no demonstrable incoördination otherwise. Very slight tremor of fingers. Left knee-jerk absent, right obtained on reinforcement. Achilles jerk absent. Triceps, wrist and normal plantar reflexes present. Pupils react to accommodation, but very slightly, if at all, to light. Sensations normal except in legs. The legs show preservation of tactile and temperature senses, but abolition of pain sense except over dorsum of foot.

Speech showed slurring of syllables and “brigrade” for “brigade.” Disorientation for time, place and in part for persons. Admitted that his work had been deficient but regarded himself as well. Emotionally variable, crying at times and suddenly becoming jocular. Eloped July 3 and somehow reached his wife’s house in a neighboring city.

Euphoria persisted. The pupils continued Argyll-Robertson, and the knee-jerks remained absent. Became oriented for place and partially as to time (month and day of week correct).

During 1905 failure became rapid, with ataxia of legs, persistent euphoria, and loss of weight.

Convulsions, regarded as general paretic, developed in 1906. Death sudden, December 7, 1906.

Post Mortem Findings. The cause of death was streptococcus septicemia, probably derived from a gangrenous bronchopneumonia or related with a small thrombus of the right auricular appendix. There was also an acute purulent otitis media, mastoiditis and sphenoidal sinusitis, as well as extensive decubitus. From this decubitus or from the intestinal tract may have been derived the numerous colonies of bacillus coli communis which developed on plates from the cerebrospinal fluid.

Arteriosclerosis was little in evidence, being confined to the coronary, right vertebral and carotid arteries (slight in all). Cysts of softening existed in the posterior part of each dentate nucleus and may probably be interpreted as indicating vascular disease.

Chronic disease outside the nervous system was prominent and in part suggestive of senile findings; milky patches of pericardium, adhesions about liver and gall-bladder, adhesions about spleen, adhesions and fibrous thickening of parietal peritoneum, adhesions in both pleural cavities, chronic diffuse nephritis, hypertrophy of bladder wall, dense calvarium, dural adhesions.

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.

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.

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.

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.

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.

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.

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.

1. How shall we explain such a symptom as the transient diplopia? This diplopia is probably an example of a neurorecidive, but it will be observed that it occurred without salvarsan therapy. See discussion above under the case of Bennett (34), where the general result of the neurorecidive inquiry launched by Ehrlich early in the history of salvarsan therapy showed that precisely similar phenomena had always occurred in neurosyphilis, whether under treatment or not. The anatomical and histopathological explanation of such phenomena is, of course, doubtful, but a review of the findings in the case of Alice Morton (1) will show how many apparently serious symptoms in neurosyphilitics are actually irritative or at least due to lesions which are entirely recoverable. We may suppose, first, a local proliferation of spirochetes; second, a local over-formation of toxic substances, directly or indirectly the product of spirochetosis; thirdly, a local exudation; fourthly, a local proliferation; fifthly, a combination of these phenomena, any or all of which may be regarded as but transient. We have sometimes found at autopsy very little exudate except in small areas; sometimes not more than a few mm. or cm. in superficial extent. Note, for example, the small areas of lymphocytosis demonstrable in but two foci in the case of Alice Morton, the paradigm placed at the beginning of this book.

Case 46. Alice Caperson was a colored girl of 18 years. She had acquired syphilis five months before admission to the hospital, and the secondary symptoms of this syphilis had just disappeared before admission.

Very shortly after acquiring syphilis, the young negress began to act peculiarly. She describes herself as having a sort of nightmare, both when asleep and also when awake. For instance, she saw her dead grandmother. It appeared at first like a seraph; then it came nearer to her and seemed to fill out; and then was dressed precisely as her grandmother had been. This seraph appeared as though trying to tell her something, but she could not make out what the something was. The vision had appeared on two or three occasions.

Our examination detected little beyond instability and irritability of mood with some depression. The patient readily fell to weeping. She soon made friends in the wards, however, and got on well. Physical examination was entirely negative but the W. R. of the blood serum was positive. The W. R. of the spinal fluid was negative, as was the gold sol reaction; there was an excess of albumin and a positive globulin test; there were seven cells per cmm.

The psychiatric diagnosis of a case like that of Alice Caperson would waver between hysteria and dementia praecox. However, as for dementia praecox there are hardly any typical symptoms. There is insight into the hallucinations, which are hypnagogic. There are, however, no hysterical stigmata.

The spinal fluid reaction is typical of the secondary stage of syphilis. It is commonly said that in every case of syphilis the nervous system is involved at some period, if only to the degree shown in the present case. However, such involvement tends to disappear both with and without antisyphilitic treatment, just as do the secondary skin symptoms. So far as syphilis is concerned, the prognosis under radical treatment is as good as usual. We are inclined to regard the case as one of the Hysterical or Psychopathic group and inasmuch as cases occurring in the developmental stage of a patient’s life are of fairly good general prognosis, we are inclined to regard the prognosis in this particular case as good under proper therapy and hygiene.

1. What is the relation of neuroses to syphilis? Neurasthenia, chorea, hysteria, and epilepsy are often grouped (for example, by Nonne) as neuroses bearing at times important relations to neurosyphilis. (For the relations of neurasthenia, chorea, and epilepsy, see cases of Greeley Harrison (9), Margaret Green (72), and David Borofski (49), respectively.) As for the hysteria shown in Caperson, Charcot enumerated syphilis among agents provocateurs of hysteria along with alcohol, lead, arsenic, and the like. Fournier has also considered the problem. It is clearly necessary to show that before infection there were no hysterical symptoms, and that the hysteria developed during the operation of the syphilitic process, and it is probably necessary to show that the symptoms will clear up under antisyphilitic treatment, if we are to concede the existence of a syphilitic hysteria.

2. What are the evidences of neurosyphilis in the secondary and primary stages of syphilis? As above stated, the findings in Caperson are typical enough. Wile and Stokes at first stated that 60 to 70% of the secondary syphilitics show changes in the spinal fluid; in a further article they maintain that probably every case shows such changes and that clinical symptoms of neurosyphilis of the secondary period can probably be determined. They claim that it is probable also that the same holds for primary syphilis itself. The importance of these claims lodges partly in the relation of these early signs of neurosyphilis to the whole question of latency and to the question of paresis sine paresi. For a discussion of paresis sine paresi see cases Lawlor (25), Vogel (52).

Case 47. As in other instances (compare Martha Bartlett (21) and Annie Monks (85)) so also in the case of Ethel Hunter, a woman 61 years of age, there was no initial suspicion of neurosyphilis. Mrs. Hunter was brought to the hospital stuporous as a result of an overdose of paraldehyd. The paraldehyd had been administered by a physician to combat insomnia and agitation. As soon as Mrs. H. had recovered from the drug stupor, this agitation appeared once more, and it was clear that she was suffering from marked depression. There was tremendous worry over the sickness of a woman with whom the patient lived. The patient was very self-accusatory, blaming herself for many things that had happened in the household. Besides her agitation, depression, self-accusations, and insomnia, the patient showed a good deal of the symptom frequently termed “retardation”—a kind of lagging of all mental processes found, according to Kraepelin, in manic-depressive psychosis.

Accordingly, the diagnosis of manic-depressive psychosis might well have been rendered. The fact that the psychosis so far as known began in the involution period was not against the diagnosis since the so-called involution-melancholia of this period is at least in a certain fraction of cases nothing more or less than a form of manic-depressive psychosis. However, the physical examination made the diagnosis of manic-depressive psychosis a little doubtful. There was a superficial thickening of the arteries (blood pressure: systolic, 170; diastolic, 104), which thickening would not in itself be against the diagnosis of manic-depressive psychosis. (In point of fact, arteriosclerosis is rather common late in this disease and previous attacks could not be excluded on the basis of available history.) The contracted pupils were irregular and both reacted sluggishly to light, although better to accommodation; the right pupil was larger than the left. The arm reflexes were pretty active. The left knee-jerk could not be obtained, nor was the right knee-jerk more than very sluggish. The Achilles reflexes could not be obtained. Although there was not a positive Romberg sign, there was a considerable swaying in Romberg position. There was no speech defect. The other reflexes showed nothing abnormal. On the whole, we had to conclude that, although Mrs. Hunter might be an instance of manic-depressive psychosis, still there was much of neurological interest in the case.

This conclusion was emphasized when the W. R. of the blood serum was found to be positive. The spinal fluid W. R. was also positive, and the gold sol index was of the “paretic” type. There were 74 cells to the cmm. Globulin stood at ++++, and albumin at ++++.

This case, therefore, again illustrates, as well the protean nature of General Paresis (the diagnosis rendered), as the doubtful value of making a psychiatric diagnosis without due consideration of the physical examination and laboratory findings. How easy might it have been, at least some years ago, to consider that this patient of 61 years had suffered a slight shock at some previous time (left knee-jerk absent), but was as a matter of fact a case of manic-depressive psychosis with a vascular complication!

Note: We must again duly insist that the merely sluggish light reactions of the pupils in such a case as this do not especially point to general paresis. The literature seems to establish that sluggishness of light reaction precedes the classical Argyll-Robertson pupil. Yet it does not do to say that, if the Argyll-Robertson pupil pretty conclusively points to neurosyphilis (for exceptions see cases Falvey (55), Murphy (60)), then a sluggish pupillary reaction to light looks in the same direction. Sluggishness may precede stiffness in many, or perhaps all, cases, but sluggishness of pupils is a frequent phenomenon outside the syphilitic group of cases.

1. What part is played by emotional shock and psychic causes in the starting up of general paresis? The answer to this question cannot be definite. That a paretic process can be started up after trauma is admitted on all sides; but we here suppose actual physical or chemical brain disturbance permitting increased spirochetosis or inflammatory reaction. In the case of psychic shock, or what might be called psychogenic general paresis, our best resort will be to the indirect effects of hormone action, or of vasomotor and other autonomic disturbances produced directly or indirectly by emotion. We are clearly here dealing with material too speculative to be of practical service at this time.

2. Was the depressive drug therapy in the case of Hunter justifiable? The paraldehyd had been administered by a physician apparently on purely symptomatic grounds to combat the insomnia and agitation of this woman of 61 years. With all due acknowledgment of the difficulties of private practice, we must insist that when ordinary measures in the relief of insomnia and agitation are insufficient to curb these conditions, then a positive danger ensues with the larger doses. As a rule, with these larger doses and with the withdrawal of sensory stimulation, the patients relapse into a stupor of grave moment. We need only recall the situation in delirium tremens where adequately depressive drugs often tend to kill the patient.