Chapter X: Introduction (2)

The =microscopic examination= confirmed the diagnosis of paresis. The hypertrophic nodules were of special interest. They were found to be overlain by a characteristic though thin exudate of lymphocytes and plasma cells, together with pigmented cells. The nodules appeared to be supplied with an unusual number of vessels of small calibre, about which were a few lymphocytes. The large vessels and those with well developed adventitiæ were surrounded by more numerous lymphocytes and by more focal accumulations of pigmented cells. The cortex in the middle of a nodule had almost lost its characteristic cortical layering. The cortex was here reduced (specimen from temporal lobe) to about one-quarter of its normal thickness, and was found to be composed largely of expanded neuroglia cells and vascular tissue, with a few nerve elements, small, shrunken, and dark-staining. The destructive process appeared to have borne hardest on the layer of internal large pyramids and the fusiform layer. There was, however, nowhere any evidence of focal necrosis such as ought to characterize a true gumma. The sections stained by the Marchi method failed to show evidence of fatty degeneration within the focus, although there was a marked diffuse accumulation of fatty granulations along the nerve fibres in the underlying white matter. A special study of the cerebellar material was made by one of the authors.[4] Occasional Purkinje cells showed the characteristic binucleate condition, which has frequently been noted in recent literature.

The cerebellum of this case was perhaps the most markedly diseased of all portions of the nervous system. As noted, the cerebellar tissue was exceedingly firm. How far the notable incoördination of the case (he was observed on staff rounds characteristically curled up in a heap, showing quite an unusual degree of general incoördination) was due to the cerebellar lesions, it is perhaps not possible to say.

=Summary=: John Lawrence, JUVENILE PARETIC NEUROSYPHILIS, is a foil to Case 3 (James Dixon), paretic neurosyphilis due to acquired syphilis.

Both showed =Cerebral Atrophy=, but Lawrence the more markedly because of hypoplasia incidental to the congenital origin of his condition.

Whereas Dixon gave little or no sign of =stigmata=, Lawrence (besides being under-sized, having suspicious teeth, and showing at autopsy a persistent thymus) showed a =Hydromyelia= and curious trefoil shape to the spinal cord. Dixon on the other hand had liver lesions and arterial lesions of the leg.

The suggestion of =Tuberous Sclerosis= in Lawrence is not found in Dixon; but we have not found it elsewhere. Bourneville did not describe tuberous sclerosis as syphilitic.

Binucleate Purkinje cells emphasize the congenital source of the lesions in Lawrence.

=Plasmocytosis and Lymphocytosis=, =Perivascular=, and (less marked) =Meningeal=, are found in both the congenital and the acquired cases, as also parenchymatous changes, both =nerve cell losses= and =gliosis=. Both also show granular =ependymitis=.

It is clear that, over and above the factors of destruction evident in both Lawrence and Dixon, the congenital case, Lawrence exhibits also the effects of arrest (in brief not merely atrophy but also hypoplasia). Early treatment is, therefore, theoretically indicated in the juvenile group, which means early diagnosis. Early diagnosis and treatment are still more to be recommended because these juvenile cases progress often very slowly at first.

=FOCAL BASILAR MENINGEAL NEUROSYPHILIS (“syphilitic extraocular
palsy,” plus other symptoms). Autopsy.=

=Case 6.= Flora Black, a housewife of 43 years, had been tired out for a year but had been apparently in fair health. She awoke one day with double vision due to a left internal strabismus. The visual difficulty gradually passed away so that five months after the sudden seizure she was apparently quite well again. There was one exception: about three or four months after the attack of diplopia, Mrs. Black had begun to feel a kind of weakness in various parts of the face and there were also fairly definite paresthesiæ. In the sixth month after the initial attack, the patient began to be unable to chew and was fain to support the lower jaw with a bandage to aid in mastication. Deglutition was, however, quite unaffected and there was never any regurgitation of food. There were pains in the face, the forehead and the back of the neck.

Upon =physical examination= at entrance to a general hospital, no changes in the body at large were discoverable. There was a slight edema of the ankles, otherwise no sign of bodily disease.

Conditions in the =head= were as follows: The facial lines were (notes by courtesy of Dr. E. W. Taylor) smoothed out; both upper and lower eyelids and the corners of the mouth drooped slightly and more markedly on the left side. There was slight photophobia and considerable lachrymation. The patient was unable to pucker forehead, nose or mouth. The unsupported lower jaw fell and the patient was unable to open the mouth widely. The movements of the tongue were normally performed. Speech was mumbling. Sensations of touch, heat and cold were preserved all over the face except that the left cheek below the level of the mouth yielded a less accurate registration of tactile sensations. A hot test tube did not feel as hot in the lower left cheek as elsewhere. Quinine and sugar could not be tasted over the left half of the tongue in front. Smell and hearing were also diminished on the left side. It appeared that there was a complete paralysis of the 5th and 7th nerves and a partial paralysis of the 8th, 11th and 12th, as well as a defect in smell.

The patient died suddenly, three weeks after admission, running a slight temperature during her stay. The autopsy showed (rather surprisingly) a double ovarian carcinoma with metastases into the retroperitoneal glands. Both kidneys were found to be riddled with nodules of carcinoma. The pelvic veins were thrombosed and there was a complete occlusion of the pulmonary artery. There was a riding embolus in the foramen ovale and there was coronary embolism.

The striking nature of these complications and the interest of the case neurologically would warrant its publication in complete detail. We here present the case with utmost brevity as an example of a SYPHILITIC CRANIAL NEURITIS by extension from the meninges.

The =brain= was in general without change but there was a considerable exudate over the entire =pontine region= which had involved several cranial nerves. The 5th nerves, especially the left, showed gross effects of the inflammatory lesion. There seems to be little or no doubt that this neuritis was of syphilitic origin despite the complication of the case with carcinoma of the ovary and despite the fact that the case was observed and came to autopsy before the modern methods of systematic diagnosis could be applied. It is the best case available to us for the demonstration of a focal cranial nerve lesion of the type characteristic of neurosyphilis. We may well suppose that similar conditions would have been found at various stages in the development of Case 1 (Alice Morton). The pontine region of Case 1 was entirely free from lymphocytic exudate at the time of the autopsy. Possibly the clearing up of the pontine pia mater in Case 1 was a therapeutic effect of the thorough treatment therein used. Whether a case like Mrs. Black’s could be cured (aside from the ovarian carcinoma and its complications) by the institution of vigorous systematic treatment is a matter of doubt. Still, in a general way, these cases of focal syphilitic neuritis are among the most favorable cases for treatment.

=Summary=: We present the case of Flora Black to emphasize how slight in extent and theoretically curable neurosyphilis may be. We fear that Case 1 (Alice Morton) may present too unrelieved and pessimistic a picture. The extensive vascular lesions and complications of Alice Morton, of Case 2 (Francis Garfield), of Case 4 (James Pierce) arrest attention by the incurability of their residual effects (if we omit modern attempts at reeducation of lower arcs). On the other hand the unrelenting progress to destruction of important parenchymatous structures, as shown in the paretic James Dixon (Case 3) and his juvenile replica John Lawrence (Case 5), as well as in Alice Morton (Case 1) and the tabetic Francis Garfield (Case 2), lead to a certain justifiable pessimism. For it is only the meningeal and fine vascular infiltrations of these cases that we can theoretically hope to combat, probably by destroying the spirochetes in these meningeal and perivascular loci. We seem theoretically less able to stop the progress of the often highly systemic and symmetrical, parenchymatous lesions of the tabetic and paretic group.

The condition in Flora Black is clearly much more hopeful, both being more focal and being almost purely meningeal and therefore accessible to therapy.

The two cases which conclude our general survey of neurosyphilis are also focal cases, one of gumma (Lecompte) and one of focal dural lesion (Wyman).

1. Pons, normal except for focal infiltration of left fifth nerve.
]

2. Higher power view of infiltrated left fifth nerve.
]

3. Detail of infiltrated left fifth nerve, showing: 1, diffuse
infiltration with mononuclear cells; 2, perivascular infiltration;
3, strands of relatively unaffected nerve fibers.
]

Microscopic appearances in Case 6. Extraocular palsy (focal meningeal syphilis, especially of left fifth nerve). Illustrates exquisite focality of the syphilitic process sometimes found, as well as its unilaterality (giving rise to asymmetrical symptoms and signs). Process in itself probably curable.

=GUMMATOUS NEUROSYPHILIS (“gumma of brain”). Autopsy.=

=Case 7.= Mrs. Lecompte was a woman of middle age, who, according to the history given by her son, had been entirely well until her final illness, which began approximately two years before admission to Danvers Hospital. The beginning of her trouble seemed to be chiefly headaches, which would last continuously for several days, or more than a week at a time. These headaches lasted throughout the course of the disease. In the morning, on arising, she would feel very dizzy, but this would pass away during the day. She had had a number of spells of unconsciousness, lasting about fifteen minutes. In these attacks she would breathe heavily, there was frothing at the mouth, twitching of the hands, and the eyes would roll about. Her memory failed gradually, her disposition changed and she became very irritable. Vomiting occurred almost every day, and at times was of a projectile character. She became hallucinated; the hallucinations were chiefly of a visual nature.

About four months before admission to the hospital, after one of her seizures, the entire right side was found to be completely paralyzed, and she complained that it was numb. At this time, she had difficulty with her speech. In a few days, however, she was able to talk correctly again, and in a week she was back at work, although the right side was weak and awkward. She continued to grow worse, and then began to have spells lasting several days, so that it became necessary to have her placed in a hospital.

On admission to the hospital, aside from obesity, the general viscera showed no points of special interest, and there was no evidence of any new growth outside of the nervous system. She was unsteady on her feet, standing with them wide apart. The gait was quite ataxic; the whole right side was weaker than the left and used more awkwardly. There was a paralysis of the right side of the face; the right angle of the mouth drooped; the right eyelid could not be closed but remained continuously open; nor could the right side of the forehead be wrinkled. Vision and hearing were not affected. She miscalled tastes and smells; whether this was due to aphasic difficulties or to cranial nerve involvement could not be divined. There seemed to be some difficulty in deglutition. The knee-jerks were markedly exaggerated; slight clonus was obtained but was not always present. Both pupils reacted well to light and distance and consensually. Sensation could not be readily tested. There was marked ataxia, especially with the eyes closed. The speech was thick and mumbling. The patient was unable to write or copy. Mentally the patient was quite dull; at times, stuporous; when aroused, was found to be entirely disoriented. Memory almost entirely absent. In general she showed herself to be very much confused.

She remained practically in this condition, even gaining in weight, for the following two years, when suddenly one morning, she had an epileptic seizure, vomited, coughed a great deal, with bleeding from the mouth and ears, and died in a few hours.

The symptoms in this case pointed to brain tumor. The only inconsistent thing was the long-continued life,—four years,—after the symptoms were observed. As she lived before the W. R. and spinal fluid tests were known, no light was gained in these ways. The post mortem examination showed the patient had a GUMMA OF THE BRAIN.

The =summary of the anatomical diagnoses= at autopsy was:

Decubitus.

Lymphadenitis of the mesenteric nodes.

Chronic fibrous peritonitis.

Chronic fibrous myocarditis.

Pulmonary hypostasis.

Thrombosis of vein in right adrenal, with hemorrhage.

Syphilitic leptomeningitis.

Gumma of left hemisphere.

Focal softenings in the pons.

The =anatomical description of the head= (Dr. A. M. Barrett) is as follows:

The sutures in the =calvarium= are well outlined; diploë large in
amount. The =dura= is diffusely but lightly adherent to the
calvarium; it is very dense, especially over the left hemisphere.
The meningeal arteries are thickened but not atheromatous. The
sinuses contain a small amount of fluid blood and post mortem clot.
The inner surface shows nothing abnormal. There is a great
flattening of the convolutions of the left hemisphere, which is not
the case on the right side. Over the convexity, the =pia= is thin
and not abnormal except for some slight adhesions between the
frontal lobes and the two lips of the Sylvian fissures. The pia at
the base over the cisterna, pons, and medulla is thick, cloudy, and
of a grayish gelatinous appearance. It is so thick that it is easily
removable in a large piece.

The surface of the left hemisphere is dry, and the whole brain is
flabby and bulges as if from internal pressure. A section through
the hemispheres at the region of the optic chiasm shows a hard, firm
area in the left hemisphere deep down in the white substance. It is
about 2½ cm. in diameter, with a wavy border. The central part is of
a silver-gray gelatinous-like appearance, with red spots and whitish
streaks radiating from the centre. In the pons on the right side, in
a plane passing through the posterior corpora quadrigemina, are two
pinhead size softenings among the pyramidal fibres. The ependyma of
the fourth ventricle is granular.

=Microscopic examination of the tumor=: The area evidently contains
several central necrotic foci surrounded by zones of infiltration
and proliferation, with bordering areas of nervous tissue showing
secondary reactions. The necrotic area stains poorly. From the edge
there are projections of reddish homogeneous bands, some intermixed
with well-differentiated fibrillæ, probably glia fibrils. The
bordering zone is densely infiltrated with lymphoid, plasma, and a
few epithelial cells. The nerve tissue outside of this zone is
spongy and infiltrated with lymphoid and plasma cells. There are a
few scattered, shrunken nerve cells. In this zone and in the zone of
infiltration near the necrotic area, there are scattered cells
resembling giant cells. There are many obliterated vessels in the
area, and other vessels show many infiltrating lymphoid and plasma
cells in the walls. The examination of the specimen stained by the
methods for bacilli of tuberculosis are negative. The growth is a
classical gumma.

=GUMMATOUS NEUROSYPHILIS (gumma of spinal meninges, “meningitis
hypertrophica cervicalis of Charcot?”). Autopsy.=

=Case 8.= John Wyman was first seen in his thirty-sixth year by Dr. James J. Putnam. He denied syphilitic infection and stated that the first symptoms had come four months before. He had begun to notice a numbness of the fingers, at first of the right hand and shortly thereafter of the left hand. After a few weeks there had been difficulty in walking, and a few weeks later headaches, especially on the right side, developed. Two weeks before he was first seen medically, he had begun to have a feeling of tightness or constriction in his arms.

It appears that micturition had been impaired early, that is to say, a few weeks after the initial sensory disorder had begun. A catheter was used for a time and improvement followed. Shortly before consultation retention of urine developed again, this time associated with rectal incontinence. The feet began to feel heavy and dead. Then the legs began to be increasingly weak so that the patient was almost bedridden. Vision appeared to be normal except that reading was followed by fatigue. The speech was also slow but the slowness could be attributed to fatigue.

Notes of Dr. Putnam’s =physical examination= are as follows: The patient lay in bed on the left side, without motion, and almost incapable of motion. The tongue was protruded, and there was no paralysis of facial muscles, or of the eye muscles (the right pupil had been reported to be slightly larger than the left). There seemed to be a disinclination to move the head, but with some effort it could be moved, and without pain. The arms and hands were held rigidly in median positions; many movements were possible, but all were imperfect and of slight amplitude. The fingers were flexed to a moderate degree, and could not easily be straightened, and there was, in fact, a general rigidity of most of the muscles of the body below the neck, and even, in some degree, of the neck. The immobility was so great that the general impression made was almost that of a patient with fracture of the spine in the cervical region. Even the breath, and especially the inspiration, was imperfect. The legs were more freely movable than the arms, but still the motions were very stiff and awkward, and of slight amplitude; with effort the whole leg could be lifted from the bed, and flexed or extended with moderate force. The right leg was rather stronger than the left, but the left hand and arm were stronger than the right. The sensibility was almost absent over the hands and lower part of the arms, and was impaired over the entire head and neck, except the forehead, the middle part of the face, and the nose. It is interesting to compare the conditions of the sensibility here present with those seen in cervical syringomyelia. The sensibility of the upper part of the forehead was less good than of the lower part, and there was slight impairment even over portions of the lower jaw. The sensibility of the left (stronger) arm was rather more impaired than that of the right arm, while on the contrary the sensibility of the left leg was better than that of the right leg, though the difference between them was not great. These statements apply to sensory tests by contact, heat, cold, and pricking. Knee-jerks were highly exaggerated, and likewise the wrist-jerks. All forced attempts at movements were attended by a high degree of muscular tremor, especially when the patient was fatigued or under emotional strain. The fingers especially were the seat of coarse tremor.

The remainder of this clinical description (courteously supplied us by Dr. Putnam) may be quoted. A second examination which included also a few facts not given in the first examination was made on the following March 28, 1905. This report says “the ends of the fingers became numb about June 1, 1904. Work was given up on July 3, and at that time the patient was walking very badly. No treatment was used and no satisfactory diagnosis made. In the course of July he improved somewhat, and during August he was able to ride out a little (these spontaneous improvements are of interest for the diagnosis). He went away from home for a short time, but from the time of his return, about the last of September, he grew worse rapidly, and fell into the condition above described, in which he was wholly unable to help himself, even to turning in bed. At times he had a great deal of pain in the neck and forehead. Antisyphilitic treatment was recommended, and for a time potassium iodid and other iodid preparations were given, but at first in relatively small doses (grs. 75 daily). Under this treatment the excretion of urine rose to four quarts daily as a maximum though sometimes the quantity was not so great.”

Under this treatment the patient began soon to improve, and continued doing somewhat better till about five months later. He became able to walk downstairs and out of doors, and regained considerable use of his hands. The quantity of urine passed became greatly increased by the use of the iodid.

About the middle of March he became worse again. A careful examination of the sensibility showed that in general the condition was much the same as that previously reported. The iodid treatment, with perhaps some mercurial, was resumed; the potassium iodid was given in doses which were increased up to 850 grains daily, although this maximum dose was taken only for about one week. This large quantity gradually impaired the sense of taste for the time being, and blurred his vision, but otherwise did him no harm. Under this he improved, so that he became able to run more or less, and went about freely, and attended to his business, though still retaining some stiffness in his movements.

This improvement continued until about two years later, when he again had a relapse, and was seen medically once more. His condition at this time was still a pretty good one, but the movements were stiff and awkward. The bin-iodid of mercury was advised, which was taken in doses of 9⁄25 grain daily. It will be remembered that this was long before the days of salvarsan treatment.

This was toward the end of June, 1907. Contrary to expectation, there was no material gain from this treatment, and the patient died early in October, without being seen again.

The =autopsy= was limited to the =nervous system= and the findings were as follows (Dr. A. R. Robertson):

=Head=: Hair abundant, fair, of fine texture and rather curly. Scalp
of medium thickness and strips readily from calvarium. The latter
appears normal and upon removal is of about the normal thickness. It
lifts readily from the dura mater, except for the numerous
attachments of Pacchionian granulations.

=Meninges=: The dura is smooth, moderately injected and shows no
areas of thickening; it lifts readily from the pia-arachnoid. The
pia-arachnoid shows discrete and in many places diffuse areas of
opacity. There is a moderate amount of subpial clear fluid and the
vessels are moderately injected. Over the anterior surface of the
medulla and lower portion of the pons and largely confined to the
right side there is a very marked thickening of the pia-arachnoid to
which the dura is densely adherent. This thickening extends down
anteriorly and laterally on the right side over the upper part of
the cervical cord. The thickened meninges over the upper part of the
medulla completely surround the right vertebral artery, shortly
before it joins its fellow of the opposite side to form the basilar.
Dissection of the arteries shows them to be patent and thin walled.
Over the =cerebrum= and cerebellum the pia-arachnoid strips readily
leaving a smooth surface. Section of the cerebral cortex, basal
nuclei, pons and cerebellum show no gross lesions. The ventricles
are moderately distended with fluid. The ependyma contains numerous
small cysts. Section of the =pons= shows no lesions of the nervous
tissue, but very marked thickening of the surrounding meninges as
noted above.

=Cord=: Throughout the cervical and dorsal region the dura is quite
tensely distended with an abundance of clear, light, straw-colored
fluid. Upon snipping the dura this fluid escapes with a small spurt,
as if under considerable pressure. The cord within, for the most
part, lies free, but over the upper three or four centimeters of the
cervical portion it is densely adherent to the dura anteriorly and
laterally on the right side. Cross sections were made through the
upper three or four centimeters of the cord, and over this area the
cord is constricted by very marked thickening of all the meninges.
The meninges here average from one to three millimeters in
thickness. On the right side and somewhat anteriorly opposite the
junction of the atlas and axis there is a single nodular, firm mass
which on section shows a yellowish, firm center surrounded by very
dense, pearl-gray tissue. The demarcation between the homogeneous
yellowish centre and its surrounding gray tissue is very sharp. This
nodule measures about 0.75 to 1 cm. in diameter. The adjacent cord
is deeply indented by it. Below this nodule there is a translucent,
grayish appearance of both posterior sensory columns which extends
downwards and diminishes in intensity until it finally disappears in
the upper dorsal region. This same appearance is well marked on the
right outer margin of the upper cervical cord corresponding to the
crossed pyramidal tract, and extends downwards diminishing in
intensity until it disappears about the mid-dorsal region. The left
pyramidal tract appears to be similarly but very slightly involved;
section of the lower dorsal cord entirely negative.
=Microscopically=, characteristic GUMMA.

It is a question whether this case is one of the group described in 1871 by Charcot under the name of _pachymeningitis cervicalis hypertrophica_. Charcot did not regard his new disease as syphilitic, and it is very probable that syphilis is not responsible for all cases. Charcot, however, noted that his new disease was not incurable: he noted that the resulting paraplegia, although it might be very marked and accompanied by flexion of the leg on the thigh and although the paraplegia might have lasted a very long time, might end in recovery. Charcot thought that surgical intervention was necessary. He described three periods in the disease, the first or neuralgic (pseudo-neuralgic) was characterized by sharp pains in the neck and by the sensation of constriction in the upper part of the thorax. The second phase of the disease was, according to Charcot, the paralytic phase, in which a cervical paraplegia accompanied by muscular atrophy developed. Sometimes cases were found to remain in this paralytic phase and even to end spontaneously in cure. If the muscular atrophy was degenerative, then the atrophy was never replaced; but, according to Charcot, some cases of atrophy were simple and accordingly curable. If, however, the spinal cord itself became involved in the meningeal inflammation, then phenomena of transverse myelitis set in with a spastic paraplegia and involvement of the bladder and rectum. Muscular atrophy never developed in the legs, at least in typical cases.

Among the causes of this condition the following have been mentioned: cold, overexertion, alcoholism, tuberculosis and syphilis. Syphilis undoubtedly plays the major part. Even before the days of the W. R., observers, among whom may be mentioned Dejerine-Tinel and Pförringer, discovered syphilis in nearly all sufferers from _pachymeningitis cervicalis hypertrophica_.

It should be differentiated from caries of the spine and cord and meningeal tumors. The spinal fluid examination makes this somewhat easy.

Antisyphilitic remedies are indicated, and should be tried even when the etiology is obscure, if only as a therapeutic test.

But what have been thy answers? What but dark,
Ambiguous, and with double sense deluding,
Which they who asked have seldom understood,
And, not well understood, as well not known?

Paradise Regained, Book I, lines 434–437

II. THE SYSTEMATIC DIAGNOSIS OF THE MAIN FORMS OF NEUROSYPHILIS

=PARETIC NEUROSYPHILIS (“general paresis”) sometimes persistently
receives the diagnosis NEURASTHENIA simply through omission to apply
approved diagnostic methods.=

=Case 9.= Greeley Harrison, a man of 46, certainly looked like a neurasthenic. He wanted aid for nervous indigestion of years’ standing, headache, insomnia, nervousness, failing memory, and deafness. He volunteered, in fact, that he had neurasthenia, and that he had been treated for this by hypophosphites.

During the practically negative =physical examination=, Harrison complained of headache and throbbing in the head, and during examination of the abdomen felt much nauseated and proceeded to vomit rather persistently. There were hemorrhoids.

=Neurological examination= showed that the left pupil was smaller than the right, was irregular, failed to react consensually, and reacted very slowly to direct light. For the rest, however, the neurological examination was negative. On account of the nausea and vomiting, special examination of the gastric contents was made, but nothing abnormal was found.

=Mentally=, it was rather striking that the patient’s memory was quite inaccurate both for remote and for recent events. His school knowledge was very meagre. As for delusions, the only approximation thereto was the patient’s continually dwelling upon his bodily symptoms. Emotionally, he varied between depression and a sanguine attitude.

Although there was no symptom directly suggesting syphilis in the Harrison case, the slightly abnormal pupillary reactions and the amnesia warranted the suspicion of syphilis. The blood and spinal fluid both proved positive to the W. R.; the gold sol reaction was of the “paretic” type; there were 18 cells per cmm.; there was considerable globulin, and an excess of albumin. On the whole, therefore, we felt entitled to make the diagnosis GENERAL PARESIS. Why should not a careful observer have considered syphilis seriously? Yet in our experience such cases are frequently diagnosticated neurasthenia, thus entailing dangerous delay in treatment (in this case, five years’ delay).

Going over the history of the case with still greater detail, we learned that for a number of years past, there had been symptoms of a neurological nature. For instance, five years before, at the age of 41, the patient had been apparently overcome when working near a stove, and went upstairs talking incoherently, but recovered shortly. Thereafter, such spells occurred almost every month; later, more frequently; still later, the attacks were associated with unconsciousness and amnesia. Occasionally preceding the attack there would be twitching of the mouth, jerking of the arms, and incoherent talk. Throughout these last five years, in point of fact, the patient had been unable to do regular work, had been given to much complaining, and had been far less efficient than formerly. In short, it would seem that, with the improved technique now in the possession of medical science for the diagnosis of general paresis, cases like that of Harrison will be diagnosticated earlier and earlier.

1. How typical is the insidious onset of symptoms in the case of
Harrison? The onset of symptoms in neurosyphilis is ordinarily
considered to be sudden, and this statement is generally true
despite the fact that after the diagnosis is established a number
of mild prodromal symptoms can be remembered by the relatives.
However, some cases, of which Harrison is an example, have an
exceedingly insidious onset without sudden access of striking
symptoms. Joffroy and Mignot remark that with the improvement of
clinical methods, the course of paretic neurosyphilis must now be
stated to take some six or seven years for completion. In point of
fact, there were early episodic symptoms (seizures almost monthly)
which should not have escaped medical attention. They did escape
medical attention, however, and Harrison was wont to say “Why
wasn’t I told that my disease was syphilis five years ago?”

2. Is there such a disease as syphilitic neurasthenia? According to
Kraepelin, syphilitic neurasthenia has been described as occurring
shortly after infection and in the first stages of syphilis. There
are milder and severer forms; the milder forms show discomfort,
difficulty in thinking, irritability, insomnia, cephalic pressure,
indefinite variable, uncomfortable sensations, and pains. The
severer cases acquire anxiety, more pronounced emotional disorder,
dizziness, disorder of consciousness, difficulty in finding the
right word, transient palsies, pronounced sensory disorders,
nausea, and increase of temperature. Kraepelin is in doubt whether
there is any definite clinical picture of this sort, and whether
there is any causal relation between the syphilitic infection and
such symptoms as those described. If the effect of knowledge
concerning infection is a merely psychic effect, then it is
improper to term the neurasthenia in question a syphilitic
neurasthenia. For the relation of hysteria to the acquisition of
syphilis, see below the case of Alice Caperson (46). In point of
fact, modern work has shown even in the primary and secondary
stages of general syphilis more or less pronounced neurosyphilitic
phenomena in the shape of the so-called meningitic irritation of
French authors. (Besides the case of Caperson (46), see the case
of Fitzgerald and the discussions under these cases.)

3. What is the relation of the early symptoms of this case to the
so-called preparesis of Dana? The case might well have been an
example of Dana’s preparesis. For a discussion of this, see Case
of William Twist (13).

4. What is the classical differential diagnosis between paretic
neurosyphilis and neurasthenia? The testing of the blood by the W.
R. is unconditionally necessary. If the W. R. is negative, the
diagnosis of paretic neurosyphilis is extremely improbable. (It
must be borne in mind that a number of cases of paretic
neurosyphilis have been shown to have a negative W. R. in the
serum, and receive a proper diagnosis only after spinal fluid
examination.) Next to the serum W. R. stand the pupillary and
aphasic symptoms. In the presence of Argyll-Robertson pupil or
even a slight speech defect, the diagnosis of neurasthenia must
certainly be made with caution if at all. Kraepelin remarks: The
sudden occurrence of neurasthenic disorders in a male of middle
age without any evident cause therefor is always suspicious. Yet
it must be emphasized that a complaint of occasional dizziness,
slight speech defect, tremor of tongue, and a moderate increase of
tendon reflexes do not possess any marked diagnostic significance.
Clear insight and understanding of the nature of the disease
phenomena, a persistent search for recovery, reasonableness in
conversation, progressive improvement under appropriate treatment,
speak for neurasthenia.

Joffroy and Mignot differentiate what they call preparetic
neurasthenia from other neurasthenic states, not only on the basis
of its etiology but on the basis of its symptoms. They also call
attention to the fact that neurasthenia, being a pure neurosis,
develops either on a manifestly hereditary basis or upon some
physical injury, weakening disease, or moral shock. The pure
neurotic suffers a great deal more than the patient who is
destined to become a victim of paresis. The character change in
neurasthenia does not amount to that entire transformation of
personality (even to the performance of criminal acts) that we
find in paretic neurosyphilis; at the most, the neurasthenic shows
minor emotional disturbances and a certain pathological egoism.
The psychotherapeutic test also rather readily dissipates many of
the neurotic, hypochondriacal fears and feelings. Although both
pure neurasthenia and the paretic pseudoneurasthenia are
characterized by sexual weakness, the sexual anæsthesia of the
preparetic is practically always preceded by a stage of sexual
over-excitement. These finer clinical indications, however, fade
into insignificance beside the data that can and should be
obtained from laboratory tests.

5. How exceptional is such a case as that of Harrison? We have in
our experience seen many patients with a similar course and
configuration of symptoms, although the majority of these cases in
a community advanced enough to provide easy access to a Wassermann
laboratory are now diagnosticated far earlier than was the case of
Harrison.

6. What attitude shall we take toward so-called syphilophobia? It
seems to us that resort to a serum W. R. is indicated, both from
the standpoint of the community and still more importantly from
the standpoint of the patient. We are even inclined to suggest for
a case of persistent syphilophobia, when the serum W. R. has
proved negative, a lumbar puncture. Syphilophobia must be
considered, not as a syphilitic psychosis, but as a phobia to be
classified among the psychoneuroses. It becomes a difficult
question to decide at times whether a patient who has had
syphilis, has had a considerable course of treatment and shows the
symptoms of a syphilophobiac should be further treated for
syphilis or merely for his phobia. We have seen recently such a
patient who gave a certain history of syphilis and who was greatly
disturbed lest he should be developing paresis. This fear bothered
him greatly. Examination showed irregular pupils, but no other
signs of syphilis. The W. R. in blood and spinal fluid was
negative as were the other spinal fluid tests. It was considered
wise to treat him only for his phobia and under this treatment he
was given some relief.

=PARETIC NEUROSYPHILIS (“general paresis”) may look precisely like
MANIC-DEPRESSIVE PSYCHOSIS.=

=Case 10.= The mental picture in Lyman Agnew, an architect, 58 years of age, was wholly characteristic of manic-depressive psychosis. In the first place, there had been (at 55) a previous attack of depression, lasting a few months, from which Agnew had completely recovered. He had remained entirely well up to four months before consultation. (Manic-depressive psychosis is, at least in a majority of cases, hereditary. There had been mental disorder in one maternal cousin, and mental impairment in the patient’s mother some time before her death from cerebral hemorrhage. There was no other report of mental disease in the family.)

It appears that in the interval between attacks, Agnew had been working very hard and had been fairly successful in paying off a mortgage on his house. A marked elation, somewhat natural, followed this success and continued to an abnormal degree. Agnew labored under considerable excitement, was over-fussy, and at times showed a flight of ideas. His mania or hypomania gradually diminished and depression set in, in which depression he arrived for consultation. He had marked ideas of self-accusation, was emotionally unstable, wept much, and showed a characteristic retardation of activities and unrest.

=Physically=, there was no neurological disorder. The patient appeared rather under-nourished. The heart borders lay 2 cm. to the right and at 11½ cm. to the left of the mid-sternal line. The aortic second sound was very loud. There was a moderate radial arteriosclerosis. Systolic blood pressure was 210, diastolic 155.

The high blood pressure suggested nephritis, possibly of arteriosclerotic origin, but urine examination and blood-nitrogen tests yielded no evidence of kidney disease. Moreover, it is our experience that a manic-depressive psychosis in persons past middle life is not infrequently complicated by high blood pressure. In point of fact, some authors insist upon a relation between manic-depressive psychosis and the arteriosclerosis which rather frequently sets in in this disease.

Routine examination of the blood serum, however, yielded a positive W. R. Following the approved rule of making an examination of the spinal fluid in all mental cases having a positive serum W. R., we proceeded to lumbar puncture. The fluid was clear and contained 35 cells per cmm., the albumin was in excess, and there was a positive globulin reaction. The gold sol reaction was of the “paretic” type; the W. R. was strongly positive.

On this basis, it seems worth while to consider the diagnosis of GENERAL PARESIS or that of some form of non-paretic neurosyphilis. The former is the diagnosis which we prefer.

1. What is the classical differential diagnosis between
manic-depressive psychosis and neurosyphilis? The laboratory tests
have naturally supplanted the older purely clinical methods of
differential diagnosis. The difficulties lodge, in the first
instance, in depressive states. It would appear to be impossible
on purely clinical grounds in certain cases to tell the depression
of neurosyphilis from the depression of manic-depressive
psychosis, since the slightly greater interest in the outer world
taken by manic-depressive patients and their greater
responsiveness to diagnostic threats (suggestion that patient is
to be pinched or cut) are of no special value in the individual
case. Identical considerations hold for the maniacal phases of
manic-depressive psychosis, for these maniacal phases may even
develop delusions (Kraepelin) of precisely the same nature as the
characteristic expansive delusions of the excited paretic.

2. If the clinical symptoms are insufficient in differential
diagnosis, are not the pupillary signs and the speech defect of
greater value? They are of value if present, but as in the case of
Agnew, the victim of neurosyphilis may show no pupillary or speech
disorder. Instances are familiar, also, in which the pupillary and
speech signs are absent in very advanced cases of non-paretic or
even of paretic neurosyphilis.

3. Would not a circular course or recurrence of attacks be decisive
for manic-depressive psychosis? Paretic neurosyphilis sometimes
exhibits the same circular or recurrent course. We conclude that
neither the clinical symptoms, the classical pupillary and speech
signs, nor the ups and downs of a particular disease, are at all
decisive as between manic-depressive psychosis and paretic
neurosyphilis. Resort must be had to laboratory tests.

4. What is the significance of the high blood pressure in paretic
neurosyphilis? Work from our laboratory (Southard and Canavan) has
shown plasma cells in the kidneys in 17 out of 30 paretics (56%),
and in 16 of these 17 paretics with renal plasmocytosis, the
plasma cells were found in the periglomerular region. What the
relation of these findings may be to heightened blood pressure is
as yet unknown. The severe syphilitic involvement of the aorta so
characteristic in paretic neurosyphilis, as in other forms, may
possibly have a bearing on blood pressure.

=A POSITIVE SERUM WASSERMANN REACTION associated with mental
symptoms (even with grandiosity) does NOT prove the EXISTENCE OF
PARETIC NEUROSYPHILIS (“general paresis”).=

=Case 11.= Juliette Lachine came to a general hospital with pain in the right upper quadrant of the abdomen, wherein was found an enlarged liver. This liver was regarded as syphilitic on the ground that the patient had a positive serum W. R. and that her two elder children were clearly suffering from congenital syphilis. The liver mass was promptly reduced by antisyphilitic treatment of the classical sort. When, however, the patient was given an injection of salvarsan, she shortly began to develop marked mental symptoms, whereupon she was removed to the Psychopathic Hospital.

The =mental picture= at the Psychopathic Hospital was as follows: Lack of orientation for time, marked distractibility of attention, with a certain jumping from one subject to another, delusions of a religious nature, claims of wonderful powers possessed by the patient, moods variable, though as a rule of a euphoric and elated nature, with laughing and singing. The activity seemed to be of a mental rather than a peripheral nature. The patient did not regard herself as mentally abnormal. The liver was still 4 cm. below the costal margin in the nipple line. We found the W. R. to be positive in the serum but negative in the spinal fluid. In fact, the spinal fluid was entirely negative.

So far as we are aware the picture presented by this case is one of MANIC-DEPRESSIVE PSYCHOSIS. We regard the disease as merely complicating the syphilis, although it is entirely possible that some visceral condition incidental to the syphilis might be proved (in a higher stage of psychiatric science) to have produced the mania.

In any event, the patient quite recovered from her mental symptoms in a month. She was then able to tell us of a previous attack of depression some 12 years previously, namely, at the age of 26. It appears that she had at that time been committed to a hospital for the insane.

1. In this case, in which the diagnosis of manic-depressive
psychosis and not paretic neurosyphilis was made, are we sure that
the symptoms that we term manic-depressive psychosis were not
actually produced by syphilotoxins? In other words, in the absence
of spinal fluid signs of inflammation or chemical change, might it
not be possible for generalized syphilis outside the nervous
system to produce manic-depressive symptoms? There is so far in
the literature no experimental or other evidence of syphilotoxins.
The existence of products and substances permitting the W. R. and
the gold sol reaction is not of course evidence of syphilotoxins.
Although there is no evidence of soluble syphilotoxins, it is
thought that in the so-called Järisch-Herxheimer reaction (the
intensification of clinical symptoms after salvarsan injection)
effects may be due to the liberation of products from the killed
bodies of spirochetes. Such endotoxins are not here in question.

2. Is visceral syphilis, such as gumma of the liver, able to produce
characteristic syphilitic reactions in the spinal fluid? We have
had an autopsied case in which there was a “paretic” gold sol
reaction of the fluid (though without other signs). The autopsy
showed gummata of the liver. However, the finer anatomy of the
nervous system showed a mild but definite meningo-encephalitic
process, which was doubtless responsible for the gold sol
reaction.

3. What is the value of grandiose ideas? Ballet distinguishes two
groups of grandiose ideas: (_a_) ideas of self-satisfaction,
including ideas concerning extraordinary capacity, strength,
power, and wealth on the part of the patient; and (_b_) ideas of
ambition; the latter being of a more exact, constant, uniform and
systematizing nature. The more vague and less systematized ideas
of self-satisfaction rest in a phase of contentedness and
optimism; the more definite ideas of pride and ambition are
responsible for striking transformations of personality. General
paresis shows, according to Ballet, these ideas of
self-satisfaction in their most developed form. A certain
variability, absurdity, incoherence, and contradictoriness
characterize these ideas and the patient has little or no insight
into their nature. When such ideas occur at the outset of the
disease, they naturally may be of medicolegal interest. Cotard
explains these ideas of megalomania on the part of paretics on the
ground that they are essentially motor or will disorders and rest
upon a sort of hyperbulia, exhibiting itself in exuberant
activity. Régis has thought that the delusional generosity and
liberality of the paretic, and his willingness to lend his wealth
and talents to social progress, is helpful for diagnosis when
contrasted with the more personal egoism of the victim of
manic-depressive psychosis. The self-satisfaction of the
manic-depressive patient often does not reach a delusional stage,
but remains a mere feeling of pathological well-being or euphoria.
The maniacal patient may compare himself with some great man but
he does not identify himself with him. It must be remembered that
these ideas of self-satisfaction occur also in alcoholism, but
according to Ballet they occur only in the dementing phase of
chronic alcoholism, and have no special diagnostic value. They may
be a clinical stumbling-block for a time in the cases of alcoholic
pseudoparesis. As for the ideas of ambition in which the patients
believe themselves to be princes, emperors, divine messengers, and
the like, these are less characteristic of paretic neurosyphilis
than of delusional psychoses of a non-syphilitic nature. At all
events, such ideas if definite, of long-standing, and systematized
by the patient to form a thorough-going portion of his life, are
not characteristic of neurosyphilis. The victim of paretic
neurosyphilis can as a rule be persuaded out of his delusions, at
least for the time being. These distinctions, it must be added,
are hardly of value in the early cases of any of the psychoses in
question, and cannot be made as a rule in either private or
psychopathic hospital practice. Typical examples of grandiosity,
although not so frequent as might be thought from textbooks, are
always on display in institutions for the chronic insane.

=PARETIC NEUROSYPHILIS (“general paresis”) may look precisely like
DEMENTIA PRAECOX. Autopsy.=

=Case 12.= Henry Phillips remains a striking case in the memory of those who knew him and his medical findings. Phillips came to the hospital voluntarily at 42 years of age from the bank where he worked as a clerk; he came at the suggestion of his employer. It seems that he had been annoying his associates because he had fallen into a habit of continually scratching himself. Phillips was entirely sure that he was the victim of what he called the “Scotch itch,” and explained off-hand that this itch had been put upon him by the Free Masons as a matter of revenge because he would not join their order. He said once, for example: “At times I feel like raising Hell; then I get a psychic intimation; and then I get to using a foot-rule on my back and to slapping my face.” He explained this psychic intimation as coming from the order of Scottish Rites. Another example of talk is as follows: “My father is a fighting man; that is part of it. They mean to throw me down. I am through now trying for membership in the Free Masons. They have good cause, they must fight. They do not want me for some personal matters. I can go just so far in agreeing and seconding their advances, but in the end it fails. I have no strength nor endurance.”

Aside from these delusions, there was little abnormality to be found, though his recollection for minor events of the immediate present was inaccurate. He was rather abnormally impulsive, gesticulating a good deal while talking, and was of the appearance that the laity call “nervous.” It appears that he had always been peculiar, subject to violent fits of temper, in which fits he might throw things at other members of the family. He always had pronounced likes and dislikes which he never concealed. He had never had friends, had always been secretive; and he was often termed a great student. For some five years he had been studying Japanese from time to time, associating himself with a Japanese.

It never does to jump at the diagnosis dementia praecox. However, the picture seemed characteristic enough for the paranoid form of this disease. Physically, Phillips had no particular abnormality; the knee-jerks were a little lively, and the pupils reacted a little sluggishly. However, the routine W. R. of the serum proved to be positive. Examination of the spinal fluid was resorted to,—as in all cases with a positive serum W. R.—and it also proved to be positive and strongly so; the globulin and albumin were increased, and there was a pleocytosis. A diagnosis of neurosyphilis was hardly avoidable. Phillips later admitted a chancre, which he claimed was located on the mucous membrane of the cheek and acquired by using the same utensils as his Japanese friend, which friend, he stated, had active syphilis.

Antisyphilitic treatment of considerable intensiveness was begun, with intravenous injections of salvarsan and intraspinous injections of salvarsanized serum, but the patient grew steadily worse. His mental symptoms became more marked, although not especially characteristic of general paresis. =Neurologically,= he did develop signs more suggestive of general paresis, and 18 months later died.

The =autopsy= showed features of GENERAL PARESIS. It is not necessary to enter into the question of the details of histological correlation at this time.

1. What conclusion can be drawn from lively knee-jerks? Lively
knee-jerks are of very little significance. Not only certain
neurosyphilitics but also a variety of neurotic persons, victims
of dementia praecox and hysteria, are very prone to have active
tendon reflexes. Of course, extreme degrees of exaggeration are of
importance, and especially an association of the hyperreflexia
with the Babinski reaction, the Gordon, or Oppenheim reflexes,
ankle clonus, and the like.

2. Is there any special or differentiating factor in an extragenital
chancre as against a genital chancre? Probably this question
should be answered in the negative. Some have claimed that
chancres draining by lymphatic channels of the head are more
likely to lead to cerebral syphilis. This idea cannot be said to
be established.

3. Is there any significance in the story, if true, that Phillips
acquired his syphilis from a Mongolian? It seems to be fairly well
established that syphilis of the nervous system is extremely rare
in China and Japan, whereas bone syphilis is very frequent there.
It has been held that this has to do (_a_) with strains of
spirochetes, (_b_) with the state of civilization, or (_c_) with
the degree of “syphilization.” Apparently when a race is first
infected with syphilis the lesions are chiefly of the cutaneous
and osseous systems; only in later generations the vascular and
nervous systems suffer. However, involvement of the nervous
systems of Mongolians resident in this country is no rarity, a
point possibly in favor of the theory of special strains affecting
the nervous system as prevalent in western countries. Little or
nothing is known as to the effect of transmission from one race to
another, as from Mongolian to Caucasian in Phillips’ story.

=NEUROSYPHILIS is NOT to be entirely ruled out by a negative serum
Wassermann Reaction; for the fluid Wassermann Reaction may be
positive.=

=Case 13.= William Twist is a case of note in the matter of the so-called preparetic period (the idea of Charles L. Dana which was scoffed at when first proposed by him in 1910). The patient, a very successful traveling salesman, 35 years of age, was admitted to the Psychopathic Hospital showing a typical picture of general paresis.

Thus, =mentally=, the patient showed elation, grandiosity (millions of dollars to give away), intellectual weakness, disorder of memory, lack of judgment, rambling talk, speech defect, omission of letters in writing and spelling.

=Neurologically=, there was tremor of the lips, slight irregularity of the pupils, which however reacted well, and lively knee-jerks.