Neurosyphilis

by Elmer Ernest Southard; Harry C. Solomon

I. THE NATURE AND FORMS OF SYPHILIS OF THE NERVOUS SYSTEM (NEUROSYPHILIS)

PARADIGM to show possible abundance and variety of symptoms and lesions in DIFFUSE NEUROSYPHILIS (“cerebrospinal syphilis”). Autopsy.

Case 1. Mrs. Alice Morton[^[1]] was in the hands of at least five well-known specialists in different branches of medicine and surgery during the nineteen years of her disease. It appears that she acquired syphilis upon marriage at the age of 23 to a man who later became tabetic and acknowledged syphilitic infection previous to marriage. Mrs. Morton remained without children and there were no miscarriages.

At the age of 27, she developed iritis, paresis of the left eye muscles, and ulceration of the throat, with destruction of the uvula. The syphilitic nature of her disease was at once recognized and the classical treatment was given, although, through numerous shifts in consultants, this treatment was never pushed to the limit. At 28 Mrs. M. began to suffer from severe headaches resembling migraine and accompanied by attacks of paræsthesia; at 35, came severe pains in the back and difficulty in walking.

At 36, the migraine attacks began to be accompanied by blurring of vision and dizziness. The difficulty in walking became extreme, affecting particularly the right foot. The legs became spastic, there were pains and hyperæsthesia of the chest, and severe cramps of the legs. Antisyphilitic treatment at this time yielded marked improvement.

During her thirty-sixth year, Mrs. M. sustained curious transient losses of vision and of hearing. She was also irritable, and at this time developed her first pronounced mental symptoms, namely, delusions concerning her relatives. There were also a few seizures of an epileptiform nature.

At 38 there was a spell of total deafness, followed by improvement. The eye muscles were also subject to a variable involvement with intervening spells of improvement. The knee-jerks were lost, but after a time returned in less pronounced form. Shortly, an absolute paralysis and extensive decubitus developed, and death occurred at 39.

The autopsy is briefly summarized below, but it is important in the understanding of Mrs. M.’s case (particularly some of the sensory symptoms and the transiency of certain symptoms) to consider the pre-infective history. Although there seems to be no doubt that the patient acquired syphilis at about 23 years of age from a syphilitic husband, who himself later became tabetic, yet it is of note that the patient was the only child of parents, both of whom also suffered from mental disease. Mrs. M.’s father died of what was called softening of the brain (one should avoid terming all old cases of so-called “softening of the brain” syphilitic, since the older diagnosticians did not always distinguish between non-syphilitic arteriosclerotic effects and syphilitic disease). Mrs. M.’s mother also died insane (confusion and emotional depression). It is clear, then, that we do not need to suppose that every symptom shown by Mrs. M. is directly due to destructive or irritative lesions immediately due to the spirocheta pallida. The case is, in fact, an excellent lesson as to the association of structural and functional effects in neuropathological cases.

Mrs. M. as a child had shown talent, but was somewhat nervous and eccentric. At one time, she had an attack of hysterical dysphasia; at another time, an attack of hysterical dyspnea; during another period, an apparent obsession (kicking the mopboard at regular intervals). Moreover, she had for years suffered from migraines of a severe and unusual type. Both the hysterical tendency and the migrainous tendency became mingled with the results of the neurosyphilis in later stages of the disease in such wise that it was hard to tell exactly where the structural phenomena left off and the functional phenomena began.

For example, at the age of 32, nine years after infection and four years after the earliest nerve symptoms traceable to syphilis, and at about the time of the onset of spinal cord symptoms, an attack was described as follows:

The patient had a very severe attack of migraine (?) yesterday, preceded and accompanied by paraphasia, so severe that for three hours she was unable to make herself understood, and indeed felt “as if her ideas were getting away from her.” This attack was ushered in by a numbness of the forefinger and thumb of the right hand, which lasted for about three hours, though the earlier attacks had lasted for only about ten minutes. During this period the hand felt as if it had been frozen and the loss of muscular power was so great that she was unable to hold objects in the hand. In some of the attacks this paræsthesia has affected the entire left half of the body, and occasionally the right half. Sometimes the seizures come on with great suddenness, so that once, when she was attacked while in the middle of the street, she had considerable difficulty in reaching the sidewalk. After the worst part of the attack is over a certain amount of paraphasia may persist for some days, together with awkwardness in the use of the right hand and numbness. She has had a great deal of nausea and vomiting, without reference to the taking of food.[^[2]]

Bearing in mind the mingling of structural with functional symptoms in this case, let us consider the autopsy findings.

ANATOMICAL

FORMS OF NEUROSYPHILIS

AUTONOMIC (SYMPATHETIC) NEUROSYPHILIS?

PERIPHERAL NEUROSYPHILIS

CENTRAL NEUROSYPHILIS

MENINGEAL

VASCULAR

PARENCHYMATOUS

MENINGOVASCULAR

VASCULOPARENCHYMATOUS

DIFFUSE ( = MENINGOVASCULOPARENCHYMATOUS)

GUMMA

Chart 1

CLINICAL FORMS OF NEUROSYPHILIS

HEAD AND FEARNSIDES, 1914

SYPHILIS MENINGOVASCULARIS

CEREBRAL FORMS

HEMIPLEGIA

AFFECTION OF THE CRANIAL NERVES

MUSCULAR ATROPHY

LATERAL AND COMBINED DEGENERATIONS

EPILEPSY

SYPHILIS CENTRALIS

DEMENTIA PARALYTICA

TABES DORSALIS

MUSCULAR ATROPHY

OPTIC ATROPHY

GASTRIC CRISES

EPILEPTIC MANIFESTATIONS

Chart 2

Peripheral neurosyphilis: The lesions of the cranial nerves were characteristically asymmetrical. Whereas the left third nerve looked entirely normal, the right third nerve had its diameter reduced two-thirds. On the other hand, the fourth nerves were equal and apparently normal. The sensory portion of the left fifth nerve was normal; the right fifth nerve was normal. The right sixth nerve agreed with the right third nerve in being atrophic, and was in fact reduced to a mere thread without contained nerve fibres at a point 2 mm. from its superficial origin. Although the right third nerve was atrophic, it was the left seventh and eighth nerves which had become atrophic; the process had spared the right seventh and eighth nerves. The remainder of the cranial nerves were grossly normal, except that the optic nerves had an outer zone of a translucent nature. So far, no spirochetes have been demonstrated in any portion of the nervous system of this case, but such asymmetrical and focal cranial nerve lesions are perhaps due to local spirochetal infection, punctuating (as it were) the diffuse process.

How much of the transient blindness, deafness, and ocular paralysis can be explained on the anatomical findings in these nerves? Possibly a portion of the phenomena can be so explained. Thus, the mechanical conditions of pressure inside and outside these nerves, both in their peripheral course and in their passage through the membranes, can be readily understood to differ during the acute and subacute inflammation, during the process of repair in the pial tissues, and during the process of overgrowth of neuroglia tissue about the superficial origins of the nerves. Of course, the majority of lesions of these nerves were entirely extinct at the time of the autopsy, and their history could be surmised only from the appearances in the left eighth nerve. Here occurred a sharply marked focal area of gliosis with apparently total destruction of nerve fibres and related with a lymphocytosis of the investing membrane (one of the few areas of lymphocytosis found anywhere in this case).

If it were not for the pre-infective history, the hysterical dysphasia and dypsnea, the youthful obsessions, the migrainous tendency, and the psychopathic inheritance, we might be tempted to try to explain the transient blindness, the deafness, and ocular palsies on the basis of mechanical and toxic variations in the conditions of the peripheral cranial nerves. The existence of a trace of lymphocytosis in the left eighth nerve leads to the hypothesis that treatment might still be effective in this particular region (see below in discussion of spinal symptoms).

Spinal neurosyphilis: Not only the spinal cord but also the posterior and anterior nerve roots exhibited severe lesions. These lesions were both meningeal and parenchymatous. The meningeal process differed in its intensity in different parts of the spinal cord, being severest in the thoracic region. At one point in this region, the dura mater was so firmly attached to the pia mater that the line of demarcation between the two membranes was hard to make out. In fact, it seems clear that there could have been no free intercommunication between the spinal fluid above these adhesions of dura to pia mater and the spinal fluid below the adhesions. Accordingly, it seems that lumbar puncture, had it been practised in this case, would have failed to show features representative of the whole cerebrospinal fluid system. Moreover, since at no point in this region of adhesions or in the pia mater of the spinal cord below this point, were found any lymphocytes, it seems clear that the ordinary lumbar puncture would have failed to reveal a pleocytosis. Whether this fluid would have yielded a positive globulin and excess albumin test, it is now impossible to say; but it appears that the process in the lower part of the spinal cord was to all intents and purposes extinct.

However, there was one region of more severe inflammatory involvement. The spinal cord in the cervical region showed a lymphocyte infiltration of its vessels amounting to a mild myelitis (meaning, thereby, an inflammatory process of the spinal cord remote from the pia mater). Moreover, in this region, there was, besides the perivascular infiltration of the substance, also an infiltration of the overlying membranes themselves, especially in and near the posterior root zones.

The lessons of this finding are several: The inflammatory process in this case does not appear to have been entirely extinct! Can we not suppose that treatment might still have benefited this local inflammation (perivascular infiltration of the cervical spinal cord substance and overlying lymphocytic meningitis)? Can we not also picture the gradual ascent of the inflammatory lesions from lower segments to higher segments and possibly conceive of the gradual elevation of the zone of hyperæsthesia manifested in this case as following the gradual displacement upward of the lymphocytic process? Are there spirochetes in this tissue? So far none have been discovered, possibly through inaccuracies of available technique. To the neuropathologist, however, the lesion looks like a local reaction to organisms.

In addition to the spinal meningitis, chronic and acute, as above described, there were extensive parenchymatous spinal lesions.

In the first place, the meningitis had affected practically all the posterior roots so that the explanation of the posterior column sclerosis of this case is clear. The meningitis had apparently been so marked, also, that all the fibres anywhere near the periphery of the spinal cord had been likewise destroyed. The posterior columns and the posterior root zones were markedly sclerotic; or as we say (having reference to the overgrowth of neuroglia tissue) gliotic. But there was as much sclerosis (gliosis) of the lateral columns (particularly in the posterior two-thirds) as there was in the posterior columns and root zones. In fact, the entire posterior half or two-thirds of the spinal cord markedly outstripped the anterior portions of the cord in the severity of the gliosis (sclerosis) shown.

But although we can explain the posterior column sclerosis, the sclerosis of the posterior root zones and the marginal sclerosis (Randsklerose) round the entire periphery of the cord, on the basis of long-standing effects of old meningitis, we cannot thus explain another finding, namely, the destruction of the fibres in the lateral columns. This, in fact, is explained through lesions (mentioned below) that affected the encephalon. The net result of all these lesions of the spinal cord was to leave only the gray matter and a small amount of surrounding fibres (belonging to short tracts uniting nearby segments) intact. Briefly stated, every long tract in the spinal cord appeared upon examination to be extensively degenerated. The genesis of this parenchymatous loss was, however, double, being in part due to a local meningeal process (sometimes known as “perimeningitis”) and in part due to a cutting off of the pyramidal tract fibres on both sides by lesions higher up in the nervous system.

Case I. Spinal Cord (Three Levels) Showing:
A. Marginal sclerosis—effect of old meningitis now extinct.
B. Posterior column sclerosis—effect of meningitis about posterior roots also now extinct.
C. Bilateral pyramidal tract sclerosis—effect of cerebral thrombotic lesions.
Note distortion of tissues in B and C, partly artificial (tissues in places diffluent).

ANATOMICAL FORMULAE
MENINGOVASCULOPARENCHYMATOUS INVOLVEMENT
M, V, P, or Combinations Applied to the Classification of Head and Fearnsides
I.	SYPHILIS MENINGOVASCULARIS
	CEREBRAL FORMS	M or V or MV[[3]]
	HEMIPLEGIA	V
	AFFECTION OF THE CRANIAL NERVES	M
	MUSCULAR ATROPHY	M
	LATERAL AND COMBINED DEGENERATIONS	M
	EPILEPSY	M or V
II.	SYPHILIS CENTRALIS
	DEMENTIA PARALYTICA	MVP or VP
	TABES DORSALIS	MP
	MUSCULAR ATROPHY	P
	OPTIC ATROPHY	P
	GASTRIC CRISES	(M? or) P?
EPILEPTIC MANIFESTATIONS		P?
Chart 3

Can we offer any explanation of the partial return of knee-jerks after their temporary total loss at a certain period of the disease? We may assume that the knee-jerks were functionally lost about a year before the death of the patient through the partial or even almost complete destruction of the entering posterior root fibres at that level of the spinal cord which is directly related with the knee-jerk. The later partial return of the knee-jerks apparently requires us to suppose the maintenance of some fibres and collaterals by which a functional connection can be effected between the fibres of the posterior roots and the anterior horn cells which innervate the quadriceps femoris. Let us now suppose that pari passu with the actual return of the knee-jerks, the destructive processes that are affecting both pyramidal tracts high up in the nervous system are now advancing. It is clear that, whatever inhibitory influence these pyramidal tracts have been exerting up to this time upon the knee-jerk reflex arc, that influence is now to be decidedly reduced in amount and possibly absolutely lost. Upon the loss of such inhibitory influences exerted from above, the few persisting connections of the posterior roots and anterior horn cells are now permitted to resume their functions.

Encephalic neurosyphilis: The lesions mentioned above as causing destruction of the pyramidal tracts of the spinal cord were symmetrically destructive and atrophic lesions of the gray matter of both corpora striata with atrophy of the anterior segments of the internal capsules. There was a degenerative process of the corpus callosum especially affecting the forceps minor of the tapetum. The ventricles were largely dilated, indicating a considerable destruction and atrophy of the white matter in general.

After the above discussion of the possible effects of pyramidal tract lesion in this case, it is unnecessary further to discuss the paraplegia produced by the cystic lesions of the corpora striata. The theorist might inquire how these cystic lesions are produced: whether by vascular blocking or by toxic effects of the accumulations of spirochetes. Evidence is lacking which would completely sustain either hypothesis. Still, we do know that lesions almost identical in appearance may be produced by the necrosis consequent to the plugging of nutritive vessels in an organ like the brain supplied with end arteries. Therefore, it is probable that most pathologists would believe these lesions of the corpora striata to be produced by vascular plugging of the nature of thrombosis.

It is worth while to note that there was a suggestion of foci of encephalitis made out upon the gross examination. The cortex in general showed strikingly few lesions. However, the convolutions did show in places numerous ill-defined areas of hyperemia and slight swelling. These areas were of irregular distribution and only a few mm. or cm. in diameter. No gross vascular lesions were demonstrable in connection with these focal areas. Microscopically, however, venous plugs of polymorphonuclear leucocytes were found, and the local hyperemias were found to be largely due to venous congestion. However, very few polymorphonuclear leucocytes were found outside the blood vessels.

The white matter of numerous convolutions showed microscopically certain pale spots suggestive of an early atrophic process. Very possibly these represent a general tendency in the cerebrum to the same process of parenchymatous loss which had proceeded to such a marked degree in the spinal cord.

There was a single large so-called cyst of softening in the cerebellum (1.5 mm. across by 0.5–7.5 cm. in depth).

How far can we explain the symptoms of this case on the basis of these encephalic lesions? We can offer no correlation with the cerebellar lesion; and possibly this lack of correlation is to be expected on account of its failure to affect the vermis. As to the cystic lesions of the corpora striata, their effect in producing paraplegia at the close of life is obvious, and their possible relation to the partial return of knee-jerks has been discussed. Literally amazing was the comparative integrity of the cortical gray matter of this case when the spinal cord and the interior structures of the encephalon had been subjected to such severe and numerous lesions. The only mental symptoms noted in the case were sundry delusions directed against the patient’s relatives and a certain optimism which led the patient to cling as if with an obsession to the belief that in the end she would get well.

VARIOUS FORMS OF NEUROSYPHILIS COLLECTED FROM SEVERAL SOURCES
MENINGEAL NEUROSYPHILIS (M)
GUMMA OF DURA MATER	M
GUMMATOUS MENINGITIS (Pial)	M
SYPHILITIC MENINGITIS (Pial)	M
SYPHILITIC CRANIAL NERVE PALSIES (Primarily Pial)	M
SYPHILITIC BULBAR PALSY	M
SYPHILITIC ROOT NEURITIS	M
SYPHILITIC TRANSVERSE MYELITIS	M
SYPHILITIC NEURITIS (Some Cases by Extension)	M
SYPHILITIC EPILEPSY (Some Cases)	M
SYPHILITIC MUSCULAR ATROPHY (Some Cases)	M
VASCULAR NEUROSYPHILIS (V)
SYPHILITIC ARTERIOSCLEROSIS	V
SYPHILITIC CEREBRAL THROMBOSIS	V
SYPHILITIC APOPLEXY	V
ANEURYSM	V
SYPHILITIC EPILEPSY	V
PARENCHYMATOUS NEUROSYPHILIS (P)
GUMMA	P
CEREBROSPINAL SCLEROSIS	P
SYPHILITIC PARANOIA	P?
SYPHILITIC CHOREA	P
SYPHILITIC EPILEPSY	P
TABETIC PSYCHOSIS	P?
SYPHILITIC MUSCULAR ATROPHY	P
SYPHILITIC NEURITIS	P
Chart 4a

MENINGOVASCULAR NEUROSYPHILIS (MV)
CEREBRAL SYPHILIS	MV
CEREBROSPINAL SYPHILIS	MV
SYPHILITIC EPILEPSY	MV
MENINGOPARENCHYMATOUS NEUROSYPHILIS (MP)
CEREBRAL SYPHILIS	MP
CEREBROSPINAL SYPHILIS	MP
TABES DORSALIS	MP
ERB’S SYPHILITIC SPASTIC SPINAL PALSY	MP
VASCULOPARENCHYMATOUS NEUROSYPHILIS (VP)
CEREBRAL SYPHILIS	VP
CEREBROSPINAL SYPHILIS	VP
PARETIC NEUROSYPHILIS (GENERAL PARESIS)	VP
LISSAUER’S GENERAL PARESIS	VP
MENINGOVASCULOPARENCHYMATOUS NEUROSYPHILIS (MVP)
CEREBRAL SYPHILIS	MVP
CEREBROSPINAL SYPHILIS	MVP
PARETIC NEUROSYPHILIS	MVP
TABOPARESIS	MVP
DOUBTFUL (TOXIC?, IRRITATIVE?) NEUROSYPHILIS (?)
“PARESIS SINE PARESI”
SYPHILITIC NEURASTHENIA
TABETIC PSYCHOSIS
SYPHILITIC PARANOIA
SYPHILITIC POLYURIA, POLYDIPSIA
SYPHILITIC NEURALGIA
Chart 4b

Summary: We have here dealt at length with a long-standing Diffuse Neurosyphilis affecting to some extent the entire meninges and producing a destruction of posterior column fibres and numerous other fibres of the spinal cord (tabetiform portion of the neurosyphilis picture). We have also found central lesions of the corpora striata affecting the destruction of both pyramidal tracts (paraplegic portion of the neurosyphilis picture). We have found evidences of acute inflammation (lymphocytosis) in the cervical region of the spinal cord and in the left eighth nerve (progressive inflammatory neurosyphilis picture). In short, we have presented a case of diffuse (meningovasculoparenchymatous) neurosyphilis characterized by an ascending character in a course of at least 16 years; we have indicated a number of possible clinical correlations, not only with the major portion of the clinical course (symptoms of myelitis and pyramidal tract destruction), but we have also mentioned, merely for their suggestive value, a number of finer correlations between histological findings and certain clinical features (notably transient losses of vision and hearing, and a partial return of the lost knee-jerks). Bearing in mind the clinical and anatomical findings of this case, we shall be able to discuss the cases that follow in a briefer and more condensed fashion.

TABETIC NEUROSYPHILIS (“tabes dorsalis,” “locomotor ataxia”) complicated by vascular neurosyphilis (hemiplegia). Autopsy.

Case 2. Francis Garfield had been a successful lumberman and had enjoyed good health until his forty-fifth year. Suddenly one day, while walking on the street, Garfield lost the use of his legs and for a time was quite unable to walk. However, he recovered locomotion and after a time there was nothing wrong with his leg movements except a slight ataxia.

At the age of 52 Garfield had to give up work. It appears that he had been becoming cranky, sometimes, for example, shouting, whistling and slamming doors, apparently to annoy the family. His intellectual capacity seemed to be maintained, although his memory was slightly impaired.

At 67 years there was an ill-defined seizure, followed a few days later by another seizure with aphasia (wrong words used and lack of understanding of things said).

For years Garfield had been totally deaf in the right ear (following explosion of a gun?). Now, however, the left ear also showed a sensory impairment. Slight slurring of speech had been noticed first in the sixty-sixth year.

Physically there was a slightly enlarged heart with accentuated second aortic sound and irregular rhythm. Neurologically, inability to stand or walk; marked ataxia in his leg movements; upper extremities quite well controlled; the pupils were small and unequal, the left being larger than the right; although the reactions were difficult to test, the pupils seemed to react slightly to direct light stimuli; the knee-jerks were absent; tests for sensibility so far as could be determined did not show any abnormalities; there was much complaint of sharp pains in the legs.

There is no doubt that we are here dealing with a case of Tabes Dorsalis plus certain complications due to Vascular Lesions. The case went on to death from rupture of aortic aneurysm (also doubtless a syphilitic complication). The death occurred at 71, four years after admission to Danvers Hospital.

MAIN FORMS OF NEUROSYPHILIS

(CLASSIFICATION OF THIS BOOK)

DIFFUSE NEUROSYPHILIS

(non-vascular forms of “cerebral,” “spinal” and “cerebrospinal syphilis”)

VASCULAR NEUROSYPHILIS

(“cerebral arteriosclerosis,” “cerebral thrombosis”)

PARETIC NEUROSYPHILIS

(“general paresis”)

TABETIC NEUROSYPHILIS

(“tabes dorsalis”)

GUMMATOUS NEUROSYPHILIS

(“gumma of membranes, of brain”)

JUVENILE NEUROSYPHILIS

(paretic, tabetic, diffuse)

Chart 5

POSSIBLE INVOLVEMENT
BRAIN AND CORD SYPHILIS
[M]embranes, [V]essels, [P]arenchyma
[MVP]	EARLY, LATENT?, SYMBIOSIS?, ATTENUATION?....
MVP	CEREBRAL, CEREBROSPINAL SYPHILIS, PARESIS	MVP
[M]VP	PARESIS; SYPHILITIC ARTERIOSCLEROSIS	VP
M[V]P	?SYPHILOTOXIN FROM MENINGITIS	MP
MV[P]	SYPHILITIC MENINGITIS; CEREBRAL OR CEREBROSPINAL SYPHILIS	MV
[MV]P	SYPHILOTOXIC ATROPHY OR SCLEROSIS	P
M[VP]	SYPHILITIC MENINGITIS	M
[M]V[P]	SYPHILITIC ARTERIOSCLEROSIS	V
M, V or P in brackets [] means not involved.
Chart 6

NEUROSYPHILIS

SIX TESTS

BLOOD WASSERMANN

SPINAL FLUID WASSERMANN

SPINAL FLUID CYTOLOGY

SPINAL FLUID GLOBULIN

SPINAL FLUID ALBUMIN

SPINAL FLUID GOLD SOL

Chart 7

This case has been especially worked up and published by Dr. A. M. Barrett on account of the fact that the vascular lesions of the brain had produced a condition of pure word-deafness. Reference is made to the Journal of Nervous and Mental Disease, Vol. 37, 1910, for a complete description of the brain findings and an analysis of the word-deafness, a summary of which is as follows:

“Reaction to Words and Sounds.—Total deafness to words spoken, but gives attention to sounds; no ability to recognize meaning of sounds heard; no ability to repeat words heard. Spontaneous Speech.—Retained ability to speak spontaneously, with rare paraphasic utterances; occasional inability to speak readily the word desired, but later always giving the correct reaction; calculation fair; spelling good except for occasional paraphasia; spelling good for words pronounced. Reaction to Things Seen.—Objects correctly recognized and named except for an occasional paraphasic reply; mistakes in pronunciation not recognized; correct color recognition. Reaction to Things Felt.—Good for familiar objects; an occasional paraphasic reply. Reaction to Words Seen.—Reads printing and writing understandingly; unimpaired reading except for an occasional paraphasic reply; meaning of familiar signs recognized; slight difficulty in readily understanding meaning of arithmetical signs. Writing.—Spontaneous writing and drawing ability retained; ataxia (tabetic) in writing movements; no ability to write from dictation. Internal language.—No evidence of impairment.”

The brain post mortem showed severe atheromatous degeneration of the arteries at the base of the brain. Both middle cerebral arteries showed scattered atheromatous patches. The pia mater was transparent and delicate, except in the regions of both Sylvian fissures. There were residuals of old softening in both temporal lobes. In the fresh brain the regions of the right and left first temporal convolutions were sunken inward, and the pia intimately adherent to the softened areas. The limits and more exact localizing of these softenings were worked out from serial sections.

Barrett found in his serial sections that, although the transverse temporal convolutions of the left hemispheres were intact, these convolutions were undermined throughout their entire extent by degenerations in the fibres of the center of the first temporal convolution. Barrett, accordingly, regarded his case as essentially a case of subcortical tissue destruction. He agrees with various authors that the pure word-deafness of his case is the result of an isolation of the receiving station in the transverse convolutions of the left hemisphere. The tissue destruction produced by the vascular lesion had cut off the transverse convolutions from the internal geniculate body.

We are here, however, not considering the origin and relations of pure word-deafness but present the case as one of tabes dorsalis of 20 years standing, terminated by two characteristic syphilitic complications, first, an extensive destruction of brain tissue through cerebral thrombosis and secondly, fatal aortic aneurysm.

Summary: We have here dealt briefly with a long-standing case of Neurosyphilis of the Tabetic type: A characteristic but not necessary complication of the case is the Late Cerebral Vascular Involvement. The posterior column sclerosis is virtually the only spinal change. Spinal meningeal changes are absent (although it is to be assumed that chronic inflammatory changes in the posterior roots were at one time present in some quantity and although the spinal fluid characteristically shows lymphocytosis in tabetic neurosyphilis).

Whether the spirochetes produce special toxic components able to cause tabes or whether special kinds of spirochete are the tabes-making kinds is hard to say. Special qualities of individual tissue may be involved.

The cerebral lesions of a cystic nature are of vascular origin, like the differently localized encephalic lesions of Case 1 (Alice Morton). Vascular syphilis is not a special property of the vessels of the nervous system. In fact this very case died of aortic aneurysm.

PARETIC NEUROSYPHILIS (“general paresis,” “dementia paralytica,” “softening of the brain”). Autopsy.

Case 3. James Dixon, 44, was first seen at the Danvers Hospital, reciting verses in a dramatic and noisy way. He remained good-natured and jolly; nor was there any change in his euphoria until he had become physically weaker and more generally demented. In fact, Dixon appeared to become more and more expansive as he became physically weaker. He was in the habit of describing himself as “O. K., No. 1, Superfine.”

Physically the patient was gray and bald on vertex, had a dusky complexion, was very thin (6 ft. in height, weight 155 lbs.); the mucous membranes were pallid; the teeth rather poorly preserved; the heart was somewhat enlarged; the pulse irregular in rhythm, of poor volume and tension.

Neurologically, the patient showed a characteristic Romberg sign and ataxia in walking a straight line. The tremulous tongue was protruded to the left, and there was a coarse tremor of the extended fingers. The knee-jerks were absent, and the Achilles jerks could not be obtained; the plantar reactions were slight; the arm reflexes were present. The pupils were stiff to light. There was a marked vocal tremor. The sensations could not be tested on account of the patient’s mental state.

It appears that Dixon had left school at about 16, at about 22 had gone into the provision business, and later had become a hotel clerk. He had married at 28; there had been two miscarriages, at three months and six weeks respectively; one child was stillborn; four children were living.

The patient was not very alcoholic. The patient’s wife thought the symptoms had been coming on since his forty-first year when irritability set in, but he was not discharged from work until about a year since. He was taken back again after his wife’s pleas, and remained at work about three months; but for ten months before admission to the hospital, Dixon had done practically nothing, had shown a marked memory failure and speech defect, at the same time claiming to be a person capable of doing and accomplishing everything. He had become careless of his personal appearance, collected a drawer-full of stumps of cigars, carried lumps of coal in his pocket, laughed causelessly, and spat on the carpet.

We here deal with a case of unknown duration from the initial infection, but with symptoms lasting about three years and three months. Aside from the cause of death (empyema of left pleural cavity associated with acute hemorrhagic splenitis, acute ileitis, and bronchial lymphnoditis), the body showed a number of other lesions outside the nervous system. There was the usual sclerosis of the aorta, though perhaps less marked than usual. There was a curious acute arteritis with fusiform dilatation of the arteria profunda femoris, with an edema of the thigh muscles and blebs of the overlying skin. There were also multiple chronic caseating lesions of the liver, without evidence of fibrosis. The explanation of these liver lesions is not yet clear. There was a cloudy swelling of the kidney.

The calvarium was dense and the dura mater thick and adherent. There was a chronic leptomeningitis, which, however, was rather unusual in being most marked in the posterior cisterna and along the sulci of the cerebellar hemispheres. There was a general cerebral sclerosis, with a question of atrophy of the superior temporal gyri (suggesting the so-called Lissauer’s paresis). There was a marked cerebellar sclerosis with a consequent sclerosis (grossly palpable) of the commissural fibres of the pons. There was a generalized slight spinal sclerosis. As a fair sample of the variety of head findings in paretic neurosyphilis, the details of the head examination are presented.

A. Normal postcentral cortex. (Compare B.)

B. Nerve cell losses. Perivascular deposits of mononuclear cells, amongst which are numerous plasma cells. Note decrease in number of nerve cells. Note irregular disposition of nerve cells. From paretic neurosyphilis.

Crown bald, with a slight fuzzy growth of short hairs. Scalp slightly adherent to calvarium; latter of usual thickness but denser than normal. Dura adherent to calvarium in region of vertex; dura not remarkable. Sinuses normal. Arachnoid villi moderately developed. Pia mater a trifle thickened and rather evenly throughout the cerebral portion. Linear sulcal markings are remarkable for their absence. The wall of the cerebellomedullary cisterna is thick and opaque. The most prominent pial thickenings are over the cerebellum. These are linear or may show feathery out-growths and are seated over the sulci, particularly in the neighborhood of the fissure and about the great cerebellar notch. They correspond fairly well with the focal variation in consistence of underlying tissues noted below.

Brain weight, 1265 grams. Consistence somewhat increased throughout and somewhat evenly increased. The prefrontal region shows the maximal increase of consistence but the remainder of the frontal region and corresponding occipital region are much firmer than normal. The two superior temporal gyri appear to be firmer than adjacent gyri and are possibly slightly diminished in superficial diameter. The hippocampal gyri are fairly firm. The substance on section is a trifle more moist than normal. The gray and white matter cut quite evenly. Diminution in depth of gray matter, if existent, could not be demonstrated. The ventricles show a moderate sanding throughout, best marked in the fourth ventricle. The basal ganglia are not remarkable except for the development of numerous dilated perivascular spaces about the lenticulostriate vessels. The pons is atrophic, but more so on the right side. The pons, like the prefrontal cortex, shows on section a distinct increase of consistence immediately beneath the pia mater. The white bands of the pons on section are distinctly firmer than the intervening substance. The olives are of equal consistence. Weight of cerebellum, pons, and medulla, 155 grams. The cerebellum shows an obvious atrophic and gliotic process of a symmetrical character. The superior surface, including both vermis and hemispheres, shows a consistence above normal and general reduction of the depth measured from the white matter. The reduction in depth gives rise to a visible depression as compared with tissue posterior to the postclival sulci. The lobus cacuminis, though slightly raised from the surrounding lobes, is equally firm, if not firmer. The superior and inferior surfaces show practically an equal increase of consistence. The dentate nuclei are not especially increased in consistence. The flocculi are reduced in size about one-third.

There was slight universal increase in consistence of spinal cord, best marked in lumbar region.

Microscopic findings are here presented merely in sufficient detail to establish the diagnosis. The left superior frontal gyrus shows extensive and somewhat irregular cellular and fibrillar gliosis of the plexiform layer, together with an increase of thickened vessels having lymphocytes and plasma cells in their sheaths.

The perivascular infiltrations are most extensive in the lower layers of the cortex. The lamination is in places thoroughly obscured, except that representatives of the layer of large external pyramids are almost always demonstrable.

The layer of medium-sized pyramids has undergone more numerical loss of elements than have the other layers.

Gliosis of white matter.

Specimens from the cerebellum show a destructive process of great severity, but a little irregular in extent, affecting chiefly the Purkinje cell belt. The Purkinje cells are often absent throughout one side of a given lamina, and there has ensued a dense accumulation of neuroglia cells along a former Purkinje cell belt, together with a considerable gliosis of the molecular layer. Considerable gliosis of the white matter, both diffuse and perivascular in distribution.

Perivascular plasma cell infiltrations as in cerebrum, but largely meningeal or in the white matter.

Sections from the corpora striata demonstrate a mild and early granular ependymitis, considerable subependymal gliosis of cellular type, considerable perivascular gliosis in the white portions of the tissue, and a moderate infiltration of perivascular sheaths with pigmented cells, lymphocytes, and plasma cells. There is little evidence of alteration in the nerve cells. Some are unevenly pigmented.

Summary: We here present a case with numerous and widespread neurosyphilitic lesions. However, the gross cerebral vascular complications of Case 1 (Alice Morton) and of Case 2 (Francis Garfield) are notably absent in James Dixon. Rather atypical (there seems to be always something atypical in cases of neurosyphilis!) are the liver lesions and arteritis of the leg, atypical, that is to say, for Paretic Neurosyphilis. Highly typical of paretic neurosyphilis and almost constant therein is the aortic sclerosis.

Apparent new formation of small blood vessel. Photographed by Dr. A. M. Barrett.

Rod cells (Stäbchenzellen) in paretic neurosyphilis. Photographed by Dr. A. M. Barrett.

Granular ependymitis—microscopic appearance of a marked example of “sanding” of ventricle.

Characteristic and constant in paretic neurosyphilis is the Plasmocytosis and Lymphocytosis, Perivascular in distribution about small cortical vessels. There is also a characteristic (though characteristically less prominent) Plasmocytosis and Lymphocytosis, Meningeal in distribution. The pleocytosis of the spinal fluid, almost constant though variable in amount in life, is an indicator of the meningeal picture and less directly of the parenchymatous picture.

Granular Ependymitis (“sanding” of ventricle floors) is characteristic and may be regarded as part of the parenchymatous picture. This ependymitis is an indicator how chemical changes could be readily produced at least in the ventricular fluids, since the limiting membranes of the nerve tissue are here subject to multiple breaks. The “sanding” is a neuroglia reaction to these multiple small breaks (Weigert’s explanation).

Parenchymatous losses have led to Atrophy and Sclerosis, of very varying extent in different parts of the encephalon. The atrophy is characteristic in paretic neurosyphilis, but by no means constant. Numerous cases have come to autopsy without clearly defined gross atrophy. Sclerosis is also characteristic and even more frequent than atrophy, doubtless because sclerosis represents an earlier phase of a process eventuating in gross atrophy.

A Tabetiform Picture characterizes the spinal cord, but in this case the tabetic clinical picture did not precede the paretic clinical picture. We are consequently to regard the tabetic spinal process as incidental and on all fours with the Cerebellar and Pontine Atrophy.

VASCULAR NEUROSYPHILIS (“syphilitic cerebral thrombosis”). Autopsy.

Case 4. James Pierce was an almshouse transfer to the Danvers Hospital in his fiftieth year. He died three years later. The accompanying brain pictures demonstrate so extensive a lesion of the left hemisphere that it is of great interest to determine if possible the genesis and course of his disease. It appears that syphilis had been acquired somewhere about the age of 38 or 40, so that the total duration of the process was between 13 and 15 years. In Pierce’s forty-third or forty-fourth year, he had a shock while walking in the streets of his native city, whereupon he was subsequently transferred to the Danvers Hospital, whose data have been summed up as follows (we are obliged to Dr. Charles T. Ryder for these data):

Neurological examination: Neuromuscular condition: Barely able to walk or stand without assistance; hemiplegia of right side; swings foot out and drags toe out and around in attempting to walk. Right hand held by side, flexed at right angle; fingers contracted and thumb thrown across palm. Can lift arm from side; practically no movements of forearms or fingers; atrophy of deltoid, arm, forearm, and hand. Muscular movements of left upper extremities fairly well performed; good strength.

Cranial nerves: Refuses to respond to any tests to determine hearing or vision, but evidently hears what is said to him, and in his movements gives no evidence of deafness. Right corner of mouth droops; tongue protrudes straight.

Reflexes: Pupils dilated; margins irregular; left pupil larger; they vary in size but it is impossible to determine whether the variation is due to light or accommodation reflex. Reflexes of right side extremely exaggerated throughout; there is little ankle clonus; Babinski is not obtained, patient holding his toes in flexed position in resisting attempts to elicit reflexes.

Sensations: Reaction to pain stimuli on either side. Evidently some anesthesia on right side, but pressure is apparently very painful. There is considerable spasticity of limbs on right side on passive motion. Too demented to make accurate tests.

The above examination was made on May 6, 1904. On May 20th the record states:

There is almost complete sensory aphasia with word-deafness; some paraphasic circumlocution. Many of his words are very well enunciated but have no meaning. Is apparently unable to recognize objects or their uses.

Brother stated that he was always supposed not to be over bright. Physician’s certificate states that he is epileptic, averaging two attacks per week. On the 15th of May he had a general convulsion; was unconscious for half an hour, and dull and drowsy for two hours afterwards. On the 19th, he had a similar attack in the afternoon, the convulsion lasting a minute, and he was stuporous for an hour.

On November 8th he had a severe epileptic convulsion. His body was curled up to the right. The convulsive seizure lasted for two minutes and was followed by complete unconsciousness for an hour, when the patient roused and appeared as usual in a few minutes. From that time to December 15th he had five epileptic convulsions; he was much more feeble, and unable to help himself as much as formerly.

Nov. 7, 1905: Patient has had occasional convulsions since last note, but none during the last three months. He is confined to bed, has become very much demented, and shows very marked speech defect, so that he is almost unintelligible. He understands only the simplest directions. Legs are considerably contracted and knees are flexed. Arm and hand on the right are paralyzed and show some atrophic changes; partially flexed. Left elbow jerk is very lively. On May 23, 1906 he was reported as having Achilles on right side only, and Babinski on right side. He died January 5, 1907.

The autopsy findings were as follows:

Head: Calvarium of moderate thickness; diploë present; dura slightly adherent over bregmatic region. Longitudinal sinus contains cruor clot. Dura is somewhat thickened and slightly more opaque than normal. Pacchionian granulations, small but fairly numerous. Pia contains throughout a considerable excess of clear serous fluid. The convolutions in general are of good breadth and proportion. There is an atrophic area roughly circular in outline and about 2 cm. in diameter in the posterior part of the right third frontal convolution corresponding to Broca’s area on the opposite hemisphere. The space thus formed is filled with edema held by the pia. On the left side is a similar subpial collection which covers the site of the posterior portions of all of the third frontal convolutions, parts of the lower end of the precentral convolution, and the whole of the first temporal convolution, which have disappeared entirely. The basal vessels show slight changes.

Cerebellum and basal ganglia are grossly normal.

The spinal membranes are negative. The regions of the pyramidal tracts in the cord are firm, project slightly from surface of section, and are china white.

Summary: Here is a picture made up almost purely of Vascular Neurosyphilis, with Secondary Spinal (Pyramidal Tract) Changes. Doubtless the genesis of this picture is allied to that of Case 1 (Alice Morton) and to that of the terminal vascular complications in a tabetic, Case 2 (Francis Garfield).

The absence of meningeal and parenchymatous (i.e., outside the region of necrosis produced by the vascular disease) lesions is characteristic of an important group of neurosyphilitic diseases. It is clear that the case, although one of extensive lesions, is not one of diffuse lesions in the sense of Case 1 (Alice Morton).

The spinal fluid picture in life may nevertheless show (as other cases amply demonstrate) a certain amount of lymphocytosis and possibly plasmocytosis, together with a variety of other changes. Treatment might be expected to keep down these associated changes, although obviously the effects of the necrosis are final and definite. Franz in Washington has succeeded in “reeducating” some of these hemiplegics, employing lower mechanisms of the nervous system.

Vascular neurosyphilis—effects of syphilitic thrombosis of Sylvian artery 10 years before death. (Case 4.)

Case 4. (See previous figure for brain lesion.) Three levels of the spinal cord showing unilateral pyramidal tract sclerosis, 10 years after cerebral thrombosis.

JUVENILE PARETIC NEUROSYPHILIS (“juvenile paresis”). Autopsy.

Case 5. John Lawrence was an under-sized negro, who came under hospital observation when he was 23 years of age. There was some evidence that the patient’s father was a neurosyphilitic although accurate data were out of the question. At all events, John had Hutchinsonian teeth, a forward bowing of the tibiae, and Argyll-Robertson pupils. These findings together with a history of backwardness at school seem to stamp the diagnosis. It seems that there had been a change for the worse from the age of 18, though the boy had been able to sell newspapers and black shoes up to within a year of his arrival at the hospital. During the last months of his life, he showed a general incoördination, with false movements suggesting those of a drunken person. There were numerous tremors, the glance was shifting, and there was a tendency to nystagmus. Some of these phenomena (taking into account that the Hutchinsonian teeth were not entirely typical and there was even at times some doubt as to whether the pupils were actually stiff) led to a question of the diagnosis multiple sclerosis.

There was, however, little doubt that the case was one of juvenile paresis. Among the symptoms found at various times in this case are the following: disorientation for time, place and persons, confusion, with coarsely irrelevant replies to questions, ill-defined and transitory delusions of persecution, auditory, tactile, and visual hallucinations, and defective memory.

Early in life, the patient had had a habit of falling asleep in school hours, and had experienced a number of falls at various times. During an attack of measles he had had a number of spasms, each of which lasted ten minutes or more.

The autopsy showed death to be due to an early bronchial pneumonia. The thymus was persistent, measuring 3 × 2 × .5 cm. The marrow of the femur was red.

There was a moderate degree of sclerosis of the aorta confined to a few plaques in the arch (not a characteristic syphilitic scarring of the aorta). The spleen was small and had a thickened capsule.

The majority of the lesions, however, were in the nervous system, and the following description is taken from the routine hospital records to exemplify the findings in a fairly characteristic case of Juvenile Paresis.

Head: Scalp closely adherent to calvarium. Calvarium heavy without diploë. Dura adherent to calvarium in bregmatic region. Sinuses contain liquid blood. Arachnoidal villi in considerable quantity. Pia mater contains considerable clear fluid and shows diffuse haziness and focal thickenings. The diffuse haziness is almost universal and is best marked over the superior surface of the cerebellum. The focal thickenings are of general distribution over the veins of the sulci on the superior surface of the brim and are heaped up to form considerable linear mounds near the region of the arachnoidal villi. The superior surface of the cerebellum is traversed by similar linear mounds of fibrous tissue running at an angle to the laminæ. There is no notable increase of fibrous tissue at the base.

Brain: Weight 965 grams. The sulcation is roughly symmetrical except in the occipital poles where there is unusually rich and complex but shallow sulcation. The cortical substance is everywhere firmer than normal, but the sulci fail to flare notably. In a few places there is a focal increase of consistence of still greater degree with apparent local hypertrophy (or gliosis with increase of substance). These foci are in the right second temporal gyrus (3 cm. in diameter) and in the left first temporal gyrus (of same size but somewhat less firm) and are of a whitish, waxen appearance, being visible several feet away by reason of their color and apparent encroachment upon the adjacent sulci. The foci are sharply limited by the sulci laterally, but pale out gradually before and behind.

The convolutions of the vertex show another type of lesion. The tissue of the greater part of the vertex resembles that of the flanks and base in being firmer than normal and of a grayish pink color. Behind the fissure of Rolando on the right side and behind the anterior limits of the ascending frontal region on the left side the brain tissue of the vertex becomes suddenly still firmer and of a yellowish gray color. This lesion disappears gradually into the occipital microgyria behind and the gyri gradually lose their yellowish tint. The lesion fades away gradually so that it fails to involve the temporal convolutions.

The cerebral tissue cuts firmly and smoothly. The tissue of the frontal region is a little edematous. The white matter is of a normal appearance. The ependyma of all the ventricles is somewhat sanded. The fourth ventricle is most affected.

The cerebellum is not edematous and is as firm as the normal olivary bodies. The cerebellar hemispheres are symmetrical and of a normal appearance, save that the laminæ are slightly narrower than usual and very compactly set. The color, where not obscured by the haziness of the pia mater, is of a grayish pink somewhat suggestive of freshly tanned shoe leather. The substance cuts smoothly and firmly. The dentate nuclei are unusually firm. The pons is small, but of the usual color. Lower structures normal except the cord which is small and shows curious deviations from the normal markings. The posterior horns and gray commissure are at many levels the only structures to preserve the normal gray appearance, so that the H or butterfly appearance is replaced by a crescent. At these levels, traces of gray matter often stand out in the loci of the anterior horns.

The important anatomical diagnoses in the nervous system are as follows:

Atrophy of cerebrum, 965 grams (there is of course a question whether we are not dealing with a degree of cerebral hypoplasia).

Focal scleroses of cerebrum, suggesting the tuberous scleroses of Bourneville.

Occipital microgyria.

Cerebral and cerebellar gliosis.

Chronic ependymitis.

Gliosis of the gray matter of the spinal cord.

Chronic diffuse and focal leptomeningitis.

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