Transcriber’s Note:

The cover image was created by the transcriber and is placed in the public domain.

THE

CASE HISTORY SERIES

CASE HISTORIES IN MEDICINE

BY

Richard C. Cabot, M.D.

Third edition, revised and enlarged

CASE HISTORIES IN PEDIATRICS

BY

John Lovett Morse, M.D.

Second edition, revised and enlarged

ONE HUNDRED SURGICAL PROBLEMS

BY

James G. Mumford, M.D.

Second Printing

CASE HISTORIES IN NEUROLOGY

BY

E. W. Taylor, M.D.

Second Printing

CASE HISTORIES IN OBSTETRICS

BY

Robert L. DeNormandie, M.D.

Second Edition

CASE HISTORIES IN DISEASES OF WOMEN

BY

Charles M. Green, M.D.

NEUROSYPHILIS

MODERN SYSTEMATIC DIAGNOSIS AND TREATMENT

Presented in one hundred and thirty-seven Case Histories

BY

E. E. Southard, M.D., Sc.D.

AND

H. C. Solomon, M.D.

Being Monograph Number Two of the Psychopathic Hospital, Boston, Massachusetts. (Monograph Number One was A Point Scale for Measuring Mental Ability by Robert M. Yerkes, James W. Bridges and Rose S. Hardwick. Published by Warwick and York. Baltimore 1915.)

NEUROSYPHILIS
MODERN SYSTEMATIC DIAGNOSIS AND TREATMENT
PRESENTED IN ONE HUNDRED AND THIRTY-SEVEN CASE HISTORIES

BY

E. E. SOUTHARD, M.D., Sc.D.,

Bullard Professor of Neuropathology, Harvard Medical School; Pathologist, Massachusetts Commission on Mental Diseases; Director, Psychopathic Department, Boston State Hospital; Vice-President, American Medico-Psychological Association

AND

H. C. SOLOMON, M.D.,

Instructor in Neuropathology and in Psychiatry, Harvard Medical School; Special Investigator in Brain Syphilis, Massachusetts Commission on Mental Diseases; Acting Chief-of-Staff, Psychopathic Department, Boston State Hospital

WITH AN INTRODUCTION BY

JAMES JACKSON PUTNAM, M.D.,

Professor Emeritus of Diseases of the Nervous System, Harvard Medical School

BY VOTE OF THE TRUSTEES OF THE BOSTON STATE HOSPITAL

MONOGRAPH NUMBER TWO

OF THE

PSYCHOPATHIC HOSPITAL BOSTON, MASSACHUSETTS

BOSTON

W. M. LEONARD, Publisher

1917

Copyright, 1917.

By W. M. Leonard

In

MASSACHUSETTS

A STATE THAT

BOTH TOLERATES AND FOSTERS

RESEARCH

PREFACE

This book is written primarily for the general practitioner and secondarily for the syphilographer, the neurologist, and the psychiatrist. Our material is drawn chiefly from a psychopathic hospital, that modern type of institution in which the mental problems of general medical practice come to a diagnostic head weeks, months, or years before the asylum is thought of.

It is this peculiar nature of psychopathic hospital material—a concentrated essence of the most difficult daily problems of general practice—that brings together such an apparent mélange of cases as are here described, ranging from mild single-symptom diseases like extraocular palsy up to genuine magazines of symptoms as in general paresis; from feeblemindedness, apparently simple, up to apparently simple dotage, both feeblemindedness and dotage really syphilitic; from the mind-clear tabetic to the maniacal or deluded subject who looks physically perfectly fit; from the early secondaries to the late tertiaries or so-called quaternaries; from peracute to the most chronic of known conditions; from the most delicate character changes to the profoundest ruin of the psyche.

Although the bulk of our case-material is drawn from general practice through the thinnest of intermediary membranes, the psychopathic hospital, yet we have tried to depict the whole story by presenting enough autopsied cases from district state hospitals to show exactly what treatment has to face. Nor have we hesitated to insert cases in which treatment has failed.

In addition to (a) the Psychopathic Hospital, Boston, group of incipient, doubtful, obscure, or complicated cases (the early clinical group) and (b) the Danvers State Hospital, Hathorne, group of longer-standing, committed, fatal cases (the finished or autopsied group) we present (c) a miscellaneous group of cases, including many from private neurological or psychiatric practice. No doubt those familiar with Boston medicine will see traces of the teaching of our former chiefs, notably Professors James Jackson Putnam and Edward Wyllys Taylor. We are obliged to them for some well-observed cases.

We have dedicated our work to the Commonwealth, but perhaps we should more specifically ascribe to the Massachusetts Commission on Mental Diseases (formerly the State Board of Insanity) the spirit that permitted our special study of neurosyphilis treatment. To these authorities, who have countenanced and encouraged a somewhat costly piece of special work since 1914, we offer our thanks, hoping that other states will be one by one stimulated to the state-endowment of research. States doing full duty by research can be counted on one hand.

To our Psychopathic Hospital colleagues and the internes, and especially to Drs. Myrtelle M. Canavan and Douglas A. Thom of the Commission’s Pathological Service, we also offer our best thanks.

The Danvers traditions are tangible here: cases of Drs. A. M. Barrett, H. A. Cotton, H. W. Mitchell, H. M. Swift, and others are presented. We have been especially aided by the more recent work of Dr. Lawson G. Lowrey.

Nor should we have been able to present our samples of brain correlation without drawing on the collection arranged and analyzed by Dr. Annie E. Taft, Custodian, Harvard Department of Neuropathology. The photographs, part of a collection of brain photographs now numbering over 10,000 representing 700 brains of all sorts, were made by Mr. Herbert W. Taylor.

The Wassermann testing work has been done by Dr. W. A. Hinton of the State Board of Health. Dr. Hinton himself wrote out the text description of the Wassermann method. The method of his laboratory is held to the standards of control set by previous chiefs, viz. by Professor F. P. Gay, who brought immunological methods direct from the laboratory of Bordet (whose method the Wassermann method essentially is), Prof. W. P. Lucas, and the late Dr. Emma W. D. Mooers, who had assisted Plaut in his first work with the Wassermann method in Kraepelin’s Munich Clinic.

The material combed by us to secure this illustrative series amounts to over 2000 cases of syphilis of the nervous system, including over 100 autopsies in all types of case. We have presented these with very varying fulness, chiefly to illustrate the contentions at the heads of the case-descriptions.

In using the book, we suggest early reference to the Summary and Key, where for convenience are placed numerous cross-references permitting extended illustration of almost every proposition from several cases.

We have not made a large feature of the Medicolegal and Social section. This kind of thing well deserves a volume by itself, with all the legal and social-service implications drawn out in their amazing richness and detail. The social service slogan, “A paretic’s child is a syphilitic’s child” has already accomplished a great deal of good in our local world. Some day we may not be compelled to drive the paretic’s spouse and offspring to the Wassermann serum test! The general practitioner must help here.

A note on the Treatment section. This is manifestly not the last word or even, we hope, our own last word, since the systematic work of the Massachusetts Commission must be kept up for some years to get a reliable verdict. Some of the results give rise to greater optimism than has prevailed in asylum circles, especially re general paresis. We are confident that no one can now successfully make a differential diagnosis between the paretic and the diffuse non-paretic forms of neurosyphilis in many phases of either disease, even with all laboratory refinements. If this be so, it is improper not to give the full benefits of modern treatment to all cases in which the diagnosis remains doubtful between the paretic and the diffuse non-paretic forms of neurosyphilis. We ourselves advocate modern treatment, not only in the diffuse, but also in early paretic forms of neurosyphilis.

It would have been out of place in a book in this Case History Series to have dealt extensively with the history of our topic. We have compensated inadequately for this lack by a few remarks at the head of the Summary and Key. We are, like all others in the field, under the inevitable obligation to Nonne of Hamburg, whose great work has gone into three editions, the second of which has appeared in English translation (Nonne’s Syphilis of the Nervous System, C. R. Ball, translator). Mott’s work, embodied in a large volume of the Power-Murphy System of Syphilis, has also been attentively consulted, as well as the various systematic works on neurology and psychiatry. The topic of Neurosyphilis is getting wide and appropriate attention in this country through special journals, both those dealing with nervous and mental diseases, and those dealing with syphilis. Syphilis is in a sense the making of psychiatry and will go far to pushing psychiatry into general practice.

At the last moment we have been led to deviate from our plan of presenting only local cases familiar and accessible to us. In a section on Neurosyphilis and the War, we present excerpts and digests of English, French, and German cases of neurosyphilis that have appeared in association with the war. Our own country has not suffered greatly as yet either from the lighting up of neurosyphilis under martial stress or from the immediate or remote effects of syphilis obtained in the unholy congress of Mars and Venus. Space forbids a large collection of these martial cases, but, as will be seen, a fair sample of problems is presented.

Speaking for the moment as the senior author of this book, I wish to say that, were it not for the energy, industry, and ingenuity of the junior author, Dr. H. C. Solomon, the book would not have been written. Nor, in all probability, would the systematic work of the Commonwealth on neurosyphilis and its treatment ever have been begun. I can also accord the highest praise to Mrs. Maida Herman Solomon for her social-service work in this new field.

Perhaps, in closing, we owe an apology to John Milton for our borrowings from the two Paradises. Had he known much about syphilis, Milton might have written still stronger mottoes for us.

E. E. Southard

74 Fenwood Road

Boston, Massachusetts

TABLE OF CONTENTS

INTRODUCTION

It is a privilege to be allowed to write a word of introduction to a textbook which so richly fulfils its function as does this volume on the manifold disorders classified under Neurosyphilis, a subject of which the importance for the welfare of society is found to loom the larger the more deeply its mysteries are probed.

The case histories with which its pages are so amply stocked are carefully analyzed in accordance with a broadly chosen plan, and the generalizations that precede and follow them are obviously based on a wide and varied personal experience such as alone could render a familiarity with the literature of the subjects treated adequate to its best usefulness. Both writers were indeed well adapted for this task. Dr. Southard, as everyone is aware, has long been a highly conscientious, ardent and productive worker in the department of pathological anatomy, and of late years a careful student of clinical diagnosis and methods, both at the Danvers State Hospital and still more, at the Psychopathic Hospital which he worked so hard to found; while Dr. Solomon’s researches, in the special field of neurosyphilis, have been of the highest order.

Undoubted as are the merits of the case-system of instruction that has been so much in vogue in recent years, and excellent as is the modern supplementation of this method by the use of published records, the danger is still real that the student will have presented to him a picture of nature in disease that is too diagrammatic, too concise, with the result that while the task of memory is lightened through simplified formulation, the training of the doubting and inquiring instincts is often given too little stimulus and scope. In this book this danger is deliberately met through the casting of emphasis rather on the pluralistic aspects of the processes at stake than (primarily) on their unitary aspects.

The student who utilizes this volume cannot but emerge from his study a more thoughtful person than he was at the period of his entry. He will have seen that clinical rules of thumb cannot be followed to advantage, and that, on the contrary, surprises are to be expected and prepared for. Let the recognition of this fact, if it seems to increase the difficulties in the way of diagnosis, not lead to pessimism in that respect, or to hopelessness in therapeutics. On the contrary the writers’ bias is towards the worth-whileness of clinical efforts and an increased respect for accuracy and thoroughness in the utilization of modern methods of research. The chance is indeed held open that even the gaunt spectre of “General Paresis” may prove to be less terrible than it seems, and for this hope good grounds are given.

It is in this way made clear, on the strength of anatomical evidence of much interest, that even if in the treatment of a given patient, the time arrives when a fatal or unfavorable result seems manifestly foreshadowed, it may be still worth while to renew the treatment with fresh zeal, for the sake of combatting some symptom or exacerbation, for which a locally fresh process furnishes the cause.

Another noteworthy principle here emphasized and illustrated is that the relationship between “functional” (hysterical, neurasthenic, migrainoid) symptoms and the signs (or symptoms) of organic processes is clinically important and worthy of much further study. This is a matter which, in a general sense, has interested me for many years. Above and over the “organic” hovers always the “functional,” as representing the first indication of the marvelous tendency to repair, or substitution, for which the resources of nature are so vast. Yet this functional tendency also has its laws, of which, in their turn, the organic processes display the action in quasi diagrammatic form. Hysteria, neurasthenia, migraine, etc., do not arise de novo in each case, but conform to typical, though not rigid, formulas, susceptible of description. I have recently had the opportunity to study in detail an analogous series of transitions between the movements (and emotions) indicative of apparently purposeless myoclonic movements (on an epileptoid basis) and the movements of surprise, engrossment, purposeful effort, the excitement and joy by which the former were excited and into which they shaded over.

Taken altogether, this book represents work and thought in which, for amount and kind, the neurologists of Boston may take just pride.

James J. Putnam.

St. Hubert’s, Keene Valley, New York.

August, 1917.

Me miserable! which way shall I fly

Infinite wrath and infinite despair?

Which way I fly is Hell; myself am Hell;

And, in the lowest deep, a lower deep

Still threatening to devour me opens wide,

To which the Hell I suffer seems a Heaven.

Paradise Lost, Book IV, lines 73–78.

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).

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.

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

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

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.

Mr. Twist had sought advice at our out-patient department in his thirty-third year. The records show that at that time he was somewhat depressed, and his speech was even then, according to his own statement, stammering. However, we found the W. R. at that time to be negative in the blood serum. It appeared that his mother had died of consumption; his father was said to have committed suicide. A brother had once recovered from an attack of depression, presumably an attack of manic-depressive psychosis. Accordingly, we thought at the time that the case was probably one of manic-depressive psychosis. Moreover, our routine serum W. R. failed to indicate any syphilitic process. As for the so-called stammering of speech, this appeared to be a matter of the patient’s own recollection rather than of our observation. In any event, the patient had gone into the country and appears to have entirely recovered; falling, again, however, into mental difficulties after a short period, and finally arriving at the hospital in the above-mentioned classical condition.

The W. R. in the blood serum proved again negative. The test was repeated a number of times; also, after salvarsan had been given. The salvarsan did not act provocatively, and the blood serum has remained consistently negative.

In cases of syphilis the W. R. is at times negative. Swift claims that in such cases an injection of salvarsan will often produce a positive W. R. if the blood is tested on several days following the injection.

The spinal fluid, however, did show a positive W. R. as well as a gold sol reaction of a “paretic” type. There were at the first examination 194 cells per cmm., there was a moderate excess of albumin, and a positive globulin test. In short, there was no question of any other diagnosis than General Paresis.

1. How can the negative W. R. of the blood serum be explained? It is difficult or impossible to explain this. Figures differ as to the percentage of cases of general paresis with negative blood serum; perhaps 3 to 5% of these cases yield a negative serum W. R.

It is important to note the long preparetic period: at least a year and a half. Could our diagnostic methods be sharpened a trifle, such cases as these could be obtained early in this preparetic period and it might then be safe to promise good therapeutic results.

2. What is the nature of the preparesis of Dana? When Dana’s brief paper on preparesis was written, there was of course hardly any idea that cases of paretic neurosyphilis could be cured or would recover, except possibly vanishingly few curiosa about which there would always rage a diagnostic question. Accordingly, Dana, having found certain cases that seemed to him to have early signs of paresis but had apparently been cured by treatment, proposed to call them cases of preparesis. His idea was that he would thereby not offend those who held that general paresis was theoretically a fatal disease. With modern work and the display of more and more atypical cases of neurosyphilis, and the observation of relatively numerous cures or remissions under treatment, the designation of preparesis for a separate entity, or even for a sub-form of neurosyphilis, becomes superfluous.

3. What is the percentage of cases of paretic neurosyphilis that show a negative serum W. R.? Among the best figures are those of Müller, who found that of 386 examples of paretic neurosyphilis, 379 showed all reactions positive, or 98.5%.

4. What is the meaning and value of the so-called provocative salvarsan injection? In practice, there may be a series of negative W. R.’s in the blood serum before a positive reaction is finally obtained, owing to technical difficulties or biological peculiarities. Where intensive work is being done upon the neurosyphilis problem, it is beyond question desirable to make the W. R. test upon at least three separate samples of blood drawn at intervals, for the second or third test may prove positive. This situation makes the interpretation of the so-called provocative salvarsan injection exceedingly doubtful; that is, the reaction might have been positive on repetition without the injection of salvarsan. The present case, as above stated, failed to yield a serum W. R. even after repeated tests and the “provocative.”

5. What is the significance of the irregular pupils in this group? Paretic neurosyphilis shows inequality of the pupils in a high per cent of cases. Irregularity of outline of the pupils is commonly thought to be an important sign and to suggest neurosyphilis. It is true that many cases of pupillary irregularity are syphilitic, but the sign is of little or no differential value since congenital malformations and relics of old injuries and adhesions may produce effects identical with those of neurosyphilis.

DIFFUSE (that is, meningovasculoparenchymatous[^[5]]) NEUROSYPHILIS is typically associated with six positive tests (serum Wassermann reaction, fluid Wassermann reaction, spinal fluid gold sol reaction, pleocytosis, positive globulin, excessive albumin); but one or more, and frequently several, of these tests are likely to run mild as compared with the tests in PARETIC NEUROSYPHILIS (“general paresis”). The clinical course of the diffuse (and especially the meningovascular) cases is likely to be protracted, with a good prognosis as to life (barring fatal vascular insults).

Case 14. We shall present the case of John Jackson, a surveyor, 31 years of age, suffering from a left hemiplegia, with this in mind: To exhibit difficulties in diagnosis in the presence of an embarrassment of symptomatic riches.

The patient arrived at the hospital, in the first place, because he had been threatening a woman who lived next door to him. He believed that this neighbor had been talking about him and circulating reports against him. Excited by these ideas, he had threatened to cut her throat.

Now the occurrence of hemiplegia in adult life before the approach of senium is always suspicious of syphilis, and this suspicion we naturally entertained from the beginning. However, there was upon the scalp a crooked linear furrow about six inches long, running from the vertex to the right parietal eminence. Another furrow about an inch long was present upon the forehead. These furrows appeared to be of a bony nature and were not tender. There was evidence of an old decompression operation on the right side of the head; there were also large scars on both sides of the neck, evidently the result of old operations; and there were numerous palpable glands—the largest about the size of a lima bean—all firm and not tender.

Station in syphilitic hemiplegia. Syphilitic pigmentation of skin.

It seems that at the age of eight, according to the patient’s mother, Jackson had received a head injury and had remained unconscious for three weeks. Upon recovery, he had to relearn both to walk and to talk; however, he was able to begin school where he left off. He became more nervous and irritable after the accident than previously. Nothing further had developed until, at about 25 years of age, a tubercle was discovered in his eye (the right pupil was smaller than the left, reacting more slowly; right iris bound down by adhesions, with white opacity of anterior chamber). For two years, 25 to 27, the patient was under medical treatment for tuberculosis, and at the conclusion of this period numerous glands were removed from the neck and diagnosticated tuberculous. However, the neck did not heal and he carried bandages upon it for two years.

At 28, the patient’s mother described the occurrence of a slight shock, with head retraction, for a minute or two, and inability to speak. Thereafter there had been five or six similar attacks, less severe, and without loss of speech. The attacks were never accompanied by convulsive movements. Then occurred a paralytic stroke, leaving the patient with a left hemiplegia, which had somewhat improved. Mentally, the patient had gone down hill, becoming less alert and more apathetic, and to some extent amnestic. One had to consider, accordingly, the somewhat doubtful possibility of post-traumatic and post-operative conditions, and the question of tuberculosis (possibly errors in diagnosis; the lungs showed no evidence of tuberculosis).

Physically, the signs of a left hemiplegia were appropriate. Spasticity on the left side was found; there were Babinski, Gordon, Oppenheim reflexes and ankle clonus on the left side (all absent on the right). Speech defect was present. Mentally, aside from the delusions noted at the beginning of our analysis, a striking feature was the patient’s childishness. While reciting delusions, the patient was overactive and evinced a somewhat childish interest. Arithmetically, Jackson had preserved a fair ability but his apathy and lack of interest interfered with tests, and possibly also with the exercise of memory. As above noted, we were compelled to maintain the suspicion of syphilis throughout despite the attractive hypotheses of traumatic and post-decompressive effects and cerebral tuberculosis. A history of the acquisition of syphilis an unknown number of years before admission entered to strengthen the suspicion of the syphilitic nature of the mental symptoms.

Syphilitic thrombosis. Contours of brain preserved.

The W. R. proved positive in blood and spinal fluid. The gold sol reaction was of the syphilitic type; 37 cells were found per cmm.; there was a slight amount of globulin and a slight excess of albumin.

We made a diagnosis of Cerebrospinal Syphilis rather than general paresis on account of, first, the slow course of the disease; second, the vascular type of the cerebral insult, hardly typical of paresis; and third, the mild spinal fluid reaction. Treatment will hardly cure the hemiplegia, at least so far as restoration of cerebral tissues lost in the insult is concerned. We were perhaps entitled to consider that, as in the cases of Petrofski (17), O’Neil (19), Robinson (45), the meningitic process could be arrested. Unfortunately, our treatment of 20 injections of salvarsan over a period of 10 weeks, followed by a number of months of bi-weekly injections of mercury salicylate, proved incapable of making any change in the mental and physical picture or in the laboratory findings.

1. Can we explain the apparently poor reaction to treatment of the cerebrospinal syphilis in the case of Jackson by supposing a more deep-seated involvement than the meningovascular involvement indicated by the hemiplegia and the signs in the fluid? Autopsied cases in our experience show focal parenchymatous involvements that have not caused obvious clinical symptoms at any time during the course of the disease. These symptomatically silent lesions may have been present.

2. What is the comparative prognostic value of seizures in paretic neurosyphilis and in such a meningovascular case as that of Jackson? Paretic seizures are often and indeed characteristically recovered from. Moreover, autopsies in paretic neurosyphilis characteristically show no gross focal destructive lesions to correspond with the seizures. The paretic seizures are apparently more irritative than paralytic. However, the seizures of the meningovascular group of neurosyphilis are also, though less commonly, recovered from, so that the differential diagnosis on the basis of the outcome of seizures is not safe. Rarely paretic neurosyphilis itself also develops seizures from which no recovery is made.

3. What is the relation of neuropathic heredity to neurosyphilis? The family history of John Jackson is undoubtedly poor, since his father died of diabetes and a paternal uncle was insane; and on the mother’s side, the grandmother died of tuberculosis and an aunt died insane. This general question was more interesting in the days before the syphilitic nature of general paresis and of allied diseases was known. However, we may still hold perhaps that not only syphilis but also various intoxications, especially alcoholism, do flourish upon a neuropathic soil. This question, like that of Krafft-Ebing’s celebrated claim of the relation between syphilization and civilization, needs revision in the light of more extensive applications of the W. R. in larger and larger groups of persons under various community conditions.

The SIX TESTS (serum Wassermann reaction, fluid Wassermann reaction, pleocytosis, gold sol reaction, globulin, excess albumin) are likely to run STRONGER in PARETIC NEUROSYPHILIS (“general paresis”) than in DIFFUSE (especially meningovascular) NEUROSYPHILIS; in particular, the gold sol reaction is likely to prove “paretic” rather than “syphilitic.” The clinical course of paretic neurosyphilis (“general paresis”) is likely to terminate in death within a few years.

Case 15. Pietro Martiro was a well developed and nourished man, 30 years of age, who had been doing erratic things and acting peculiarly for a few weeks before entering the hospital. In the hospital, Martiro proved to be very excitable and given to violence. He had marked delusions of grandeur, saying he was worth many millions of dollars, was the greatest singer in the world, the greatest athlete in the world, and the like.

Physically, there was no disorder except overactivity of some reflexes. The diagnosis of General Paresis offered no difficulties, and it was confirmed by the laboratory tests (positive serum and fluid W. R., “paretic” gold sol reaction, 42 cells per cmm., an excess of albumin, and a positive globulin test).

Treatment: The perfect physique of this case and the extremely brief clinical duration (a few weeks) would naturally suggest a probably favorable outcome. However, cases with marked delusions of grandeur have very frequently proved to be cases with extensive brain tissue loss as shown in certain studies with Danvers material.

In any event, the treatment in this case proved unavailing. Enormous doses of salvarsan, twice a week, aided by mercury and potassium iodid, were given. Although other cases had been helped by such intensive treatment, Martiro went steadily downhill, nor was there the slightest diminution in the intensity of any of the spinal fluid reactions. After 50 injections of salvarsan over a period of 30 weeks without improvement, treatment was discontinued. A few months later, the patient died.

PARETIC NEUROSYPHILIS (GENERAL PARESIS)

PHYSICAL SYMPTOMS

EARLY HEADACHE

VISUAL DISORDER

HYPALGESIA

ADIADOCHOKINESIS

ATAXIA

NASOLABIAL FLATTENING

VOCAL CHANGE

SPEECH DISORDER

WRITING DISORDER

LOSS OF MANUAL DEXTERITY

PUPILLARY CHANGES

REFLEX CHANGES

SEIZURES

LATE: PARALYSIS, CONTRACTURE

Chart 9

PARETIC NEUROSYPHILIS (GENERAL PARESIS)

MENTAL SYMPTOMS

INTAKE IMPAIRED

CONSCIOUSNESS CLOUDED

FATIGUABILITY INCREASED

HALLUCINOSIS RARE

AMNESIA—RECENT! CHRONOLOGY AND STORAGE IMPAIRED. FABULATION

OVER-SUGGESTIBILITY

JUDGMENT IMPAIRED

FANTASTIC DELUSIONS

INSIGHT INTO ILLNESS NIL

EARLY IRRITABILITY OR HEBETUDE

QUICK SHIFTING EMOTION

CHARACTER CHANGE

CONDUCT SLUMP

Chart 10

1. What is the duration of paretic neurosyphilis (“general paresis”)? If we omit the doubtful, early, and prodromal stages and count the beginning of the disease with the occurrence of definite symptoms, we find (Kraepelin) that almost half the patients with pronounced paretic signs die within the first two years of their disease. Kraepelin’s observations upon 244 cases are as follows:

The average duration of the disease in months has been calculated as varying from 24 to 32 months. Juvenile paresis runs a slower and more insidious course. The duration of paresis, according to many observers, diminishes with the increasing age of the patient. It is now held that a combination of tabes with paresis does not prolong the duration of the paresis. As noted above in the discussion of Case Harrison (9), our conceptions of the characteristic duration of paretic neurosyphilis must alter with the increase of our knowledge due to the early application of laboratory tests.

2. What is the significance of the term general paresis? The case of Martiro is, of course, a good instance to show that the term is sometimes a misnomer. The characteristic generalized motor incapacity denoted by the term general paresis is shown in patients in the institutions for the chronic insane in their last few months of life. The term paresis is perhaps to be preferred to the term paralysis because the paralysis is not complete but partial; but perhaps the best reason is that the word paresis is a shorter word. When the mental side is to be emphasized, the term paralytic dementia is employed. In this book we have used the term paretic neurosyphilis to mean a more precise statement of the etiology of general paresis (general paralysis, paralytic dementia). The lay term, softening of the brain, like the terms metasyphilis and parasyphilis is in the present phase of our knowledge to be eschewed.

Euphoria in paretic neurosyphilis (“general paresis”). The head, arms and trunk were shaking with mirth; hence, the indistinct outlines of the photograph.

3. If this fatal case be typical of general paresis (for more favorable results, see Part V), what is the toll of deaths from this disease in the community at large? A striking statement may be quoted from Dr. Thomas W. Salmon’s “Analysis of General Paralysis as a Public Health Problem:”

“With the information in our possession at the present time, we are able to state that not fewer than 1000 persons in whom general paralysis is recognized die in New York State every year. Let us compare this with the lives lost from some other important preventable diseases. It means that one in nine of the 6909 men who died between the ages of 40 and 60 in New York last year died from recognized general paralysis and that one in thirty of the 5299 women who died in the same age-period died from this disease.

“The number of deaths from general paralysis in New York last year about equalled the number of deaths from typhoid fever. The following table gives the number of deaths due to the ten most important specific infectious diseases. Of course, deaths in measles, typhoid fever and scarlet fever will be found also under the names of some of the complications of these diseases, but it should be remembered that these primary diseases are not invariably fatal as general paralysis is. Many of the patients with measles who died from bronchopneumonia would have recovered but for this complication, while the paretics with bronchopneumonia would have died even if this complication had not arisen. No attempt is being made to compare the prevalence of general paralysis with that of other diseases—we are trying only to estimate its share in the mortality.

PARETIC NEUROSYPHILIS (GENERAL PARESIS)

CHARACTERISTICS

AMNESIA

QUICK SHIFTING EMOTIONS

CHARACTER CHANGE

CONDUCT SLUMP

NERVOUS DISORDERS

SPEECH DISORDERS

PUPILLARY CHANGES

REFLEX CHANGES

SEIZURES

CEREBROSPINAL FLUID PICTURE

Chart 11

SYPHILITIC PSYCHOSES

SYPHILITIC NEURASTHENIA

GUMMA

SYPHILITIC PSEUDOPARESIS

APOPLECTIC CEREBRAL SYPHILIS

SYPHILITIC EPILEPSY

SYPHILITIC PARANOIA

TABETIC PSYCHOSIS

HEREDITARY

PARESIS

Kraepelin, 1910

Chart 12

TABOPARETIC NEUROSYPHILIS (“taboparesis”) is CLINICALLY a combination of the symptoms of TABES DORSALIS and those of GENERAL PARESIS. The COURSE of TABOPARESIS is likely to be from a characteristic tabes dorsalis (often of years’ standing) to a characteristic general paresis; the ultimate paretic picture is likely to retain various characteristics of tabes. The LABORATORY TESTS in the paretic phase are characteristic of ordinary (non-tabetic) general paresis. The PROGNOSIS, after the paretic phase has arrived, is apt to be that of general paresis.

Case 16. Joseph Sullivan, a waiter, 50 years of age, sought assistance at the Psychopathic Hospital voluntarily. His complaint of severe and lancinating pains in the legs, difficulty with his gait, and a feeling of constriction about the waist, was forthwith suggestive of tabes dorsalis. He was a rather poorly nourished, white-haired man, with a drooping of the left side of the face. The pupils reacted sluggishly to light, the right somewhat better than the left. A marked Romberg reaction could be demonstrated. Ataxia in walking was marked. There was some incoördination of the hands, considerable tremor, and writing was poorly performed. The ankle-jerks and knee-jerks were absent. On the whole, the diagnosis of Tabes Dorsalis was clear enough.

The most appealing situation was mental. Sullivan was exceedingly apprehensive about his condition on the ground that it was growing progressively worse; if it was to get worse, Sullivan feared he would commit suicide. From his own account, he had become irritable, quick-tempered, and often unreasonable. As usual in these cases, the question arose whether the depression was psychopathic or natural.

While in the hospital things shortly came to a crisis. In the midst of a fit of depression, Sullivan attempted suicide by beating his head against the wall. Whether this attempt could be regarded psychopathic, however, remained in question. Sullivan had been drinking very heavily although he had stopped about six weeks before admission, fearing that the alcohol was causing a development of symptoms. The remedy was almost worse than the disease because he then became more nervous, lost his appetite, and had a marked insomnia.

According to the patient’s own history, he had had several attacks of gonorrhœa and a syphilitic infection at the age of 19; that is, some 31 years before admission to the hospital. However, the first neurological symptoms of which the patient was aware came about 27 or 28 years after infection, namely, 3 or 4 years before admission, when facial paralysis developed. At that time, he had suddenly felt a peculiar sensation in the throat and became unable to swallow for a time. His voice remained hoarse and low for some time, and his face began to droop. The lancinating pains and the ataxia also dated back several years.

1. How shall we evaluate the mental symptoms? The prognosis of tabes dorsalis is relatively good so far as life is concerned, and it might even be possible for Sullivan by training to remain capable of being a waiter. The manual incoördination was not marked, and possibly the manual tremor was in part due to alcohol. Accordingly, the mental symptoms, such as emotional lability and memory defect, were in the foreground of attention. In point of fact, the laboratory examinations showed positive W. R. in the serum and the spinal fluid, which latter also contained 60 cells per cmm., positive globulin, and an excess of albumin. The Diagnosis made was that of Taboparesis, meaning thereby a tabes associated with appropriate symptoms of a mental nature.

2. How shall the term taboparesis be used? Some use the term, as we feel erroneously, for instances of general paresis which happen to show crural areflexia (absence of knee-jerks). We feel that the best usage of the term is for instances in which well-defined symptoms of tabes (as well as of paresis) are present, namely, characteristic ataxia, lightning pains, and the like. If the term is used more loosely, as above mentioned, then practically every case of general paresis might perhaps be termed taboparesis, since almost every case of paresis does show involvement of the cord as well as of the cerebrum. Such involvement may lead to hyperreflexia, hyporeflexia, or areflexia according to the localization of the process. In true taboparesis, in which there is a commingling of the features of tabes with those of paresis, we should find the posterior roots of the spinal cord affected. The spinal lesions of paresis itself are more apt to be intraspinal; that is, confined to the nervous system within the pial investment.

3. Bearing in mind that Sullivan was a waiter, what shall be said about the infectivity of these cases? It is counted as a rule as negative, since there are no open spirochete-bearing lesions. The longer the period since infection the less, as a rule, is the chance of contagion in syphilis; and as tabes and paresis occur fairly late in the disease, the infectiousness at this stage is practically negligible.

4. Of what differential value is the insight shown by Sullivan into the nature of his symptoms? Kraepelin remarks that a genuine insight into the nature of the disease does not as a rule occur in paresis. At the beginning of the disease, there may sometimes be a correct understanding of the nature of the disease and of its probable outcome; but the presence or absence of insight into the fact of mental disease is by no means a differential sign of practical value.

5. What is to be said of the occurrence of depression and excited states in paretic neurosyphilis? A variety of classifications of sub-forms of paretic neurosyphilis have been propounded. Kraepelin, for example, deals with four: the demented, depressive, expansive, and agitated forms, but remarks that the division is merely convenient for exposition. The institutional intake does not accurately represent the distribution of cases. Under psychopathic hospital conditions with the relatively easy resort to such institutions, the number of quiet cases increases; under the less advanced conditions in Heidelberg, Kraepelin took in 53% demented paretics as against 56% at Munich (73% women) under the easier conditions of admission. The admissions of demented paretics varied from 37 to 56%. The variations depend much upon the facility with which the cases can be brought to institutions. Where admission is beset with various legal restrictions, the quiet and demented cases are more apt to be treated for long periods at home. The depressive type of paretic neurosyphilis forms a much smaller group, according to Kraepelin, as only about 12% of his Heidelberg admissions were of this type, and still fewer of his Munich admissions. Other authors give percentages as high as 16 and 19. The so-called expansive group is larger, Kraepelin finding 30% of his Heidelberg cases to be of this group, and 21 to 22% of his Munich cases. The rarest sub-form of paretic neurosyphilis is the agitated form: 6% of Kraepelin’s Heidelberg admissions; 14% among males and 5% among females in his Munich admissions, where the diagnosis of agitated paresis was entered on somewhat broader lines. French authors (Sérieux and Ducaste) have enlarged the number of sub-forms of paretic neurosyphilis as follows: Expansive 27%; sensory 24%; demented 24%; persecutory 3%; depressive 2%; circular 7%; hypochondriacal 7%; and maniacal 6%.

DIFFUSE (meningovasculoparenchymatous) NEUROSYPHILIS may look precisely like PARETIC NEUROSYPHILIS (“general paresis”) at certain periods of clinical and laboratory examination.

Case 17. The police found Gregorian Petrofski crouching on his knees on a Boston sidewalk, attempting to take pickets off a fence. Petrofski knew little English; he said that he had slept in Poland the night before. He did not appear to be alcoholic.

When he was examined, through an interpreter, he told how he had been in America two days, and in Boston two years; that he was at the present time in Poland, and that his brother had brought him to the hospital and left him there.

The physical examination showed Petrofski to be well developed and nourished. His pupils were somewhat dilated and reacted somewhat slowly to light and accommodation. Neurologically, there was nothing else abnormal found upon systematic examination although, through lack of coöperation, sensory and coördination tests proved difficult if not impossible. There was a large ulcer on the under surface of the glans penis, with several small smooth scars on the upper surface. There was a purulent discharge from the external meatus. There were exostoses of both tibiae.

The initial diagnosis had to consider uremia and diabetes, which could be easily excluded on examination. Alcoholism was excluded through absence of alcohol on the breath. There remained such diagnoses as epilepsy, some post-traumatic condition, or meningitis, to say nothing of the hypothesis of syphilis raised by the tibial exostoses and the lesions of the penis. The hypothesis of trauma was given up, as well as epilepsy and meningitis upon the data of the lumbar puncture. The spinal fluid proved to be clear but with enormous amounts of globulin and albumin, 80 cells per cmm., a “paretic” gold sol reaction, and a positive spinal fluid W. R. (the serum W. R. was also positive). Accordingly, it was clear that the case was one of neurosyphilis.

Treatment was instituted with injections of mercury salicylate, a grain and a half twice a week, and potassium iodid. After some weeks, diarrhoea and salivation with marked symptoms of mercury poisoning set in; the treatment was suspended, but later re-instituted. In a few weeks Petrofski was apparently quite well, the spinal fluid tests had all become negative, as had the serum W. R.

Petrofski now began to pick up a good deal of English, and gave a consistent narrative of his past life, although the period just prior to and during his early stay in the hospital has remained blank. Without further treatment Petrofski has remained well for over a year.

1. Does the “paretic” gold sol reaction mean general paresis? In connection with this general question, a brief summary of the significance of the gold sol reaction in this group may be made. (1) Fluids from cases of general paresis in the vast majority of cases will give a strong and fairly characteristic reaction, especially if more than one sample is tested. (2) Very rarely general paresis fluid will give a reaction weaker than the characteristic one. (3) Fluids from cases of syphilitic involvement of the central nervous system other than general paresis often give a weaker reaction than the paretic, but in a fairly high percentage of cases give the same reaction as the paretics. (4) Non-syphilitic cases may give the same reaction as the paretics; these cases are usually chronic inflammatory conditions of the central nervous system. (5) When a syphilitic fluid does not give the strong “paretic reaction” it is presumptive evidence that the case is not general paresis, and this test offers a very valuable differential diagnostic aid between general paresis, tabes, and cerebrospinal syphilis. (6) The term “syphilitic zone” is a misnomer, as non-syphilitic as well as syphilitic cases give reactions in this zone, but no fluid of a case with syphilitic central nervous system disease has given a reaction out of this zone, so that the finding may be used negatively; and any fluid giving a reaction outside of this zone may be considered non-syphilitic. (7) Mild reactions may occur without any evident significance, while a reaction of no greater strength may mean marked inflammatory reaction. (8) Tuberculous meningitis, brain tumor, and purulent meningitis fluids characteristically, though not invariably, give reactions in higher dilutions than syphilitic fluids. (9) The unsupplemented gold sol test is insufficient evidence on which to make any diagnosis, but used in conjunction with the W. R., chemical and cytological examinations, it offers much information, aiding in the differential diagnosis of general paresis, cerebrospinal syphilis, tabes dorsalis, brain tumor, tuberculous meningitis, and purulent meningitis. (10) We believe that no cerebrospinal fluid examination is complete for clinical purposes without the gold sol test.

FREQUENT SYMPTOMS IN DIFFUSE AND VASCULAR NEUROSYPHILIS

(“CEREBRAL” AND “CEREBROSPINAL SYPHILIS”)

PUPILLARY DISORDER

HEADACHE

VERTIGO

INSOMNIA

DROWSINESS

CHANGE IN DISPOSITION

Irritability Slow thinking

SEIZURES

PARALYSES

Permanent Transient

APHASIA

HEMIANOPSIA

SENSORY DISTURBANCES

GASTRIC CRISES

SPHINCTER DISTURBANCES

INTRACRANIAL PRESSURE SYMPTOMS

POLYURIA, POLYDIPSIA, GLYCOSURIA

MÉNIÈRE’S SYNDROME

NYSTAGMUS

Chart 14

See Appendix B for technical details.

2. What is the relation of the tibial exostosis to neurosyphilis? The syphilographers have always stressed the tibial lesions in the diagnosis of syphilis. Although not so much attention has been paid to these and kindred osseous lesions in neurosyphilis, yet we have frequently found such lesions and they afford an important auxiliary means of diagnosis.

A POSITIVE SERUM Wassermann reaction with a NEGATIVE FLUID Wassermann Reaction may be found in NEUROSYPHILIS, particularly in VASCULAR NEUROSYPHILIS: the remaining signs in the fluid, although frequently positive, may even be negative.

Case 18. Frederick Wescott was a promoter, an elderly looking man of 60 years. His health had been failing for 18 months. There had been shortness of breath, dizziness, a tired feeling, inability to “get the words he wanted,” and forgetfulness of names. About eight weeks before examination, Wescott had had a convulsion, following which he had been unable to express himself at all well. This convulsion was not accompanied by loss of consciousness. Besides a marked motor aphasia, there was agraphia.

Physically, Wescott showed arteriosclerosis and a blood pressure of 135 systolic, but, except very lively knee-jerks, no other reflex disorders or anomalies were discovered. In particular, the pupils reacted fairly well.

There was, perhaps, no special reason to implicate syphilis in the case, yet Wescott gave a history of syphilis at 35 years. The W. R. of the blood serum proved positive; that of the spinal fluid was negative, and the albumin was but slightly increased; there was a very slight amount of globulin, and there were 16 cells per cmm. in the fluid. The gold sol reaction suggested syphilis.

We felt entitled to make a diagnosis of Syphilitic Cerebral Arteriosclerosis, regarding the convulsion or seizure eight weeks before as due to a vascular insult. The laboratory picture in the spinal fluid in Wescott’s case seems to be rather characteristic of this group of syphilitic arteriosclerotics.

1. What is the reason for the negative spinal fluid W. R.? The theory would be that the syphilitic lesion is localized in the vascular system and that the parenchyma is only secondarily, if at all, involved. The W. R. producing bodies are accordingly not found in the fluid.

2. How frequently are several of the spinal fluid tests negative, while others are positive? Whereas, clinically speaking, the five tests in the spinal fluid (W. R., globulin reaction, excess albumin, pleocytosis, and gold sol reaction) are each indicative of a pathological condition in the central nervous system, yet a specially intensive study of the distribution of these tests has shown that they are prone to occur independently. Consequently, we must concede that they do not all represent the same inflammatory products and chemical conditions. The W. R. producing bodies, the gold sol reaction producing bodies, as well as the globulins and albumins, have been proved to be separate. Special work has also shown that these tests disappear under treatment at different rates. There is, unfortunately, no doubt that the rate and intensity, presence or absence, and the order of disappearance of these tests in either treated or untreated cases, do not at all parallel the clinical conditions of the patients.

3. What is the prognosis in vascular neurosyphilis, such as in the case of Wescott? The prognosis is identical with that of cerebral arteriosclerosis in general, that is to say, bad, but with frequent periods of improvement. In the neurosyphilitic type of arterial disease thromboid formation is frequent. Where the lesion is chiefly perivascular infiltration, rather than disintegration of the vessel wall, improvement may very well occur as a result of treatment. Wescott showed slight improvement under treatment. He has already lived two years since his first convulsion, and three and a half years since the onset of symptoms.

DIFFUSE NEUROSYPHILIS (so-called “cerebrospinal syphilis”) is often marked by SEIZURES.

Case 19. Agnes O’Neil, an unmarried woman of 28 years, was first examined five weeks after the initial symptoms. It appears that she had had certain seizures, with unconsciousness and twitching of the limbs (otherwise not well described), followed by confusion of mind and sometimes by a weakness of the left side and a difficulty in speaking. Headache had been almost constant, as well as pains in the arms and legs.

Physically, both in general and neurologically, there were no signs or symptoms; mentally, we could discover no symptoms. Syphilis was denied, although possible exposure to syphilis was admitted.

The diagnosis of some form of organic brain disease was clear with the picture of convulsions followed by slight aphasia with headaches and limb pains. With onset at 28, the most frequent cause for such epileptiform seizures is certainly syphilis. Examination of the blood and spinal fluid showed a positive W. R., in both. The albumin was also somewhat increased. The clinical picture suggested a fairly generalized meningitic involvement.

The prognosis in such cases of generalized meningitic involvement is in general good, and this principle was illustrated in the O’Neil case, in which the symptoms soon disappeared under intensive antisyphilitic treatment. In fact the spinal fluid W. R. became negative in the course of four weeks. The blood serum W. R., however, has remained positive despite eight months of active treatment.

CONDITIONS IN WHICH CONVULSIONS OCCUR

NEUROSYPHILIS

HYSTERIA

EPILEPSY MAJOR (Grand Mal)

EPILEPSY MINOR (Petit Mal)

DEMENTIA PRAECOX

TOXIC CONDITIONS:

Asphyxia, Uremia, Alcohol, Absinthe, Lead, Mercury, etc.

ORGANIC BRAIN LESIONS

Apoplexy, Meningitis, Intracranial Growths

STOKES-ADAMS DISEASE

MALINGERING

DISSEMINATED SCLEROSIS

Chart 15

1. Are certain cases of syphilitic epilepsy really cases of Jacksonian epilepsy? As a matter of nomenclature, Jacksonian cortical epilepsy is usually the result of a focal and circumscribed irritative lesion in the cortex. Gumma, local syphilitic meningitis, and syphilitic vascular lesions, as well as scars consequent upon the latter, are among the causes of Jacksonian epilepsy, along with such other focal lesions as trauma, tumor abscess, tubercle, and the like. Even non-syphilitic Jacksonian epilepsy has been observed from time to time in cases of diffuse intracranial pressure. Jacksonian attacks also have been found in so-called genuine epilepsy. Accordingly, we must not conclude from the occurrence of Jacksonian convulsions, even though in a proved syphilitic case, that the convulsions in question are surely due to a focal lesion, for they may be due to diffuse syphilitic lesions.

2. What is the significance of aphasia in Agnes O’Neil? Aphasia is not a characteristic symptom in ordinary Jacksonian epilepsy, but the aphasia is another sign of focal lesion and forms an added argument against the diagnosis of genuine or idiopathic epilepsy. See also discussion of aphasia in paretic neurosyphilis under Case Levenson (22).

3. What is the behavior of the serum W. R. and the spinal fluid W. R. under systematic treatment? Sometimes, as in this case, the serum W. R. remains positive and the fluid W. R. becomes negative; but in other equally well-defined cases, the reverse holds true, and the serum W. R. reaction becomes negative whereas the spinal fluid reaction remains positive. The obvious conclusion is that we cannot always be sure even by faithful tests of either the serum or the fluid alone, whether the treatment has succeeded in abolishing the laboratory signs.

4. Can this case be regarded as one of cure? Not by the definition adopted in this book or by the syphilographers who take into account not only the nervous system but the body which contains it. To be sure, the spinal fluid of Agnes O’Neil is now entirely negative and she is clinically free from symptoms; yet from the broad standpoint of syphilis therapy in general, this patient is not cured, as is evidenced by the positive serum W. R.

PARETIC NEUROSYPHILIS (“general paresis”) is often marked by SEIZURES.

Case 20. Lester Crane, a plumber, 37 years of age, came to the hospital with a slow and defective speech. Moreover, there seemed to be some mental disorder since his answers to questions were not always relevant. It appeared that he was seeing bugs on the wall.

Physically, Crane was a well developed and nourished man, with overactive knee-jerks and a Babinski reaction on the left side.

It developed that there was an impairment in hearing. The pupils reacted well both to light and to distance. The patient was very restless and smiled in a silly fashion. His memory was decidedly defective in all spheres, and he was very slow in the intake of ideas.

The plumber’s wife said that, at about the age of 23 or 24, he had a spell of confusion lasting two or three days, with peculiar conduct, unintelligible talk, and a good deal of weeping. The medical diagnosis at that time took into account the fact that Crane was a plumber and was “lead encephalopathy.”

However, according to his wife, Crane had acquired chancre at about 26 years, was treated mercurially for about three years and declared well. He had remained well up to about 18 months before entrance, when, without previous warning, the patient had a convulsion with the continuous movements for about half an hour. He was semi-conscious for about 18 hours and vomited continuously. There was amnesia for the whole affair on regaining consciousness. In a week’s time, Crane was entirely well. But six weeks later there was another convulsion. Upon removal to a hospital, the diagnosis of general paresis was made, and the patient was given the Swift-Ellis intraspinous treatment. This seemed to be very successful, and the patient discontinued treatment after 14 weeks (during which time there had been seven treatments) on the ground that he was entirely well.

However, after discontinuing treatment, there was another convulsion in about a month, and further convulsions occurred once a month. For six months, however, the patient took no treatment, but finally returned to the hospital and was given mercury. This treatment appeared to suspend convulsions again for three months, but at the expiration of six months, the patient had three convulsions in one day, and several more during the following days. After the last of these convulsions, there had been numbness on the right side of the body and considerable headache.

The diagnosis of Paretic Neurosyphilis (“general paresis”) is borne out by the laboratory tests. The W. R. of the blood serum was, to be sure, negative, but the W. R. of the spinal fluid was positive, and there was a “paretic” type of gold reaction, together with other laboratory signs.

The case well demonstrates that group of paretic cases in which convulsions periodically occur, leaving the patient worse after each convulsion. Treatment with salvarsan was instituted, and mercury and iodid was given by mouth. During the period of eight months which have now elapsed since the beginning of this treatment, there have been no convulsions; there has been a great improvement in the memory, the hearing has improved, the W. R. in the spinal fluid is much less intense, the gold sol test has become negative, and the other tests are all less intense.

The patient, however, has not been entirely well, for in place of the generalized convulsions, he has had minor seizures, beginning as a rule with a tingling sensation in the right hand, extending up the arm, down the trunk and leg, and through the right side of the face, with a bitter sensation on the right half of the tongue. The patient maintains that this sensation is absolutely confined to the right half of the body (in this connection we may recall case Morton (1), in which there was also a hemiplegia together with other apparently hysterical symptoms at several times during the long course of a disease with abundant structural correlations). During these minor seizures, the patient is unable to talk, although he does not lose consciousness and is entirely aware of everything going on about him. These attacks have of late been growing somewhat less frequent.

LOSS OF DEEP REFLEXES

NEUROSYPHILIS

NEURITIS

(alcohol, diabetes, diphtheria, lead, arsenic, tubercle, cachexia, etc.)

Peripheral nerves sensory or motor

PERIPHERAL NERVE PALSIES

TEMPORARILY FROM COMPRESSION BY TOURNIQUET

FRIEDREICH’S ATAXIA

SUBACUTE COMBINED DEGENERATION OF POSTERIOR AND LATERAL COLUMNS

Posterior column disease

FOCAL LESION IN GRAY MATTER OF CORD

INFANTILE PARALYSIS (ACUTE ANTERIOR POLIOMYELITIS)

PROGRESSIVE MUSCULAR ATROPHY

(chronic anterior poliomyelitis)

Anterior cornua of cord

AMYOTROPHIC LATERAL SCLEROSIS

SYRINGOMYELIA

THROMBOSIS OF ANTERIOR SPINAL ARTERY

LANDRY’S PARALYSIS

Anterior cornua and peripheral motor nerves

MYOPATHIES

(pseudohypertrophic and atrophic types)

MuscLe itself

AMYOTONIA CONGENITA

FAMILY PERIODIC PARALYSIS

(during attacks)

INCREASED INTRACRANIAL PRESSURE

(especially hydrocephalus and tumors of posterior fossa)

PNEUMONIA

IMMEDIATELY AFTER ATTACK OF MAJOR EPILEPSY

(post-epileptic coma)

TOXIC COMA

(uremia, morphine, etc.)

DURING SPINAL ANESTHESIA

COMPLETE TRANSVERSE LESION OF CORD

Purves Stuart

Chart 16

1. What is the cause of the negative serum W. R.? It is claimed that 3 to 5% of all cases of general paresis yield a negative blood serum. In this particular case, there had been considerable treatment, including some Swift-Ellis treatment, so that it may be that this treatment had reduced a formerly positive blood serum W. R. to a negative one.

2. What is the nature of the typical seizures of general paresis? The most frequent seizures are epileptiform and bear a general resemblance to cortical epilepsy; but more rarely these seizures resemble the ordinary epileptic attack or consist of a violent general shaking of the whole body. A variety of initial minor disorders usher in the attacks: the temperature is often increased. The attacks are over after one or at most after a few hours. Kraepelin speaks of one that lasted 14 days. Sometimes a status paralyticus develops, suggestive of the status epilepticus. Another rarer form of characteristic seizure is the apoplectiform, which can hardly be told from an ordinary stroke, and may be followed by the usual post-apoplectic phenomena. A good many of the strokes leading to sudden death in middle life are probably cases of neurosyphilis although often set down as early arteriosclerosis of a non-syphilitic nature. Besides the epileptiform and apoplectiform seizures, there are certain seizures of a less definite and complete nature, ranging from simple fainting spells, dizzy spells and petit mal attacks, to various special forms of irritative muscular contractions and temporary speech disorders. Sometimes these attacks occur with complete preservation of consciousness. Transient paresthesias, visual field defects, and especially attacks of vomiting, which, according to Kraepelin, may precede paresis by years (of course in this connection gastric crises of tabes must be thought of), may be counted as sensory seizures.

3. What is the proportion of paretic cases developing seizures? Figures vary from 30 to 90%. According to Kraepelin, seizures occurred in 30 to 40% of his cases at Heidelberg; he was of the impression that treatment in bed had reduced the number of seizures. 65% of paretics admitted to Munich (under very free conditions of admission) were determined to have shown seizures before their admission to the hospital. Seizures are said to be somewhat more frequent in men than in women. These paretic seizures are not due to either hemorrhages or vascular plugging—at least in the vast majority of cases—and must be ascribed to the effects of microscopic injuries.

4. What is the effect of seizures upon the future course of paretic neurosyphilis? The current idea as expressed, for example, by Mercier, is that “immediately after each crisis the patient is much worse than he was before it, and thereafter there is some improvement, but he never improves up to the point at which he was before the occurrence of the crisis.” That is, “The course of the disease is one of sudden plunges, each deeper than the last, each followed by a gradual recovery that is less complete than the recovery from the previous plunge.”

5. During what period of the disease are seizures most common? Late in the disease many cases have convulsions, even though there were none for the first year or two. In other cases the convulsion is the first indication of paresis.

DIFFUSE (non-paretic) NEUROSYPHILIS (“cerebrospinal syphilis”) is often marked by APHASIA.

Case 21. Martha Bartlett, a woman of 40 years, was brought to the Psychopathic Hospital aphasic, or at least unable to talk distinctly enough to be understood, or even to give name and address. The police had found her wandering aimlessly about the streets. Although she was well-dressed, she was mud-bespattered and apparently had not changed her garments for several days. It shortly developed that the patient, although unable to express herself either in words or by writing, could understand everything that was said to her and could indicate by the monosyllables yes or no whether she agreed or disagreed with statements made. It was thus determined that she was pretty well oriented. She was able to understand both speech and printed words. Although she approximated more than is at all common a pure type of motor aphasia, it appeared that there was a slight involvement on the sensory side, especially in the sphere of visual imagery.

Neurologically, the patient showed moderate strabismus, slight deviation of the tongue to the right, and considerable tremor on protrusion of the tongue. The right side of the palate hung lower than the left. The ankle and arm reflexes were possibly more active on the left side, and the left grasp was somewhat better than the right. Both knee-jerks were active, but again the reflex on the left side was more active than the right. No other abnormalities of reflex were determined. There was no Rombergism but the gait was somewhat ataxic. For the rest, the physical examination was normal. The blood pressure was 120 systolic, 85 diastolic.

CONDITIONS IN WHICH SPEECH DEFECT IS FOUND

NEUROSYPHILIS

HYPOGLOSSAL PARALYSIS

FACIAL PALSY

PARALYSIS OF PALATE (Post-Diptheritic)

BULBAR PALSY

PSEUDOBULBAR PALSY

MYOPATHY—FACIO-SCAPULO-HUMERAL TYPE OF LANDOUZY AND DEJERINE

MYASTHENIA GRAVIS

FRIEDREICH’S ATAXIA

LARYNGEAL TABES

ALCOHOLIC INTOXICATION

POST HEMIPLEGIC

LENTICULAR DISEASE

BILATERAL ATHETOSIS

MULTIPLE SCLEROSIS

DEAF MUTISM

PARALYSIS AGITANS

CHOREA

STAMMERING

TICS

HYSTERICAL APHONIA

Chart 17

The ready suspicion was that the case was one of apoplexy of slight degree with post-apoplectic phenomena. Upon investigation, this suspicion was confirmed since it appeared that Mrs. B. had been apparently quite well until about six months before admission, when without particular warning she began to act strangely and promptly fell into a series of convulsions. These convulsions would begin with twitchings of the face, and then spread throughout the body. There would be a period of unconsciousness for two or three hours. It is not certain how many of these convulsive seizures the patient had. At all events she is reported to have recovered therefrom completely, remaining well for three months; whereupon, suddenly, while visiting a friend, she suffered a paralysis of the left side of the body. She remained dazed and had hospital treatment for about a week. Ever since this left-sided paralysis, the aphasic condition above described has persisted.

Such a phenomenon has often been dismissed in the past as due to an early arteriosclerosis, but most neurologists and internists of today would look beyond the diagnosis of mere arteriosclerosis and consider syphilis. The only suggestive feature in the case, aside from the post-apoplectic reflex disorder and spastic phenomena, is the irregularity and diminished light reaction of the pupils. Our suspicions were confirmed by the positive serum W. R. The W. R. of the spinal fluid proved, however, to be negative. There was a moderately strong gold sol reaction of the syphilitic type. There was a slight excess of albumin, and there was an exceedingly slight amount of globulin. There was but one cell per cmm.

On the whole, it would seem best to consider the case of Mrs. Bartlett to be one of Cerebral Arteriosclerosis of Syphilitic Origin, and a case in which there is no evidence of meningitis or meningoencephalitis.

1. What is the explanation of the negative spinal fluid W. R.? It may be that none of the W. R. producing bodies have gone over into the spinal fluid. It has been shown by the work of Weston that the W. R. producing body is not identical with the bodies responsible for the other tests in cerebrospinal syphilis. Moreover, it has been clearly shown that these several tests of the spinal fluid do not run at all parallel with one another. Especially is it true that the chemical tests do not correspond at all with the degree or nature of the pleocytosis. On the whole, when involvement of the nervous system is entirely vascular, it is not only theoretically proper but also practically common, to find a spinal fluid negative to several tests.

2. Omitting consideration of the syphilitic gold sol of this case, what conclusion could be drawn from the albumin and globulin findings? It would not be warrantable to assume syphilis since it is a common finding after cerebral hemorrhage due to non-syphilitic arteriosclerosis to find excess albumin and also globulin in the spinal fluid. Occasionally, also, pleocytosis occurs in cases of cerebral hemorrhage even when the hypothesis of an active meningitis can be excluded. We may recall in this connection the pleocytosis in so-called meningitis sympathica of certain brain tumors. (See also the case of Milton Safsky (48), a case of brain tumor in which there was an excess of albumin, a large quantity of globulin, and a pleocytosis of 146 cells per cmm.)

3. What can be expected from treatment in these cases of vascular cerebral syphilis? The condition offers very little opportunity for therapeutic results. However, antisyphilitic therapy is indicated to prevent if possible further progress of the lesions. Since the lesions are, however, vascular, and since it must remain a question how far these vascular lesions are due directly to spirochetal action, and since in any event it may be difficult to reach the spirochetes thus active, perhaps it is best to place most reliance on potassium iodid. In any event, potassium iodid should be given. Salvarsan and mercury are also indicated. It is common to warn against administration of large doses of salvarsan in this type of case on the ground that further vascular ruptures may be produced. (See Friedberg, 108.)

4. If we conclude that the aphasia of the Bartlett case is due to vascular disease, can we conclude a relation between this vascular disease and vascular tension? It is not safe to draw such a conclusion. The Bartlett case itself showed low blood pressure. To be sure, some cases of neurosyphilis show high blood pressure from which one draws the à la mode clinical conclusion to the effect that the kidneys are probably involved in the arteriosclerosis; but other cases do not show a high blood pressure but may in fact show a low blood pressure. The vascular disease doubtless responsible for the aphasia in the Bartlett case is probably not at all an effect of blood pressure conditions, but is, on the contrary, an effect of local syphilitic vascular lesions.

PARETIC NEUROSYPHILIS (“general paresis”) is often marked by APHASIA.

Case 22. Meyer Levenson, a traveling salesman of 36 years, had for the last two or three years been undergoing a change of disposition, quite interfering with his work. He had begun to take unreasonable aversions to people, had become irritable and emotionally depressed, and often fell to weeping without cause.

About nine months before hospital observation, it seems that a trunk-cover had fallen on Levenson’s head, and there is some question as to whether he did not have a convulsion at that time. However, a month later he had a definite seizure, followed by speech disorder, a slight paralysis, and a staggering gait. Four weeks later, however, he had gotten over these post-convulsive difficulties and had gone back to work.

At his work, he became tired easily, his gait and speech did not seem entirely normal, and there was a considerable memory disorder. After five more months, another attack of a convulsive nature, with twitching of hands and face and tongue-biting occurred, and the attending unconsciousness remained for two days. Again improvement followed, though without ability to return to work. Four (?) months later there were several severe convulsions and Levenson would remain unconscious for a day or two at a time. Restlessness, irritability, and irrational talking followed.

Physically, the patient was fairly well developed and nourished; blood pressure 168 systolic, 68 diastolic; pupils reacted very sluggishly to light. There was a marked motor aphasia, which the patient recognized as a speech difficulty. On the whole, however, Levenson was very euphoric and was entirely sure that he was improving and would surely get well.

Shortly after entrance, Levenson had a severe convulsion, with unconsciousness. The movements were mainly on the right side of the body, and there was a post-convulsive weakness of the right side for several days, followed by a slow recovery of strength.

The course of the disease—convulsions followed by improvement—is very characteristic of a paretic onset. The laboratory findings were in all respects confirmatory. It was rather striking that a permanent motor aphasia followed the convulsions in this case, since the seizures of paresis do not in the vast majority of cases leave permanent paralyses. The course of the disease continued to show convulsions, which would in each instance leave him at a lower terrace of capacity than had been before shown. The patient died four years after the onset of symptoms of a general asthenia. With the exception of the permanent motor aphasia, this case might be regarded as a fairly typical one of general paresis.

1. What is the general nature of speech disorder in paretic neurosyphilis? Speech disorder is, along with the pupillary changes, one of the most important clinical symptoms in paretic neurosyphilis. There are aphasic and articulatory disturbances. The aphasia that accompanies paretic seizures is of a transient nature as a rule. A case with such long-standing motor aphasia as shown by Levenson is not common. Paraphasia, with incorrect naming of objects, may last longer. The so-called “sticking” phenomenon is often observed.

Word-deafness is said to be rarer but is difficult to test on account of the patient’s dementia. Agrammatism (incapacity to form correct sentences) is sometimes observed. But the most characteristic disorder is in the syllabic composition of words. Syllables are left out (“medaltricity” for medical electricity), or fused (“exity”), or doubled (“electricicity”). Besides the central speech disorders of which the above are examples, there are disorders in articulation, which at first occur as a consequence of paretic seizures or in states of excitement, but later become permanent. These are divided into paretic and ataxic disturbances.

2. What is the structural basis of these forms of aphasia? It is believed that they are due to microscopic changes, not to coarse destructive lesions.

BROOKLINE, MASS.

BROOKLINE, MASS.
Mss. of Levenson, case 22. Paretic neurosyphilis. Tremor, misspelling. Metathesis of letters (Bk, not Br) omission of letters (Book).

God save the Commonwealth of Massachusetts
Mss. of Safsky, case 48, brain tumor. Tremor not marked. Misspelling, omission of letters. Wrong letters (h in hweth).

Mss. of Halleck, case 31, cervical tabes. No brain disorder. Pen-holding and bearing on difficulties. Crowding of phrases result of ataxia.

Mss. of Collins, case 61, paretic neurosyphilis. One misspelling (-chussetts); not psychopathic? Characteristic tremor.

REMISSIONS of identical appearance occur in PARETIC and in DIFFUSE (non-paretic meningovascular) NEUROSYPHILIS.

Case 23. Thomas Donovan, a merchant 44 years of age, acquired syphilis according to his own story at the age of 31, and he was at that time treated at a well-known watering-place with mercurial injections. Later he continued treatment under his family physician, and at 34 was pronounced cured. However, four years later—that is seven years after his initial infection and in his 38th year—he had his blood examined and it proved positive. He was accordingly treated by salvarsan and his W. R. became negative. The story did not end there, however, for at 43, mental symptoms appeared of the nature of depression and a diagnosis of paresis was made. He was released from the institution against advice at that time, and without treatment, made a partial recovery.

A sudden outburst of violence brought Mr. Donovan to the Psychopathic Hospital; he was very surly, combative, and difficult to manage, standing 6′ 2″, and weighing 210 pounds. He was oriented only fairly well and his surliness was streaked with humor. He facetiously said that the Psychopathic Hospital was the largest hospital in the country, and that it was, in fact, a horse hospital; that he had come because he liked the surroundings, not to make money; that he was the healthiest man in the world, never having been sick; that the Psychopathic Hospital was a club, for which you have to get somebody to propose your name. There was amnesia and no knowledge of current events. He regarded the food as poisoned, refused to eat, and was very irritable and untidy.

Physically, there were few abnormalities, but the pupils failed to react either to light or accommodation, and the knee-jerks and ankle-jerks were absent. There was a slight Rombergism. There was a marked speech defect to test phrases. Both serum and spinal fluid W. R.’s were positive; the fluid showed 41 cells per cmm., there were large amounts of globulin and albumin, and the gold sol reaction was of the “paretic” type.

ATAXIA OR INCOÖRDINATION

NEUROSYPHILIS

LESION OF PERIPHERAL SENSORY NERVES

DIVISION OF POSTERIOR ROOTS

TUMORS OR CHRONIC SCLEROSIS OF POSTERIOR COLUMNS

SUBACUTE COMBINED DEGENERATION

VESTIBULAR ATAXIA

FRIEDREICH’S ATAXIA

FAMILY PROGRESSIVE HYPERTROPHIC NEURITIS

THROMBOSIS POSTERIOR INFERIOR CEREBELLAR ARTERY

MARIE’S HEREDITARY CEREBELLAR ATAXIA

LESIONS OF CEREBELLUM, TUMORS, ETC.

WRITERS’ CRAMP

PREHEMIPLEGIA

MULTIPLE SCLEROSIS

PSEUDO-SCLEROSIS

HYSTERIA

Chart 18

CONDITIONS IN WHICH VERTIGO IS FOUND

NEUROSYPHILIS

HEAD TRAUMA

CEREBRAL ANEMIA AND HYPEREMIA

MENOPAUSE

ARTERIOSCLEROSIS

RENAL DISEASE

CEREBRAL HEMORRHAGE AND THROMBOSIS

INTRACRANIAL TUMORS

MULTIPLE SCLEROSIS

EPILEPSY (Aura)

TOXIC CONDITIONS:

alcohol, tobacco, constipation

PSYCHONEUROSIS

OCULAR DISTURBANCES

EAR DISEASE

MÉNIÈRE’S DISEASE

MIGRAINE

Chart 19

Salvarsanized serum was injected intraventricularly through a trephine opening in the right frontal region. Injections were made through the corpus callosum into the third ventricle. There was progressive symptomatic improvement after each of four injections. In fact, after the fourth injection the patient was allowed to leave the hospital despite the fact that there was only a slight improvement in the spinal fluid findings. The speech defect had entirely disappeared. (Speech defect, according to many authorities, including Kraepelin, is of very grave diagnostic significance.) His memory returned. Mr. Donovan is now able to handle figures rather extraordinarily well. He now has a good insight into his delusions and tells stories about them with great humor.

1. What is the definition of a remission in general paresis? Remissions form a foil to seizures; just as seizures mark a sudden advance in the severity of the disease or may even lead to death; so remissions may cause a sudden cessation of both mental and nervous phenomena in the disease. Whereas the seizures occur most often, according to Kraepelin, in the demented types of paresis, the remissions occur in all cases except in the terminal phase. Kraepelin quotes Hoppe as observing pronounced remissions of long duration in 17% of male and 15% of female paretics. Gaupp observed marked improvement in less than 10%, and very marked improvement indeed in only 1% of his cases. Kraepelin states that such improvements are most frequent in agitated and especially in expansive forms of paresis, and that they are rarer and less complete in the depressive and demented forms. Sometimes the improvement occurs over night, although the full extent of the remission becomes complete only gradually, perhaps in the course of months. The sensorium clears, the disorientation disappears, the delusions retreat, and the former delusions are treated as dreams and imaginations. There is often a good deal of persistent uncertainty as to events during the height of the disease. The nervous disorders are far more obstinate than the mental. Still, both speech and writing may often greatly improve.

Cotton in New Jersey found, among 127 cases of paresis diagnosticated by modern methods during seven years, that remissions occurred in but five, or about 4%, lasting from a half to three years.

2. Does a remission ever amount to a cure? The classical case quoted in this connection is one observed by Tuczek. This case developed a picture of paresis in 1876, at the age of 36; and a remission, or cessation, of symptoms, occurred in 1878; but in 1883, at 43 years, the patient developed a tabes without any trace of mental disorder, which tabes gradually advanced. By the middle of 1898, when the patient was 58, certain symptoms of excitement and confusion occurred, which led to death with dementia, 22 years after the beginning of the disease. Nissl pronounced the cortex to be undoubtedly the characteristic cortex of a paretic. This observation seems to indicate that a clinical remission tantamount to a clinical recovery may occur without the death of the spirochetes engaged. This observation is to be held in mind in connection with all therapeutic work with neurosyphilis.

Nonne states that during his clinical experience of 19 years he had followed 10 cases of paresis with apparent recovery; but of these ten cases, four had to be thrown out by Nonne because the apparent recoveries turned out to be only long and almost complete remissions, finally issuing in characteristic dementia. Of the remaining six cases, perhaps two should hardly be counted as paretic and Nonne rather preferred to term them cases of syphilitic dementia in the sense of a non-paretic cerebral syphilis. At the end, therefore, of his review of observations, Nonne found himself with four cases of true recovery from paresis.

Spielmeyer holds that there is no theoretical reason why paresis might not be cured, since all the different changes that have been described in the disease can be halted, and many of them can be repaired. In particular, he reminds us that the acute infiltrative process, the neuroglia reaction, and the phagocytic action of the large mononuclear cells are distinctly removable processes. (See discussion below under Section V, for apparent cures and remissions occasionally secured under treatment.)

REMISSIONS of identical appearance occur in PARETIC (“general paresis”) and in DIFFUSE (non-paretic) NEUROSYPHILIS.

Case 24. Michael O’Donnell, a laborer of 48 years, came home, one day, at 5:30, complaining of severe headache. His wife told him he should lie down and, taking him by the arm, tried to help him to the bed. At this moment, O’Donnell lost control of both left arm and left leg, and fell, unable to move but with consciousness preserved. The wife noted that the left side of his face was drawn up and that he drooled. He was at once carried to a general hospital, remaining there for about three weeks, talking at random in a delirious manner and tied in bed. Two intraspinous injections of salvarsan were given, and O’Donnell showed considerable improvement and went home.

However, upon his return from the hospital, he became very wilful, would not remain in bed, and on one occasion actually took the mattress from the bed, carried it to another room, and then returned to his own room and slept upon the springs. He became irritable and emotional, insisted upon going to the hospital, did not go there but upon returning home insisted that he had been there. That night, O’Donnell left the house only partly dressed.

It appears that O’Donnell had been excessively alcoholic, but that before August 15, when he sustained the left-sided hemiplegia above mentioned, there had been no symptoms except that in February he had once been very dizzy. It appears that there had been another dizzy spell, three nights before the paralysis, accompanied by a fall and unconsciousness for about 15 minutes.

TRANSIENT OR FLEETING PARALYSES

NEUROSYPHILIS

MYASTHENIA GRAVIS

MYOTONIA CONGENITA (THOMSEN’S DISEASE)

PARAMYOTONIA CONGENITA

MYOTONIA ATROPHICA

INTERMITTENT CLAUDICATION

OCCUPATION NEUROSES

FAMILY PERIODIC PARALYSES

ETANY

EPILEPSY MINOR

HYSTERIA

MULTIPLE SCLEROSIS

APOPLEXY

CEREBRAL THROMBOSIS

Chart 20

O’Donnell was brought to the Psychopathic Hospital some six weeks after the paralysis, complaining merely of a slight headache and desirous of treatment. There were no mental symptoms of any sort. Physically, O’Donnell was in general not abnormal (there was a slight pre-systolic murmur and a blood pressure of 190 mm. systolic). The pupils were slightly irregular, the left larger than the right; both reacted sluggishly. Both ears were moderately deaf; the tendon reflexes of the left arm and leg were somewhat more lively than those on the right. The systematic neurological examination otherwise revealed no abnormalities. The urine was negative. The serum W. R. was positive but the spinal fluid reaction was negative. There were but 2 cells per cmm., and there was a very slight trace of albumin.

1. How shall we account for O’Donnell’s transient paralysis? We might invoke brain tumor, alcoholic pseudoparesis, or some form of neurosyphilis. The diagnosis of brain tumor seems quite untenable in view of the absence of premonitory symptoms and in the absence of intracranial pressure. As for alcoholic pseudoparesis it is true that the patient was excessively alcoholic.

However, against these two diagnoses and in favor of the diagnosis of Neurosyphilis, are the positive serum W. R. and the pupillary reactions (although these are short of the true Argyll-Robertson phenomenon). Dizziness with retention of consciousness and associated with the paralyses mentioned suggests rather a subcortical than a cortical lesion. We are inclined to regard this lesion as probably Thrombotic, and to place it possibly in the region of the internal capsule. We are inclined to regard the phenomenon as purely vascular and as not in this case associated with an encephalitis. We are, however, not entirely satisfied with the diagnosis.

2. What shall be said as to treatment? A full-blown left-sided hemiplegia may be produced even when the thrombotic lesion is itself exceedingly small. It is common to explain this on the basis that there is an area of collateral edema about the small necrotic, thrombotic, or hemorrhagic area responsible for the lesion. In short, numerous neurones are functionally rather than structurally affected, or at all events capable of early restitution of function.

3. What is the prognosis in such cases? It appears that now and again patients run for several years without further trouble, both with and without treatment. We are inclined, however, to advocate treatment rather than absence of treatment for a variety of reasons. In the first place, vascular lesions may at any time become associated with meningitic lesions, and treatment by salvarsan may perhaps be counted on to head off this process; secondly, the treatment with iodids may possibly aid in the resolution of a local thrombotic process.

4. What are the prodromal symptoms of cerebrospinal syphilis? According to Nonne, headache, dizziness, sleeplessness, mental symptoms of the irritability group, loss of capacity as to mental work, whether severe or not, and loss of capacity for difficult thinking; also impairment of memory. Nonne does not regard these phenomena as characteristic of syphilitic vascular disease, and calls attention to the fact that in every organic disease the same subjective symptoms occur. The triad—headache, dizziness, and impairment of memory—is for example now counted as a prodromal symptom complex for arteriosclerotic apoplexy (Cramer). Of course, apoplectic attacks occur without such preliminary symptoms: particularly, according to Nonne, the nocturnal attacks.

5. Can the fleeting paralysis be of service in differentiating the diffuse from the paretic form of neurosyphilis? Probably not. In both forms transient paralyses occur as well as the permanent ones. In general, however, the transient paralyses are more frequent in paretic neurosyphilis, whereas the permanent ones occur more often in diffuse neurosyphilis.

There are cases of NEUROSYPHILIS in which the laboratory signs are positive but in which there are no clinical signs or symptoms (PARESIS SINE PARESI?).

Case 25. Richard Lawlor[^[6]] was admitted to the Psychopathic Hospital, October 29, 1914, being sent there from a general hospital where he had gone on account of a self-inflicted wound of the wrist, apparently made in a period of depression with suicidal intent. Routine notes follow.

Family History. Paternal grandparents both died of heart disease. Maternal grandfather died at seventy-two of dropsy. Moderately alcoholic. Maternal grandmother died of shock at fifty-six. Father died at age of forty, after an illness of eight years, from heart disease. Father all his life was subject to fainting spells and headaches. The only paternal cousin died at thirteen months of brain fever. Mother, aged forty-seven, is, to say the least, eccentric. Says “she has several times been given up from tuberculosis.” Two maternal uncles died of tuberculosis, one from rupture, one from heart disease. One uncle who “doesn’t know anything after he has a teaspoonful of liquor.” Several other uncles and aunts whose history is not obtained. Patient is mother’s only child. Mother was twice married. There were several miscarriages by both husbands; patient child by first marriage.

Past History. Patient born thirty-two years ago, full term, normal delivery and development. Measles, mumps, and chickenpox in childhood. Subject to headaches since seven or eight years old. Kicked in the face by horse at seventeen or eighteen, not considered serious. Hit by a baseball three or four years ago, leaving him hard of hearing on left side. Married ten years ago; no children because he says his wife needed an operation. He denies venereal disease by name and symptoms. For past ten years has had attacks of depression lasting but a short time, but quite severe. Never caused him to quit work as a barber and he felt better when working. His married life he says was fairly happy except for his wife’s extravagances, and on this account he left her a little over a year ago, and she has applied for a divorce, which he is willing that she should have, but does not wish to give her alimony. He admits moderate alcoholism.

Present Trouble. Patient states that since he left his wife a year ago he has felt sorry a number of times. He has wished he had her back. He has felt lonely. He has had six or eight periods of depression in that time similar to those he has had for many years, lasting two or three days, and sometimes a week. These were always precipitated by some cause for worry. In these attacks he feels nervous, sleeps poorly, has little or no appetite, sweats during his work and everything looks black. Several times in these attacks he has had suicidal ideas. Ten months ago he considered taking corrosive sublimate. For a little over a week before entrance to hospital he had been out of work and had been “sporting.” The day before entrance he had a telephone message from his lawyer which upset him somewhat and he walked the floor all night. He had just been shaving when the idea of suicide came to him. He sat down a minute when suddenly the thought “to hell with the world” came to him; he took the razor and slashed his wrist. He does not remember drawing the razor across his wrist. As soon as he saw the blood he felt sorry, called his mother, and was taken to an emergency hospital and then sent to the Psychopathic Hospital.

Physical Examination. Patient is a well developed and nourished man thirty-two years of age. Head is normal as to size and shape; there are no scars or marks of injury. Hair and skin not remarkable in any way. Ears negative to external examination. Teeth well kept; two missing, several gold fillings. Tongue very slightly coated. Throat negative. Tonsils easily visible without evidence of inflammation or exudation. Neck, no thyroid enlargement, no abnormal pulsations, no adenopathy. Chest, symmetrical, expansion good, resonant throughout. Breath sounds transmitted normally. No râles or rubs heard. Heart, no enlargement or cardiac dulness. Sounds of good quality, no murmurs heard. Rate regular. Pulses equal, regular and synchronous, and of good volume and tension. Systolic blood pressure 130, diastolic 65. Abdomen, flat, soft and tympanitic throughout; no masses; no tenderness. Liver edge not felt, below costal margin. Spleen not palpable. Extremities negative, except for incised wound on left wrist.

Neuromuscular Examination. Pupils are large, round, regular, equal and react readily to light and accommodation. No nystagmus, strabismus or ptosis. No weaknesses or paresis of facial muscles. The tongue projects medially and shows no tremor. The triceps and biceps reflexes are readily elicited, and are quite active, as are the knee-jerks and ankle-jerks. On one occasion it was thought that the tendon reflexes were slightly more active on the left than on the right. This was never confirmed; always afterwards found equal. There was no tremor of extended hands. Abdominal reflexes not elicited. Cremasteric present on both sides. The plantar response is flexor. There is no Babinski, Gordon or Oppenheim. No Romberg. Coördination tests well performed. No speech defect. No sensory disturbances. Urine examination negative.

Wassermann reaction in the serum: Positive, with cholesterinized antigen; negative, with syphilitic fetal liver antigen.

Wassermann reaction in fluid positive on two occasions. Examination of spinal fluid, November 4: globulin +++, albumin ++, 100 cells per cubic millimeter; large lymphocytes, 8 per cent; small lymphocytes, 90 per cent; plasma cells, 0.7 per cent; endothelial cells, 1.3 per cent. November 11, globulin +++, albumin +++, cells 18 per cubic millimeter. November 26, globulin ++, albumin ++, cells 92 per cubic millimeter; large lymphocytes, 13.1 per cent; small lymphocytes, 82.1 per cent; plasma, 1.2 per cent; endothelial, 3.6 per cent.

Gold sol, November 4, 5555432100.

Gold sol, November 26, 3332100000.

Mental Examination. On entrance to hospital patient seemed slightly depressed and a bit irritable. This condition lasted two days, after which he was agreeable and apparently entirely over his depression. Even during his mild depression, however, he talked freely. There was no evidence of retardation. He told his story readily. Orientation was intact. Memory excellent. Educational knowledge well retained. There was no evidence of any hallucinations or delusions.

1. Was Richard Lawlor insane?

There was, then, on the mental and physical examination nothing to make a definite suggestion of a psychosis, and the most one could think of was a psychoneurosis or a cyclothymia of at least ten years’ duration. The findings in the cerebrospinal fluid and the Wassermann reactions, however, give us material for thought. Certainly one cannot call the man insane; all who saw him agreed on this point.

2. If Richard Lawlor should some day develop mental symptoms, what would be the genesis of the new psychosis? Though writers such as Fildes and McIntosh, and Swift, have suggested an anaphylactic or hyperallergic explanation for the development of symptoms after a normal interval; such a hypothesis could hardly obtain in the present case. The hyperallergic hypothesis for the development of tertiary neurosyphilis would run to the effect that in the secondary stages there had been a definite disease of the nervous system, which, however, absolutely cleared up, leaving no inflammatory vascular or parenchymatous relics of its existence. Nothing would on this hypothesis remain except a hypersensitisation of the tissues. In some later period of the now clinically normal person, one or more spirochetes from a lesion outside the nervous system are carried into the nerve tissues and there set up an anaphylactic or hyperallergic reaction. It is obviously difficult to prove the correctness or incorrectness of the hyperallergic theory without numerous examinations of the spinal fluid, in clinically normal persons after the secondaries have passed. The present case, so far from demonstrating a normal fluid, demonstrates a highly pathological fluid, even though there are absolutely no clinical symptoms which could be regarded as of nervous origin. The burden of proof at the present time would seem to lie with those who claim hyperallergy in neurosyphilis. We prefer on present evidence to think that at the conclusion of the secondaries a disease process often remains in the nerve tissues despite clinical quiescence.

3. What is the prognosis in the case of Richard Lawlor? The prognosis re neurosyphilis is doubtful. We have, however, boldly termed the condition PARESIS SINE PARESI, meaning thereby to suggest that the patient is in considerable danger of the efflorescence of a true diffuse or paretic neurosyphilis. We have no means of telling, however, whether the positive symptoms would be those of a paretic or a non-paretic neurosyphilis. As data accumulate regarding these cases of paresis sine paresi, we may be able finally to come upon some case in which trauma shall bring out the clinical symptoms of neurosyphilis. For discussion of this matter, see the case of Bessie Vogel (52) in Part III of this book.

4. Should Lawlor have been brought to a psychopathic hospital? It is a safe working rule to have any person who attempts suicide observed. A large percentage of suicides occur in psychotic individuals and a suicidal attempt is not infrequently the first recognized abnormality. Immediate observation is a necessary safeguard against another more successful attempt.

Demonstrates SYMPTOMS and LESIONS of PARETIC NEUROSYPHILIS (“general paresis”). Autopsy.

Case 26. John Morrill, 49, an operative in a mill town in Essex County, Mass., was described as a “Saturday night and Sunday drinker,” with a history of very serious long sprees at the age of 43. It seems that he had had what was called “sciatica” at 35, and was treated in hospital for seven weeks at that time. The nature of this sciatica is in doubt, but there was a history of syphilitic infection at 36 years (scar of glans).

Morrill had been married twice, and two of the children were dead; one daughter was described as “very nervous,” but there were four children under ten years of age, all regarded as perfectly healthy.

Morrill had been a mill operative of average capacity, was industrious, and had supported his family despite alcoholism. The syphilis had been treated with reasonable thoroughness.

Aside from alcoholism, there had been no symptoms up to two months before admission to Danvers Hospital. Then there had been insomnia, fatigue, agitation, eruption on foot, loss of ten pounds in weight, hypochondriacal fears, apprehensiveness for the future of the children, incoherent talk; and just before admission, his talk was described as foolish. He had taken to running away and hiding in bushes by a pond and in the cellars of other people’s houses.

The patient was of medium height and weight, with thin grayish hair and grayish irides; musculature was slender. The face was blank in expression, the teeth poorly preserved with atrophy of gums, the tongue coated, and the breath foul. There was a gummy secretion of the eyelids, an area of brownish branny eruption over both clavicles, a number of depressed scars over the limbs and back, and another area of scaly eruption on the right heel and the sole of the foot. The heart area was increased, and the sounds were faint at the base, with the first sound accentuated at the apex. The urine showed a trace of albumin.

Neurologically, the Romberg position was maintained with a general tremor and fluttering of the eyelids. In complicated movements, the patient was slightly ataxic. The pupils were irregular, the left being much larger than the right. There were no light reactions to be obtained in window light. The reaction to accommodation was present, though slight. Vision was poor, ¼-inch capitals could not be read by left eye at reading distance. The knee-jerks were diminished equally; the Achilles jerks were absent; the other reflexes were normal. Upon the sensory side, the patient gave a history of pains in the legs at irregular intervals for several years. These pains he described as of a darting character. There was little or no sensory disorder, although the outer surface of the right leg required a deeper pressure to elicit sensation. There were no disorders of muscle sense.

If Morrill was to be trusted, he had been born in Ireland, and had come to the United States at the age of 17. He married at 18; there had been seven pregnancies by the first wife, with one stillborn child; one child had died at five weeks. The four children by the second wife were healthy. The first signs of neuritis had occurred at 45 and had received the diagnosis neuritis, although no connection between the neuritis and the syphilis had been noted.

The patient entered the hospital July 26, 1904, and was discharged, improved, January 5, 1905. He returned a little more than a year later, January 15, 1906, and died March 21, 1906. The total duration of the disease from the onset of mental symptoms may therefore be stated as somewhat under two years. When the patient appeared at the hospital the second time, he showed a positive Romberg sign, an unsteady gait, an ataxia that still was moderate, and somewhat more marked tremors, involving fingers, tongue, and face. He was now unable to read ½-inch type with the left eye. The knee-jerks, formerly diminished, were both exaggerated, the left slightly more so. The Achilles reaction, not obtained formerly, now appeared on the right side. The pupils reacted as before. The sensory loss had become more marked, since sharp and dull points could hardly be distinguished. Deep pinpricks were not felt in the leg, and heat could not be told from cold.

The speech in 1904 had been somewhat defective (“truly rural” rendered as “tooly lualal,” “sifted soft thistles” as “thoft thsistles”), and there had been little further development of the speech defect. The handwriting had lost appreciably in legibility and had become much more tremulous. During the first period of hospital observation Morrill had what might possibly have been visual hallucinations, but it was impossible to tell whether his story of seeing his wife and children trying to get in through the window was hallucinatory or a matter of fabrication. Memory was decidedly imperfect and few details of recent events could be produced. The association of ideas was almost a so-called “flight” of apprehensive, fearful ideas, loosely connected, incoherently expressed, and dealing chiefly with his work and his children. Judgment was imperfect; the height of the room was estimated as 24 feet, but the height and weight of persons were estimated with fair accuracy, and also the length of small objects, whose lengths were doubtless remembered rather than estimated. The estimate of time elapsing during a medical examination was accurate, but the estimate of longer durations involving over-night memories was hopelessly imperfect. Emotionally, there was a dulling of sensibility, an appearance of suspicion and apprehensiveness; the patient fancied himself to be in a hopeless condition as a result of syphilis, but at the same time accompanied his statement of his hopelessness with laughter. A sample of his hypochondriacal ideas: “I am all gone; I am good for nothing; I am all gone now; I can’t drink now; can’t write or talk at all; worse than when you saw me first; nothing in my inside; all wrong through me again; I aint got no swallow now; I can’t die even; my heart aint much good; I can’t hear it beat; I don’t think it flutters; no life in these hands; they are all cold and dead” (pointing to his arms and moving them about). During such a portrayal the patient laughed in a silly way.

During the second hospital stay, Morrill was at first restless, sleepless, profane, imperfectly oriented for time, possibly for place, and also for the attendants. A few weeks later he became stuporous and confused, and his feebleness and physical exhaustion were finally ended by death, March 21, 1906. Death was preceded by a semi-comatose condition; a left otitis media had developed.

At the autopsy, it appeared that death was due to an early bronchopneumonia associated with acute splenitis and doubtless related to the otitis media of the left side. The body at large showed, aside from these acute lesions, a few chronic lesions, including slight scars of the left apex, and chronic adhesive pleuritis, chronic diffuse nephritis, and aortic and coronary syphilis. The aorta showed slight linear and nodular markings, with a single small dark ulcer in the upper thoracic region, but the aorta did not show the characteristic scarring which syphilitic aortas often show. The femoral marrow was of a dark red chocolate color. The thyroid appeared to be smaller than normal. A slight sacral decubitus had developed.

The description of the head (E.E.S.) is given in full on account of the encephalitic lesions shown. These encephalitic lesions may be summed up as follows:

Local cerebral atrophy and sclerosis of the frontal, orbital, and central regions, especially of the left operculum and left supramarginal gyrus.

Extension of sclerosis to hippocampal gyri with effacement of substantia reticularis alba.

Slight chronic internal hydrocephalus.

Granular ependymitis (especially of floor of 4th ventricle).

Compensatory edema of frontal and central pia mater.

Cerebellar sclerosis (culmen monticuli, lobus culminis, lobus cacuminis).

Spinal sclerosis (grossly evident in the posterior columns of the upper thoracic region and of the lumbar enlargement).

The details are as follows:

Head:—Bald on top. Hair gray. Scalp normal. Calvarium thin, deeply excavated by arachnoidal villi to right of vertex. Diploë absent. Dura closely adherent in bregmatic region. Dura of usual thickness. Sinuses contain cruor clot. Arachnoidal villi slight. Pia mater hazy and over sulcal veins porcelain white over all of vertex except occipital poles and over flanks (notably left). Thickened also around circle of Willis, over culmen monticuli and in posterior cerebellar notch. Edema of pia corresponding to atrophy of frontal and central regions. Cerebral atrophy most marked in orbital surfaces of both frontal lobes, in left area of Broca, and in left supramarginal region. The ascending branch and the ascending ramus of the posterior limb of the left Sylvian fossæ both readily admit the thumb by reason of atrophy of adjacent substance. Induration corresponds closely with atrophy, but is not more marked about the left Sylvian fossa. There is sclerosis of both hippocampal gyri, with loss of the substantia reticularis alba. The culmen monticuli and lobus culminis are firmer than the clival regions, and the lobus cacuminis is again slightly firmer than the clival region. Cerebellum a little softer than usual. Pia strips with usual readiness from all regions. The subpial region of the frontal lobes is a trifle grayer than that of the rest of cerebrum. Ventricles slightly dilated. Surfaces evenly sanded. Floor of fourth ventricle shows numerous coarse, closely set granules. Brain wt. 1200 grms. Cord shows a slight increase of consistence over one or two upper thoracic segments and in lumbar enlargement corresponding with a slight graying out of posterior columns. In places there is a suggestion of graying out also in lateral columns. A few calcified plaques in posterior lumbar pia.

Analysis of these details shows a number of lesions that characterize paretic neurosyphilis (among others, granular ependymitis, frontal atrophy, chronic leptomeningitis), but the lesions are more than merely frontal, extending as they do back as far as the postcentral regions on both sides, and even as far as the left supramarginal gyrus. The cerebellar involvement although frequent, can hardly be said to be characteristic in paretic neurosyphilis. The spinal involvement is characteristic of a case which is probably to be regarded as one of taboparesis; that is, of paretic neurosyphilis following a number of years after the establishment of tabetic neurosyphilis. The aorta is almost constantly affected by sclerosis in paretic neurosyphilis. The absence of diploë in the skull is not infrequent and the adherent dura mater is often found.

Microscopically, the tissues showed the characteristic lesions of Paretic Neurosyphilis; nerve cell destruction, fibrillar and cellular gliosis, lymphocytic and plasma cell deposits about the small vessels.

1. What are the clinical evidences of syphilis outside the nervous system? The brownish branny eruptions of the skin, the depressed scars and the scaly eruption on right heel and sole are very suggestive of syphilis. Such clinical evidences of syphilis are very important in systematic examination. Although the laboratory tests are of the utmost assistance in the diagnosis of syphilis, the clinical signs should not be neglected, and no physician should rest satisfied with laboratory signs alone. X-ray diagnosis of bone conditions sometimes succeeds when all other methods have failed.

GUMMA of cerebral cortex verified by operation; death.

Case 27. The presenting picture in the case of David Tannenbaum was that of deep dementia, in which condition the patient was brought to the hospital. There was a meagre history to the effect that about four months before admission, he had lost his job in a hotel through lack of further work. We heard that at this time he had begun to suffer with excruciating pains in the head; at first, worse at night, later, worse by day. It appeared that this pain, though it came and went, was chiefly localized on the left side of the head. For a fortnight, Tannenbaum had been dragging his legs, until finally he had become unable to walk at all.

Pari passu with these developments, Tannenbaum had become mentally confused and irritable, and his memory had become untrustworthy. For several days before admission, an appearance of marked dementia was presented, with slow incoherent, or at all events, irrelevant words, and a complete disorientation for person. However, his vision had become so poor that it would have been hard for him to have recognized any one.

It appeared that the family history was entirely negative; that the patient was without education but had been physically very strong, and had been fairly successful at first in the junk business, and later in the clothing business; but latterly he had been less fortunate in the clothing business, and finally had to resort to work as a laborer around a hotel.

His wife had had eleven pregnancies with but one miscarriage. Nevertheless, out of the eleven pregnancies, there were now but four living children.

Physically, Tannenbaum was a rather small man; he was flabby and looked as if he had recently lost weight. The skin showed areas of pigmentation on the face and sides of the neck, and some dark copper-colored circular areas, marble-size, in the neck (syphilitic?). There was a slight radial arteriosclerosis. The heart was slightly enlarged with distant and indistinct sounds. There was a small pedunculated growth on the right side of the abdomen.

The pupils failed to react to flash-light but they reacted to sunlight. They both were slightly irregular but were equal in size, and reacted in accommodation. There was apparently almost complete blindness and extreme deafness. Arm-jerks and knee-jerks were absent; there was an occasional slight response of the left ankle-jerk, but the right ankle-jerk was absent; the left abdominal reflex was very feeble; the right absent; the cremasteric reflexes were absent, but there were no other abnormalities in the systematic examination. Hand grips weak; gait awkward, with right leg held somewhat flaccidly.

It was significant that percussion over the left frontal and parietal regions was able to elicit great pain. Either through the patient’s deafness or through sensory aphasia, spoken language was not understood. The serum W. R. was positive, the fluid W. R. negative.

Diagnosis: The clinical symptoms seem clearly to indicate syphilis. The local skull tenderness and impairment of vision might well suggest intracranial pressure. Uniting these suggestions, we might automatically arrive at a diagnosis of cerebral gumma. We have learned to be rather cautious of making a diagnosis of gumma of the brain through its mere rarity.

Decompression was suggested and executed. A deep growth resembling a Gumma, in the view of the surgeon, was discovered. No attempt could be made to remove it. The patient died without recovering consciousness.

1. What is the significance of the negative fluid W. R. in this case of cerebral gumma? The W. R. producing substances not infrequently fail to appear in the spinal fluid from a gumma of the brain. The serum W. R. was positive in this case, but even the serum W. R. may be negative in cases of gumma, both of the brain and of the body at large. It must be remembered that the serum W. R. may be negative in paretic neurosyphilis (general paresis); the serum W. R. is even more apt to be negative in cases of gumma.

Gummatous meningitis. Compression of hemisphere. Tissue destruction of underlying cortex.

2. Is operative procedure to be advised in cerebral gumma? There are cases in which the acute and threatening symptoms of heightened intracranial pressure require operative treatment simply because the therapeutist cannot wait for the effect of antisyphilitic treatment. Moreover, antisyphilitic treatment of cerebral gumma is not always as successful as that of most syphilitic lesions.

3. Could the intracranial pressure be caused by other syphilitic lesions than gumma? A heavy meningitis may cause symptoms such as produced by an intracranial tumor. In such a case one will usually find evidences of inflammation in the spinal fluid. Cysts caused by syphilitic lesions may also produce identical symptoms.

4. What is the significance of cranial tenderness? Where sensitiveness to cranial percussion is not due to a scalp lesion it is very suggestive of a tumor underlying this point. A gummatous lesion of the cranium itself, may occur without causing pain or increased sensitiveness.

CRANIAL NEUROSYPHILIS (focal syphilitic extraocular palsy) without mental symptoms.

Case 28. A chef, Paolo Marini, 28 years of age, reported that on awaking one morning, everything appeared double to him and that his right eyelid had begun to drop. In the following month Marini had begun to feel weak and to have difficulty in swallowing, as well as at times difficulty in breathing. The diplopia was found to develop when Marini looked to the right. Mentally, the patient was in all respects normal, and no other physical signs were found except the diplopia and ptosis above mentioned. The W. serum test was positive, but the tests of the spinal fluid were negative.

Diagnosis: “Cerebral syphilis.”

1. What is the anatomical cause of this condition? It is thought to be due in a number of cases to a small diffuse gummatous lesion at the basis cerebri. In the case of Marini this lesion appears to have been a little more extensive and to have interfered with the tenth and twelfth nerves also.

2. Why is the spinal fluid negative in such a case as that of Marini? Head and Fearnsides believe that intracerebral lues is characterized by a negative spinal fluid, under which circumstance one has always to consider the possibility of brain tumor or migraine in addition to the suspicion of syphilis.

3. What other causes besides syphilis should one consider for the sudden diplopia? Brain tumor, multiple sclerosis, cerebral arteriosclerosis, tuberculous meningitis, trauma and migrainous ophthalmoplegia, are not infrequently at the bottom of this condition. Cases also occur in which the etiology remains obscure, even at autopsy.

Under antisyphilitic treatment, Marini slowly improved.

The SIX TESTS in TABETIC NEUROSYPHILIS (“tabes dorsalis”) may run milder than in paretic neurosyphilis (“general paresis”) and characteristically run somewhat like those of diffuse (meningovascular) neurosyphilis; in particular, the fluid Wassermann Reaction and the gold sol reaction are apt to run milder. The clinical course of tabes dorsalis is protracted and the prognosis as to life is good.

Case 29. Mario Sanzi, 55 years of age, had been having what he called rheumatism since his 43d year. This rheumatism affected only the hips and legs, had at times been very severe, and for two years past had been almost constant. Before that time, pains had come at intervals, lasted a variable period, and suddenly disappeared. They were of knife-thrust character, and could probably be called “lancinating.” In a given attack, these pains would come at intervals of seconds or more. There was also a certain unsteadiness in locomotion and inability to control the vesical sphincter.

Physically, the patient was entirely normal so far as could be made out except neurologically. Argyll-Robertson pupils, absence of knee-jerks, and ankle-jerks, Romberg sign, and characteristic gait, left no cause for doubting the diagnosis of Tabes Dorsalis. The blood and spinal fluid both proved positive to the W. R., though the W. R. in the fluid gave a negative reaction with 0.1 cm. and became positive with 0.3 cm. or more. The globulin was somewhat increased though less markedly so than in paresis. The gold sol reaction was “syphilitic” but weak. It is to be noted that the disease had run a 12–years’ course before a doctor had been consulted. The primary infection occurred at 32 years, namely, 11 years before the symptoms began. At the time of his primary infection, Sanzi had received several years of treatment, chiefly in the form of mercury by mouth.

1. What is the value of mercurial treatment of syphilis in the prevention of tabetic or other forms of neurosyphilis? “Fournier strove for many years to convince the medical profession that a syphilitic patient should be treated for at least two years after his infection, whether the syphilis seemed latent or patent. The method of treating only the symptoms he characterized as the opportunist method; treatment in the absence of definite symptoms the preventive method, as preventing the later manifestations. That prolonged treatment does prevent is shown by Fournier’s figures analyzing 2396 cases presenting tertiary signs. These he divides into three groups: Group I, comprising 1878 cases, or 78 per cent of the whole number, having no treatment or inadequate treatment—that is mercury for less than one year; Group 2, comprising 455 cases, or 19 per cent, having moderate treatment—that is, mercury for one to three years; and Group 3, comprising the remaining 19 cases which represent only 3 per cent of the whole number, having treatment for more than three years.”[^[7]]

In the light of what we now know concerning latent neurosyphilis, it would seem well for patients to be followed from time to time with the W. R. on blood and spinal fluid after the supposed completion of the treatment of primary and secondary syphilis. The examination of the spinal fluid is not superfluous, as our experience with the so-called paresis sine paresi abundantly shows. At the present day it is not good practice to assure a patient that he is cured after two years of ordinary mercurial treatment without resort to frequent spinal fluid tests, even though the serum W. R. be negative.

TABETIC NEUROSYPHILIS (“tabes dorsalis”) is often quite ATYPICAL clinically and may even show no single symptom warranting the old clinical name “locomotor ataxia.”

Case 30. Stephen Green is a case of Tabes Dorsalis with active knee-jerks and without locomotor or muscle-sense disorder. When observed at the age of 45, it appeared that there were but two complaints: lack of control of the vesical sphincter and shooting pains in the legs. It appeared that the urinary disorder dated back ten years, when there had been difficulty in passing the urine. Sounds had been passed at the time; occasionally there had been incontinence during after years, ascribed by Mr. Green to the passing of the sound. However, the physician at that time stated that the incontinence was a symptom of tabes dorsalis. The incontinence had recently become worse, especially marked at night, though also occurring in the day; much worse during excitement, and very much worse after taking alcoholic drinks. Besides incontinence, there is also difficulty at times in passing the urine, as well as dysuria.

As for the pains in the legs, they had been first noticed some three or four years ago and considered to be mild rheumatic effects. Now, however, they have grown progressively worse and have been the effective cause of giving up business. The pains are sharp, darting, pinching, and burning, and last, say, about a second with an interval of about the same length. The attack will continue sometimes for many hours.

There is a strabismus of the left eye, ascribed by the patient to an accident with an umbrella (there had been operation without relief). The pupils showed the Argyll-Robertson effect and were markedly irregular. Despite the divergent strabismus with diplopia, the eye movements were well performed although not in parallel axes. Ankle-jerks could not be obtained even on reinforcement, but the knee-jerks were lively, and the other deep and skin reflexes proved normal. The blood and spinal fluid tests were characteristic of tabes dorsalis.

It appears that the syphilis was acquired by this patient 15 years before; that is, 5 years before neurological symptoms began. Three courses of treatment had been taken at a well-known watering-place, and mercury pills had been taken for two years by mouth. The patient is married; has no children; there have been no pregnancies.

1. What causes may be assigned for the absence of children in the family of a tabetic? There may be lesions of the genital apparatus (orchitis, or more specialized toxic lesions). But impotence such as characterized the present case must also be taken into account.

2. What is the therapy for tabetic pains? Pyramidon is nowadays much in favor; morphine may be used; some authors recommend that the patients be instructed to chloroform or etherize themselves slightly for relief of the pain. Surgery of the nerve roots may be resorted to in extreme cases. Intraspinous therapy, suggested by various authors, seems to exert beneficial effect in many cases.

3. Is the lack of control of the vesical sphincter an unusual initial symptom? On the contrary, the more careful the clinical observation, according to some observers, the more likely is the examiner to find that vesical symptoms were the earliest or among the earliest complaints of the patient. Baldwin Lucke found sphincter disturbances to be initial in 8¼% of his long Blockley series. He found sphincter disturbance to occur in some stage of the disease in 67.6%, being exceeded in frequency only by staggering gait (87.2%) and lancinating pain (71.6%). According to Lucke, the most frequent initial symptom is lancinating pain in the lower extremity, which, it will be noticed, occurred also in our case of Stephen Green as an initial symptom along with vesical disturbance. Lucke’s figures show that paresthesia of the lower extremities (17.6%) and weakness of the extremities (16.4%) are the next initial symptoms in frequency.

4. Could the early treatment in the case of Stephen Green be considered as adequate? No better answer can be given to this question than by quoting from Dr. Joseph Collins,[^[8]] who probably has done more than any other one man in this country in insisting on the need of proper treatment of syphilis. As to the adequate treatment of syphilis he says:

“It consists in the proper use of salvarsan and mercury begun at the earliest possible moment after infection and kept up till all biochemical evidence of the disease has ceased, while the metabolism of the individual is maintained as nearly normal as possible. But the physician does not do his whole duty when he has accomplished this. He must solicitously watch the individual to see that no evidence reappears for months and even years after the apparent cure. As an index of such reappearance the Wassermann test of the blood serum and of the cerebrospinal fluid is the safest guide.

“Until there is a definite unanimity of belief among physicians as to when the treatment of syphilis shall be begun, and some concert of action as to what constitutes the adequate treatment of syphilis, we cannot hope to make any considerable progress in the prevention of syphilis of the nervous system, save by educating the individual toward infection.”

TABETIC NEUROSYPHILIS may produce symptoms chiefly if not entirely in the region supplied by the CERVICAL plexus (“cervical tabes”).

Case 31. Paul Halleck, 35, was a salesman who had begun to find it hard to carry his sample case, since he was unable to tell whether or not he had it in his hand. There was not only an anesthesia of the hands, but they felt numb and there was often a tingling sensation. Of late it had become hard for Halleck to dress himself or to write, and these symptoms had been slowly growing worse. There was no other complaint. There was, however, a history of a chancre about 7½ years before, which had been followed by a rash and a sore throat. There had been treatment with mercury and potassium iodid alternating for a period of two years.

Physically, there was no evidence of disease except neurologically. The pupils were unequal (the right larger than the left) and reacted slowly to accommodation and not at all to light. A marked ataxia of the hands was shown in coat-buttoning. The finger-to-nose test showed a marked dysmetria. Arm-jerks as well as knee- and ankle-jerks were absent. There was a slight swaying in the Romberg position but no true Romberg sign. There was no difficulty in locomotion. Both blood and spinal fluid proved positive to the W. R.; globulin and albumin were increased. The gold sol reaction was syphilitic, and there were 85 cells per cmm.

This case is probably not a pure example of Cervical Tabes, since the knee-jerks are also absent, and we may suppose a degree of lumbar spinal cord changes in addition to the cervical changes. It well illustrates, however, that the tabetic involvement of the cord may be quite generalized and that it may strike high as well as low.

ERB’S SYPHILITIC SPASTIC PARAPLEGIA.

Case 32. Margaret Neal, a maid-of-all-work, 36 years of age, was committed to a home for inebriates on account of her excessive alcoholism, but she was shortly transferred to the Psychopathic Hospital on account of difficulty with locomotion. We found a very marked spasticity in walking, with a characteristic scissors gait. The pupils were somewhat irregular, and although both reacted to light, the left reacted far more slowly than the right and the reaction failed to hold well. The arm reflexes were very active, and the knee-jerks and the ankle-jerks were particularly exaggerated. There was a double Babinski reaction, as well as Oppenheim and Gordon reflexes and a bilateral ankle clonus. There seemed to be tenderness over the nerve trunks in the back of the leg, below the knee. There was no evidence of incoördination, no Rombergism, no disturbance of sensation, no disorder of the special senses, and not even a tremor of the tongue or hands.

Mentally, the patient was entirely negative.

Diagnosis: Symptomatically, it is entirely clear that the patient was suffering from Spastic Paraplegia. One would have to consider besides spinal syphilis, also amyotrophic lateral sclerosis, syringomyelia, and spinal cord tumor. However, there appeared to be no definite wasting of muscles, and the fact that the sensations were intact seems to rule out also syringomyelia. There was none of the characteristic pain associated with a cord tumor. There was, in fact, a strong clinical premonition that the case was one of spinal syphilis, simply because syphilis is the most common cause of spastic paraplegia in the adult. The pupillary anomalies were also highly suggestive.

The serum W. R. proved to be weakly positive, as was also the gold sol reaction in the zones characteristic of syphilis. The spinal fluid examination yielded 14 cells per cmm. There was a positive globulin test and a moderate increase in albumin. The W. R. of the spinal fluid was negative.

1. Why was the spinal fluid W. R. negative in this case of spinal syphilis? The explanation of negative W. R.’s in spinal syphilis is not easy. Possibly, however, in the course of years the intensity of the process has been reduced and possibly the W. R. has been one of the first tests to disappear.

2. How shall we explain the nerve trunk tenderness? We might consider this to be due possibly to an inflammation about the posterior roots. On the whole, partly on account of the situation of the pains below the knee, it seems probable that the nerve trunk tenderness of this case is the residuum of an alcoholic neuritis.

Treatment: Under injections of mercury salicylate, there was a rapid improvement. In fact, in the course of several months, the patient regained an ability to walk long distances. There still remains a certain spasticity, but the abnormal spinal reflexes above mentioned are no longer present.

SYPHILITIC MUSCULAR ATROPHY, probably due either to spinal parenchymal lesions, or to root neuritis, or to both.

Case 33. Joseph Graham, now 50 years of age, seemed no longer to be able to do good work as a teamster. His arms had become weak and the muscles had become tremulous and apparently wasted. There was also pain in the left leg and hip. It appears that this latter symptom had been thought to be rheumatism, having begun about 8 years before with a sudden sharp shooting pain in the left hip, about the region of the sciatic notch. Graham had rubbed the hip with liniment, but without reducing the so-called rheumatism. The trembling of the hands had begun some years later, but no wasting had been noticed except during the past year. The pain in the leg had suddenly become so severe that a month before medical observation he had quit work. The question immediately arose whether Graham was not suffering from some familial form of muscular atrophy; but according to his representations, there was nothing of the sort in the family.

Physically, there was little to note. Neurologically, there was more. The pupils were somewhat irregular in outline, and the right was larger than the left. The left pupil failed to react to light, and the right pupil reacted very slowly and with but a slight excursion. There was no tremor of the tongue and no evidence of facial palsy nor was there smoothing of the nasolabial folds. It was somewhat remarkable, that in the absence of these signs, there was a marked speech defect. The atrophy of arms, forearms, and hands was well marked, especially the atrophy of the thenar and hypothenar eminences of the right hand. The extended hands, especially the right, showed a marked coarse tremor. Fibrillation was found in the muscles of the hands, forearms, arms, and pectoral muscles. There was no dysmetria, and the diadochokinesia was normal. Strength was diminished (dynamometer right hand, 32 kg., left 31 kg.). There was little or no atrophy of the legs, although the left thigh was perhaps slightly atrophic and the gluteal muscles of the left side were somewhat flabby. The patellar and Achilles reflexes were absent on both sides. There was a slight swaying in Romberg position. Gait was normal. There was a marked tenderness on the left side of the sciatic notch, as well as over the entire distribution of both external and internal popliteal nerves. This area of skin was also hyperesthetic. There were no other neurological signs on systematic examination.

Diagnosis: The sensory disorder, the speech defect, and the pupillary abnormalities seem to render the diagnosis of progressive muscular atrophy doubtful. Nor was there any dissociation of sensations to suggest a syringomyelia. Under such circumstances, one must fall back upon the question of syphilis. Both blood and spinal fluid proved to be positive to the W. R.; the globulin was increased and the albumin markedly so; there were 61 cells per cmm., and the gold sol reaction read 4 4 4 4 3 2 1 0 0 0.

1. Is there a relation of Syphilitic Muscular Atrophy to amyotrophic lateral sclerosis? Spiller, some years since, claimed such a relation, and it would seem with some justice.

2. How shall the present case be classified? There is evidence of root pains (left hip). We may naturally suppose that these root pains are reasonably good clinical evidence of a meningitic lesion, of which the spinal fluid clinically gave a confirmation. The fibrillation in this case somewhat suggests, however, a central origin for the muscular atrophy. Accordingly, it would be difficult to definitely classify the present case as either one of meningovascular syphilis or one of central syphilis. It will be remembered that Head and Fearnsides classify muscular atrophy under both these headings.

The period of SECONDARY SYPHILIS is frequently (over a third of all cases?) MARKED BY approved signs of NEUROSYPHILIS precisely like those of full-blown paretic or diffuse (meningovascular non-paretic) neurosyphilis. These signs occur sometimes in association with severe clinical symptoms, sometimes without clinical symptoms.

Case 34. John Bennett, 28, was brought to the Psychopathic Hospital much confused. His brother, who came with him, said that he had been a very heavy drinker but had given up drinking about four months before. He had recently had a cold but was otherwise in good health up to the night before admission. On this night, Bennett had become suddenly excited and went into his mother’s room, at the common home, and began to curse her. However, he was put to bed safely, but on the next morning began to moan continuously. After some hours of moaning, he was brought to the hospital. Here he remained difficult to manage, being irritable, noisy, and resistive. Questions he either would not or could not answer, and there was even no evidence that he understood questions. However, within a few hours, it was clear that he was slowly coming out of the confused state. On the following day, it was possible even to rouse him and get his name. The confusion gradually cleared still further and, by the end of three days, he had become mentally absolutely well so far as could be determined.

He then informed us that he had had a chancre about five or six months before, followed by a secondary skin eruption; that he had received four injections of salvarsan (the last, a month before admission) and three injections of mercury. At about the time of the last injection of salvarsan, he had developed headache with pain and slight stiffness in the back of his neck; and a fortnight later, he began to have dizzy spells, followed during the last week by difficulty in hearing. There was amnesia for everything that happened after his spell of sudden excitement on the evening before admission, and this amnesia was never lifted for the four days that followed.

Physically, Bennett was very well built and muscular. Nor were there any evidences of disease outside the nervous system. There was some slight stiffness of the neck and slight pain on movement of the head, which probably ought to be attributed to meningitis. The neurological examination showed tendon reflexes all normal, and normal sensations. There were, in fact, no neurological signs except that both pupils were dilated; the left was larger than the right. Both pupils reacted to light but reacted very poorly. They reacted much better to accommodation.

The W. R. proved to be positive, as might well be expected in a man whose infection had taken place less than six months before. The globulin and albumin of the cerebrospinal fluid were in great excess, of a degree which we clinically express by ++++. The W. R. of the fluid also was strongly positive down to 0.1 of a cmm. The gold sol reaction was the “paretic” type, and there were 228 cells per cmm.

1. How early may clinical evidence of neurosyphilis set in after infection? Craig found one case of “brain syphilis” occurring one month after infection. Frye claims a case of tabes dorsalis developing six weeks after infection. Craig states that he has had three cases of brain syphilis occurring within six months, and six within a year of infection.

2. What effect did the salvarsan injections have in causing or preventing the symptoms in this case? Nonne sums up the neurorecidive question as follows: Since the introduction of salvarsan therapy for neurosyphilis, paralyses of various cranial nerves are seen more frequently. This higher frequency is in part only apparent since more attention has been paid of late to auditory and labyrinthine disorders. On the whole, however, it must be considered that salvarsan does mobilize spirochete foci which without salvarsan therapy would perhaps have remained latent. Probably we are here dealing in some instances with fresh infections of neurosyphilis, in other cases with a Herxheimer reaction. Ehrlich believed that these latent foci occur particularly in places with stagnant blood current; as, for instance, in the narrow bony canals. This hypothesis, sufficient in some instances, is less satisfactory for cases of peripheral neuritis, for example.

3. What treatment is indicated? Intensive antisyphilitic treatment is strongly indicated. Whatever may be the truth concerning the production of neuro-recurrences (“neurorecidives”) it is certain that the symptoms usually vanish with a continuance of salvarsan therapy. The important point is to give efficient treatment, and in a case like Bennett’s improvement is fairly certain unless some serious insult occurs before the remedial efforts have been given time. It is still an open question whether intraspinous treatment is more efficient in such cases than intensive intravenous injections of salvarsan. In Bennett’s case diarsenol was injected intravenously twice a week in 0.6 gm. doses, reënforced with intramuscular injections of mercury salicylate and potassium iodid by mouth. Under this treatment improvement began slowly and in a few months he was symptomatically well and after three months his tests were practically negative.

JUVENILE PARETIC NEUROSYPHILIS (“juvenile paresis”) with OPTIC ATROPHY.

Case 35. Mary Coughlin, a blind girl of 16 years, was brought to the hospital in a state of great excitement, laughing and crying alternately. The neurologist is entitled to think of blindness, and particularly of the optic atrophy which Mary showed, as probably due to syphilis. However, there was no history of syphilis in the father, who died in an accident at the age of 40, or the mother, who died at 45, of heart trouble. An elder sister was married and well; two younger sisters were living and well. The fifth sibling, a boy, had died in infancy. There had been no miscarriages. In fact, the only point in favor of syphilis was the somewhat far-fetched point that the younger brother of the patient had died in infancy.

The patient’s history was rather suggestive of some other diagnosis. Her birth had been normal, she walked and talked at 13 months, was at school from six to twelve, reaching the seventh grade, and was considered bright. At three years of age, she had been run down by a car and dragged under the fender for a considerable distance. Her head was hurt but the patient did not lose consciousness in the accident. Fainting spells began at 11, in which spells the patient would lose consciousness for a minute or two. About this time, the patient’s eyesight had begun to fail, and for some four years she had been entirely blind. Headaches had come on of late.

The Coughlin case, except for the above-mentioned suspicion of syphilitic optic atrophy, might be regarded as an unusual example of a post-traumatic disease.

We found her to be fairly well developed and nourished; there was a deformity of the lower half of the sternum and of the third and fourth ribs on the right side. There were no other physical phenomena found upon systematic examination. The left pupil still reacted to light; the right failed to react, but this lack of reaction could not be regarded as of Argyll-Robertson nature on account of the finding of optic atrophy with the ophthalmoscope.

Mentally, it appeared that the patient’s retention of school knowledge was poor, though her blindness for four years had doubtless given her little opportunity to keep such information fresh. Rather strangely, Mary gave utterance to many delusions: first, expecting to receive her sight by an operation on the head; second, to write a book of her doings; third, to buy a house for the children; fourth, would pay $3000 for the house, earning the money by working at a tailor’s or as a trained nurse; fifth, to go on the stage to earn money by dancing; sixth, will have lots of money.

One of Mary’s characteristic statements is as follows: “Won’t it be lovely when I can see Dr. H.’s face in heaven or some other lovely place? Dr. H. was a grand doctor to me, and when we get together again we are going to Tremont Temple and keep us together. I am going to do some dancing and play the piano. I am going to graduate at the high school and go to Trinity College in Washington, and I hope I shall be a faithful keeper of mother’s tomb.”

The patient was at times euphoric and expansive.

At this stage, what with optic atrophy, euphoria, and expansive delusions, we should perhaps be entitled, had Mary been an adult, to offer the diagnosis General Paresis. In fact, on the whole, any other than a syphilitic cause for the optic atrophy was exceedingly doubtful. Brain tumor of a nature to produce optic atrophy might very improbably last so long as five years. There was no evidence of any intoxication at the time when the blindness occurred.

The W. R. was positive in the blood and spinal fluid; there was a positive globulin test, and an excess albumin as well as 15 cells per cmm.

1. What is the significance of Mary’s trauma at three years? So far as we are aware, none.

2. What light could be thrown by a W. R. study of the family? In some instances, much light is thrown; in the present case all three living sisters of the patient have been examined and their serum W. R.’s have been found negative.

3. What is the prognosis of juvenile general paresis? Death within a few years, as in general paresis in adults. The patients live rarely more than four or five years after the onset of symptoms. Mary Coughlin died a year and a half after the above examination, namely, in her eighteenth year, some seven years after the onset of symptoms.

4. What can be said of treatment? A few favorable results have been reported after intraspinous therapy (Swift-Ellis). Too little work has been done with systematic treatment of juvenile neurosyphilis, both paretic and non-paretic, to permit important conclusions at this time.

5. How can we explain the infection of this sibling whereas the others, both younger and older, escaped? It would seem that we would have to discard the hypothesis of a congenital infection and consider that it was acquired accidentally during the lifetime of the patient. Considering the prevalence of syphilis it is rather to be wondered that more such cases of “innocent” infection do not occur in children. We may recall how many instances of juvenile gonorrhea occur. In a case as this where the symptoms calling attention to syphilis necessarily occur so long after the original infection it is practically impossible to trace the origin of the infection.

The diagnosis of JUVENILE PARESIS is often easy.

Case 36. Theresa Mullen, an under-sized girl of 12 years, presented a remarkable appearance due to congenital amputations of the fingers and toes. She lay in bed, drivelling and making unintelligible cries. It appeared that the patient weighed about 12 pounds at birth and was very fat; that she had been fed on condensed milk, had survived cholera infantum, whooping cough, and, as the parents said, “two kinds of measles.”

Theresa had gone to school at 5 years, reaching the third grade at the age of 9; but at this time, she began to lose ground and was put in a class for backward children. Moreover, at about this time, the teachers noticed spells of causeless laughter and meaningless twisting back and forth. Theresa would also scream at night, looking about the room; once, rising and crying, “Take him away, that black thing,” though no appropriate object was present. There had been little or no complaint of headache. Theresa had been deteriorating for some time, and for a year past had been having increased difficulty in walking. For two months the child had not spoken intelligible words; for the last week, she had been incontinent.

The diagnosis was almost obvious from the manual and pedal deformities taken in connection with the saddle-back deformity of the nose. It was interesting in connection with the contentions of W. W. Graves, that the scapulae were scaphoid in type.

Accordingly, the history given by the parents seemed consistent enough. The parents were both 36 years of age, having married at 23. The first pregnancy was a miscarriage at two months, of unknown cause. Theresa came next; thirdly, came a miscarriage at three months; fourthly, a girl, who is not strong or well physically, has suffered much from headaches and sore throat, but is fairly bright. The fifth pregnancy resulted in a boy, who is bright but of under-size. Three more pregnancies resulted in miscarriage.

Taking into account the above-mentioned physical characteristics, the personal history, and the family history of Theresa, the diagnosis could hardly be in doubt even in the absence of a lack of pupillary reaction to light on the right side, infantilism of genitalia, positive W. R.’s of serum and spinal fluid, positive globulin, and excess albumin, 34 cells per cmm. and the paretic type of gold sol reaction which were found.

The prognosis of this case appears to be rapid deterioration, terminating in death within a few months. Now and again, however, some such cases spontaneously improve. Such a case as that of Theresa Mullen is always disheartening in itself but suggests the social value of Wassermann tests in the other members of the family. The other children of the Mullen family proved to be suffering also from syphilis, since their blood sera all showed a positive W. R.

1. What is the characteristic age of onset in Juvenile Paresis? An impression has prevailed in some quarters that the typical onset of juvenile paresis is in the adolescent years, and Clouston’s first case (1877) developed in a boy of 16. Thierry’s 58 cases, developing from the 8th to the 20th year, averaged 14 years of age at onset. Mott’s 22 cases from the 8th to the 23d year, averaged 17 years at onset. According to Clouston, juvenile paresis develops most often at puberty (15 to 17 years). It is sometimes claimed that cases developing symptoms early live longer, and that juvenile cases developing symptoms after the 20th year run a short course. For a case developing in the 5th year, see John Friedreich, Case No. 77.

2. What may be concluded from the physical signs (congenital amputations) present in this case before the development of mental symptoms? Some cases of juvenile paresis appear to show no physical signs whatever in childhood. While these amputations might be the accidental result of a difficult delivery, it is more probable that they are due to a syphilitic process.

Juvenile paresis—congenital amputation of digits. This case reached fourth grade in school before deterioration.

CONGENITAL SYPHILIS is apparently capable of producing simple FEEBLEMINDEDNESS (that is, a form of disease non-paretic, non-tabetic, without special tendency to progression, and without tendency to vascular insults).

Case 37. Isaac Goldstein was a small boy of six years and seven months, with a father known to be suffering from general paresis. The child was very irritable and nervous and very difficult to manage, but would hardly have been the subject of medical attention except in a family study suggested by the paresis of the father.

The child had been born at term and had apparently undergone a normal development. Physically, he showed no definite signs of congenital syphilis. In fact, the physical examination was to all intents and purposes negative. The W. R. of the serum, however, proved to be positive. Mental tests showed that his mental age was that of a child of a little over five years. Taking all things into account, it is probable that he should be regarded, therefore, as somewhat retarded mentally.

1. Is syphilis answerable for the mental retardation in this case? Provided that the family is free from feeblemindedness and mental disease, it would seem that the retardation of a congenital syphilitic should perhaps be regarded as syphilitic in origin. Of course, the institutions for the feebleminded have not shown exceedingly high percentages of syphilitic children in various W. R. surveys; still, the percentage of positive reactions in institutions for the feebleminded is clearly higher than the incidence of congenital syphilis shown in the population at large. Hence, we may conclude that syphilis is one of the etiological factors in the production of feeblemindedness. Dr. W. E. Fernald, of the Waverley School for the Feebleminded, has recently pointed out that the syphilitic cases belong rather in the lower grades (idiots and imbeciles) of feeblemindedness than in the higher (morons).

2. Can we guess what the pathological anatomy and histology of the brain may be in such cases? The Waverley studies now in process seem to indicate that some cases have little or no gross alterations, but show a few slight traces of lymphocytic accumulations discovered upon extended search, and a certain tendency to the appearance of rod cells in various foci. But the whole matter is still sub judice. It is a question whether these traces of chronic inflammation are the residuals of a more active process or the beginnings of a process that is about to be more active.

3. How characteristic is a positive W. R. in the serum of a child without physical stigmata of congenital syphilis? If we limit the term stigmata to the major and more important signs, we must reply that it is not unusual to find positive W. R.’s in sera of physically normal-looking children. Except in family studies, such cases will often escape notice, either because there are no stigmata whatever, or because such stigmata as exist are of a minor nature and regarded as unimportant anomalies. Some of these cases occur in the clinics later in life as so-called syphilis hereditaria tarda. If one wishes to discover these cases with late development of symptoms before their full bloom, the most obvious method is to examine carefully the children of known syphilitics.

Scaphoid Scapulae.

JUVENILE TABETIC NEUROSYPHILIS (“juvenile tabes”); TREATMENT.

Case 38. The point in presenting Archibald Sherry, a Juvenile Tabetic of 12 years on admission, is perhaps to exhibit pride in therapeutic results.

There was little or no doubt of the diagnosis; in an adult, the phenomenon would be called tabes dorsalis with a question of general paresis. The right pupil was larger than the left and reacted neither to light nor to distance. There was a slight tremor of the tongue and of the outstretched hands. The knee-jerks and ankle-jerks could not be obtained, nor could the periosteal reflexes in the legs. There was a slight unsteadiness in the gait and in various finer movements, and a slight ataxia of the legs. There was not a classical Romberg sign but there was slight swaying in Romberg position. The teeth were Hutchinsonian. For the rest, the physical examination was practically negative.

The family history was of interest. On the paternal side there was nervousness as well as alcoholism and degeneracy. The maternal grandmother had cancer. Archibald’s father was immoral and alcoholic. There was a girl four years older than Archibald, who, though nervous and unstable, has shown no signs or symptoms of syphilis and does not yield a W. R. in blood or spinal fluid.

Archibald himself was born at term, a large child, who, however, lost weight rapidly, developing a marked skin eruption on head and back three weeks after birth. This skin disease lasted for a month and a half and then spontaneously disappeared. Archibald remained weak and sickly, not walking until three years of age. However, he did well in school up to the end of his 11th year, when he failed to keep up with the children. He had been an amiable child and had gotten on well with his playmates. Some time in his 10th year physical disability had begun; there was numbness in the legs with weakness; at times, actual inability to walk. The right pupil was noticed by the mother to have increased in size; the eyelashes had turned white. There was pain over the left eye and a feeling of weight on top of the head. Speech became difficult or even confused.

Consistently enough, the W. R. both in blood and spinal fluid was positive. Globulin and albumin were present in large amounts; there were 150 cells per cmm.

Granting that this be in some sense a case of juvenile tabes we may raise a doubt whether the case is one of congenital syphilis. The W. R.’s of the blood of both father and mother are negative. Syphilis is denied by them. The nervous and unstable older sister failed to show definite symptoms of syphilis or a positive W. R. There had been no miscarriages or stillbirths. The question arises whether the Hutchinsonian teeth do not indicate congenital syphilis. It appears, however, that it is possible to develop Hutchinsonian teeth if syphilis is acquired before the teeth are formed. We have no data as to how or why this particular baby should have acquired syphilis, if he did so acquire it, at the age of three weeks. On the whole, sceptics may doubt our suggestion that the case is one of acquired juvenile tabes. Possibly the question is academic so far as treatment is concerned.

Prognosis: The rarity of juvenile tabes is such that little can be said as to prognosis. Three and a half years have passed since a few injections of salvarsan were made. The pains above mentioned rapidly disappeared, the gait became steadier, the attacks of confusion ceased, and the speech improved. Unfortunately, on account of a lack of coöperation on the part of Archibald’s mother, we have been unable to continue treatment. However, we have from time to time followed the patient in his home and he seems to have shown no falling back after the initial improvement. It would be of great value could we know the situation in the spinal fluid at the present time.

1. Is there any explanation why paresis should occur in some juveniles and tabes in others? There is no available explanation for this difference nor any for the characteristic early optic atrophy of juvenile tabetics.

Be frustrate, all ye stratagems of Hell,

And, devilish machinations, come to nought!

Paradise Regained, lines 180–181

III. PUZZLES AND ERRORS IN THE DIAGNOSIS OF NEUROSYPHILIS

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

DIFFUSE NEUROSYPHILIS (“cerebrospinal syphilis”) versus PARETIC NEUROSYPHILIS (“general paresis”). Autopsy.

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

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

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

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

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

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

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

The anatomical diagnoses were as follows:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Death after gradual failure July 29, 1908.

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

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

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

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

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

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

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

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

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

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

The autopsy showed a general arteriosclerosis with chronic and acute meningitis. The brain weighed 1110 grams; the pia mater was moderately thickened; the basal vessels were highly arteriosclerotic. The brain itself, however, normal externally, upon dissection, showed a number of small cysts irregularly scattered in the white substance. The basal ganglia were porous, and there were several small cysts in the pons. Microscopically, there was evidence of severe vascular disease, involving not only the arteries but also the veins. It was the superficial rather than the deep arteries that were more often attacked. There was a marked perivascular gliosis. Extensive search yielded no evidence of lymphocyte infiltrations, either in the brain or in the spinal cord.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Delusions somewhat doubtful. At no time euphoria.

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

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

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

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

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

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

Differential diagnosis between NEUROSYPHILIS and NEURASTHENIA.

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

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

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

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

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

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

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

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

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

NEUROSYPHILIS(?) in the SECONDARY STAGE of syphilis. HYSTERICAL symptoms. Diagnosis?

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

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