Neurosyphilis

No more important human problem now exists than syphilis. Syphilis of the nervous system or, briefly, neurosyphilis is a highly important fraction of the total problem. The few outstanding dates and items which we present on the following page give but a faint idea of the amount of observation and thinking which the medical aspects of neurosyphilis alone have required. The present work deals with but a small fraction of the results of this work, nor can we more than glance at the scientific history of syphilis and neurosyphilis—a history that would form an epoch in itself.

It is only in the most recent years that syphilology and the narrower science of neurosyphilology have threatened to become separate disciplines boasting full time specialized workers. Up to recent years the contributions to the theory of syphilis have been largely by-products of work in larger sciences and arts. Thus, the cellular pathology of syphilis as worked out by Virchow and the more special vascular features as worked out by Heubner were incidental in the progress of pathological anatomy and histology. The bold procedure of Quincke in proposing lumbar puncture also had its more general ground in the extension of clinical medicine,—an interpretation likewise true of the French achievements in the cyto-diagnosis and chemical diagnosis of the lumbar puncture fluids. The careful histological definitions of the Nissl-Alzheimer group were incidental to the application of approved and classical pathological methods to neurological and psychiatric material.

Again, the work of Schaudinn, as well as that of Metchnikoff and Roux, was ingenious work with the methods of parasitology and experimental pathology. The great work of Schaudinn in establishing the constancy of the spirocheta pallida in syphilis may be said to have started syphilology as something approaching a special discipline. The ideas of one of the greatest of immunologists, Bordet, were almost immediately applied to the serum diagnosis of syphilis by Wassermann and the further application of this method to the problems of neurosyphilis was almost immediate, with the spirocheta pallida as an object of attack. The commanding intelligence of Ehrlich could at once seek application of long incubated ideas of chemotherapy with the startling outcome, salvarsan.

The history of syphilis and neurosyphilis was now to be thickly sown with ideas and results growing from the achievements of Schaudinn and Ehrlich. The positive reactions in the blood and spinal fluid in the most striking of mental diseases, general paresis, led to the impression that general paresis itself might at last be proved to be what Mœbius had suspected, namely, 100% syphilitic. We know how difficult is the technical proof of spirochetosis in the brains of general paretics both post mortem and ante mortem, but no one doubts the certainty of the syphilitic hypothesis concerning the origin of general paresis.

The data of the gold sol reaction ultimately obtained from the ideas of Thomas Graham concerning colloids, as developed by Szigmondi and effectively applied by Lange, have broadened and solidified the whole plane of attack.

The ingenious suggestions of Swift and Ellis (salvarsanized serum) and the notable work of Noguchi and Moore (spirochetosis in paretic brains) indicate to us as Americans what the establishment of scientific institutes may do to permit the rapid application of new ideas to branches of inquiry that are opened out. Scientific institutes do not manufacture a Virchow, a Metchnikoff, a Schaudinn, a Bordet or an Ehrlich but they directly permit such men to work and indirectly stimulate the development of more.

The series of 137 cases here at least presented does not touch systematically the problems of the neuropathology of syphilis, which would themselves require a textbook of respectable size. We have, however, presented in Part I, cases 1 to 8, some indication of the protean nature of the material and from time to time in the remainder of the book somewhat fuller accounts of the pathological anatomy and histology have been presented than are strictly necessary in the demonstration of the principles of modern systematic diagnosis and treatment.

Our work may be said to represent psychopathic hospital practice as available to us in our official capacities at the Psychopathic Department of the Boston State Hospital. A word is necessary concerning the nature of this practice. The dispensary and ward practice of a modern state psychopathic hospital, such as the Boston institution (founded in 1912) and the Ann Arbor institution (founded in 1906), is to be sharply distinguished from asylum practice. Those who have not followed the evolution of the modern psychopathic hospital with the lowering of bars to the admission of patients and the extension of its benefits to a group of sick persons far removed from the medicolegal concept “insanity” may not soon grasp the general nature of psychopathic hospital material. Psychopathic hospital practice stands, in fact, almost midway between asylum practice in the classical sense and private practice. This has come about through the great extension of the so-called voluntary relation under which hundreds of patients now resort to the beds and out-patient rooms of a psychopathic hospital, who would formerly have remained untreated or inadequately treated. Moreover, the broadening of the concept of mental diseases as a whole has permitted in some parts of the world the establishment of laws under which psychopathic and psychotic patients may be brought to psychopathic hospitals and even to asylums under the easiest possible conditions and restrictions, omitting court procedure altogether. The operation of the voluntary and temporary care provisions of law has accordingly yielded us, in the Boston institution, a great group of cases formerly not at all accessible to hospital diagnosis and treatment. Needless to say, as always under such conditions, we have been able to show not merely that hospital diagnosis or treatment is of importance to a new group of cases, but also that home treatment, especially home treatment under supervision, is possible and even ideal for a large group of cases about which utter darkness or profound misgivings ruled in the not very distant past.

Accordingly, we are fain to insist that our material is of importance in new programs of community organization for the stamping out of disease. The work in psychopathic hospitals upon neurosyphilis in particular is essentially a part of the public health program, although our special work will not soon be taken over by the public health officers, so complicated are the ramifications of medical and social diagnosis and treatment in the neurosyphilis group.

We have tried in Part IV (medicolegal and social cases) to give a few examples to illustrate the part played by neurosyphilis in society; but we regard this part of our work as the least satisfactory and the least representative in the total work. Our colleagues in social service, in mental hygiene, in psychopathology and in criminology will easily in the next few years provide a far more adequate basis for a full account of the public and social aspects of neurosyphilis. One point we should emphasize here. The psychopathic hospital worker, whether physician or social worker, must shortly decide upon and consolidate a program with relation to the families of neurosyphilitics.

The syphilographers of the dermatological and special syphilis clinics have their identical problems with the families of syphilitics; but the dispensaries for mental cases and in particular the psychopathic hospital and asylum out-patient departments tap another reservoir of syphilitic families at a stage when the memory of the initial horrors of syphilitic infection is dimmed or erased. Any program for the diagnosis and treatment of syphilis of the innocent must take into account not only the skin, syphilis, and internal medicine clinics but also the clinics for mental and nervous diseases wherein neurosyphilitics are not infrequent. Whether the ultimate percentage will stand at 10, 15 or 20% for the neurosyphilitics in mental clinics, is of no importance to the principle. There are enough neurosyphilitics having economical importance and humanly precious families to warrant definite steps.

The Massachusetts Commission for Mental Diseases has in the last few years employed the services of two medical workers whose time has been largely devoted to the applications of our recent knowledge in neurosyphilis and has gone so far as to establish a neurosyphilis ward in one of the district state institutions (Summer Street, Worcester, under the Grafton Hospital Board). Special social workers in the field of neurosyphilis have also been available from time to time. These social workers are enabled with the support of the medical profession to do a great deal of good, for example, with the slogan The Child of a Paretic is the Child of a Syphilitic.

The nature of the intake of patients into psychopathic hospital wards and out-patient clinics is such that great numbers of non-mental syphilitics arrive for diagnosis and possible treatment. Moreover, the existence of syphilis in non-suspects is a fact picked up by the way in routine Wassermann serum diagnosis.

The mental clinic in the modern sense with the medicolegal bars lowered or well nigh removed, turns rapidly into a clinic for neurological cases as well. The German models for mental and nerve clinics are rapidly being imitated. The result of this administrative novelty in our hospital procedure has incidentally yielded us many representative cases of entirely non-psychotic and even non-psychopathic neurosyphilis. Our impression grows and deepens that the neurosyphilitic is seldom merely a spinal syphilitic. The neurosyphilitic is nearly always the victim not merely of spinal disease but also of intracranial disease. Per contra, the victim of intracranial neurosyphilis is almost always more or less importantly affected by spinal neurosyphilis.

The net result of the modern work on neurosyphilis has been to bring the neurologist and the psychiatrist together upon one platform in diagnosis and more and more upon one platform in treatment. But aside from the clinical evidence that the neurosyphilitic is apt to be a victim of both brain syphilis and cord syphilis, the autopsy evidence is stronger still. Even the victim of tabetic neurosyphilis (“tabes dorsalis”) himself is rarely found at autopsy without more or less evidence of significant encephalic disease of a chronic inflammatory or degenerative nature. Aside from tabes dorsalis and Erb’s paraplegia, the rule is almost universal that neurosyphilis is a matter of the entire nervous system.

In view of the generalization of neurosyphilitic process, one might question the advantage of any topical grouping of neurosyphilitic disease. Practically speaking, however, as we have shown in Chart 5, it seems advisable to separate the neurosyphilitic diseases into six roughly distinguishable groups. First, there is the great group that we have chosen to term diffuse neurosyphilis, including many of the cases of so-called cerebral or cerebrospinal syphilis of the neurological clinics and the group of cases that have been treated in private practice by internists and neurologists without recourse to institutions. These cases have lived at home and have not been socially hard to manage until the late phases of their disease when the victims, if poor, are sent to almshouses and infirmaries under municipal or state care. These are the cases which have been in the past regarded as most amenable to the classical iodid and mercurial treatment. Indeed there is record of numerous therapeutic successes in the group.

Whereas the lesions in diffuse neurosyphilis are chiefly chronic inflammatory and degenerative changes of a diffuse nature (with vascular changes incidental or subordinate to the inflammation and the degeneration), there is an important and large group of cases that we have termed vascular neurosyphilis in which the factors of inflammation and degeneration are subordinate to vascular insults. These are cases of syphilitic arteriosclerosis and the best examples are victims of cerebral thrombosis. The clinical symptoms of the immediate attacks (of apoplectiform, epileptiform or other acute nature) are not in themselves distinguishable from the immediate effects of non-syphilitic vascular disease; nevertheless the establishment of their syphilitic etiology is of the utmost importance on account of the possibilities of treatment of the underlying syphilis. For, as the neuropathologist must always insist, the immediate effects of vascular insults whether syphilitic or non-syphilitic are much more extensive than the ultimate paralytic or residual irritative effects; and by consequence a greater optimism is justifiable in the confronting of these cases than the nihilistic observer is likely to entertain.

Physicians dealing with chronic disease in general are apt to be somewhat nihilistic, but this nihilism is increased a hundred fold in disease of the nervous system. How important then is any work which shall demonstrate partial or even complete recovery from serious looking apoplectic and other seizures, besides all of which the point of syphilitic treatment naturally lies in the prevention of future insults of the same sort. Therapeutic experience in this vascular group has almost as good a toll of successes as in the diffuse neurosyphilis group above mentioned, that is to say, the modern systematic treatment and even the old pre-salvarsan treatments have succeeded fairly well in removing the products of inflammation from the membranes of the nervous system and in abolishing vascular disease.

The old principle that the dead neurone in the central nervous system cannot be regenerated remains a perfectly firm principle; but there are any number of neurones and even neurone systems that are not essential to life or to the pursuit of happiness. We accordingly have just as good a theoretical therapeutic outlook in many instances of chronic neurosyphilis as we have in chronic diseases of many other organs. Add to this the fact that a great number of the most sharply-defined and grave symptoms are probably not due to destruction of neurones but to irritation and functional disability of neurones, and the conclusion is compelled that, as hinted above, an entirely unjustifiable pessimism and nihilism have prevailed in some quarters. Of course, the recoil from such pessimism with the onset of salvarsan treatment led various enthusiasts to an undue optimism.

Another great group distinguished by the existence of spinal cord disease is the group we have termed tabetic neurosyphilis, which group contains the classical tabes dorsalis or locomotor ataxia and its congeners.

The question of therapeutic optimism comes up most forcibly in the field of tabes. It is hard, however, at this time to give a proper and scientifically founded estimate of the therapeutic outcome in tabetic neurosyphilis with modern methods. So much can be said: namely, that the alleviation of pain and the palliation of other symptoms can be successfully claimed as a result of the renewed interest in the treatment of this affection. What was said above concerning the finality of the death process in a dead neurone is very strikingly true, of course, of some of the neurones of the posterior columns in tabes dorsalis. Still only portions of these neurones (namely, those which run an intradural course) are strikingly altered in a great many cases. Now and again one is greatly astonished to observe the restoration of the lost knee-jerk in cases of neurosyphilis (see for instance the case of Alice Morton (1), with discussion). In short, the relation of several tabetic symptoms to irritative conditions and functional disability of neurones may be considered established. Naturally, moreover, if therapy can stop the upward course of the affection as it passes from lower to higher nerve roots (according to reasonably well-established ideas of the genesis and progress of this affection), we are entitled to a further degree of optimism.

The question of therapeutic optimism versus pessimism is forced upon attention in the fourth great group of neurosyphilitic diseases which we have chosen to distinguish, namely, the group of paretic neurosyphilis including the disease formerly known as general paresis, paralytic dementia, softening of the brain and the like.

Of course, no one can gainsay there is a group of cases having in the natural course of events a prognosis of fatality within a term of years, say three to five years, and we have cases in our series which go to show that even with the modern intensive treatment the characteristic down-grade symptomatic progress and ultimate fatality occur. Still, we have other cases diagnostically on all fours with the fatal cases that have seemed to get either entirely well with the laboratory tests returning to normal and without further mental symptoms, or else lose mental symptoms on the one hand or laboratory signs on the other. We should strongly object to any account of paretic neurosyphilis which should insist that its necessary outcome is fatality within a term of years. Of course, viewing our knowledge of the affection in the past, we should be compelled to object to the generalization “paresis fatal” on the evidences of the universally recognized remissions. If nature can stop a paretic process, why cannot man do as much? Can it be alleged that our own apparent therapeutic successes and those of others are merely curious examples of coincidences, namely, that remissions have chosen to occur precisely when therapy was systematically applied? The percentage of therapeutic successes with modern intensive treatment, wherever it may ultimately stand, is already too high for this hypothesis of fortuitous remissions.^[31]

Moreover, we believe that the details of the clinical progress of some of the reported cases are convincing on this point. What, however, is the distinguishing feature of paretic neurosyphilis? It is in one sense a particular kind of diffuse neurosyphilis. The tissues are apt to show not only encephalic but also spinal changes. There is apt to be a more or less well-defined meningitis, but the characteristic feature, without which the diagnosis of paretic neurosyphilis would hardly be rendered, is the existence of disease of the cerebral cortex. This disease is parenchymatous in the sense of showing nerve cell destruction. There is also an interstitial reaction in the shape of a neuroglia overgrowth, but the striking and pathognomonic feature is the infiltration of the sheaths of the small vessels in the cortex, giving evidence of an inflammation very intimately affecting the cellular mechanisms of the nervous system. It is striking how often a smaller or larger share of the cells found in the vessel sheaths are plasma cells. It does not appear, however, that the diagnosis of paretic neurosyphilis as against diffuse non-paretic neurosyphilis can be made in the stained sections with complete safety on the basis of plasmocytosis in the former and lymphocytosis in the latter. Whatever the results of careful histological differentiation by future neuropathologists may yield, it is at all events true that we cannot yet make an important differentiation clinically on the basis of the differential count of plasma cells and lymphocytes in the puncture fluids. However this may be, there is an important distinction between diffuse neurosyphilis of the non-paretic type and paretic neurosyphilis in that paretic neurosyphilis rarely if ever fails to show important degrees of intracortical perivascular inflammation with larger or smaller numbers of plasma cells.

What has the therapeutist to face in this matter? The answer, as elsewhere, depends somewhat upon what the future may decide as to the habitat and toxic or antitoxic activities of the spirocheta pallida. The early claims that the spirocheta pallida was extravascular and lay for the most part in the parenchyma and not in the vessel sheaths were perhaps overbold, since other workers have found the spirochete in the vessel sheaths also (Mott).

Aside from the spirochete and its accessibility to spirochetocidal drugs, there seems to be no reason for supposing that the perivascular sheaths cannot be cleansed of their inflammatory contents. There is, again, no reason why the phagocytic cells should not continue to perform their scavenger function until such time as the degenerative process in the parenchyma (a process not necessarily progressive in the absence of the spirochete or its products) ceases. There is every reason to suppose that a great many of the clinical phenomena are not necessarily due to permanent destruction of neurones and neuronic organs (dendrites, axis-cylinders, nets and the like) but are due to various microphysical conditions of pressure, intoxication and the like.

The inflammatory conditions in the spinal cord of poliomyelitis, which conditions are precisely as striking as those of the paretic cortex, are beyond a question cleared away in the progress of the affection. Reference to the paradigm case (1) will show the type of our argument. There is no manner of doubt that in this paradigm case almost every portion of the nervous system had been sometime swept by spirochetosis and many of its small vessel sheaths stuffed with chronic inflammatory products. As for paretic neurosyphilis itself, a great many of its most striking clinical phenomena, such as loss of memory and disorientation, as well as great degrees of apparent dementia, are found virtually as often in cases with very slight anatomical changes as in cases with marked cortical devastation. The inference is plain, that these phenomena are to a degree functional rather than structural.

In brief, we conclude not only from therapeutic experience but also on a priori grounds that the histological conditions in paretic neurosyphilis are not entirely hopeless, and certainly not more hopeless than conditions in many chronic diseases outside the nervous system. Accordingly, we plead for a temperate optimism as to therapeutic results in general paresis.

A fifth group of neurosyphilitic cases bulking rather largely in textbooks of pathology is the group of the gummata. For a variety of reasons (therapeutic and otherwise) the actual number of gummata of the nervous system available for clinical or even for anatomical study is much smaller than the books might lead one to infer.

The sixth and last of the main groups of neurosyphilitic diseases is that of the juvenile forms, among which we find not only diffuse forms without a special and well-defined course, but also characteristic examples of paretic and tabetic neurosyphilis. The distinction of a juvenile or congenital group of neurosyphilitics is, on theoretical grounds, perhaps hardly defensible. On practical grounds, however, the juvenile neurosyphilitics do form a group having special relations to feeblemindedness, epilepsy and the like.

We must be clearly understood as to the rough, six-unit classification just given. It is practical merely. For comparison we have given in other charts more expanded lists of the diagnostic entities in neurosyphilis among which that of Head and Fearnsides is of special interest, see Chart 2, page 21.

We shall now proceed to a brief analysis of the findings in our chosen series of 137 cases. We shall not reproduce the case headings of these cases, but expand their statements where necessary and tie them together so far as possible into a reasonable and systematic statement of the situation in neurosyphilis. The footnotes will contain references to other cases in which identical points are illustrated as in the leading cases. The leading cases will in all instances be placed first in the footnotes.

The paradigm^[32] shows meningeal, vascular and parenchymatous lesions and thus illustrates our definition of the term Diffuse which means precisely meningeal, vascular and parenchymatous. The meningeal lesions gave rise to two prominent sets of lesions, first, the marked tabetic lesions of the spinal cord (due to the spinal root neuritis incidental to the spinal meningeal inflammation), secondly, the characteristic asymmetrical and focal atrophy of cranial nerves incidental to a now largely extinct meningeal process at the base of the brain. The vascular lesions are responsible for another important and characteristic factor in the case, namely, the bilateral pyramidal tract sclerosis; the bilateral cysts of softening of the corpora striata are characteristic effects of old syphilitic cerebral thromboses. The parenchymatous disease in our paradigm is everywhere obvious, less so perhaps in the cortex itself than elsewhere, although here also evident in the shape of lesions suggesting an early phase of tissue atrophy.

The paradigm is of interest in demonstrating what in broad lines must be taken as an ascending disease proceeding not only from spinal cord to encephalon but also traceable as proceeding from lower parts of the spinal cord to upper parts thereof and from the lower encephalon to the higher structures of the cerebral cortex itself.

The paradigm insistently calls attention to the advantage of persistent therapy not only in its display of remarkable successive recoveries from permanent looking symptoms but also histologically from the remnants of inflammatory process to be found in an otherwise almost wholly dismantled nervous system with extinct lesions.

Tabetic Neurosyphilis^[33] (“tabes dorsalis”), of course, often proceeds to death without special complications of syphilitic nature. We have chosen a case, however, to demonstrate a terminal complication with vascular insult. Incidentally the case shows another complication inasmuch as the cause of death was rupture of aortic aneurysm. It is important to bear in mind these complications in tabes dorsalis which go to prove that the spirochetosis of tabetic neurosyphilis is not limited to the region of the spinal roots or to the spinal region in general. Tabetic neurosyphilis is apt to be only a part of a total picture of neurosyphilis just as neurosyphilis itself is only a part of the general syphilitic process.

Our case of Paretic Neurosyphilis^[34] (“general paresis”) is a characteristic one in duration (three years and three months). The aortic sclerosis almost constantly found in neurosyphilis and especially in paretic neurosyphilis is here also shown. The spinal cord showed lesions which are also almost always found in paretic neurosyphilis. The characteristic frontal emphasis of the atrophic and indurative lesions is shown. There is also a display of gross changes in the pia mater. The characteristic so-called granular ependymitis or sanding of the ventricular surface is shown. The case is distinguishable from the paradigm in not showing the effects of vascular insults in the shape of cysts of softening. The cerebellar sclerosis of the case is fairly characteristic of paretic cases. There is even a suggestion of atrophy in the temporal region suggesting the so-called Lissauer’s paresis. Clinically the case belongs in the classical grandiose group of paretics (“O. K. No. 1 superfine”).

Vascular Neurosyphilis^[35] is illustrated in a fourth autopsied case. It may be noted that the pia mater in this case is practically normal. The tissues outside the area of softening due to the syphilitic thrombosis of nutrient vessels are practically normal. The case was one of almost complete sensory aphasia with word-deafness. The clinical picture is accordingly quite distinct from those of the paradigm (1) and of the case of general paresis (3) just discussed.

Juvenile Paresis^[36] is illustrated by a case with exceedingly extensive lesions, largely meningeal and parenchymatous. The cerebral lesions are atypical since in places they suggest the tuberous sclerosis of Bourneville. The brain atrophy is extreme (965 grams) and it is possible that this apparent brain atrophy was in part hypoplasia, since the spirochetosis of this case was doubtless congenital. However, clinically the patient was fairly normal up to the age of 18.

A case of so-called Syphilitic Extraocular Palsy^[37] demonstrates a characteristic meningeal process more extensive than the clinical symptoms would have indicated. In fact, focal clinical nerve palsies are as a rule, if not constantly, partial phenomena of a far more extensive process of neurosyphilis. They are far more limited clinically than anatomically and histologically. It seems at first sight improper to term them cases of diffuse neurosyphilis in view of their clinical focality, yet they are best described as partial cases of diffuse neurosyphilis.

A case of Gumma^[38] of the left Hemisphere is presented which appears to have led to death in about four years from onset. This case, like many others, is not an example of purely focalized syphilitic process inasmuch as cysts of softening indicating slight vascular insults are present elsewhere (pons). There is also a degree of leptomeningitis, particularly basal.

Our discussion of the nature and forms of neurosyphilis is completed by a rare case probably belonging in the so-called cervical hypertrophic meningitis of Charcot but actually due to a Gumma of the Spinal Meninges.^[39] The importance of therapeutic optimism is emphasized in this case as in the paradigm. Theoretically the meningeal inflammation of neurosyphilis ought to be almost entirely if not entirely removed by therapy, and these two cases, like several others in the series, seem to illustrate this possibility.

Neurosyphilis sometimes receives the clinical diagnosis neurasthenia simply through omission to apply proved diagnostic methods. An instance is given in which the Paretic form of Neurosyphilis (“general paresis”) received the diagnosis neurasthenia^[40] for a period of five years, at any time during which period it would doubtless have been possible to render the correct diagnosis and apply treatment.

Neurosyphilis may imitate not only the psychoneuroses but also the psychoses themselves. We present a case of an architect, which looked almost precisely like manic-depressive psychosis^[41] and had a history of attacks, but in which the positive serum W. R. led (in accordance with hospital rules) to an examination of the spinal fluid. The spinal fluid tests proved the case to be one of Paretic Neurosyphilis.

However, a positive serum W. R., even when associated with mental symptoms, and when those mental symptoms include grandiosity, does not prove the existence of neurosyphilis either in its paretic or non-paretic form. Our instance seems to be one of Manic-Depressive Psychosis.^[42] The spinal fluid tests were entirely negative. The course of the disease was also that of manic-depressive psychosis. In the absence of positive spinal fluid tests, the diagnosis neurosyphilis was excluded.

Neurosyphilis and even Paretic Neurosyphilis may result in symptoms that would ordinarily lead to the diagnosis dementia praecox.^[43]

It is important not to rule out neurosyphilis on the ground of a negative serum W. R. The fluid W. R. may turn out positive. We present a case (of a salesman)^[44] in which the serum W. R. was repeatedly negative (even salvarsan did not act provocatively) yet the spinal fluid W. R. proved positive. The case was clinically one of classical Paretic Neurosyphilis (“general paresis”). It is a good rule to proceed to lumbar puncture, even when the serum W. R. is negative, if there are suspicious symptoms (e.g., speech defect and memory impairment, grandiosity) or signs (e.g., marked reflex disorder, especially pupillary disorder).

Diffuse Neurosyphilis was above defined as “meningovasculoparenchymatous.” This disease is typically associated with six positive tests (positive serum W. R., positive fluid W. R., pleocytosis, gold sol reaction, positive globulin reaction and excess albumin). One or more and frequently several of these six tests are likely to run mild in diffuse neurosyphilis; that is to say, these tests are apt to run milder than the identical tests in paretic neurosyphilis (“general paresis”). The clinical course of the diffuse, and especially the meningovascular cases, is likely to be protracted. The prognosis as to life is good, barring fatal vascular insults. The illustrative case^[45] was a case with slow course. There was a series of attacks followed by a paralytic stroke, a finding highly typical of the diffuse form of neurosyphilis. The spinal fluid reactions were mild, suitable to the general principle above stated.

These tests are likely to run stronger, as above stated, in paretic neurosyphilis (“general paresis”), than in the diffuse form. In particular, the gold sol reaction is likely to be shown in what is termed “paretic” form rather than in what is termed “syphilitic” form. The clinical course of Paretic Neurosyphilis is likely to be brief. A characteristic case^[46] with very heavy globulin and albumin tests is presented.

Taboparetic Neurosyphilis^[47] (“taboparesis”) is clinically a combination of the symptoms of tabetic (“tabes dorsalis”) and those of paretic neurosyphilis (“general paresis”). First comes the tabes dorsalis lasting often for many years. Afterward follows a characteristic general paresis. The ultimate paretic picture is likely to retain, however, various characteristics of tabes. The laboratory tests in the paretic phase of taboparesis are characteristic of general paresis and not of tabes dorsalis. The prognosis after the paretic phase has arrived is that of general paresis.

The diagnosis of the neurosyphilitic forms would be easy if these principles were always carried out to the letter. The important fact is as follows: diffuse (that is, meningovasculoparenchymatous neurosyphilis) may look like paretic neurosyphilis (“general paresis”)^[48] at certain periods of the clinical and laboratory examination. This fact is of obvious importance. The general prognosis of diffuse neurosyphilis is regarded as good quoad vitam. The general prognosis of paresis is bad. If, however, the differential diagnosis cannot be rendered at particular phases of a given case, then no safe prognosis can be offered in the individual case. In particular no prognosis affecting the administration or non-administration of modern systematic treatment can or should be offered in these doubtful phases.

It is not always safe to exclude neurosyphilis even when the fluid W. R. is negative.^[49] Particularly in vascular neurosyphilis the fluid W. R. and even all the other laboratory signs in the spinal fluid may sometimes be negative. A positive serum W. R. yields the correct pointer to diagnosis. Of course, also in many cases of vascular neurosyphilis one or more of the laboratory signs may be suggestive even when the fluid W. R. is negative. Theoretically there may be cases in which all the six tests are negative and yet the diagnosis neurosyphilis be the correct one.

A clinically important sign in neurosyphilis is the so-called seizures. These occur both in Diffuse Non-paretic Neurosyphilis^[50] and in Paretic Neurosyphilis.^[51]

Aphasia is likewise a symptom in both these forms of neurosyphilis, namely, in the Diffuse non-paretic^[52] and in the Paretic form.^[53]

The literature contains reference not only to seizures and aphasia as characteristically paretic but also to remissions. Remissions like seizures and aphasia are found in both the Paretic^[54] and Non-Paretic forms of neurosyphilis.^[55] They have important bearings on prognosis in all forms of neurosyphilis and are of especial significance in the evaluation of treatment. (Remissions coincident with apparent cure.)

So far we have been dealing with cases of neurosyphilis in which there was no doubt of the existence of mental symptoms. There are cases, however, in which although the laboratory signs of neurosyphilis exist, proving beyond doubt the existence of a chronic inflammatory reaction and allied pathological conditions in the cerebrospinal axis, there are no mental symptoms of neurosyphilis. We have called some of these cases Paresis Sine Paresi^[56] and present examples.

To illustrate complications we give a case of Paretic Neurosyphilis with autopsy in which there were ante mortem signs of Herpes Zoster^[57] or, at all events, of a skin eruption limited to the area of a thoracic nerve.

A case of Gumma of the brain^[58] in which decompression was warranted and performed is presented. The fluid W. R., as in many such cases, was negative; serum positive.

A case of Cranial Neurosyphilis (extraocular palsy^[59] without mental symptoms) showed a positive Wassermann serum test and a negative spinal fluid.

The laboratory reactions in Tabetic Neurosyphilis^[60] (“tabes dorsalis”) run somewhat like those of diffuse non-paretic neurosyphilis and are accordingly milder than those of paretic neurosyphilis. The fluid W. R. and the gold sol reaction in particular are apt to run mild. The clinical course of tabes dorsalis is well known to be protracted and the prognosis quoad vitam is good except that we must always bear in mind the possibility of vascular insults and complications of a syphilitic origin in the rest of the body.

It is important to remember that Tabetic Neurosyphilis is often quite atypical^[61] clinically and may even show no single symptom warranting the old clinical name locomotor ataxia.

There are even cases in which the name tabes dorsalis is not warranted in view of the fact that the lesions are not low in the cord but are higher up (Tabes Cervicalis^[62]).

A rare form of neurosyphilis is Erb’s Syphilitic Spastic Paraplegia^[63] against which one needs to consider a number of non-syphilitic spinal cord diseases. Our case showed a weakly positive serum W. R., a negative fluid W. R., and the other tests of the spinal fluid were moderately positive.

Syphilitic Muscular Atrophy^[64] is classified by Head and Fearnsides both in their meningovascular group and in their group of the so-called syphilis centralis. Our case affecting in large part the small muscles of the hands in a teamster, may be due either to spinal parenchymal lesions or to root neuritis or to both.

It is a little extraordinary and very important that the laboratory signs are apt to be positive even in the Secondary period of Syphilis. Perhaps a third of all cases of syphilis in the secondaries would, if tested, yield positives precisely like those of full-blown paretic or diffuse neurosyphilis. Strangely enough, these signs may occur without clinical symptoms. The illustrative case,^[65] a mechanic, yielded various mental symptoms. The cases of secondary syphilis with laboratory signs of neurosyphilis but without clinical symptoms are of the greatest theoretical importance in relation to the problem above mentioned of paresis sine paresi. It may well be inquired whether in some instances the neurosyphilis of the secondaries does not persist until the exhibition of mental or physical symptoms of neurosyphilis years later. It must be remembered that this conception is hardly more than a hypothesis at the present time. That such signs of chronic inflammation could exist without symptoms is not so surprising when one thinks of the startling immediate improvement seen after treatment or even in remissions without treatment. One is reminded of the crisis in pneumonia wherein clinical improvement takes place entirely independent of the mechanical conditions in the lung which just after the crisis remain as suppurative as before.

The diagnosis of Juvenile Neurosyphilis is made upon the same lines as that of neurosyphilis in the adult. We present two cases, one with optic atrophy^[66] and the other with signs of congenital syphilis antedating the symptoms of paresis.^[67]

Congenital syphilis is also apparently capable of producing a simple form of Feeblemindedness,^[68] that is to say, a form of disease non-paretic, non-tabetic, and without special tendency to vascular insults.

We present a case of Juvenile Tabetic Neurosyphilis (“juvenile tabes”).^[69] The tests were all positive.

The line of separation between typical and atypical cases of neurosyphilis is vague and indistinct and some of the cases classified by us amongst puzzles perhaps belong under systematic diagnosis and vice versa. The section on PUZZLES AND ERRORS in the diagnosis of neurosyphilis is introduced by six cases of error in the diagnosis of the paretic form of neurosyphilis.^[70] These errors were made known by autopsy. Aside from the sixth case, whose etiology must remain in doubt and which was a unique case of Perivascular Gliosis, there is ground for the belief that the other five cases in this Danvers Hospital study of diagnostic errors were perhaps actually syphilitic though not of the paretic form of neurosyphilis. At all events, the brain tissues in these cases failed to show the plasma cell deposits which are characteristic in the sheaths of the intracortical vessels in paretic neurosyphilis.

A case illustrates the complication of Tabes by arteriosclerotic symptoms, in which case the arteriosclerosis may naturally have been of syphilitic origin. Two cases especially illustrate the possibility of confusing the ataxia of general paresis with Cerebellar Ataxia. These cases showed lesions of the cerebellar structures, notably of the dentate nucleus. No one can read these cases or any of the autopsied cases in our series, without perceiving how fundamental and even critical is the demand for autopsies in fatal cases of neurosyphilis. The practitioner who can secure an autopsy in a fatal case of neurosyphilis and have the tissues worked up by approved neuropathological methods is almost bound to add his bit to neurological theory. Even cases of classical tabes dorsalis are often signally important to the theorist on account of the relations of the neural to the non-neural complications.

We then proceed to a group of cases without special order in which a variety of diagnostic questions arose.

A case of questionable neurosyphilis in the secondary stage of syphilis brings up the problems of syphilitic neurasthenia.^[71]

Syphilis may act as agent provocateur of Hysteria as Charcot insisted.^[72]

A case illustrative of difficulties in diagnosis between neurosyphilis and manic-depressive psychosis follows.^[73]

A case for diagnosis is given which shows that errors in the diagnosis of neurosyphilis are entirely possible even when abundant clinical and laboratory data are available. A case with a weakly positive Wassermann reaction in the spinal fluid finally turned out to be one of Brain Tumor.^[74]

Some questions as to the diagnosis of Neurosyphilis versus Idiopathic Epilepsy are brought up by a case in which phenomena of paresis seemed to have occurred very early, about two years after the initial syphilitic infection.^[75]

A case of Paretic Neurosyphilis is offered in which hemiplegia and hemitremor strongly suggested vascular lesions; but the autopsy showed no coarse lesions and merely confirmed the diagnosis paresis microscopically.^[76]

An autopsied case of Paretic Neurosyphilis is given, in which the pupils persisted in reacting normally. Herpes zoster-like lesions in life yielded no special signs at autopsy (all root-ganglia looked alike above and below zone of “shingles.”)^[77]

An example of Neurosyphilis, probably Paretic, yielded symptoms highly suggestive of manic-depressive psychosis.^[78] An interesting feature in this case was the birth of a healthy child nine months after the onset of the psychotic attack.

An example of exophthalmic goitre^[79] following the acquisition of Syphilis showed at autopsy a heavy scarring of the optic thalamus and unilaterally atrophic process in the cerebral cortex.

We come to some questions concerning the Argyll-Robertson pupil. It is agreed on all hands that the Argyll-Robertson pupil is characteristic of the paretic and tabetic forms, but the sign occurs also in other neurosyphilitic conditions;^[80] in fact the sign does not necessarily indicate neurosyphilis as an instance of Pineal Tumor demonstrates.^[81]

The question raised above as to the possibility that neurosyphilis may exist in the absence of positive findings in the spinal fluid is illustrated in a man, a mechanic, who claimed syphilitic infection and showed an Argyll-Robertson pupil on one side.^[82] The serum W. R. was positive; the fluid tests were negative.

An extraordinary case is given in some detail in which Neurosyphilis in the form termed Disseminated Encephalitis^[83] proved fatal within seven months of the initial infection.

We have frequently mentioned the classical assumption that paretic neurosyphilis (“general paresis”) is a fatal disease. Some have suggested that there is another form clinically almost identical with general paresis except that it pursues a long course and the suggestion has been made that these cases be termed pseudoparesis.^[84] We are of the opinion that this term should be dropped and advocate the use of the word pseudoparesis only for non-syphilitic disease looking like paresis, such as alcoholic pseudoparesis and the like.

The question whether there is a form of mental disease Syphilitic Paranoia^[85] is raised by a case with auditory hallucinations, ideas of persecution and attacks of excitement. The diagnosis of alcoholic hallucinosis was actually made although there is no proof that the patient ever drank alcohol.

Alcohol may cause symptoms identical with those of paretic neurosyphilis, including seizures, Argyll-Robertson pupils, speech defect and mental symptoms. The differentiation is readily made by the negative laboratory findings. An illustration is given in our case of the alcoholic teamster. Cases such as this bear the name Alcoholic Pseudoparesis.^[86]

However, when the clinical picture is the same as in the case of our teamster, the alcohol may only be a complicating factor in neurosyphilis, as shown by our next case of the alcoholic steamfitter who in fact was shown to have Neurosyphilis.^[87]

Sometimes cases of apparently frank alcoholism, even with apparently characteristic delirium tremens and neuritis, prove to be essentially neurosyphilitic.^[88] On the other hand, true combinations of Alcoholism and Neurosyphilis occur which it would be proper to classify under either heading and in which therapy must take serious account of both conditions.^[89]

As above stated, we elect to use the term pseudoparesis only for non-syphilitic cases. There are other forms of pseudoparesis than alcoholic pseudoparesis. The question of Diabetic Pseudoparesis is raised by an exceedingly complicated case of which our best interpretation is that the patient, a proved syphilitic (with syphilitic osteomyelitis (?)), a huge doorkeeper, was perhaps suffering from an old Syphilitic scarring of the Pituitary body.^[90] Neither this case nor a second case, one of Paretic Neurosyphilis with glycosuria is actually entitled to the diagnosis diabetic pseudoparesis. The second case of paretic neurosyphilis with glycosuria brings up some unanswerable questions as to the pancreatic or basal meningitic or other origin for the glycosuria.^[91]

Isolated symptoms are often presented by neurosyphilitics (e.g., hemianopsia);^[92] but we tend to regard these cases as due to focal lesions that are merely part and parcel of Diffuse Lesions.

A neurosyphilitic case (a steward) with the rather unusual complication (for our northern region) of severe Malaria producing cerebral thrombosis is reported.^[93]

The diagnosis Dementia Praecox^[94] was actually made in the case of a young school-teacher in whom the laboratory findings proved conclusively that the condition was one of Neurosyphilis. The gold sol reaction in this case was mild. The chief lesion at autopsy was a fresh looking, gelatinous pial exudate over the spinal cord which turned out to contain an almost pure display of very numerous plasma cells.

The question of Lues Maligna^[95] is brought up in a rectifier of spirits in whom the characteristic tremendous destruction of tissue, toxemia and failure to react to antisyphilitic treatment were illustrated. Moreover, this case had a trauma (cautery) to the tonsil, as in other cases of lues maligna.

A case somewhat suggestive of brain tumor, of neurosyphilis and of multiple sclerosis^[96] turned out to be Multiple Sclerosis (the fluid showed a pleocytosis and a moderate amount of globulin with a paretic type of gold sol reaction).

As a foil to this case that we regard as multiple sclerosis, we present a second case with nystagmus, optic atrophy and spasticity in which the suspicion of multiple sclerosis might well be raised but which the tests demonstrated to be Neurosyphilitic.^[97]

An even stranger imitation of well-defined non-syphilitic entities was presented by a case apparently of Huntington’s chorea^[98] (except for absence of the hereditary taint) which case, however, proved to the surprise of all diagnosticians to be one of Neurosyphilis.

Frequent errors of diagnosis must occur in the field of the senile psychoses. We present a case that would at first blush warrant the diagnosis of senile arteriosclerotic psychosis^[99] in a sea captain of 75 years (wife dead 15 years before of general paresis) who turned out to be a characteristic case from the laboratory standpoint of Neurosyphilis.

The Protean nature of the symptomatology of neurosyphilis is sufficiently established. Still, a case that might fit into textbooks concerning Dissociation of Personality^[100] is certainly a clinical oddity, as illustrated by a fugacious musician.

A case with strong suspicions of neurosyphilis of tabetic type turned out to be more probably one of neural complications in Pernicious Anemia.^[101]

Neurosyphilis in Juveniles presents puzzling conditions.

One case was marked clinically by attacks of excitement.^[102] It is impossible to place this case among the main groups of juvenile neurosyphilis.

Another case of Feeblemindedness,^[103] also Neurosyphilitic in origin, presented physical symptoms and laboratory signs of paretic neurosyphilis; yet this case had been considered one of simple feeblemindedness.

A case apparently of Juvenile Paretic Neurosyphilis in a 15 year old boy presented the rather unusual complication of shocks with quadriplegia,^[104] a vascular complication not usually expected in the paretic type of neurosyphilis in adults.

Epileptic phenomena^[105] are rare as the effect of Juvenile Neurosyphilis, but occur as demonstrated in a case which slipshod methods of diagnosis might well have regarded as one of idiopathic epilepsy.

A case of Juvenile Paretic Neurosyphilis with the complication of Addison’s Disease^[106] is given (autopsy confirmation).

The puzzle in diagnosis offered by syphilis in the secondary stage^[107] is illustrated by a case which showed the characteristic Neurosyphilitic complications of the Secondary Stage of syphilis. This patient may well have been a moron at the outset and exhibited some reactions (refusal to talk) explicable on the basis of feeblemindedness. She was a neurosyphilitic only in the sense of the neural complication that we find in the secondary stage of syphilis. As stated above, we do not yet know what the fate of these neural complications of secondary syphilis is to be. The frequency of this finding in secondary syphilis is probably too great to warrant the hypothesis that it must always go on to a chronic neurosyphilis; but we certainly are warranted in regarding these cases as potential chronic neurosyphilitics.

A case of Taboparetic Neurosyphilis in which the heavy exudate characteristic of paresis became a soil for a growth of the typhoid bacillus is presented with autopsy.^[108] This fatality with Typhoid Meningitis is merely a concrete example of the many complications which syphilitics and especially neurosyphilitics have to sustain.

The case series then goes on to illustrate, though quite inadequately, a variety of MEDICOLEGAL AND SOCIAL complications of neurosyphilis. It is well known that many social complications with grave moral, economic and even political difficulties occur.

Our series starts with a “public character”^[109] whose eloquence and reformatory efforts led to a considerable notoriety. The autopsy in this case showed singularly few lesions despite the fact that the case was microscopically one of wholly characteristic Paretic Neurosyphilis. The question might arise how far we are entitled to correlate the reformatory efforts of this always eccentric character with syphilis. The man himself a physician, was aware of the doubt which his Argyll-Robertson pupils threw upon his medical situation. He explained them on the basis of an old smallpox! We are inclined to think that the whole of this man’s life, from his giving up of medical practice to live as a kind of literary and political hack, was due to subtle changes of neurosyphilitic origin. The fact that there was a certain delinquent streak in the man is not inconsistent with this idea. Interestingly enough, a fall on the ice in the man’s 61st year actually started up the fatal process, a condition of affairs amply illustrated in cases of neurosyphilis, brought out by trauma that come to the attention of the Industrial Accident Board in connection with claims for compensation.

A case of sudden grandiosity^[110] illustrates an episode of Neurosyphilitic origin. Such a person might well be regarded by the lay newspaper reader as a crank or a grafter but the neurosyphilitic possibility should always be entertained in cases of this order.

As against the social difficulties that look in the direction of the classical paretic grandeur, we present a case of apparent suicidal attempt by gas, which attempt was followed by a period of amnesia that, taking into account the laboratory findings, was probably Neurosyphilitic.^[111]

Vistas of extraordinary interest are opened out by studies of the relation of neurosyphilis to delinquency. The case of the psychopathic reformer (Case 83) above mentioned was one in which the delinquency may possibly have been related to acquired syphilis. We present also a case of juvenile neurosyphilis, a young man of reform school type^[112] in which Juvenile Paretic Neurosyphilis was established. This patient, in fact, deteriorated very rapidly to a condition of considerable dementia a few months after the diagnosis was established.

A striking case of so-called Defective Delinquency is presented, an alcoholic prostitute of the reformatory group.^[113] The Neurosyphilis in this case was a complication rather than an original factor in the delinquency.

One case of Paresis Sine Paresi was that of an habitual criminal^[114] and forger who, without showing mental or physical symptoms of neurosyphilis, yielded the laboratory signs of paretic neurosyphilis. Again, as in the case of the prostitute just mentioned, the Criminality^[115] seems to have antedated the neurosyphilis and even to have been hereditary.

The Industrial Board group is of note in that the signs of the traumatic form^[116] of paretic neurosyphilis do not occur immediately upon the accident. Some time elapses in which the physical, chemical or parasitological changes have time to work themselves out in the injured tissues. Many hypotheses may be raised as to the reason why a trauma lights up a syphilitic process. Of course, false claims^[117] may be made for compensation by neurosyphilitics in whom the symptoms were already in existence before the accident and in whom they may not even be markedly exacerbated by the accident. The false claimants can probably not readily frame a story which the expert psychiatrist cannot discredit if he is allowed to perform laboratory tests and give the patient the benefit of thorough examination. However, some cases of established Paretic Neurosyphilis are perhaps truly subject to exacerbations^[118] of the clinical process and it may well be held that such exacerbations warrant partial compensation.