Part 34

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.