CHAPTER IVGENERAL PARALYSIS
General paralysis of the insane, general paresis, or dementia paralytica, as it is variously known, from the standpoint of etiology, symptomatology and pathology, is unquestionably the most clearly differentiated and sharply circumscribed of the psychoses at this time. Its history, like its pathology, is inseparable from that of syphilis—a subject of never failing interest and importance, from the time of the first appearance of that word in a poem (Syphilidis, sive morbi Gallici) written by the Italian physician and poet Fracastoro in 1530. Guarinoni referred to epilepsies due to syphilis in the seventeenth century. Frequent allusions are made in the literature of that period to manifestations of the disease in the nervous system. Thomas Willis called attention to the association of paralysis with mental disorders as early as 1672. A form of mania due to syphilis was described by Sanché in 1777. Jelliffe found references in literature to a specific leptomeningitis in 1766 and paraplegias in 1771. Haslam, a pharmacist at the Bethlem Hospital, is said to have given a fairly accurate description of general paresis in 1798. A French writer, A. L. Bayle, is usually spoken of as having clearly differentiated the disease in 1822. The work of Calmeil, "De la Paralysie Consididérée chez les aliénés," in 1826, was, however, the first elaborate monograph ever written on this important psychosis and established its recognition as an entity. Griesinger looked upon it as a combination of different mental conditions. Esquirol is credited with having been the first to describe the speech defect nowconsidered such an important symptom. Baillarger is said to have introduced the term dementia paralytica in 1846.
The etiology of the disease was a subject of controversy for many years. The early writers ascribed it to sexual excesses, masturbation, alcoholism, heredity, overwork, and various other causes. It was looked upon by some as one of the sequelae of syphilis and was described as a "meta syphilitic" disease by Möbius and a "para syphilitic" disorder by Fournier. It was noted by many as occurring only in the more intellectual and highly developed races and was therefore referred to by Krafft-Ebing as a disease of "syphilization and civilization." Both Bayle and Esquirol mentioned syphilis very casually in their writings. Sandras in 1852 spoke of it as one of the principal causes of general paresis. Its etiological importance was, however, first given serious consideration by Esmarch and Jessen, prominent Danish writers, in 1857. Their views were corroborated by Steenberg in 1860 and by Kjellberg in 1863. The theory of an exclusively specific origin was not generally accepted, however, for many years. Rieger published elaborate statistics in 1886 showing that the incidence of general paresis was sixteen or seventeen times as great in syphilitics as it was in healthy persons. The fact that a definite history of infection was not available in many cases led to considerable doubt. Such eminent authorities as Charcot, Binswanger and Déjerine went so far as to deny that there was any relation between the two diseases. That some uncertainty was warranted by the information at hand is shown by the fact that Kraepelin[169]found a history of syphilis in seventy-eight per cent of his cases, while Sprengeler reported 41.5 per cent, Räcke 57.3 per cent, Torkel fifty-one per cent, Marcus seventy-six per cent, Houghberg 86.9 per cent, and Alzheimer over ninetyper cent. This is not at all surprising in view of the statement made by Kraepelin[170]that Hirschl could find a definite history of an initial lesion in only thirty-six per cent of his cases of tertiary syphilis. Hudovernig found that 42.3 per cent of the women suffering from syphilis did not know when they were infected. In discussing this subject in 1897 Krafft-Ebing reported the inoculation of nine paretics with syphilitic virus without the appearance of luetic symptoms in any instance, although reinfections have been mentioned by other authorities.
One of the first advances which contributed materially to the ultimate solution of the general paresis problem was the study of the cerebrospinal fluid by Widal, Sicard and others after the introduction of lumbar puncture by Quincke in 1890. This led eventually to discoveries which were of great diagnostic importance. The isolation of the spirochaeta pallidum, now known as the treponema pallidum, by Schaudinn in 1905 settled the question for all time as to the cause of syphilis. The adaptation of the principle of complement fixation, the so-called Bordet-Gengon phenomenon, to the study of syphilitic fluids by Wassermann, Neisser and Bruck in 1906 practically removed all doubt as to the relation between that disease and general paresis. The demonstration of the treponema in the cortex of paretics by Moore and Noguchi in 1913 was practically the only other contribution necessary. They have since been found in the cerebrospinal fluid. Notwithstanding the fact that general paresis must now be looked upon as being a manifestation of syphilis beyond all peradventure of a doubt, it is nevertheless true that we are unable to explain why that disease does not always yield to specific treatment. This is undeniably the case at this time. Just why this should be so cannot be explained in the light of our present knowledge. It is, however, presumably for the same reasonthat tabes and other diseases of the cord and nervous system, the specific origin of which cannot logically be questioned, are equally resistant to salvarsan and mercury, whatever that reason may be.
As soon as the findings of the Wassermann reaction became evident, renewed efforts on the part of clinicians to find a cure for general paresis naturally followed. One of the first suggested was the Swift-Ellis treatment. This was based on the injection of salvarsanized blood serum into the subdural space of the spinal canal. Results were exceedingly encouraging for a while, but time showed that this was not the solution of the problem. Intravenous salvarsan administration was next tried. This, too, gave excellent results at first. The cases which were apparently cured, however, eventually relapsed sooner or later in almost every instance. The intraspinous use of salvarsan in minute doses has been no more successful than the Swift-Ellis method. Intracranial subdural treatments have been tried and salvarsan has even been injected directly into the lateral ventricles. The logical conclusion is either that the destruction of the nervous tissue has already reached a stage which is beyond repair or that the treatment does not reach the site of the disease.
Clinically we are on much safer ground. In his third edition Krafft-Ebing[171]referred to dementia paralytica as "periencephalomeningitis diffusa," the term originally employed by Calmeil. "Clinically this disease is manifested as a rule as a chronic disease of the brain with vasomotor, psychic, and motor, functional disturbances, progressive in course, with a duration of from two to three years and nearly always a fatal termination."
Régis,[172]before the cause of the disease was definitelydetermined, defined general paralysis as a "cerebral disorder, sometimes cerebro-spinal (diffuse chronic interstitial meningo-myelo-encephalitis) essentially characterized by progressive symptoms of dementia and paralysis (paralytic dementia) with which are frequently associated various accessory symptoms, and especially an insanity of the maniacal, melancholic, or circular type (paralytic insanity)."
Since the time the disease was described by Bayle, general paresis has usually been spoken of as being represented clinically by three different stages. White[173]speaks of a prodromal period, one of full development and a terminal stage. In the first period he emphasizes the importance of physical symptoms, more particularly the oculomotor and tendon reflex disturbances. These include the sluggish reaction to light (28.3 per cent) or an actual Argyll-Robertson pupil (45 per cent), with an increased, decreased or absent knee-jerk, the exaggerated form being the most common. The mental symptoms may be entirely overlooked in the first stage. There is a gradual progressive deterioration of the personality, with a loss of efficiency, impairment of memory, and failure of judgment. There may be episodes of excitement, depression or delirium, with or without hallucinations and delusions, the latter being either hypochondriacal or grandiose. "The demented type, without marked delusions or sensory falsifications, is the truly typical variety of the disease and the dementia the basal element of all forms" (White). There may be an incipient speech disorder and beginning tremor.
Characteristic of the second stage is a marked increase of the physical symptoms already described, together with the appearance of seizures. Muscular weakness develops and the patient often shows a marked gain in weight. The mental symptoms are merely an exacerbationof those shown in the first stage. The expansive variety constitutes the classic form so often spoken of. There may be agitations, depressions, alternations of these symptoms or even paranoid forms.
In the third stage there is a continued exaggeration of the physical signs of the disease with an advancing mental deterioration. The patient becomes helpless and practically speechless, contractures and bedsores develop, and death often occurs as the result of an unusually violent seizure. The description of this disease in the three traditional stages so often referred to is practically without significance and of very questionable value. It is, of course, a well-known fact that the disease may progress rapidly to a termination in two or three years or may continue for an almost indefinite period of time. It may manifest itself, furthermore, in various ways. The physical signs show much greater constancy than the mental symptoms.
Kraepelin[174]describes demented, depressed, expansive and agitated forms of general paresis. The "demented" form he finds to be much more common than the others. This is characterized by a progressive mental deterioration with "paralysis." The onset is marked by a poverty of thought, forgetfulness, moodiness, instability and indifference. Consciousness gradually becomes somewhat clouded and the patient more or less disoriented. Transitory delusions supervene. These are of a depressive type, somatic or expansive in nature. The delusional ideas as a general rule are rather childish. Memory disorder becomes conspicuous and delirious excitements occur at times. All of this leads to a gradual deterioration. Speech defects appear sooner or later and conduct disorders are common. Kraepelin finds that fifty-three per cent of his Heidelberg cases were of the demented form. At Munich they constituted fifty-six per cent ofthe men and seventy-three per cent of the women. Forty-four per cent of the cases died within the first two years.
The "depressive" form of paresis as described by Kraepelin is characterized by emotional depression or anxiety with delusions of various kinds. It may begin with a general sensation of illness and a gradual weakness of memory or intellect followed by symptoms of mental dulness. The unpleasant ideas are hypochondriacal in nature and often of an extravagant type. The delusions are quite frequently somatic in origin. Sometimes these are associated with self-accusation or there may be complaints of persecution. Hallucinations occur at times. In spite of this deplorable state of affairs a marked indifference on the part of the patient is the rule. Excitement, violence or suicidal impulses nevertheless occur, and stuporous states are described. Kraepelin found that the depressive form constituted twelve per cent of his cases at Heidelberg. He is of the opinion that the duration is short, much more so than in some of the other types of the disease. Fifty-eight and six-tenths per cent died within the first two years. Convulsions, however, were less frequent.
The "expansive form," according to Kraepelin, may begin with an initial depression or show excitement early. Megalomanic symptoms of the most extravagant variety soon appear. The marked mental weakness is, however, very manifest. Hallucinations of sight and hearing are frequently present but transitory. The mood is usually happy, although hypochondriacal ideas occur for short periods now and then. Excitability is more common, sometimes with unusual violence. The course tends to a complete deterioration, with occasional exacerbations of excitement. Kraepelin found that the expansive form constituted about thirty per cent of his Heidelberg cases. Convulsions were less frequent and remissions more common than in other types. He found that this form of thedisease, moreover, occurred later in life. Forty per cent died within the first two years. Some cases, on the other hand, were of long duration; one of seven, another of eight, and one of fourteen years. He also noted mixed varieties with alternations between excitement and depression.
The "agitated" form as described by Kraepelin is that type in which extreme excitements predominate. It is often of sudden onset. Grandiose ideas, even more extravagant than those of the expansive form, appear. A flight of ideas may be observed at times and stupor often intervenes. The most severe cases are those which have been referred to by some writers as "galloping" paresis. An actual delirium may lead to an early termination in death. The agitated type constituted 6.3 per cent of Kraepelin's cases. He finds this condition somewhat analogous to the delirious states due to alcoholism.
Remissions are more common in the agitated and expansive forms of the disease and may vary in duration from a few months in some instances to one of fourteen years reported by Dobrschansky. Nissl confirmed the diagnosis of paresis at autopsy in a case observed by Tuczek which had been stationary for nearly twenty years. Alzheimer reported another with a known duration of thirty-two years. Kraepelin has found, however, that fifty per cent of his paretics die within the first two years. He reports unequal pupils in from fifty to sixty per cent of those examined. He also finds that pupillary irregularity is one of the earliest physical signs in many individuals. Complete loss of light reaction was found in from fifty to sixty per cent of all cases, with a reduced range of reaction in from thirty to forty per cent. He found epileptiform or other attacks present in from thirty to forty per cent of those studied. Decreased or absent patellar reflexes were noted about twice as often as were increased reflexes. In from two-thirds to three-fourthsof all cases he found both the posterior column and lateral tracts of the cord involved.
The characteristic physical signs noted in all textbooks are described in detail by Kraepelin[175]as common to all of the clinical forms of the disease. The inequality, irregularity and immobility of the pupils, the speech defect, difficulty in writing, tremor of the lips, facial muscles and tongue, the marked changes in both superficial and deep reflexes, the alterations in the gait, the muscular incoordination, the presence of the Babinski reflex or ankle clonus, the sensory, motor, vasomotor and trophic disturbances constitute a combination of physical signs which is to be found practically nowhere else within the domain of psychiatry. The seizures, either epileptiform, apoplectiform or resembling syncopes, are almost pathognomonic when taken into consideration with the physical signs alone.
The pressure of the cerebrospinal fluid is from three to five times as great as in normal individuals. The albumen content of the fluid is increased about six times (Kraepelin). The increase in the globulin content has been very frequently referred to in the literature of general paresis. Kraepelin states that it also occurs in tabes, syphilis, brain abscess, occasional cases of extra medullary tumors, multiple sclerosis and in some infectious diseases. He attaches a great deal of importance to the increase in the cellular elements of the spinal fluid. "Cases with repeated normal findings are so rare that the correctness of the diagnosis may be justly doubted." The Wassermann findings no longer require comment. The colloidal gold test of Lange is equally well known. Nowhere else in psychiatric procedure does the laboratory render such valuable diagnostic assistance as is the rule in cases of general paresis. A positive Wassermann reaction in the spinal fluid, the presence of an increasein the albumen and globulin content, with a marked lymphocytosis in the cerebrospinal fluid and a positive gold test, is quite sufficient evidence on which to base a definite diagnosis. The results of an examination of the spinal fluid for diagnostic purposes at the time of autopsy are highly unreliable. An increase in the cell count, which may be misleading, is found in the spinal fluid of non-paretics in all cases after death. The number of cells depends entirely on the time of examination. It is not at all unusual to find from one to three hundred per cubic millimeter when a count is made from twenty-four to forty-eight hours after the death of the patient.[176]Another interesting fact is that the presence of sugar always shown by Fehling's solution during life cannot be demonstrated postmortem, at least after the lapse of a few hours.[177]The significance of this change is not clear. Nor is the increase in the globulin content of the spinal fluid, when taken alone, pathognomonic of either general paresis or syphilis, as was pointed out in 1909.[178]One of the most elaborate studies ever made of the spinal fluid, that of F. W. Mott, shows that this increase is due to degenerative processes of the nervous system which may be due to a variety of causes.[179]
In no other psychosis do we find such clear-cut pathological findings at autopsy as are readily demonstrable in general paresis. We are very largely indebted to the exhaustive researches of Nissl and Alzheimer, (1904)[180]for our information on this subject. Macroscopicallyadhesions of the dura to the calvarium and of the pia to the cortical substance are quite common. Opacities of the meninges are practically always present. Pachymeningitis hemorrhagica, externa or interna, is common, often with the formation of extensive hemorrhagic membranes. Ependymitis may be readily observed in the floor of the fourth and lateral ventricles. There is usually a reduction in the general brain weight, with atrophy of various parts, usually one side or the other of the cerebrum. The sulci are widened and the frontal lobes are often noticeably smaller in size. Less frequently the temporal, parietal or occipital regions are affected. Often there are localized foci of atrophy with cyst formation. The ventricles are frequently widely dilated, with an increase of cerebrospinal fluid.
Microscopic examination always shows a more or less diffuse leptomeningitis with a markedly thickened pia infiltrated with lymphocytes and plasma cells. In the superficial layers of the cortex there is a neuroglia proliferation with characteristic "spider cells." There is an obvious disturbance of the normal layering of the cortex which is very striking. The adventitia of the vascular walls shows an extensive infiltration by lymphocytes and particularly by plasma cells which are often very numerous. Rod cells or "stäbchenzellen" as described by Alzheimer are very noticeable as are also satellite cells or free nuclei. The neurones are often diminished in number and frequently show the "acute" or "grave" alterations described by Nissl, as well as shrinkage, sclerosis, pigmentary deposits, vacuolization, etc. The characteristic axonal alteration originally described by Turner as occurring in central neuritis is sometimes observed. Degeneration of the nerve fibres may be brought out by proper staining processes. Intimal thickening of the vessel walls and a capillary proliferation or budding should also be mentioned. Foci of softeningsometimes are to be found in the cortex. The presence of occasional gummata is now conceded, although formerly denied by Alzheimer. The changes in the cerebellum are not essentially different, but are usually not so conspicuous. In the cord a pachymeningitis and leptomeningitis are usually present, as well as the vascular changes described above. The important findings, however, are the degeneration of the posterior columns and lateral tracts, or mixed forms involving both of these. Owing doubtless to defects in staining technique, the demonstration of the treponema is difficult and unsatisfactory. It must be admitted that some of the above histopathological changes in themselves, the cell alterations, for instance, do not, when considered alone, prove the existence of general paresis. The whole picture as shown by the microscope, however, leaves no room for argument. The postmortem diagnosis is absolutely conclusive.
A consideration of the subject of general paresis without some reference to the juvenile form, first described by Clouston in 1877, would be manifestly incomplete. Although this term may be applied to a type of the disease acquired in childhood, it is usually used as referring to hereditary syphilis. Symptoms generally appear at or before the age of puberty. As a general rule the child is more or less defective mentally from birth, although this is not always true. Ordinarily the course of the disease is one of progressive deterioration, with an occasional episode of excitement. Convulsive seizures are frequent, and contractures are often noted. These cases are likely to be mistaken for idiocy and overlooked. The duration usually extends over a period of several years. The pathology is practically the same as that of the adult form of the disease. Almost invariably a positive Wassermann is obtained on examining the blood of the parents. It is equally interesting to notethat the children of syphilitic parents often show a positive Wassermann reaction without any evidence of paresis, or at least for some time before it develops.
The only question remaining at this time is whether general paresis and cerebral syphilis are separate and distinct disease entities. For many years this was held to be the case. Certainly gummata and other syphilitic processes are to be found in the brain where there is no such pathological picture as characterizes general paresis. In any event the latter must be recognized as a very well defined form of syphilis of the nervous system. In view of the very definite etiology, symptomatology and pathology of general paresis, the various clinical differentiations of Kraepelin and other writers are looked upon by many as not being of very great importance. In any and all clinical types, however described, we are unquestionably dealing with the same sharply circumscribed disease process. This subject is one of academic interest only.
The American Psychiatric Association in its classification of psychoses made no attempt to differentiate types. For purposes of statistical study the following suggestions appear in the manual:—
"The range of symptoms encountered in general paralysis is too great to be reviewed here in detail. As to mental symptoms, most stress should be laid on the early changes in disposition and character, judgment defects, difficulty about time relations and discrepancies in statements, forgetfulness and later on a diffuse memory impairment. Cases with marked grandiose trends are less likely to be overlooked than cases with depressions, paranoid ideas, alcoholic-like episodes, etc.
"Mistakes of diagnosis are most apt to be made in those cases having in the early stages pronounced psychotic symptoms and relatively slight defect symptoms, or in cases with few definite physical signs. Lumbarpuncture should always be made if there is any doubt about the diagnosis. A Wassermann examination of the blood alone is not sufficient as this does not tell us whether or not the central nervous system is involved."
A study of the statistics of the thirteen New York state hospitals in the "pre-Wassermann" days and before we had acquired our present accurate knowledge of the pathology of general paresis shows that there were 84,152 admissions during the fourteen years ending on October 1, 1888. Of this number 5,697, or 6.76 per cent, were diagnosed as general paresis. In the same hospitals, from 1912 to 1919 inclusive, 6,374 cases of general paresis were reported,—12.71 per cent of the 49,640 first admissions. During the years 1918 and 1919 that disease constituted 13.19 per cent of all admissions. This apparent increase undoubtedly is due to the fact that modern methods have materially improved facilities for accuracy of diagnosis. It is not at all probable that the admission rate has doubled during the period in question for any other reason. In the Massachusetts hospitals during the year 1919, only 7.90 per cent of the first admissions were diagnosed as general paresis. There was, however, an unusually high rate of cerebral syphilis. In twenty-one hospitals in fourteen other states, reports based on the present classification show a total of 18,336 admissions, mostly in 1917, 1918 and 1919. Of this number 1,233, or 6.72 per cent, were cases of general paresis. Thus, in a total of 70,987 admissions based on the present classification of psychoses as used by the American Psychiatric Association there were 7,845 cases of general paresis in all,—a percentage of 11.05. It is, of course, a well-known fact that general paresis is largely a psychosis of densely populated communities. This is readily shown by the New York statistics. During the year 1919, 9.6 per cent of the admissions at Binghamton were cases of general paresis. The percentage at Buffalo was 15.5; at Gowanda, 17.3; Hudson River (Poughkeepsie), 9.0; at Middletown,3.7; Rochester, 8.6; St. Lawrence (Ogdensburg), 9.2; Utica, 10.1; and Willard, 13. In the institutions caring for the insane of New York City 16.3 per cent were reported at the Manhattan State Hospital, 13.5 per cent at Kings Park, and 14.7 per cent at Central Islip. The percentage at the other institutions, except at Buffalo and Gowanda, which care almost entirely for residents of the city of Buffalo, is determined very largely by the transfer of patients from the hospitals of New York City and the metropolitan district. General paresis constitutes approximately ten per cent of the commitments in the city of Boston. On the other hand, we find an admission rate of 2.3 per cent for the Vermont State Hospital (1917 and 1918), 1.5 per cent for the Central State Hospital, Virginia (1919), 2.5 per cent for the Columbia State Hospital (South Carolina) (1918), and a period of two years at the Spencer State Hospital, West Virginia (1917 and 1918) with 262 admissions and no cases of general paresis. Of 2,895 first admissions reported by the Ohio state hospitals for the year ending June 30, 1920, 438, or 15.12 per cent, were cases of general paresis. It is interesting, at least, to note that Letelier[181]showed an admission rate for this disease of seven per cent at the Casa de Orates at Santiago, Chili.