Apprehension is much disturbed and memory weakened, in the advanced cases of deterioration. The patients cannot remember anything for more than a short time. They become disoriented as to time, place and person and forget their own names. Genuine "confabulation" sometimes appears. There are often confusional and delirious states. The mood is frequently depressed or anxious, sometimes irritable or quarrelsome and at times humorous. There is a group of cases showing genuine depressions, usually with hypochondriacal delusions, sometimes with delusions of persecution, self-accusation, and ideas of sinfulness. Even delusions of grandeur are observed. Hallucinations are not infrequent in these cases. States of excitement may intervene with occasional delusions and confused attacks. These excitements are usually of the agitated, restless type, sometimes with suicidal inclinations. Stuporous or even cataleptic states may follow. In the highest forms of excitement sensory or motor aphasia may develop, often with speech disturbances, sometimes of a genuine scanning type. Paraphasias are common. The writing is ataxic or paragraphic. Ideational or motor apraxia often is a symptom. Cyanoses and other evidences of general arteriosclerotic involvement appear. There may be an albuminuric retinitis. Albumen and sometimes sugar appear in the urine. The radials and temporals are thickened or hardened and cardiac murmurs are often found. Blood pressure is greatly increased in many instances, although Romberg found it in only ten per cent of his cases. Sleep is usually interfered with to a marked degree.
In a certain number of the more advanced cases of arteriosclerosis late epilepsies appear. The attacks usually begin between the forty-fifth and sixty-fifth years. There may be fainting spells or genuine convulsions recurring at frequent intervals. These may be associated with brief periods of delirium or may even occur without loss of consciousness. Forgetfulness and mental enfeeblement soon appear in such cases. They also show physical changes with tremors, disturbed reflexes, paralyses, increased blood pressure, etc. Alcoholism seems to be a strongly predisposing factor in this form of arteriosclerotic disorder. Kraepelin found that the epileptic attacks almost invariably appeared in cases which showed a previous history of alcoholic excesses.
In nearly half of his cases Kraepelin found apoplectiform attacks appearing without any marked psychosis preceding them. In some instances no mental symptoms appeared for many years. The attacks were, however, immediately followed, usually, by periods of confusion and clouding, sometimes of excitement and violence. The acute disturbance as a rule subsides rather quickly and clears up partially or completely. Usually there remains a memory defect, an increased fatigability and a depressed or irritable mood. These he refers to as cases of apoplectic deterioration or mental enfeeblement. Recurrent apoplectiform seizures may result in excitement, depressions or deliria. Gradual progressive deterioration is the usual picture. As a general rule the cases with marked excitements, depressions and deliria are of short duration and have a bad prognosis.
Kraepelin finds that the arteriosclerotic psychoses appear a decade earlier than the senile psychoses. Less than one per cent developed at the age of forty; 2.7 per cent at forty-five; 3.7 per cent at fifty; 7.4 per cent at fifty-five; twenty-two per cent at sixty; twenty-two per cent at sixty-five; 18.57 per cent at seventy; twelve per cent at seventy-five, etc. In the cases observed at a particularly early age he believes heredity to be a very important factor. Seventy-one and five-tenths per cent of his cases were men. Sixty-two per cent of the men and fifty-three per cent of the women were less than sixty-five years of age. The epileptic and demented forms appear earlier than the apoplectiform variety. Arteriosclerotic involvement of the smaller vessels occurs earlier than that of the larger arteries. Kraepelin found alcoholism more common in the history of his cases than syphilis. He is uncertain whether specific infections can produce a genuine arteriosclerosis or not.
Erb has shown that by the experimental injection of adrenalin into the blood stream artificial arteriosclerosis can be produced, with an increase of blood pressure, splitting of the elastica, thickening of the vessel walls and aneurysm formation. Thoma considers alcohol, tobacco, coffee, tea, and infectious poisons important causes. Cramer found the disease more common in innkeepers, actors, directors, officers, bankers and parliamentarians. Alcohol, syphilis, overwork and high living are important etiological factors. Kraepelin assumes the existence of certain metabolic products in the blood, possibly the result of infections which affect blood pressure and the structure of the vessel walls during a period of lowered resistance.
The pathological changes associated with the arteriosclerotic psychoses are quite clearly demarcated. Clinical differentiations, however, are not so well established. There is some question as to the justification of the separate entities into which Kraepelin would divide the arteriosclerotic processes. For statistical purposes the Association's committee felt that a determination of the frequency of occurrence of the arteriosclerotic group as a whole is all that should be attempted at this time. The following suggestions were offered in the manual as to the delimitations of these conditions:—
"The clinical symptoms, both mental and physical, are varied depending in the first place on the distribution and severity of the vascular cerebral disease and probably to some extent on the mental make-up of the person.
"Cerebral physical symptoms, headaches, dizziness, fainting attacks, etc., are nearly always present, and usually signs of focal brain disease appear sooner or later (aphasia, paralysis, etc.).
"The most important mental symptoms (particularly if the arteriosclerotic disease is diffuse) are impairment of mental tension, i.e., interference with the capacity to think quickly and accurately, to concentrate and to fix the attention; fatigability and lack of emotional control (alternate weeping and laughing), often a tendency to irritability is marked; the retention is impaired and with it there is more or less general defect of memory, especially in the advanced stages of the disease, or after some large destructive lesion occurs.
"Pronounced psychotic symptoms may appear in the form of depression (often of the anxious type), suspicions or paranoid ideas, or episodes of marked confusion.
"To be included in this group are the psychoses following cerebral softening or hemorrhage, if due to arterial disease. (Autopsies in state hospitals show that in arteriosclerotic cases softening is relatively much more frequent than hemorrhage.)
"Differentiation from senile psychosis is sometimes difficult particularly if the arteriosclerotic disease manifests itself in the senile period. The two conditions may be associated; when this happens preference should be given in the statistical report to the arteriosclerotic disorder.
"High blood pressure, although usually present, is not essential for the diagnosis of cerebral arteriosclerosis."
In the 49,640 admissions to the New York state hospitals during a period of eight years the 2,318 cases diagnosed as psychoses with arteriosclerosis constituted 4.67 per cent of the total number. In twenty-one hospitals in other states there were 18,336 admissions, of which 492, or 2.68 per cent, were cases of arteriosclerosis. On the other hand, the Massachusetts hospitals show 9.63 per cent of their first admissions during 1919 as arteriosclerotic psychoses. There would appear to be no way to harmonize these dissimilar findings unless it is merely a question of differentiation between the senile psychoses and those due to arteriosclerosis. In a total of 70,987 admissions to all institutions, there were 3,100 cases of arteriosclerotic psychoses, a percentage of 4.36. It is worthy of note that in all of the various groups of institutions the percentage of senile and arteriosclerotic cases combined is practically the same. This would strongly suggest varying standards of diagnosis which will undoubtedly be reconciled in time. It is only recently that any great amount of attention has been given to the psychoses due to arteriosclerosis and it must be confessed that there has been entirely too great a tendency to dismiss without further interest as senile psychoses all mental disturbances occurring in persons of advanced years. On the other hand, the custom of basing a diagnosis of arteriosclerotic psychosis on the mere presence of an increased blood pressure without the existence of any of the other symptoms which characterize that condition indicates, if nothing else, the necessity of a greater uniformity in our methods of diagnostic procedure.
CHAPTER IV
GENERAL 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 now considered 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 ninety per 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 reason that 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 definitely determined, 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 exacerbation of 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 of the 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 the disease, 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-fourths of 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 increase in 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. Macroscopically adhesions 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 softening sometimes 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 note that 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. Lumbar puncture 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.
CHAPTER V
THE PSYCHOSES WITH CEREBRAL SYPHILIS
The indications are at the present time that the psychiatry of the future will not deal with a consideration of general paralysis and cerebral syphilis, as such, but will differentiate preferably between parenchymatous and interstitial, or mesoblastic, syphilitic processes of the nervous system. The retention of the designation general paresis is little, if anything, more than a concession to the claims of tradition. Cerebral syphilis may be said in a general way at this time to include all syphilitic involvements of the brain other than general paresis, which must be accorded the precedence due to priority of recognition if nothing else. In the light of our present knowledge we may speak in rather definite terms in considering cerebral syphilis from the standpoint of pathology. On an anatomical basis it is usually divided into three forms,—the meningitic, the endarteritic and the gummatous types. It is, of course, not to be understood that these represent separate and distinct processes. Combined forms are nearly always to be expected and the different types practically always coexist more or less.
The onset of the disease may be expected anywhere from one to ten or even fifteen years from the date of the initial lesion. The early appearance of cerebral symptoms would indicate brain syphilis as a general rule rather than general paresis. Oppenheim[182] in his second edition says that cerebral syphilis often develops within a year after infection, a majority of the cases being noted within two years. He finds it a very rare occurrence after ten years. "Because," as Barker[183] puts it, "of the lawlessness of the occurrence of syphilitic lesions in the central nervous system, all clinical classifications of these cases are based only on the predominance of certain associations of lesions." Certainly the pathology of the disease is quite varied in its manifestations.
The meningeal form is the one most often encountered. This may appear on the convexity or on the base of the brain and is spoken of as being either localized or diffuse in character. It may or may not be associated with gummatous formations or cortical vascular involvement. The essential process is a leptomeningitis. The pia is thickened, opaque and adherent to the cortex. The microscope shows the presence of inflammatory elements consisting largely of lymphocytes and plasma cells which may be confined entirely to the meninges or may extend downward to the superficial cortical layers directly or by extension along the adventitial sheaths of the vessels. An examination of the cortex, however, shows a limitation of this invasion to the immediate neighborhood of the meninges. The cortical involvement, in other words, is entirely secondary and is not the important part of the pathological picture that it always is in general paresis. The meningeal condition is practically the same in the two diseases but more likely to be localized in syphilitic processes. Dunlap[184] calls attention to the important fact that in a group of cases occurring many years after infection he found involvements of the deeper cortical layers strongly suggesting general paresis pathologically and impossible of differentiation clinically. In these cases, even in the deep cortical vessel walls, occasional lymphoid and plasma cells were found, as well as typical syphilitic endarteritis in some instances. There is frequently, in addition to the simple meningeal involvement at the base, a widespread gummatous infiltration of the pia-arachnoid or in some instances numerous miliary granulomas. This is especially common in the region of the chiasm and may involve the origin of various cranial nerves, obviously in such cases determining the symptomatology to be expected. The optic and oculomotor nerves particularly are affected. The large vessels at the base are often involved either by syphilitic inflammatory processes or by direct invasion of their walls by gummas. An extensive specific meningo-encephalitis may lead either to foci or extensive areas of actual softening.
The endarteritis which occurs in syphilis is characteristic and diagnostic. This has been studied exhaustively by Heubner. The smaller vessels show an infiltration of lymphoid and plasma cells in their adventitia, as well as in the perivascular lymph spaces. The larger vessels show a great thickening of the intima which is consecutive, or, as Lambert described it, "girdling" in character. This is associated with a splitting of the membrana elastica. The proliferated intimal tissue is very susceptible to degenerative processes. Thrombosis and the formation of anemic infarctions may follow the obliteration of the vascular channels. The involvement of the larger vessels may lead to very distinctive focal symptoms. Thus, as Barker[185] has pointed out, there may be an obliterating process in the middle cerebral with hemiplegia and aphasia, invasion of the basilar artery with pontile or bulbar symptoms, or an involvement of the posterior cerebral may lead to hemianesthesia or hemianopsia, while an affection of the vertebral may show a unilateral bulbar paralysis with hemianesthesia of the same side and a hemiplegia of the opposite side. The extensive involvements of the base are usually meningeal, with gumma formation and with a secondary endarteritis in addition. Large solitary gummata may, moreover, occur practically anywhere in the brain, although they are somewhat unusual. On microscopical examination they show a characteristic infiltration of the periphery and a caseous center. They are more likely to occur in the course of a large vessel.
The symptomatology of brain syphilis necessarily varies with the nature, extent and location of the lesion. In the earlier stages of a diffuse meningitis the prominent symptoms to be expected first are headache and dizziness. In an individual with a definite specific history a persistence of such symptoms should suggest salvarsan therapy. Vomiting is a common complication. Cranial nerve palsies, optic neuritis or hemiplegia in such a case would, of course, be conclusive. Stuporous, confused or delirious states may occur, with or without hallucinations. When the syphilitic process is an extensive one with a widespread meningitis or gummatous involvement of the base, numerous focal symptoms are to be expected. Choked disc, optic tract lesions, paralysis of the ocular muscles, facial neuralgias, facial palsies, deafness, or anesthesias may occur. Mental deterioration naturally advances with the progress of the disease, but the personality is much better preserved than in general paresis. Periods of unconsciousness are not infrequent and convulsive attacks may appear. These may be general or local and paralyses often follow. These may assume the form of a hemiplegia or may involve only certain groups of muscles. Ptosis is often noted. Paralysis of other eye muscles is common, and pupillary rigidity is sometimes a symptom. Hemianopsia and diplopia are often observed: An important feature of the disease is the fact that these conditions are more or less transitory and rarely become permanent. Apoplectiform attacks followed by hemiplegia are results of gummatous growth or may be associated with areas of softening. These are due to vascular disturbances. Aphasia is not an unusual occurrence. Hemiplegias appearing suddenly in individuals under forty years of age are likely to be of specific origin. Epilepsies developing in later years should always be viewed with suspicion. The Korsakow symptom complex has been found in some cases of brain syphilis. Memory defect is present in most instances. When a marked mental deterioration takes place it is usually late in the disease. Argyll-Robertson pupils are infrequent in cerebral syphilis. Speech defect is practically never so conspicuous as it is in general paresis. Writing difficulties are also much less marked. Euphoria and grandiose delusions occasionally occur in brain syphilis but much less frequently than in general paresis. Hemiplegias, when they occur, are much more likely to be permanent than they are in general paresis. Paranoid complexes are sometimes clinical features of the disease and if they persist strongly suggest syphilis rather than paresis.
There should be a positive Wassermann reaction in the blood serum of both diseases. It is more persistent, however, in the syphilitic form. In the spinal fluid the reverse is the case and negative results are often noted in cerebral syphilis. There is usually some increase sooner or later in the albumen and globulin content in both diseases. There may be a lymphocytosis in both, although usually much greater in general paresis. A typical colloidal gold reaction is more indicative of general paresis than syphilitic conditions. Several clinical groupings have been proposed. Plant, for instance, speaks of various forms of mental deterioration, pseudo-paresis, paranoid types, epileptiform varieties, symptomatic disturbances and affective reactions suggesting manic-depressive insanity. The important contribution made by Kraepelin[186] to the literature of this subject is worthy of careful study. He describes a syphilitic neurasthenia, a mental disturbance due to the psychic effect of the disease, and various conditions resulting from gummatous growths. His most important group is a syphilitic pseudo-paralysis, which he divides into a simple dementia, delirious forms, expansive types and a variety showing the characteristic Korsakow syndrome. He also speaks of syphilitic apoplexies and epilepsy, tabetic psychoses and syphilitic paranoid conditions.
Syphilitic neurasthenia as described by Kraepelin is an affection which is likely to occur early in the disease and manifest itself shortly after the initial infection. In the milder forms, evidences of nervousness appear,—difficulty of thought, irritability, disturbances of sleep, pressure in the head, with indefinite and changeable abnormal sensations and vague pains. Later, feelings of anxiety, depression, dizziness, mental dulness, a difficulty in finding words, transient weaknesses, disturbances of sensation, nausea and a slight rise of temperature are observed. He admits that there is some question as to whether this constitutes a clinical entity and if so, whether it is directly due to the infectious process or is to be attributed to psychic disturbances. Nervous reactions of various kinds are to be found in syphilitics without psychosis. Thus, Meyer in sixty-one cases of secondary syphilis found eighteen with sluggish pupils, thirty-two with increased reflexes, and twelve with general nervous manifestations such as headache, vertigo, etc., appearing shortly after the period of infection. In only five of these patients were there any evidences of an organic disease. In twelve tertiary cases he found indications of an involvement of the nervous system in only two. In thirty examinations following lumbar puncture a lymphocytosis and an abnormal protein content were observed. Buttino, in a study of thirty syphilitics, reported that fourteen showed a diminished light reaction within one year of the time of infection. Later, after unmistakable symptoms of cortical involvement have existed for some time, neurasthenic complexes are common. These take the form of a difficulty of thought, absentmindedness, forgetfulness, and a reduction of interests. The mood may be irritable, surly, depressed, anxious, fearful, and changeable, showing at the same time considerable indifference and dulness. Some are quiet and reserved while others are excited and violent. Severe headaches may be common, more often at night. There are also occasional attacks of dizziness or fainting, disturbances of sensation, sleeplessness, sensitiveness to alcohol, and occasional diplopia. These are preliminary to more severe disturbances, which simulate nervous exhaustion, and are not strikingly unlike the earlier stages of general paresis. They may be differentiated by examination of the spinal fluid.
Another group of cases is characterized by conditions due to an increased intracranial pressure. These are marked by thoughtlessness, dulness, and indifference terminating in a complete lethargy and somnolence, during which the patient occasionally demonstrates that he is not so badly damaged mentally as he appears. Physically there may be weakness, twitchings, fainting spells, convulsions, ataxias, paralyses, dysesthesias, choked disc, etc. The basis of this disturbance is a gummatous growth, its location, of course, largely determining the symptoms. Kraepelin suggests the possibility of getting this disease picture in a syphilitic as the result of a growth of some other kind—a glioma or endothelioma.
Slightly more than a third of the cases encountered in his clinic showed the symptom-complex which he describes as syphilitic pseudo-paresis. As a rule these cases are of the simple demented type with a general mental deterioration. The patients show some disturbance of apprehension and attention, tire easily and are quite forgetful and dull. Delirious states may supervene, with clouding, confusion and disorientation, as well as hallucinations of sight and hearing. Memory is markedly impaired and confabulation may be noted. Judgment is not so much interfered with as in paresis. The patients have some insight into their condition and complain of headache, difficulty of thought, etc. Occasional delusions are observed. These may be of a hypochondriacal type or grandiose in character. As a rule the mood is cheerful, but it may be depressed, anxious or fearful, with suicidal tendencies. Sleep is disturbed and there is considerable restlessness, usually at night. With all of these symptoms there are the physical signs of a severe cortical involvement, dizziness, fainting spells, twitchings, seizures or frank convulsions, occasional paralyses, etc. Disturbance of sensation and motion may appear with a perfectly clear consciousness at times. Aphasic symptoms are not uncommon. The eye muscles are affected in many cases, with ptosis, double vision, strabismus, etc. The pupils are usually immobile or sluggish, frequently only one being involved. The field of vision is narrowed and choked disc is common. Speech is affected, as well as writing. All kinds of paralyses occur and they persist for some time. The gait may be spastic or ataxic. The reflexes are usually increased and often different on the two sides. Romberg's sign often appears. A Babinski reflex and ankle clonus may be found. The patients are usually untidy in their habits. Blood pressure is increased in some cases and the pulse slow. There may be variations in temperature. Often there are evidences of old syphilitic processes on the skin surface, enlarged glands, residuals of choroiditis, etc. Usually Kraepelin found a positive Wassermann reaction in the blood, but not in the spinal fluid, which showed a slight cell increase, often from fifteen to twenty per cubic millimeter, rarely in larger numbers. He found the course of the disease rapid, but with occasional remissions. There may be a sudden collapse and death. It usually terminates, however, in a profound dementia, often with a hemiplegia and epileptiform seizures. There are other conditions suggesting general paresis. Marcus, for instance, has described a delirious, confusional state occurring usually in the first year after the infection, sometimes later, but as a rule developing suddenly. The patients become sleepless, confused, anxious and disoriented. Numerous hallucinations appear, both of hearing and vision, usually of a very unpleasant type. The patients often become excited and violent or even suicidal. Physical signs more or less similar to those already described are to be expected. According to Marcus, these cases always respond to syphilitic treatment.
A small group of cases, as pointed out by Westphal, shows excitements strongly simulating the expansive type of general paresis. This form begins ordinarily with a depression, sometimes appearing suddenly, followed by irritability, marked restless excitement, headache, and fainting attacks. Usually there are hallucinations, and delusional ideas of a grandiose type. Above all there are pupillary disturbances, increased or decreased reflexes, seizures, paralyses, etc., strongly resembling paresis. All of these symptoms may disappear under syphilitic treatment in time. Some cases, however, last for years, dying as a rule in a seizure. Kraepelin also describes at some length a group showing the Korsakow complex. He suggests that the fact that this condition usually develops in alcoholics is not without significance.
Kraepelin is of the opinion that the mental picture is the conspicuous and characteristic feature of general paresis standing out more prominently than the physical evidences of the disease. In syphilitic pseudo-paresis, on the other hand, there is a clearer sensorium without such marked disorientation, and memory is not usually so much affected. At the same time, the physical signs are relatively more prominent, although the speech difficulty and writing defects may not be so marked. The pupils sometimes show no changes. Hemiplegias with ankle clonus and a Babinski reflex are, however, disproportionately common. The eye muscles are much more often involved than they are in general paresis. Loss of pain sense is not so noticeable. An advanced form of deterioration of many years standing is against a diagnosis of paresis and favors cerebral syphilis. In these cases the physical signs drop somewhat into the background. There are, nevertheless, stationary cases of general paresis which can be differentiated with great difficulty if at all. The development of pseudo-paresis is slower and more irregular. After a seizure and a paralysis there may be a long remission. The disease, furthermore, does not, like general paresis, always terminate in death.
Kraepelin finds the apoplectiform type of brain syphilis very common. After a few premonitory symptoms such as headache, dizziness, irritability, weakness of memory, etc., a typical apoplexy takes place, leaving a hemiplegia with or without a speech defect. This sometimes occurs without any loss of consciousness. The patient presents the appearance of an ordinary hemiplegic with increased reflexes on one side and ankle clonus followed by a Babinski reflex, etc. Writing is usually affected as well as speech. There may not be another attack for some years. There is, however, a progressive mental deterioration. Occasional confusional states or excitements may be met with. In the meanwhile, numerous physical signs appear, papillary changes, disturbances of the reflexes, ptosis, tremors, hemianopsia, etc. Epileptiform attacks may occur. The blood pressure is usually quite high. There is an increase in the cells in the spinal fluid, often with a negative Wassermann, although the blood serum is positive. Death usually results from a seizure. Three-fourths of Kraepelin's cases developed before the age of forty-five, which, of course, assists materially in the diagnosis.
In younger individuals usually, cerebral syphilis may manifest itself in the form of an epilepsy. Kraepelin is of the opinion that these conditions usually result from endarteritic involvements. In their development they show nothing differing in any way from an ordinary epilepsy. The attacks are usually mild at first, gradually increasing in severity, and are much aggravated by alcohol. There are, however, the usual physical signs of brain lues and later speech defects appear. There is eventually an emotional and intellectual deterioration. The changes in the spinal fluid are those described as characteristic of the other form of syphilis.
Kraepelin describes the paranoid forms as very uncertain in type and not so well defined. Hallucinations and delusions play the principal part with physical disturbances in the background. They become more or less prominent, however, eventually. The patient is usually anxious, restless, suspicious and develops delusions with characteristic ideas of jealousy on a sexual basis. Full-fledged persecutory trends also appear, usually with numerous hallucinations. Occasionally delusions of sin and self-accusation are noted, although ideas of grandeur mixed with complaints of persecution are more common. Consciousness remains undisturbed as a rule and there is no disorientation. The mood is changeable, at times depressed, tearful, anxious, irritable, complaining, but often cheerful and self-satisfied. There is usually more or less emotional dulness, with an indifference to the surroundings. The emotional life is shallow and superficial. Sudden excitements may occur at times with outbursts of anger. There are usually no striking conduct disorders. There may be occasional seizures of a mild form, fainting attacks, dizziness, rarely epileptiform attacks or slight apoplectiform symptoms. Sooner or later the physical signs of brain syphilis develop. The course of the disease is slow. Similar pictures are noted in tabes. The therapeutic test is not to be relied upon too strongly in making a diagnosis or differentiating between paresis and syphilis. It must be remembered that after all we are dealing here with one disease process. It has been found that in many syphilitics, even in recent cases, a positive Wassermann reaction, an increase in the cell count or in the protein content may occasionally be demonstrated in the spinal fluid.
In a study of 428 cases of neurosyphilis treated in Boston, Raeder[187] reported that 129, or practically thirty per cent, showed definite improvement, both physical and mental. He did not make any extravagant claims as to final results to be expected. "The therapia praesens of neurosyphilis is but a transition state in rational syphilography. Medical science has discovered several good clues which must be followed up; and others ferreted out and run down before the solution of the problem is complete. Indeed the successful treatment of paresis and tabes, as well as general vascular syphilis and visceral tertiaries, such as the crippling cradio-pathia, etc., may ultimately be realized in the field of preventive medicine. With chemotherapy, however, Ehrlich has doubtless found the most vulnerable approach to the treponemiatic diseases, but further research is necessary and other combinations must be found before the life of this anthropophagus pest is successfully snuffed out."
Warthin[188] at autopsy found evidences of active syphilis in a series of forty-one inactive or "cured" cases investigated by him. Eleven of these had been treated, were supposed to have recovered and showed no syphilitic manifestations at the time of death. Five had received an extended course of salvarsan therapy and in twenty-five there was no history of syphilis at all. Spirochaetes were demonstrated by the Levaditi method in thirty-six of the forty-one cases—in the aorta in thirty-two, in the testes in thirty-one, in the liver in four, in the adrenals in six, in the pancreas in six, in the spleen in one and in the nervous system in five. In some of these cases the Wassermann reaction was reported as negative. Warthin concluded that cured syphilis in many if not all instances is in a latent condition, spirochaetes of a low virulence still remaining active.