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.