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.
For purposes of statistical study the American Psychiatric Association
has not attempted any clinical differentiation of the various types
of this disease, a procedure which was felt to be inadvisable at
this time. The following suggestions appear in the manual as to the
classification of psychoses due to cerebral syphilis:—
"Since general paralysis itself is now known to be a parenchymatous
form of brain syphilis, the differentiation of the cerebral
syphilis cases might on theoretical grounds be regarded as less
important than formerly. Practically, however, the separation of the
non-parenchymatous forms is very important because the symptoms, the
course and therapeutic outlook in most of these cases are different
from those of general paralysis.
"According to the predominant pathological characteristics, three types
of cerebral syphilis may be distinguished, viz.: (a) Meningitic, (b)
Endarteritic, and (c) Gummatous. The lines of demarcation between
these types are not, however, sharp ones. We practically always find in
the endarteritic and gummatous types a certain amount of meningitis.
"The acute meningitic form is the most frequent type of cerebral
syphilis and gives little trouble in diagnosis; many of these cases
do not reach state hospitals. In most cases after prodromal symptoms
(headache, dizziness, etc.) there is a rapid development of physical
signs, usually cranial nerve involvement, and a mental picture of
dulness or confusion with few psychotic symptoms except those related
to a delirious or organic reaction.
"In the rarer chronic meningitic forms which are apt to occur a long
time after the syphilitic infection, usually in the period in which
we might expect general paralysis, the diagnostic difficulties may be
considerable.
"In the endarteritic forms the most characteristic symptoms are those
resulting from focal vascular lesions.
"In the gummatous forms the slowly developing focal and pressure
symptoms are most significant.
"In all forms of cerebral syphilis the psychotic manifestations are
less prominent than in general paralysis and the personality is much
better preserved as shown by the social reactions, ethical sense,
judgment and general behavior. The grandiose ideas and absurd trends of
the general paralytic are rarely encountered in these cases."
It is only of comparatively late years that the hospitals of this
country have shown the frequency of psychoses due to cerebral syphilis
in their reports. Statistical studies indicate that such mental
conditions are quite unusual as compared with other well recognized
clinical entities. In a total of 49,640 first admissions reported by
the New York state hospitals during a period of eight years only 342,
or .67 per cent, were reported as mental diseases due to cerebral
syphilis. The Massachusetts hospitals during 1919 reported only
twenty-seven cases, a percentage of .89. Twenty-one hospitals in
fourteen other states, in a total of 18,336 admissions, showed only 124
cases (.67 per cent) of cerebral syphilis. This represents, therefore,
a total of 70,987 admissions with only 493 diagnosed as psychoses due
to cerebral syphilis,—a percentage of .69. When this is compared
with eleven per cent as shown by the admissions for general paresis
it is probably a very fair index of the comparative frequency of the
two diseases in our institutions. It is interesting to note that the
incidence of cerebral syphilis as shown by the hospitals of the various
states is almost exactly the same. The admission rate for the Casa de
Orates in Santiago, Chili, in 1918, as shown by Letelier, was .90 per
cent.