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.

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.