CHAPTER VI

THE PSYCHOSES WITH HUNTINGTON'S CHOREA, BRAIN TUMOR AND OTHER BRAIN OR NERVOUS DISEASES

Huntington's chorea is said to have been referred to first by C. O. Waters of Franklin, N. Y., in Dunglison's "Practice of Medicine" in 1842. An article on the subject by Irving W. Lyon also appeared in the _American Medical Times_ in 1863. The name by which the disease is now generally known was the result of an elaborate description of its symptomatology by George Huntington in the _Medical and Surgical Reporter_ in 1872. He particularly called attention to the fact that it is hereditary in origin, occurs in adult life, is associated with suicidal tendencies and often exhibits mental symptoms. On the important subject of heredity Huntington made the following observation: "If one or both of the parents have shown manifestations of the disease, and more especially when these manifestations have been of a serious nature, one or more of the offspring almost invariably suffer from the disease if they live to adult life; and if by any chance these children get through life without it, the thread is broken and the grandchildren or great grandchildren may rest assured that they are free from the disease. Unstable and whimsical as the disease may be in other respects, in this it is firm; it never skips a generation to manifest itself in another; as soon as it has yielded its claims, it never regains them." A well known monograph on the subject by Osler appeared in 1894.

McCarthy[189] refers to the mental condition associated with this disease as "a severe and gradually progressive deterioration, ultimately ending in absolute dementia. In some cases the mental defect is noted from the onset of the symptoms, in others the mentality may remain unimpaired for years. Mental deterioration is the rule, and it is associated with a loss of memory and a tendency to self-destruction which gradually develops. When the mental degeneration is well marked, outbreaks of violence are sometimes noted. In one of the writer's patients, as the disease progressed, the clinical picture of paresis was presented. The chronic delusional state is more often noted than would be inferred from Huntington's description." Hamilton,[190] who made a clinical study of a considerable series of cases in 1907, expressed the opinion that mental deterioration occurs in the majority of instances before the onset of choreiform symptoms. He found a special tendency to deterioration in the cases appearing early in life, while irritability and delusional ideas were more often observed in those developing in later years. Delusions of persecution and deterioration, however, were symptoms more or less common to both groups. Diefendorf,[191] in a study of twenty-eight cases in 1908, called attention particularly to the irritability with occasional outbursts of violence as well as attacks of despondency. He emphasizes emotional deterioration and indifference.

Kraepelin[192] also refers to the fact that the mental symptoms may precede the choreiform manifestations in appearance, sometimes by a number of years. The patients become forgetful, defective in judgment, somewhat dull, show a poverty of thought and an incapacity for orderly activities. Generally there is an emotional depression, often with irritability and more rarely euphoric symptoms. Delusions gradually develop. These are of a persecutory nature, although ideas of grandeur appear at times. Suicidal tendencies are common. Disturbances of perception and memory may be very pronounced. The relation of the patient to his environment becomes very much confused. In some cases, on the other hand, the mental symptoms are not very striking. Anxious states, outbursts of anger or emotional excitements may appear at times. Appetite and sleep are often interfered with. The pathology of this disease is not characteristic. There may be a chronic meningitis or extensive atrophies. The cells of the third layer of the cortex, according to Kraepelin, are decreased in number with an increase of glia nuclei. The remaining cells are shrunken with deeply staining processes, and there is a considerable loss of tangential fibres. Sclerotic changes with thickened walls are noted in the blood vessels. Hyaline degeneration and miliary hemorrhages have been observed, although Nissl and Alzheimer found no vascular lesions worthy of note. The cortical changes, according to Räcke, are more pronounced in the central convolutions, being much less conspicuous in the frontal and occipital regions. Alzheimer found the corpus striatum particularly involved. Here he noted a striking cell loss, with glia proliferation but no vascular changes. D'Ormea, according to Kraepelin, traced the disease through five generations in one family and Browning went as far back as two hundred years in another.

The observations on the subject of Huntington's chorea in the statistical manual of the American Psychiatric Association are as follows:—

"Mental symptoms are a constant accompaniment of this form of chorea and as a rule become more marked as the disease advances. Although the disease is regarded as being hereditary in nature, a diagnosis can be made on the clinical picture in the absence of a family history.

"The chief mental symptoms are those of mental inertia and an emotional change, either apathy and silliness or a depressive irritable reaction with a tendency to passionate outbursts. As the disease progresses the memory is affected to some extent, but the patient's ability to recall past events is often found to be surprisingly well preserved when the disinclination to cooperate and give information can be overcome. Likewise the orientation is well retained even when the patient appears very apathetic and listless. Suspicions and paranoid ideas are prominent in some cases."

Statistical reports from American institutions show that comparatively few cases of Huntington's chorea are committed. In 49,640 first admissions to the New York state hospitals only forty-eight, or .09 per cent, were diagnosed as Huntington's chorea during a period of eight years. The admission rate to the Massachusetts hospitals during 1919 was exactly the same. In twenty-one hospitals in fourteen other states twenty-four cases (.13 per cent) in 18,336 admissions were reported as Huntington's chorea. There were only seventy-five cases (.1 per cent) in 70,987 admissions to forty-eight hospitals in sixteen different states.

_Psychoses with Brain Tumor_

Brain tumors are more common perhaps than is generally understood. Cushing[193] shows that they were found in fifty-five, or 1.7 per cent, of 3,150 autopsies at the Johns Hopkins Hospital. He refers to Siedel, who observed them in 1.25 per cent of his cases in Munich and states that Blackburn found them in about two per cent of 1,642 autopsies at the St. Elizabeths Hospital in Washington. He also quotes Bruns as saying that two per cent of all neurological cases show intracranial growths. In the first twenty-five hundred surgical conditions admitted to the Peter Bent Brigham Hospital in Boston eight per cent were diagnosed as brain tumor. Cushing found that 66.6 per cent of 130 carefully studied growths were gliomata. Nearly four per cent were endotheliomas. In another series of seventy cases he found twenty-seven gliomas (38.5 per cent), seventeen adenomas (twenty-four per cent), seven endotheliomas (ten per cent), five interpeduncular and mixed growths (seven per cent), and other forms in smaller percentages. Many of the endotheliomas have undoubtedly been included in the past with the sarcomas. This may also be said of gliomas.

According to Cushing, growths in the brain may give rise to no disturbance whatever, show well defined focal signs, occasion only general manifestations, or have both general and focal symptoms, depending on the location of the neoplasm. General symptoms may be briefly summarized as follows:—headache, vomiting, choked disc, vertigo, drowsiness, convulsions, disturbances of the pulse rate, respiration and temperature, as well as mental disorders. The focal signs depend wholly on the site of the growth. Cushing mentions the following symptom complex as resulting from lesions of the frontal lobes:—"Indifference, unpunctuality, mental enfeeblement, loss of memory and power of attention, change in disposition with more or less marked irritability or taciturnity or obstinacy or jocularity, etc., often a rambling speech, lack of realization of the illness, and change in the general conduct of life with habits of untidiness. These, in greater or less degree, characterize most of the cases, although it is often astonishing to find how inconspicuous the symptoms may be with a very extensive growth. They may often be of rather abrupt onset and not until the situation of the lesion is definitely disclosed and careful interrogation made into the patient's previous mental state is it possible to learn that in all probability some mental alteration has been of long standing."

Bruns did not find psychoses associated very often with frontal lesions. Jacobi, however, in reviewing the literature of growths in that region, found mental symptoms in forty-nine per cent. Schuster observed them in from fifty to sixty per cent of all brain tumors. Redlich[194] described mental conditions as being either incidental and not related to the growth, or definitely caused by it, and was even of the opinion that the neoplasm could in some instances be the result of a psychosis. Two of Redlich's patients, moderately alcoholic, showed a typical Korsakow syndrome. He refers to the fact that in cases reported by Oppenheim, Friedrich and Fürstner, "Witzelsucht," or the tendency to joke, disappeared after growths were removed from the frontal region. A patient of Begerthal, who had hallucinations, delusions and somatic symptoms, recovered after a tubercle was excised from the paracentral lobule. A case of Friedrich's which showed an alteration of the personality, erotic symptoms, sudden explosive laughter, poor memory, etc., recovered after a sarcoma was removed from the right frontal lobe. A patient of Thoma's after three attacks of mental depression showed a gliosarcoma in the occipital lobe at autopsy. Schuster, Bruns and Schönthal have reported cases of brain tumor with hysterical manifestations.

Redlich described the psychoses associated with cerebral growths as being epileptiform in character and origin and resembling post-epileptic psychoses in their symptomatology, with irritability, excitement or violence, confusion, delirium and hallucinations, often followed by partial amnesia. Epileptic manifestations may occur in the form of equivalents during the development of the growth. Bernhardt and Oppenheim have called attention to episodes of vertigo, irritability, excitement, clouding and occasional delirium with amnesia following intense paroxysms of headache. These attacks also strongly suggest the characteristics of epileptic psychoses. Nothnagel, Bernhardt, Oppenheim, Schuster, Ziehen and others attribute the mental symptoms associated with brain tumor to increased intracranial pressure producing an anaemia. Klippel, Maillard, Vigouroux, Kaplan and others believe that they are due to toxins originating in the growth. This view is based largely on the appearance of psychoses similar to the Korsakow syndrome. Knapp in 1906 called attention to the prominence of mental symptoms in growths occurring in the anterior portion of the corpus callosum. These may be associated with intellectual defects, apraxia, speech disturbances and stupor. Gianelli found mental disturbances in 209 of 318 cases examined.

Kraepelin[195] attributes the mental symptoms of growths to an injury of the brain structure, changes in intracranial pressure, circulatory disturbances, and the absorption of toxic substances. A growth of considerable size but of slow development may permit of a readjustment of pressure, etc., and show few symptoms. On the other hand, a small neoplasm on account of its site or rapidity of growth may be accompanied by profound mental disturbances resulting from chemical irritation, obstruction of the aqueduct of Sylvius, or circulatory interferences. Kraepelin quotes Schuster (1902) as finding psychotic symptoms in all cases of growths in the corpus callosum, in two-thirds of those of the hypophysis, in one-third of those of the cerebellum and in one-fourth of the cases with involvement of the brain stem. These he looks upon as pressure symptoms except in the case of the callosal neoplasms. Schuster was of the opinion that growths in the cortex usually lead to actual psychoses and those in the deeper areas to dementia. He found a general mental deterioration in 423 out of a total of 775 cases of brain tumor. The patients were indolent, inattentive, clumsy, forgetful, dull, tired easily and lost more and more their capacity and inclination for sustained exertion. Thought, decision and mental processes generally, required an unusual amount of effort. The patients usually became somewhat confused and disoriented in regard to time, place and person, as well as incoherent in speech. In many cases there is a marked memory disturbance with a tendency to fabrication suggesting Korsakow's psychosis. Delirious states with hallucinations sometimes accompany growths in the posterior lobes. Kraepelin has also observed hallucinations in cases with tumor of the cerebellum. Many develop hypochondriacal ideas, others have delusions of persecution or self-accusation and suicidal tendencies. Rarely there are delusions of grandeur. The mood is usually anxious, depressed and at times irritable or apathetic. Occasionally the patients may, on the other hand, be cheerful in spite of the hopeless condition they are in. They may even show distractibility, flight of ideas, volubility and excitement. There is more often a childish elation with a tendency to joking and facetiousness. Schuster found this more common in frontal involvements. Kraepelin also called attention to restlessness and excitements often leading to violence. This may alternate with mental dulness and cataleptic states. The patients may repeat words and make meaningless response to questions, strongly suggesting katatonia. Mental dulness becomes more and more marked, however, even reaching a stuporous stage. To this is added, according to the location of the growth, focal symptoms of various kinds—headache, disturbance of vision, seizures, paralyses, aphasia, agraphia, articulatory disturbance, ataxia, etc. Special symptoms arise where psychogenic factors play a part,—excitements with paralyses or disturbance of perception, etc. Hysterical stigmata may appear. Cases with growths in the frontal region occasionally simulate general paresis but should be distinguished without difficulty.

The Association's statistical manual has the following to say of psychoses with brain tumor:—

"A large majority of brain tumor cases show definite mental symptoms. Most frequent are mental dullness, somnolence, hebetude, slowness in thinking, memory failure, irritability and depression, although a tendency to facetiousness is sometimes observed. Episodes of confusion with hallucinations are common; some cases express suspicions and paranoid ideas.

"The diagnosis must rest in most cases on the neurological symptoms, and these will depend on the location, size and rate of growth of the tumor. Certain general physical symptoms due to an increased intracranial pressure are present in most cases, viz.: headache, dizziness, vomiting, slowing of the pulse, choked disc and interlacing of the color fields."

The number of cases reaching hospitals for mental diseases is, of course, small. In 49,640 first admissions to the New York state hospitals in eight years there were sixty-seven cases (.14 per cent) of psychoses with brain tumor. In 18,336 admissions to twenty-one hospitals in fourteen other states there were eighteen cases (.09 per cent) diagnosed as psychoses with brain tumor. There were ninety-three cases (.13 per cent) in 70,987 first admissions to forty-eight hospitals for mental diseases in sixteen different states.

_Psychoses with Other Brain or Nervous Diseases_

Cerebral hemorrhages, thrombosis and embolism are more or less intimately associated etiologically, pathologically and clinically. They all bear a rather definite relation to the general question of arteriosclerosis and may all lead to cerebral softening. Apoplexy is a term which was employed by Aristophanes, Demosthenes and Sophocles and has been in general use for centuries. It was known to Chaucer and was referred to in Shakespeare's works ("Henry IV"). It was studied very elaborately by Sydenham and many other early writers. Charcot and Bouchard in 1864 called attention to the relation existing between miliary aneurysms of the cerebral vessels and hemorrhages. In a study of the cerebral vascular lesions at the University College Hospital, London, Jones (_Brain_, 1905) found records of one hundred and sixty cases occurring during a period of sixty-five years. Of these, 123 showed hemorrhages; twenty-four, thrombosis; and thirteen were due to embolism.

Thomas[196] states that: "The symptoms following acute vascular lesions of the brain, whether the process be the rupture of a vessel or its occlusion, are in many respects identical; and clinically it is often impossible to determine which process has been effective." He calls attention to the fact that in thrombosis the final closure of a vessel may occur suddenly and the symptoms develop with great rapidity. On the other hand, the rupture of a vessel may mean the escape of only a small quantity of blood and after an embolism the circulation is not always stopped immediately. In an analysis of 401 apoplectic attacks Thomas found no loss of consciousness in 202 cases, although it was interrupted or markedly disturbed in 199. Jones found a complete loss of consciousness in 47.7 per cent of 201 cases of cerebral embolism and a partial disturbance in sixty per cent. He reported consciousness affected in seventy-five per cent of his cases of cerebral hemorrhage and in 45.5 per cent of those of thrombosis. When it occurs it is usually not the initial symptom in his experience, being preceded by headache, vertigo, weakness in certain parts of the body, etc. An analysis of the cases of embolism reported by Virchow, however, showed a sudden loss of consciousness as the initial symptom to be the general rule. Gowers is of the opinion that an initial softening is a more common occurrence than hemorrhage.

In the young, apoplectic attacks are usually due to cerebral softening, thrombosis following acute disease or embolism resulting from endocarditis. Between the ages of twenty and forty apoplexies usually mean syphilitic thrombosis. In the later decades of life, either hemorrhage, thrombosis, embolism or softening may occur. Thomas[197] collected from various hospitals, statistics of 840 cases. Of these, 499 showed hemorrhages and 341 softenings. He is of the opinion that the presence of premonitory symptoms for some days indicate thrombosis, while shorter prodromal periods point to a hemorrhage. Rapidly developing coma suggests hemorrhage, while a widespread paralysis without much disturbance of consciousness is more common in thrombosis. A marked fall of temperature and rise of blood pressure as a rule means a hemorrhage. Repeated convulsions are more often associated with softening or embolism. If the symptoms indicate a capsular lesion it favors hemorrhage, and if of a cortical type, softenings are more likely. A positive Wassermann reaction suggests thrombosis or softening. The presence of endocarditis with heart murmurs points to embolism. Thomas finds that, while the patient may recover from either of these conditions without apparent intellectual defect, he is liable to be petulant, emotional, depressed and tire easily.

In psychoses following hemorrhage, thrombosis and embolism Kraepelin[198] as a rule finds very little relation between the nature of the lesion in question and the symptoms to be expected. Immediately following the seizure the patients become dull, clouded, confused and disoriented, and peculiar in their behavior. This is followed by an active excitement with loud cries, resistiveness and struggling. These acute disturbances usually subside, leaving, however, evidences of the arteriosclerosis or syphilitic endarteritis which caused the hemorrhage or thrombosis. Embolism may leave an apparently permanent mental deterioration with aphasic and paraphasic manifestations which often entirely clear up. In lesions of younger persons due to syphilis, mental enfeeblement may follow.

Our knowledge of the psychoses accompanying paralysis agitans is very inadequate. The disease was first fully described by Parkinson in an English publication in 1817, although, according to Camp, similar cases were reported by Schwarz in 1766. The etiology of this condition is unknown and the pathology is not at all definite. It seems to be the rather general opinion of neurologists that mental disturbances are quite rare in Parkinson's Disease. Camp,[199] for instance, has the following to say on this subject:—"Mental conditions have also been described, but usually the patient's mind is entirely clear. In the very old the changes incident to senility, such as irritability, childishness, etc., insomnia and memory changes, might be expected and may require special treatment. Often these patients are emotionally unstable and spells of forced weeping or laughter occur." Krafft-Ebing refers to mental weakness in paralysis agitans and speaks of the frequency of melancholia with hallucinations and suicidal impulses occurring intermittently and appearing with exacerbations of the disease. He speaks of premature senility as playing the most important etiological rôle. McCarthy[200] expresses the opinion that: "Beyond a tendency on the part of some patients to adopt a whining and complaining manner, the mind remains very clear; in fact, the good nature and complaisance of most of the patients, in spite of the severity of the symptoms, is a matter of common observation. Dementia may, however, complicate a case of the disease." On the other hand, Parant, a French writer who made an elaborate study of this subject in 1883, described three distinct varieties of mental disturbance observed by him. In the milder cases he found changes in the personality. This is shown by irritability, egotism, restlessness, suspicion, undue sensitiveness regarding their disease, mild persecutory ideas, tendencies to depression, indifference and apathy. The second class of cases described included mental deterioration with difficulty of thought, loss of memory, etc. The third group includes definite psychoses characterized generally by depressions with or without hallucinations and delusions. Hallucinations of sight are said to be common. Delusions of persecution are prominent and hypochondriacal and somatic ideas frequently occur. Suicidal tendencies are very pronounced. According to Ball, these episodes come and go "with the aggravation of the sensory symptoms, and they seem to disappear when the tremor decreases or ceases entirely." The usual tendency in these cases, as shown by Parant, is to terminate in complete deterioration.

Of the inflammatory conditions of the meninges Kraepelin[201] makes special reference to mental disturbances associated with tuberculosis. The patient is depressed, anxious, irritable and apathetic, often with the first appearance of the disease. Dulness and memory disturbances become more and more apparent. The patient soon becomes clouded and disoriented, confused and delirious. Occasionally hallucinations appear. The disturbance of consciousness becomes more and more marked. The patient becomes incoherent, restless, noisy and often violent. The excitement may reach the stage of an actual mania with delirious confusion. Sometimes the symptoms are strongly suggestive of katatonia. In alcoholics a condition very similar to delirium tremens develops, terminating as a rule in stupor and coma. Speech disturbance, aphasia, convulsions, hyperesthesia or muscular weakness may be observed in such cases. Other forms of meningitis are quite similar but more rapid in development and of shorter duration. In some instances, as after epidemic cerebrospinal meningitis, states of mental enfeeblement may follow the disease.

It must be admitted that our information on the subject of multiple sclerosis is far from being complete. In a discussion of the mental symptoms accompanying this condition, Henderson[202] expressed the following views:—"Cases of disseminated sclerosis which present definite, well marked psychoses are extremely rare. When mental symptoms do occur, they usually come on when the condition is well advanced, the most common symptoms are mild euphoria, labile mood, apathy and dullness, and a slightly defective memory. In some cases, however, depression has been described as the outstanding feature, while hallucinations of sight and hearing are not uncommon accompaniments. In certain cases the mental symptoms may come on early, and these are usually of excessive severity and are rapidly followed by complete dementia." Dunlap has described cases associated with general paresis and showing the characteristic lesions of both diseases at autopsy. According to Kraepelin[203] mental disturbances sometimes appear before physical symptoms are observed. These take the form of depression, anxiety, fear, with occasional deliria, hysterical manifestations, emotional dulness, variable moods and a marked irritability. Later in the disease more marked euphoric or depressive tendencies appear, with excitements and confusional states. Delusions of a persecutory nature, or ideas of grandeur may be observed. Hallucinations are infrequent. According to Kraepelin, from ten to thirty per cent of the cases terminate in a general mental enfeeblement which is not usually of an advanced degree. He also describes a lobar cortical sclerosis with much more marked mental disturbances suggesting dementia praecox.

Various mental conditions have been attributed to tabes. Sachs[204] speaks of depressions and neurasthenic conditions with irritability as a special symptom. He has observed paranoid states and manic attacks, sometimes with periods of "transitory dementia" with or without aphasia. He also expresses the opinion that tabetics may develop all of the symptoms of general paresis, although he says that the coexistence of the two diseases is rare. Kraepelin[205] speaks of milder forms of psychoses characterized by uncertainty of memory, fatigability and emotional instability. Many cases exhibit a hopeless, gloomy attitude with depression and fears, or they may be surly, irritable and quarrelsome. Others show a surprisingly good humor. The emotional disturbances often suggest general paresis. Kraepelin, however, describes the characteristic psychosis of locomotor ataxia as assuming a paranoid form and quotes Meyer as reporting paranoic conditions in twenty-six tabetics and depressions of various types in fourteen. He also speaks of hallucinatory excitements resembling alcoholic conditions. These are characterized by a sudden anxiety and restlessness with hallucinations of both hearing and vision. The patients complain of poisoning and sensations of electricity, but are cheerful in mood and well oriented. This condition may last for weeks or months, ending in a sudden recovery, often with relapses. Shorter hallucinatory delirious states resembling crises are also referred to by Kraepelin. More chronic conditions are noted, with hallucinations, persecutory delusions and ideas of grandeur. Delirium tremens, manic-depressive attacks, katatonia or senile psychoses may be associated with tabes.

The literature of medicine contains many references to acute chorea. It was referred to, according to Paton, by Plat as early as 1614 and was discussed by Sydenham at some length. Wharton Sinkler, in describing chorea in Pepper's "System of Medicine" in 1886, made the following interesting remarks on the mental changes involved:—"The child is irritable and feverish, cries and laughs readily, or is sullen and morose. Sometimes he is violent to those about him but this is rare. Intellectually the patient suffers somewhat. He is not able to study as before, and the memory may be impaired. Sometimes there is a mild form of dementia." Burr[206] divides these conditions into four groups:—"First (and this includes the vast majority), patients in whom there is peevishness, fretfulness, some loss of the power of fixing the attention, and a slight loss of the moral sense shown by disobedience and selfishness. Second, those showing in addition to the above symptoms, night terrors, and transitory, visual, auditory, or other hallucinations. Third, those with distinct delirium, wild or mild, accompanied with fever. Fourth (and this group is very small when we remember how common chorea is), those showing stupor, or rather stupidity, and an acute dementia, which may follow the condition described under three, or appear without any preceding mental symptoms at all severe, and which is usually accompanied with trouble on articulation not caused by choreic movements of the lips and tongue, but the result of mental hebetude." White[207] refers to the irritability and emotional instability of choreics and describes a psychosis in "chorea insaniens" characterized by an acute confusion, sometimes of a violent type with hallucinations, or a paranoic condition with delusions of persecution. This may develop into a stuporous state. Kraepelin describes the psychotic manifestations of acute chorea as forms of delirium due to infection with characteristic states of clouding, confusion, etc. Wechsler has expressed similar views.

Encephalitis lethargica is a disease which has received a great deal of attention during the last few years. The term was first applied by von Economo[208] to a series of cases observed by him in Vienna in 1917, although, as he has pointed out, similar epidemics occurred as early as in 1712. This condition is characterized particularly by lethargy, facial and oculomotor paralyses and a rise of temperature. Cases were reported from England and France by various observers in 1918 and by Pothier, Neal and others in this country in 1919. It has been suggested frequently that the disease is in some way associated with influenza. The pathological findings have also been confused with the African sleeping sickness due to trypanosomes. After such prodromal symptoms as headache, malaise and drowsiness with muscular weakness for a few days, a lethargic or stuporous state usually develops, interrupted occasionally by delirious attacks. Ptosis has been reported, sometimes with immobility of the pupils. Paralyses of the facial and eye muscles are very common. Buzzard and Greenfield[209] after a review of twenty-two cases suggested the following symptomatological classification:—1. Cases characterized by hemiplegia, hemianesthesia, hemianopsia, etc.; 2. Cases characterized by symptoms resembling those of paralysis agitans:—the basal ganglia group; and 3. Cases characterized by a disturbance of the cranial nerve functions. In a publication issued recently by the United States Public Health Service the various types of the disease were summarized as follows:—1. A clinical affection of the third pair of nerves; 2. Affections of the brain stem and bulb; 3. Affections of the long tracts; 4. The ataxic type; 5. Affections of the cerebral cortex; 6. Cases with evidence of spinal cord involvement; and 7. The polyneuritic type with involvement of the peripheral nerves. The Massachusetts Department of Public Health has recently recommended the use of the MacNulty classification, which is quite similar in some respects:—

1. Symptoms of a general nature referable to the central nervous system with no localizing signs.

2. General symptoms with third nerve paralysis.

3. General symptoms with localizing signs of facial paralysis.

4. General symptoms with localizing signs extending down to the cord.

5. General symptoms with polyneuritic involvements.

6. Mild and abortive cases.

Autopsies have shown meningeal and cortical congestion, degeneration of the nerve cells, and thickening of the vessels with endothelial proliferation of the glia. Venous thrombosis and multiple hemorrhages also occur. In a study of the cerebrospinal fluid Boveri[210] found the pressure slightly greater in many cases with an increase in the albumen and globulin content and a mild lymphocytosis in occasional cases. The findings are not characteristic or of great diagnostic value. Efforts to isolate the organism responsible for this disease have so far been unsuccessful.

The mental symptoms associated with encephalitis lethargica have been studied recently by Abrahamson[211]. He finds that the patient can be aroused from the initial lethargy and responds quickly and coherently to questions, relapsing again into an apparent sleep. Some irritability is shown. The attitude "expresses a desire to be left alone." If the somnolence disappears it is usually followed by a period of depression. The patient complains of weariness and inability to sleep. Choreic manifestations sometimes occur. The somnolence may terminate, on the other hand, in a profound stupor resembling a drug intoxication with a restless delirium. Even then the patient can be roused momentarily. Responses are automatic with no evidences of emotional disturbance. Flexibilitas cerea is often present. This condition may be followed by a period of confusion, disorientation and amnesia suggesting Korsakow's disease. There is usually a period of mental depression with poverty of thought. Occasional hallucinations were also observed.

An exceedingly important contribution to the literature of encephalitis lethargica is an analysis recently made of the symptoms shown in eighteen cases by Kirby and Davis.[212] "The psychic disturbances of epidemic encephalitis present the general characteristics of an acute organic type of mental reaction, corresponding more specifically to a toxic-infectious psychosis. In the acute stages of the disease, psychic torpor and delirium are the most frequently observed mental disturbances although other clinical pictures may be encountered, as the Korsakoff syndrome or more complex mental disorders in which various affective and trend reactions give a special cast to the psychotic disturbance." They report two types of sleep disturbance, hypersomnia and hyposomnia. The former is characterized by drowsiness, lethargy, stupor or coma, depending entirely on the degree reached. In the latter the patient is sleepless at night and somnolent during the daytime. Usually delirium was present at some time in both types of the disease. Often there was a brief period showing a mild depression or anxiety, following lethargy or delirium. Euphoria was observed in a number of instances. In the unrecovered cases they often found residuals—"depressive affects, emotional elevations, irritability, explosive reactions, stubbornness, apathy, etc." Their findings may be summarized perhaps in the statement that "definitely formulated and persistent trends are infrequent in epidemic encephalitis ... we have found much evidence of persisting emotional alteration with little evidence of organic mental defects or dementia."

A review of the statistics of American institutions shows that psychoses associated with brain and nervous diseases other than Huntington's chorea and brain tumor, which have already been discussed, are exceedingly rare. The percentage of cases reported in the New York hospitals was .95, in the Massachusetts institutions, 1.02, and in twenty-one other hospitals only 1.56. In a total of 70,987 first admissions there were only 787 cases (1.1 per cent). The relative frequency of the various forms is illustrated by the statistics of the admissions to the New York state hospitals during a period of eight years. Of 462 cases, 160 were diagnosed as psychoses due to cerebral embolism; twelve, to meningitis; twenty, to multiple sclerosis; thirty-eight, to tabes; thirty-four, to acute chorea; and 163, to other conditions not specified. These figures are astonishing when the fact that 49,640 patients were admitted during that time is taken into consideration.