Vol. XVIII

Original Articles

ENCEPHALITIS LETHARGICA.

ELMER W. SCHNOOR, M.D.

GRAND RAPIDS, MICH.

This quite obscure and mysterious disease has been variously termed: "a new disease,” “a new syndrome," acute epidemic encephalitis, epidemic stupor, nona, Heine-Medin disease, epidemic encephalo-myelitis and sporadic polioencephalitis.

Encephalitis lethargica is an infectious inflammatory disease of unknown etiology, characterized by specific manifestations arising in the central nervous system, of which the most frequent and pronounced characteristics are: general asthenia, progressive lethargy and cranial nerve palsies.

History. Von Economo at the April, 1917, meeting of the Viennese Society of Psychiatry introduced the present common accepted term, lethargic encephalitis.

Professor A. Netter at the Paris academie de Medecine on May 7, 1918, expressed the view that the disease is a distinct entity and not a form a polio-encephalitis and believed the disease occurred at the end of the 17th century and the beginning of the 18th in Germany. It occurred in upper Italy and Hungary in 1890 when the pandemic of influenza of that era was declining. Very suggestive cases occurred in nearly all countries of Europe and in the United States in the spring of 1895. No doubt exists, that the disease occurred in Vienna in the winter of 1916-17. Harris of London and Hall of Sheffield called the attention of the British Medical profession to the disease in March, 1918. Cases have recently been recognized in the United States.

CASE I. Male, age 18, seen service in Naval Reserve at Hampton Roads Naval Base. January 21st, a week before his return home, after discharge from navy, he noticed a "twisting" of eyes and saw double, had to read with one

Read before Muskegon County Medical Society, March 21, 1919.

No. 4

Re

eye closed, felt tired and dull. En route home seemed dazed at the Station in Cincinnati and was sent to hospital by the Red Cross. mained in the hospital one day and was discharged seemingly improved. Walked to street car, which he boarded to depot; took train for Grand Rapids, his home, and arrived the morning of January 28. Staggered into home and shocked mother, seemed quite dazed, disinterested and giddy. Toward evening became delirious and trembling of whole body developed. Dr. N. (the second case of this report) was called and found patient had a temperature of 100 and talkative. January 31st I saw the patient in consultation with Dr. N. and patient gave evidence of quite profound stupor but could be aroused and would answer a few questions in a droll manner, great effort present to raise eyelids and an internal strabismus evident with marked congestion of retinal vessels but no evident hemorrhages. Distinct rigidity of neck present, as also suggestive Kernig. Tache cerebral marked. February 1st I performed a spinal puncture. The clear fluid exuded under markedly increased pressure and on examination showed a normal count and the cell present of lymphocyte type. Culture negative. No albumen reaction and no film development in specimens left in refrigerator for three days. Wassermann reaction was negative. Centrifuged sediment showed no tubercle bacilli. Blood and urine were examined and found normal. February 2nd, the right pupil was smaller than the left and a distinct bilateral ptosis. February 3rd, Asthenia marked, unable to raise extremities and profuse sweating began and has continued to date. Incontinence of urine commenced and lasted for ten days. Following spinal puncture he was brighter for three days and then passed into a stupor for seven days and then gradually became brighter. Opened eyes in a half way manner and paid attention to happenings about the room and talked to his wife whom he previously had not recognized. March 7th, was permitted out of bed and at present, March 16th, his eyes have

improved but the left ptosis remains and after prolonged focus of eyes on an object the left eye converges. He sits listless and moves his jaws frequently as if chewing. He walks about a little, slowly and somewhat uncertain. He does not venture to speak unless spoken to and rarely smiles. Appetite is voracious and thirst intense. Noise irritates patient intensely. Hearing seems to be very acute. From February 1st to the 14th carried a temperature ranging from 99.4 to 103.4, pulse 112 to 136 and rather feeble at times and respiration 22 to 28. Sleeps well but quite prolonged.

CASE II. Dr. N. Physician, male, aged 41, first saw case I on January 28 and was in attendance four days-26 days later, Saturday, February 22 seemed quite weary and surprised that his vision was somewhat blurred and he saw double. This diplopia lasted two days but the blurred vision has continued to a degree to date March 16th but is improving-weariness progressed but the doctor continued his practice for three days when he complained of cardiac palpitation and consulted Dr. Northrop, complained of extreme tiredness and seemed dull and irritable. The following day, February 26, felt weaker and drowsy and took to bed, would speak with an effort to the immediate members of his family, was quite indifferent and oblivious to surroundings. March 1st asthenia more marked and trembling of body evident with pains in forearm and next day in hip and legs which continued intermittently for a week. Sunday morning, March 1st, I saw the patient in consultation with Dr. Northrop and diagnosed the case encephalitis lethargica and suggested spinal puncture. Later in the afternoon further consul with Dr. Camp occurred, who performed spinal puncture and took blood culture. Two days later, March 4th, he began to seem brighter, talked spontaneously the next day and became very restless. This restlessness was quite extreme for a period of nine days and then began declining. With the decline of restlessness the doctor has assumed a rather euphorious state, being quite elated over his improvement. Some difficulty in raising the neck was experienced after the first week and gave evidence at my examination by a suggestion of distinct resistence on March 2nd. Profuse perspiration became evident four days after onset and a miliarial eruption appeared on March 3rd. Four days after onset an evening rise in temperature 100.6 occurred but was normal next morning. After this it ranged from 99 in the morning to 101.6 in the evening for twelve days and then became normal. March

2nd to the 8th the pulse was 120 to 128, respiration 22 to 28 after March 8th, pulse 84 to 100 and respiration 20 to 24. March 2nd to the 10th, had retention of urine, necessitating catheterization. At all times took nourishment when aroused and offered to him and now has a voracious appetite. Constipation was present throughout the course. Eye examination by Dr. Camp revealed a mild neuro-retinitis. Later Dr. Camp reported spinal fluid negative as well as blood culture, and Wassermann reaction. Urine and blood examined by Dr. Northrop negative.

CASE III. Male, age 68, February 17, complained of vague pains in back and felt tired. Five days later began to get drowsy and seemingly weak. Seen by another physician but no diagnosis made. February 25th very stuporous and hesitancy in speech noted, at times wide awake and would wander about room. February 26th marked weakness of extremities and pains in legs when I was called. Suggestion of left facial palsy and difficulty in speech. February 28th speech more distinct, weakness and drowsiness marked, facial palsy distinct and rigidity of neck present. March 1st, stuporous, slight temperature; arousable but unable to speak distinctly though an effort was made, but performed certain acts desired. March 5th neck distinctly rigid with slight retraction and dysphagia present. Dysphagia continued for six days and has improved. The period of the first four days during which the dysphagia was pronounced, the patient had intervals of Cheyne-Stokes respiration. Mentality brighter and extremely restless and 'moaning at times. developed and continues. The patient had incontinence of urine for a few days as also incontinence of stool. March 14th able to articulate and answer questions with monosyllabic words. Sits up unassisted but restlessness continues. Urine faint trace of albumen, with mucin and few leucocytes and epithelial cells present. Blood pressure 140. Eye examination by Dr. D. Emmett Welsh revealed swelling of nerve head, blurring of disc, marked venous engorgement and contraction of arterioles.

Etiology.-Von Wiesener, who studied Economo's fatal case, a girl of 14, cultured a diplostreptococcus but was unable to demonstrate the organism anywhere in nerve tissue in microscopical preparations. Wilson reports negative bacteriological findings in tissues of his two fatal cases and refuses to accept von Wiesener's diplo-streptococcus as an etiological factor. McIntosh on behalf of the Medical Research

Committee of London Hospital and Hancock and Pearse of the food branch of the Board's Medical Department of London, investigated from the view of possible food origin and concluded that neither on the bacteriological, nor on the epidemeological side could any direct or indirect evidence be obtained of an association of the illness with bacillus botulinus or with food infection. The results of the preliminary inquiry pointed to a possibility that it might be one of the many forms of the disease or group of diseases at present labeled "Heine-Medin"disease, of which acute poliomyelitis was the commonest type. Picken believes the cases first regarded as botulism, to be polioencephalitis, an aberrant form of acute anterior poliomyelitis and reported two cases. Breinl of Australia states that pathological and experimental research convinces him that the Australian "Mysterious Disease" represented the identical virus. as that of acute poliomyelitis and clinically presented a polioencephalitis. Marinesco and McIntosh concluded independently that encephalitis lethargica in the 1918 outbreak was the same disease as described by von Economo of Austria and Netter of France and was a disease clinically distinct from analogous affections. Hamer of the Royal Society of Medicine believes the epidemic merely part and parcel of a prevalence of influenza. During the last ten years evidence has been collected clearly showing close association between outbreaks of poliomyelitis, polio-encephalitis, cerebro-spinal meningitis and prevalence of influenza. Noel calls attention to the marked similarity of a large number of case to typhus fever. Lethargic encephalitis occurs in all ages and about equally in sex, and most prevalent in winter and spring.

Pathology. Marinesco, professor of Neurology at Bucharest has found disseminated miliary or punctiform hemorrhages visible to naked. eye in the grey matter in neighborhood of floor of 4th ventricle, the aqueduct of Sylvius and even the 3rd ventricle and also posterior part of pons and peduncles. Cerebral cortex showed congestion of lepto-meninges. The first segment of spinal cord same histological lesions as pons, bulb and peduncles. Microscopical study of the above mentioned regions had demonstrated existence of four kinds of lesions: (1) Infiltration of walls of small vessels, especially the veins, consisting of lymphocytes and plasma cells in the adventitia, disposed in several layers. The endothelium and filroblasts might also take part in the inflammatory process. (2) Foci of interstitial inflammation

consisting of neuroglia cells of several kinds, including large cells with voluminous eccentric nucleus and many fibrillary prolongations, lymphocytes and polynuclears. The foci appear sometimes to be altogether independent of vascular infiltrations and might occur in the nerve roots, as the hypoglossal, pneumogastric, etc. (3) Lesions of the nerve cells which did not correspond with those usually seen in infantile paralysis. There was dissolution of the soi-disant, Nissl bodies, relative achromatosis, reduction in volume of cellular body and number of neuronphagia as described by Economo. (4) Foci of hemorrhage much more numerous when microscopic examination was made. Hemorrhages remained circumscribed around walls of small-vessels and red cells mingled with inflammatory infiltration cells. The vessel walls did not appear necrosed but sometimes a solution of continuity of vessel wall could be seen.

Buzzard's microscopic study of pathological lesions showed the remarkable way in which the vessels of the brain reacted in this inflammatory process. Chief features are: (1) Perivascular infiltrations, mainly with small round cells. (2) Small capillary hemorrhages which suggest a gradual oozing of blood, through damaged walls of small veins or capillaries. (3) Throm 'bosis of small and middle sized vessels in different stage of organization. (4) Ischemic softenings presenting appearance of hemorrhagic infarction. (5) Subarachnoid hemorrhages and cellular infiltration of lepto-meninges. (6) General neuroglial proliferation. (7) Chromatolysis and coagulation-necrosis in nerve cells.

Box's case, an apoplectiform type of epidemic. encephalitis, suggested hemorrhage and at postmortem, some of the lesions suggest hemorrhagic infarction rather than true extravasation and states it is conceivable that perivascular exudation might itself lead to vascular strangulation or thrombosis.

Symptoms. The incubation period of this disease is variable and indefinite. The onset in five of sixteen of Hall's cases was sudden, the rest gradual. A prodromal period, MacNalty states, commonly ranges from one to seven days but might be as protracted as three weeks during which occurred lethargy, headache, vertigo, giddiness and diplopia, as well as lassitude, fatigue, vomiting and diarrhea. The onset is usually ingravescent especially in the type with cranial nerve palsies which usually take some time to develop fully and may vary in extent from day to day. Fever occurs in the majority of cases often of low-grade type, other times

severe and prolonged and intermittent and remittent in type. General asthenia gradually becomes pronounced with muscular pains and occasional twitchings. Cranial nerve palsies may be distinct. Ophthalmoplegia, external or internal may be distinct with ptosis symmetrical or asymmetrical, complète or incomplete. Paralysis of accommodation and corresponding indistinctness of vision or diplopia, Wilson found a frequent and early symptom. Involvement of lower cranial nerves to a variable extent is not uncommon; facies often expressionless; obliteration of facial lines; palate, tongue, larynx and pharynx may have transient implication. Pupils may be contracted, dilated and fixed or normal.

Of the general symptoms, indifference, inaptitude, oblivious to surroundings, drowsiness, lethargy and stupor is in one degree or other a feature from the onset, occasionally the lethargy appears later in the disease. After a variable period, the stupor may be replaced by extreme restlessness alternating with apathy. One is impressed by the fact that the patient in the lethargic state responds quite correctly when spoken to in word and act and takes nourishment as often as presented to him unless dysrhagia is distinct. Speech may be affected and may be droll, slurred or rapid or may suggest an aphasia. Retention of urine may occur but usually incontinence is present at sometime as 'so of feces. Hyperidrosis is pronounced and may be associated with a miliaria eruption. Tache cerebrale was pronounced in my first case. Distinct rigidity of neck muscles or only a resistance may be present associated with pain. A suggestive Kernig may be evident but Babinski, Brodzinski, Oppenheim, Gordon and Chaddock were negative in my cases. Delirious attacks and Cheyne-Stokes breathing may occur, especially if the medulla becomes involved making prognosis most grave (Case 3). Constipation is present in most cases.

Vaidya found the average leucocyte count, 7600 per c.mm. and relative cellular proportions normal. An occasional higher count was accounted for by a complication. Spinal fluid was clear in all cases, without coagulation on standing but in two of my cases, showed increased tension. Spinal fluid protein was never more than slightly increased. Cell count normal or slightly increased and type of cell always lymphoid. Pothier found a definite pleocytosis of the lymphocytic type in cases at Camp Lee, Virginia.

Various types of the disease are classified by MacNalty. (1) A type displaying general dia

turbances of the functions of the central nervous system but without localizing signs. (2) Types with nervous localizing signs: (a) affection of 3rd pair of cranial nerves, (b) affections of brain stem and bulb with localizing lesions of other cranial nerves, (c) affections of the long tracts, pyramidal, prepyramidal and upcoming afferent tracts, (d) ataxic types, (e) affections of cerebral cortex, (f) types indicating some evidence of spinal cord involvement, (g) polyneuritic type. (3) Mild or abortive. types with or without localizing signs in central nervous system.

Course. Of disease varies greatly in typical cases, it may end fatally in a few days or be prolonged for weeks or months.

The stupor may last but two or three days or often two to five weeks. I have been informed by a member of Hospital Corps, Camp Custer of a suspected fatal case of encephalitis lethargica being in a stupor for forty-seven days. Altered mentality and cranial nerve palsy may persist. Findlay reports one case with a right sided facial paralysis, ptosis of right upper eyelid, left external squint and a general mental apathy.

Prognosis.—Buzzard states some cases recover completely, others survive the acute stage but carry with them in after life permanent defects due to the morbid process. A certain number die of toxemia or hemorrhage in the acute illness or from some complication. James records a mortality of from 15.8 to 20 per cent., 8 per cent. under ten and 8 per cent. from ten to nineteen. Economo's ratio of mortality was six of eleven cases. Netter, seven out of fifteen; Wilson two out of thirteen; MacNalty collected 168 with 37 deaths; Findlay one of three.

Diagnosis. The most common error in diagnosis is to attribute the condition to tuberculous meningitis. The cardinal symptoms of lethargic encephalitis are asthenia, lethargy and cranial nerve palsies. Acute poliomyelitis is chiefly a summer or autumnal disease while epidemic stupor has been in evidence in winter and spring.

Prophylaxis.-In conference with Dr. C. C. Slemons, Health Officer of Grand Rapids, it was thought best to institute the same preventative measures as in acute poliomyelitis.

sion and two of the cases seemed much brighter the following two days. Potassium iodide was administered in moderate doses and urotropin in large doses. The urine was examined frequently to observe any urotropin irritation should it occur. Narcotics were given for rest

lessness.

Conclusions. A careful study of cases I and II, one is impressed with the fact that case II probably contracted the disease from case I, the onset similar and course similar but a lowergrade temperature in case II, and that the incubation period was from three to three and one-half weeks. (2) Whether or not this disease is a type of poliomyelitis seems quite a puzzle. In poliomyelitis the appearance of the disease is more rapid and pronounced as contrast to epidemic encephalitis. All three cases have had a gradual onset. I have been unable to trace any evidence of presence of any cases of acute anterior poliomyelitis in this section of Michigan. (3) None of the three cases had suffered a preceding attack of influenza. (4) MacNalty thinks the relationship between poliomyelitis and encephalitis might be comparable to that existing between typhoid fever and paratyphoid.

'BIBLIOGRAPHY.

von Economo: Wien. Klin. Woch., May 10, 1917.

Netter: Medical Society-Hospital of Paris.

Harris: Lancet, April 20, 1918.

Hall: Brit. Med. Jour., Oct. 26, 1918.

von Wiesener: Lancet, July 6, 1918, Wien. Klin. Woch., July 26, 1917.

McIntosh: Lancet, Nov. 2, 1918.

Hancock & Pearse: Lancet. Nov. 2, 1918.

Wilson: Lancet, July 6, 1918.

Picken: Lancet. July 13, 1918.

Breinl: Medical Jour. of Australia, March 23, 1918.

them through the public in order to call the peoples attention to the great menace of cancer, and the need of having it recognized early and promptly treated. First of all it should be understood.

THAT CANCER IS NOT HEREDITARY.

Although it may occur in the same family, this only shows that there may be a lack of resistance to cancer in that family, but it is not transmitted from parent to child.

IT IS NOT CONTAGIOUS.

People living in the same house, doctors and nurses who handle these cases a great deal, never get it that way. I know of no case where a husband or wife both had the disease.

But, I want to qualify this remark myself. The experiments of Gaylord of Buffalo with cancer in fishes seems to indicate that it is contagious. In the Bronx Zoological Garden it has been shown that snakes are peculiarly liable to cancer, and if one snake gets it, all the snakes in that cage die of cancer in a short time, unless the first case is early recognized, and promptly removed.

CANCER AGE.

Cancer occurs especially after the fortieth year. Although cases are frequently reported even younger, as early as twenty, and children especially are subjected to a form of cancer called, sarcoma. Nevertheless, it has been universally recognized that from thirty-five to forty, and over, is the so-called cancer age, and that at this time people must be especially on the lookout for such trouble.

WHAT WOMEN SHOULD KNOW.

A malignant disease affects women especially in the generative organs, of which the breast is one. Any lump, swelling, hardening in the breast during the cancer age is potentially cancer. It may be only a cystic or fibroid growth at the time, but ultimately a cancerous condition will be planted on it. Hence, every swelling, hardening, or tumor, which does not disappear in a few weeks must be promptly removed, not only removed, but no woman can afford to take the chance, but must have the whole breast removed, including the glands in the axilla, because not enough tissue is removed by simply taking out the tumor, and if an effort is made to remove half of the breast, or something like it, the whole breast might just as well be removed. No use talking to me about esthetic appearance, and preventing the wearing of low-necked dresses, when the woman has