Communicable Diseases, Table of Contents
CHAPTER XV
ENCEPHALITIS LETHARGIC
Encephalitis lethargica may be defined as a subacute infectious disease ofthe sensory nervous system, occurring sporadically in man, characterizedclinically by the triad syndrome, lethargy, cranial nerve palsies, and a febrilestate, and pathologically by multiple inflammatory foci most commonly in thebrain stem, subthalamic region, about the third ventricle, iter, andmesencephalon.
The World War period marks the origin of the term "encephalitislethargica" and the beginning of our present conception of this disease.Profound and prolonged sleep, however, has been observed in connection with manyepidemics of influenza since early times.
In 1917, von Economo1 described 13 cases that had been admitted tohis clinic with headache, lethargy, and cranial palsies. He differentiatedbetween the somnolence of brain pressure and that of encephalitis, remarkingthat in the light cases it is striking how similar the somnolence is tophysiological sleep, since the patients are easily awakened. Von Economodescribed the cases and designated the disease "encephalitis lethargica."
While outbreaks of encephalitis lethargica (Schlafkrankheit) and "nona"have been connected with epidemics of influenza, the exact etiologicalrelationship has not been satisfactorily explained. The World War occurrence,referred to by von Economo, appeared first in central Europe, thence spread intoGermany, France, and England, in early 1918, and to the United States in thefall of the same year. Siemerling2 reported 15cases. The cases occurred in or in the neighborhood of Kiel, between the end ofNovember, 1918, and April, 1919. This author observed the same symptoms noted byvon Economo, and considered his cases to be the same disease.
In the spring of 1918 it appeared in France and England. Netter,3working in France, confirmed von Economo's findings, giving a detailedhistory of the disease in 10 adults and 10 children. He expressed the opinionthat it is a maladie autonome, the specific agent of which is endowed with anaffinity for the nerve centers, stating further that the epidemic begansimultaneously in France and England late in January. In England the disease wasconfused with botulism and poliomyelitis. References were made to the disease as"Acute infective ophthalmophlegia, or botulism" by Harris,4and as "toxic ophthalmophlegia associated with acute asthenia andother nervous manifestations" by Hall.5Some 107 cases were reported in England and 121 in the provinces, mostlyin March, April, and May, 1918. The subject was eventually taken in hand by theBritish Government and a complete investigation made.6Evidence was brought forward establishing the disease as a distinct entityand differentiating it from poliomyelitis.
As further evidence of distribution, Morguio7described an occurrence in Uruguay, and Arden-Delteil8in Algeria.
aUnless otherwise stated, all figures for the World War period are derived from sick and wounded reports sent to the Surgeon General.-Ed.
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The first case of encephalitis lethargica in the United States on which anydata are available occurred in the city of New York on September 4, 1918.9Three additional cases were reported there during the following month. Theportal of entry into North America is not known. However, during the latter halfof 1918 the disease spread rapidly throughout the United States, and by May,1919, cases had been reported from 20 States, the largest numbers occurring inIllinois, New York, Louisiana, Virginia, and Ohio. During that time 255 caseswere reported.
Encephalitis lethargica is not a reportable disease in many of the States andreports of its prevalence received by the United States Public Health Serviceare fragmentary. Some States do not report cases, while others record the caseswhich come to the attention of the State health officers. The United StatesPublic Health Service has not considered it worth while to collect thesefragmentary reports and tabulate them, since they would not show the realprevalence of the disease; therefore, the total incidence in the United Statesfor the World War period can not be given. Because the disease is not foundseparately in the lists of disease published prior to 1920, the Bureau of theCensus reports no deaths due to this cause; however, during that year, 1,070deaths were reported in the registration area of the United States.10
The first cases, so far as could be ascertained, among American troops in theUnited States occurred at Camp Lee, Va., early in November, 1918. These cases, 8in number, 2 among officers and 6 among enlisted men, were later reported byPothier.11 Since the diagnosis encephalitislethargica did not appear on the list of diagnoses as published by the SurgeonGeneral until 1920, the statistical tables for the World War do not include thedisease under this designation. Therefore, it is not possible to give the totaloccurrence in the Army during that time; however, among the clinical records ofWorld War patients it is found that there were a number of primary admissionswith the diagnosis encephalitis lethargica, later classified under encephalitis.Examination of these clinical records shows 20 to have been encephalitislethargica; 8 occurred in the United States and 12 in the American ExpeditionaryForces. The cases occurring in the American Expeditionary Forces were 11 whiteand 1 colored, and in the United States, 7 white and 1 colored. Of these 20cases, 4 died, 7 were returned to duty, 7 were discharged on account ofdisability; the disposition of the remaining 2 could not be determined. Of thedeaths, 2 occurred in the United States and 2 abroad.
ETIOLOGY
Several theories have been advanced to explain the cause of encephalitislethargica. In England it was first thought to be botulism or, perhaps, due to apoison, as solanin accumulating in the sprouts of potatoes and other vegetables.This theory was exploded by the findings of the British Government Local Board.12It has been suggested to be a form of poliomyelitis.
Encephalitis lethargica belongs to the class of polyencephalitic diseases andit has been suggested that the relationship to anterior poliomyelitis may besimilar to that of paratyphoid to typhoid fever.6The influence of lowered resistance, due to war conditions, and, as aresult, the possibility of saprophytic organisms becoming pathogenic, wasstressed.6 Breinl,13reporting upon the
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"mysterious disease" in Australia, expressed the opinion that itwas an aberrant form of acute poliomyelitis. Neal,14on the other hand, thought it improbable that encephalitis lethargica is aform of poliomyelitis.
The only epidemics of encephalitis lethargica of the pasthave been in connection with epidemics of influenza. The association of thesediseases formed the basis of many recent investigations. Siemerling2attempted to associate his cases with the 1918 epidemic of influenza. Mostof the cases gave a previous history of influenza. Smith9remarked that almost all outbreaks have been preceded by influenza. Bassoe12suggested that encephalitis may be a cerebral form of influenza, that theinfection is akin to the virus of poliomyelitis, but not identical with it, andthat nearly all cases are seen in persons more or less in a run-down state orexhausted. Hershfield15 reported 15 cases, 3 of which gave a distincthistory of previous influenza attack. Twenty-five of Neal's 38 cases14and half of Pothier's cases11 gave a historyof a previous attack of influenza.
It must be acknowledged that the relationship of these twodiseases has not been definitely determined. According to Zinsser16the relationship to influenza is vague; but it is to be seriously considered, inview of the recent researches with influenza and filterable viruses inencephalitis.
In one of von Economo's cases, an emulsion of the brain andcord was injected subdurally into a monkey by von Wiesner.17The animal died 46 hours later in stupor. The brain is reported as havingbeen typical of hemorrhagic encephalitis from which von Wiesner recovered aGram-positive diplococcus. This he cultivated and, on injection into apes,produced somnolence and mental weakness. The reports of these investigators ledother scientists to search for the cause of epidemic encephalitis. Strauss,Hirshfeld, and Loewe18 obtained nasopharyngealmucus of fatal cases, passed it through Berkefeld candles and injected rabbitsboth subdurally and intracranially. They claim to have produced the disease inthese animals. Similar results were obtained with a rhesus. The monkey developedlethargy, general malaise, temperature, and ptosis of the left eyelid, butrecovered. Rabbits, intracranially injected, died in from four to five days withpunctate hemorrhages in the brain, intense congestion, marked meningitis, andmononuclear infiltrations about the vessels. The authors claim to have repeatedthese experiments many times. Loewe, Hirshfeld, and Strauss19report a filterable virus obtained from the nasopharyngeal mucus of afatal case. The virus is reported as being capable of producing lesions inmonkeys and rabbits similar to those found in the human brain. The virus hasbeen carried through four generations in rabbits, transmitted to a monkey in thefifth generation, and then brought back to rabbits. The cerebrospinal fluid of afatal case caused the disease in rabbits, and transfers from brain to brainthrough filtrates have been successful in four generations. They suggest apossible connection between the disease and influenza.
Experimental inoculations were carried out at the ArmyMedical School, Washington, D. C., with fresh material from one of Wegeforth'scases.20 The spinal dura was opened 28 hoursafter death in one case and aerobic cultures were taken from the subdural andsubarachnoid spaces. These cultures were
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negative. Specimens were also taken from three levels of thespinal cord, macerated, filtered, and injected into a monkey intracerebrally,into another monkey by lumbar subarachnoid injection, into a rabbit, a monkey,and a mouse intraperitoneally. None of these animals became sick and thecultures were negative. From a patient 11 days after the earliest symptom of thedisease disappeared, the spinal fluid was removed and injected into a monkey bylumbar inoculation, and into a rabbit by cysterna magna inoculation. Anadditional rabbit was injected into the cysterna, with this fluid and inaddition with horse serum to produce a sterile meningitis. All of these animalsremained unaffected.
Evidence of direct communicability from man to man islacking. An analysis of the available records from stations where the diseasewas reported in the Army shows no evidence of communicability.
Among the factors which may influence the occurrence of thedisease, season, age, and sex are of interest. The apex of occurrence in theUnited States among Smith's cases was in March.9Skversky's cases in the American Expeditionary Forces occurred duringJanuary, February, and March.21 Fairbanks22states that March and April showed the greatest prevalence.
The age incidence is of importance from a differentialdiagnostic viewpoint between anterior poliomyelitis and encephalitis lethargica,the former occurring more commonly among children under the age of 7 and thelatter more commonly in persons older than this. Of course, the occurrence inthe Army would fall entirely in the latter class.
PATHOLOGY
Characteristic lesions are confined to the central nervoussystem. Multiple inflammatory foci are found, particularly in the region of thebasal ganglia, lateral ventricle, and about the aqueduct of Sylvius, also aboutthe pons and medulla. Macroscopically there is usually only evidence ofcongestion of the meninges and cortex, with more or less edema. On sectioningthe brain, and especially sections through the basal nuclei, peduncle, pons, andmedulla, punctate hemorrhages are found. Microscopically miliary hemorrhages arevery numerous. Neal14 describes the lesions as mainly of three kinds: (1)Infiltration, especially of the walls of the vessels (lymphocytes and plasmacells), to a less extent in other areas; (2) hemorrhages of varying size in boththe white and gray matter; (3) lesions of the nerve cells-some degeneration ofthe ganglion cells.
Wegeforth and Ayer20 report the pathological findings offour cases as follows:
The pathology of these four cases of so-called"lethargic encephalitis" was presented with a varying degree ofcompleteness. The brains all appeared alike. A great degree of engorgement ofall vessels was conspicuous; moreover, the pia was noted as pinker than normal,and this is explained by the free blood present in the meninges. The brains wereabnormally soft to touch. In every case the chief seats of the lesions were thebrain stem and the basal ganglions. The important lesions may conveniently bedivided into (1) perivascular exudation and (2) diffuse infiltration ofparenchyma. While both types of lesions vary greatly in intensity, extent, andsymmetry, they were seen especially in the gray matter about the canal, fourthventricle, and aqueduct, though deeper tissues were also affected and whitematter was not spared. The cells concerned in both types of lesion were allmononuclear; a small mononuclear cell and a large mononuclear cell, frequentlyphagocytic, many
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of which appear to be neuroglia cells, together with thelymphocyte and plasm cells, were recognized. Polymorphonuclear leukocytes wereconspicuous by their absence even in the case of short duration. Mitotic figuresappeared in small numbers both in the perivascular and in the diffuse exudate.That the two processes were interrelated is apparent from the appearance ofdiffuse exudate chiefly in the immediate neighborhood of affected vessels. Thatthe diffuse infiltrating exudate was not necessarily related to a destructiveprocess is borne out by the normal or only slightly changed appearance of nervecells in its midst; however, when the exudate was excessive, marked nerve cellchanges, including neurophagia, resulted. Bacteria were sought for with care andnone was seen.
Lesions that may be considered subsidiary in our cases werehemorrhage and meningitis. Hemorrhages were few in number and very small, soinsignificant, in fact, that they utterly failed of detection in the grossexamination. However, a certain amount of free blood and fibrin, mixed with theperivascular exudate, was frequently seen. Blood vessel changes were of twotypes. There was almost constantly evidence of proliferation of the intima invessels in areas of exudation, those in unaffected territory usually showing noabnormality. The second type of lesion noted was infiltration of the vesselwalls (especially intraadventitial), with mononuclear cells, chiefly lymphocytesand plasma cells. This condition was observed by itself in the meninges andassociated with perivascular exudate in the substance of the brain. It is likelythat more of the exudate was intramurally situated than appearance indicates;this would explain the very moderate cellular infiltration of the meninges andassociated low cell count in the spinal fluid. The cord and organs in the casesexamined appeared essentially normal. It is unfortunate that no notes on theroot ganglions are available. Lesions in the cerebral cortex were in all eithernonexistent or negligible.
SYMPTOMS
For purposes of description, the symptoms may be dividedarbitrarily into three stages, namely, the prodromal stage, stage of activemanifestations, and state of convalescence. The prodromal stage is manifested bya more or less sudden onset, with dull headache, drowsiness, variable febrilemanifestations, sometimes diarrhea, nausea, and vomiting, with or withoutcranial nerve symptoms. The duration is ordinarily short, commonly two to fivedays. It merges into the stage of active manifestations when the triad syndrome,lethargy, cranial nerve palsies, and the more marked febrile state are present.Disturbance of vision and diplopia, ophthalmoplegia or paralysis of theoculomotor nerve, ptosis, rigidity of the neck muscles, vertigo, dysphagia,aphonia, and the more marked lethargic state characterize this stage. Twitchingof the body or face and an ataxic gait, resembling Parkinson's disease, areoften described. Sensory changes are but seldom described in the literature. Theduration of this stage is variable, lasting from one to several weeks. It istrue of this stage that confusion with anterior poliomyelitis, on the one hand,and brain tumor, on the other, exists.
The stage of convalescence is marked by improvement in thelethargic state, normal temperature, diminution or disappearance of the cranialnerves palsies, tremor, and ataxia.
Wegeforth and Ayer20 remarked that it was unusual to findsigns of organic nerve disease in the first week. In the second week, sometimeslater, widespread neurological disorders became evident, with cerebral symptoms.Drowsiness occurred in almost every case, sometimes developing into coma, and attimes alternating with irritability or anxiety. However, orientation andcerebration were usually uneffected until just before death. The long projectionnerve fibers showed profound disturbance in seven of their cases, as indicated
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by ataxia, spasticity, Babinski's reflexes, and clonus.Diplopia was present in seven cases, although oculomotor palsy was seldomactually seen. The second most frequent local disorder was weakness of thefacial muscles, usually unilateral, and seen in five cases. Pupillarydisturbances and irregularity, inequality, and abnormal reaction were common.Weakness of the jaw muscles was observed three times, while profound disturbanceof respiration was twice noted. They make special emphasis of the clinicalmanifestations-insidiousness of onset, recurrent and incomplete paralysis, andimplication of cerebral nerves confined to motor functions. Skversky21 reportedtwo of his cases as showing a fairly well-marked Parkinsonian picture. In 9 outof 10 of his cases there was a definite febrile period either preceding, orconcomitant with, the attack of encephalitis lethargica, that included coryza,mumps, bronchopneumonia, and in one case possibly paratyphoid B. Beforeadmission, the following symptoms were complained of: Headache in 5 cases;diplopia, 2; dysphagia, 1; temperature, 4; mental dullness, 6; and an unsteadygait in 1. After admission, 4 cases showed involvement of the third and seventhcranial nerves. Nystagmus was present in 3, masked face, 5; tremor, 5;insomnia, 2; slow speech, 3; and the pill-rolling movement in 1 case. Spaeth,23reporting on ocular symptoms of encephalitis, observed in 5 cases, showedreduced pupillary reaction to light in 3 and to accommodation in 4; diplopia wascomplained of in 3 cases; dilatation was present in 3 and irregularity in 1.
Hershberg24 reported involvement of the third,sixth, seventh, and ninth nerves in his patient at Base Hospital No. 69, A. E.F. There was deviation of the uvula to the right. The Kernig and Babinskireflexes were absent. Nystagmus was present and the eye grounds were negative.
It was the lethargic condition in persons suffering from thisdisease that suggested the diagnosis "sleeping sickness." Bassoe12stated that there is not so much real sleep as is indicated by the sleepyexpression. In fact, some patients suffer from insomnia and the lethargy bearsalmost the same relation to sleep that laughter of the pseudobular paralysispatient does to the normal laugh. Vaughan25 held that the stupor is partlyapparent and partly real.
Blood findings were reported upon as being negative. A mildleukocytosis was occasionally present, but often nothing of diagnostic value. Inlike manner, the spinal fluid showed no characteristic change.
COURSE AND PROGNOSIS
The course and ultimate results are extremely variable. Somecases run a rapid, mild course, ending in from two to three weeks withapparently complete recovery. Other cases run a stormy course, terminating indeath in a few days, while some show a slow convalescence extending into monthsand leaving the individual permanently incapacitated. Skversky,21discussing the slow convalescence, stated that it often requires months and thenleaves the individual with an unsteady gait, general weakness, a masked face,etc. Hershfield15 reported the duration of the active stage from 6 to 60 days,with an average of 32 days. It is difficult to prophesy as to the residualdisturbances. A spastic gait, paralyses of the limbs, speech difficulties, andmental and emotional instability have been reported. Fairbanks22 reported thatopthalmophlegia and facial
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paralysis may clear up on one side before attacking theother, and that either form of paralysis may clear up and then recur. Thisauthor further reported that the mergence from lethargy and the restoration ofgeneral health is extremely slow. Duration of the clinical phenomena is sovariable and convalescence so prolonged that it is difficult to give even anaverage duration of the affection. Eliminating the abortive cases, it is safe tostate that six weeks is the minimum duration. In the majority of cases manyweeks, even months, may pass before full restoration to health-if it occurs-isachieved. Impairment of intellect may remain. Among other sequel?, tremor anddisturbance of coordination are conspicuous. The tremor may be of the paralysisagitans type, or it may be of a finer degree and either general or confined tothe extremities. Ataxia is commonly of the cerebellar type, but is alsofrequently present for fine movement of the fingers. Disturbances in swallowing,or in speech, may be more or less noticeable for a long time, yet are rarelypersistent. According to Fairbanks,22 the lack of emotionalexpression in the face often extends over a long period.
As previously stated, a study of the cases in the Army duringthe World War can be only fragmentary. An analysis of 20 clinical records shows2 deaths in the United States among 8 cases, and 2 deaths among 12 cases in theAmerican Expeditionary Forces. These 20 cases are the only ones that permit ofdetailed analysis. The records show that 7 were returned to duty, 7 dischargedfrom the service on account of disability, 4 died, and 2 were unaccounted for.Among the cases returned to duty, the duration of hospitalization varied from 18to 115 days, an average of 53.3 days. Among those discharged on surgeon'scertificate of disability, the period of hospitalization varied from 32 to 329days, an average of 180 days.
DIAGNOSIS
Diagnosis usually can be made by the more or less suddenonset with lethargy, cranial nerve palsy, practically normal blood and spinalfluid findings, with febrile manifestations, and the absence of sensory, trophic,and meningeal irritation symptoms. This disease has been confused with others,notably botulism poliomyelitis, tubercular meningitis, myelitis, brain tumor,and brain abscess.
The strong clinical, epidemiological, and pathologicalevidence that encephalitis lethargica is a distinct disease from classicpoliomyelitis is supported by animal experimentation.
The symptoms of tuberculous meningitis may simulate those ofencephalitis lethargica. Fairbanks22 remarked that it may be impossible todifferentiate the two and may require post-mortem findings to overcome thedoubt. An onset with meningeal symptoms and pinched facial expression socharacteristic of tuberculous meningitis is strongly suggestive. The results oflumbar puncture showing increased pressure, pleocytosis of mononuclear cells,and formation of the pellicle on standing, taken along with the finding oftubercle bacilli on microscopic examination (or after animal inoculation), wouldconfirm the diagnosis.
Myelitis is differentiated by the presence of sensory,trophic, and sphincter changes, possibly optic neuritis, and absence of thecranial nerve palsies; furthermore, lethargy is not usually seen in myelitis.Although fatal cases run a
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short course and often die of respiratory failure, this failure is due toparalysis of the muscles of respiration. Respiratory paralysis is a common causeof death in encephalitis lethargica. When it occurs, it is due to involvement ofthe respiratory center.
In brain tumor, the onset is usually more gradual, there is absence ofelevated temperature and usually presence of optic nerve changes from pressure,as well as localizing symptoms. These latter, however, may be absent if thegrowth is located, for example, in the frontal lobe. As previously stated, onecase discharged from the service on account of disability was diagnosedencephalitis lethargica, later changed to psychoneurosis, and then to braintumor.
PREVENTIVE MEASURES AND TREATMENT
In the absence of any evidence of direct communicability, and in the absenceof recognized etiology, nothing is known of the prophylaxis in this disease. Sofar as the records would indicate, there were no steps taken during the war toprevent its spread. As previously mentioned, there was no discoverableconnection between the occurrence of one case and another that would point todirect or indirect transmission.
Treatment was symptomatic. Most authors agree that spinal puncture isadvisable. Some seem to think that a release of spinal fluid is beneficial andshould be repeated. At any rate, it serves a valuable purpose in diagnosis. Nospecific or prophylactic treatment is known or was developed during the warperiod.
REFERENCES
(1) Economo, C. v.; Die Encephalitis lethargica. Jahrb?cher f?r Phsychiatrie, Leipzig und Wien, 1917-18, xxxviii, 253.
(2) Siemerling, E.: Ueber eine Enzephalitisepidemie. Berliner klinische Wochenschrift, Berlin, 1919, lvi, part 1, No. 22, 505.
(3) Netter, A.: L'enc?phalite L?thargique ?pid?mique. Paris M?dical, 1918, xxix, No. 31, 81.
(4) Harris, Wilfred: Acute infective ophthalmoplegia, or botulism. Lancet, London, April 20, 1918, i, 568.
(5) Hall, Arthur J.: Note on an epidemic of toxic opthalmoplegia. Lancet, London, April 20, 1918, i, 568.
(6) Report of an Enquiry into an Obscure Disease. Encephalitis Lethargica. Reports to the Local Government Board on Public Health and Medical Subjects. His Majesty's Stationery Office, London, 1918, n. s. No. 121.
(7) Morguio, L.: Lethargic encephalitis. Revista Medica del Urguay, Montevideo, 1918, xxi, 463.
(8) Arden-Deltiel: Un cas d'enc?phalite l?thargique observ? ? Alger. Bull. et mem. Soc. med. h?p. de Paris, 1918, 3, s., xlii, 577.
(9) Smith, H. F.: Epidemic encephalitis (Encephalitis lethargica, Nona). Reports of studies conducted in the United States. U. S. Public Health Reports, Washington, 1921, xxxvi, No. 6, 207.
(10) Letter from the Assistant Surgeon General, U. S. Public Health Service, to Maj. H. C. Michie, M. C., dated March 5, 1924. Subject: Encephalitis lethargica. On file, Historical Division, S. G. O.
(11) Pothier, O. L.: Lethargic encephalitis; Preliminary report, Camp Lee, Va. The Journal of the American Medical Association, Chicago, 1919, lxxii, No. 10, 715.
(12) Bassoe, Peter: Epidemic Encephalitis (Nona). The Journal of the American Medical Association, Chicago. 1919, lxxii, No. 14, 971.
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(13) Breinl, A.: Clinical, Pathological and Experimental Observations on the "Mysterious Disease." A Clinically Aberrant Form of Acute Poliomyelitis. The Medical Journal of Australia, Sydney, 1918, i, No. 11, 209.
(14) Neal, J. B.: Lethargic Encephalitis. International Clinics, Philadelphia and London, 1919, ii, 29th Series, 184.
(15) Hershfield, A. S.: Epidemic Encephalitis in Chicago. An Analysis. Illinois Medical Journal, Chicago, 1919, July, xxxvi, No. 1, 27.
(16) Hiss, P. H., jr.; Zinsser, Hans; and Russell, F. F.: A Text Book of Bacteriology. D. Appleton and Co., New York, 1922, 919.
(17) Von Wiesner, R. R.: Die Aetiologie der Encephalitis Lethargica. Wiener klinische Wochenschrift, Wien, 1917, xxx, No. 30, 933.
(18) Strauss, I.; Hirshfeld, S.; and Loewe, L.: Studies in Epidemic Encephalitis. New York Medical Journal, New York, 1919, cix, No. 18, 772.
(19) Loewe, L.; Hirshfeld, S.; and Strauss, I.: Studies in Epidemic Encephalitis. The Journal of Infectious Diseases, Chicago, 1919, xxv, 378.
(20) Wegeforth, P., and Ayer, J. B.: Encephalitis Lethargica. The Journal of the American Medical Association, Chicago, 1919, lxxiii, No. 1, 5.
(21) Skversky, A.: Lethargic Encephalitis in the A. E. F.: A Clinical study. The American Journal of Medical Sciences, Philadelphia, 1919, n. s., clviii, No. 6, 849.
(22) Fairbanks, A. W.: Encephalitis Lethargica. The Boston Medical and Surgical Journal, Boston, 1919, clxxxi, No. 20, 578.
(23) Spaeth, E. B.: Ocular Symptoms of Encephalitis Lethargica. On file, Historical Division, S. G. O.
(24) Hershberg, H.: Report of a Case of Lethargic Encephalitis, Base Hospital No. 69, A. E. F., New York Medical Journal, 1919, cx, No. 22, 899.
(25) Vaughan, Victor C.: Encephalitis Lethargica. The Journal of Laboratory and Clinical Medicine, St. Louis, 1918-19, iv, No. 7, 381.
