S0ME RECENT CASES OF LETHARGICA.

ENCEPHAL1TtS

By JOSEPH O'CARROLL, M.D., President, Royal College of Physicians, Ireland.

AND

GEORGE NESBITT, M.D., F.R.C.P.I., Physicians ~o the House of Indus~ry IIospitals. Dub!i~.

_[Rcad in the Section of Medicine, February 7, 1919.]

0UR desire in reporting these cases before the Roya! Academy of Medicine in Irel~nd is to draw attention to the existence of this remarkable disease in this country. Our experience of the condition is, so far, too small to enable us to add anything to the admirable accounts provided by a recent report to the Local Government Board of England and Wales, dealing with nearly ~00 cases, and by various papers in the journals.

We are, however, impressed by the f~ct that the disease might be easily mistaken or overlooked, and it is with the object of assisting those who may not yet have had ah opportunity of observing a case that we venture to bring forward a brief description of those we have seen.

CAsE I . - - Mrs. B. G., aged fifty, married, with six chil- dren, a n d a history of several miscarriages, was admitted to the Whitworth Hospital under the care of Dr. O'Carroll on April 8th, 1918, in ~ condition of partiaI stupor, having been sent to the hospital a sa case of ursemi�91 Her hist~r as given by her daughter, was that she had enioyed goo~t health till abou~ two years before, when she became sorna-

490 Some Recent Cases of Encephalitis Lethargica.

what " nervous," slept badly, and suffered from indiges- tion, biliousness,and frequen,~ headaches. Her state of health did not, however, a t t ract any special attention, and she carried on her ordinary household duties till four days before admission, when she was noticed to stagger on getting out of bed. She wa.lked about her room in a slow and uncertain manner, and was inclined to drag her feet. On being questioned, she complained of not having slept, that her headache was worse than usual, that she felt a " trembling " in her limbs and body, and tha.t her right ea.r was deaf a.nd " stuffed." She continued to carry out light duties in her home for the next four d~ys, but she �9 seemed sluggish and drowsy. She staggered in her wa.lk, and carried her arms in a curious position, with her el bows bent a~ad her hands dropped at the wrists.

She sat most of the day at the tire, and, though seeming drowsy, did not sleep. :Next day she was so dazed a nd stupid that medical advice was obtained, and she was sent to hospital as stated.

On examination, the patient nourished and robust woman.

was found to be a well- She was semi-comatose,

her expression dull, with eyes staring vacantly, and mouth hanging open. She lay in whatever position she was placed, making no voluntary movements. Mentally, she was dull and apathetic, but when spoken to was quite ~ble to understand and reply intelligently, t ter speech was slow and indistinct. She had well-marked con]unctivitis , pa.rticularly of the right eye, her tongue was coated with blackish fur, and her breath was fetid.

Temperature normal, pulse 100. The respiratory and circulatory systems showed nothing abnormal, but the urine, of specific gravity 1030, contained albumen in small ~mour, t, and an occa~ional hya.line cast was found with

By DRS. J . O'CARROLL and G. ~'ESBITT. 49].

difficulty. No sugar was present. She was decidedly con- stipated. As regards the nervous system generally, no paralysis was found, but her voluntary movements were slow and incomplete, and her limbs were somewhat rigid. Knee-jerks were absent, also ankle clonus and Kernig. Pla.ntar reflex was extensive. The cranial nerves were in~c t , and the ocular fundi were normal, except for a white patch near the right disc.

Cerebro-spinal fluid of normal character was withdrawn on April 9th, and the Wassermann reaction of this and also of the blood was negative.

The subsequent course of the case was tedious and un- eventful. Temperature oscillated between 99 ~ and 100 ~ F. for a fortnight, and then settled down with a sharp rise for a few days in July, probably due to influenza. On June 24th a note was made on her chart which briefly epitomises her condition during the long period she was in hospital. " The patient is semi-comatose and has incontinence of urine and feeces. There is some paresis of the legs. :Knee- jerks, a.nkle clonus, ~nd Babinski absent. Sensation un- impaired. Speech is slow, but easily understood." Most of the time she was in a condition which stron.~ly suggested dementia, but It was remarkable how intelligently she could reply when questioned. Her condition gradually im- proved, and she was discharged on November 7th, though

still far from well. The diagnosis presented much difficulty, and numerous

hypotheses were considered and re]ected. Dr. O'Carroll considered her case for a time to be one of polio- encephalitis, but later on lectured upon her as probably a ease of lethargic encephalopathy.

When seen a few days ago she seemed quite well again, .~nd comptained only of slight " numbness " in one loor.

492 8ome I~ecent Cases o] Encephaliti8 Lethargica.

C~s~, I I . - - T h e next case was admit~ed t~ ~he Whitwe~~h Hospital 30th Au~o~st, 1918, under the care of Dr. Nesbi~.

M. S., femate, aged twenty-nine, unmarried, was se~r in by her employer, for whom she had been acting as nurse- attendant to an invalid gentleman. Her history was that four weeks previously she had gone to a hairdresser and had her hair shampooed. The following morning she awoke feeling ill, and she vomited. I-Ier head felt giddy, everything seemed to more round her, and she felt inclined to stagger when walking. She was in the habit of cycling ten miles each way to her Work, but for the next couple of days she was forced to take the tram. On attempting to cycle again she was so giddy that she actually fell off on the road, but she persŸ a t her work, and meanwhile saw a doctor. He gave her some medicine, which she said " made her so sleepy that she had to stop ir ," and short]y a fterwards she came to hospital.

On examination she seemed to be a physically healthy young woman, but she was decidedly emotional, and her general appeara.nce gave the impression that she was hys- terical. There was nothing remarkable in her previous or family history. She complained of intense giddiness, re- lieved to some extent by wearing a cardboard mask over her eyes, a.nd she staggered very badly on trying to walk. In the intervals of her emotional outbursts she was dull and apathetic. With the exception of the cranial nerves, no definite signs were detected in the nervous system. There was no pa.ralysis or loss of sensation. Knee-jerks were equal a.nd very sharp, and plantar reflex was normal. The cranial nerves, however, showed marked involvement. The pupils were equal and reacted, nystagmus was present in the left eye, but absent in the right, possibly due to weakness of the ocular muscles.

By. Das. J. O'CA~ROLL and G. NESSITT. 493

Voluntary movements were very imperfect in both. The fiel d of vision seemed extremely limited, but Dr. Cummin~ reported the fundus to be normal in both eyes. There was distinct paresis of the facial nerve in the right side. The urine was normal. She was constipated, and her pulse was curiously slow (50) but quite regular. On September 3rd lumbar puncture was performed, a.nd 20 c.cs. of clear fluid were withdrawn under somewhat increased pressure. It was reported to contain nothing pathological. Diagnosis in this case was also at the time obscure, and though an organic cerebral or cerebellar lesion was feared, an unsatis- fying label of hysteria was adopted.

On September 9th ir was noted that she complained of headache for the first time, but the giddiness was much less, and she was not distressed by looking at objects round her. The eye symptoms had also improved, paresis was less ma rked, and the nystagmus in the left eye had dis- appeared. The visual field had increased considerably. On Septell~ber 23rd she had improved stilt further; she was less giddy, could walk better, and was much brighter ~nd more natural in manner. On October l l t h i.e., ten weeks from the onset of symptoms--she was ~llowed to go homeat her own request, with instructions to have ~ pro-

longed rest. The latest news of her (on ]?ebruary 4th, 1919) is that

she ~s now perfectly weI1. She had a bad attack of in- fluenza towards the end of November. The giddiness per- sisted for some time after leaving hospital, but a ll her symptoms cleared up as she recovered from the influenza.

CASE I I I . - -Mrs . X., aged forty-eight, was seen by Dr. 0'Carroll in consultation with a.nother physician on Janu~ry '20th, 1919. He has kindly supplied notes of the case. He first saw her on January 16th. Owing to anxiety

494 Some R ecent Cases o/E~cephaliŸ Letl~,argica.

as to the health of relatives and to general war-strain, she had been somewhat neurasthenic for the past four years. She had h a d " swimming in the head " ; a tendency to fall. and had fallen once; a dislike of closed places (claustro- phobia), a nd unwillingness to go into society. At this initial visit she complained only of feeling nervous, t t e r pulse-rate was 100. No thyroid enlargement. On the 17th of January she came in~o Dublin on business, fell fil, ha.d diptopia in the street. In the evening, having gone to bed on her return, she felt chilly ; temperature 10'2 o, pulse 116. There was slight right occipital headache. The face was flushed, and she was constipated. LaxatŸ and aspirin.

January 18 th . - -The occipital headache had disappeared. No diplopia, but the eyes felt " dazed and un- natural ." She could open them, but they soon closed ol themselves. She felt very tired and sleepy. The pupi[s behaved normally. No obvious defect of eye lnovements. Knee-jerks smart ; no ankle clonus ; plantar reflex normal ; no neck stiffness. Temperature 101 ~ to 102 o.

January 19 th .~More sleepy ; but she sat up in bed and read both large ancl small print presented to her, saying, however, that her eyes were dazed. No diplopia. She dozes 0ff, a nd then begins to talk to herself a nd smfle. Perfect euphoria.; " willing to get up and go for a walk " ; rather annoyed at all the fuss being made about her.

Ja, nuary 2 0 t h . ~ D r . O'Carroll saw her late in the evening; he ~hought there was some ocular inco-ordina- tion, the eyes not moving to right or left after the finger as much as they should move normally. Ii a.ppeared as if the muscles refused the extra effort, but the patient professe~t to see the finger long after it had passed laterally quite out of the normal range of vision. That she really did not see

Bv DRS. J. O'CARROLL and G. ~ESBITT. 495

even as far as the normal range was prove o by her n o t

recognising-the number of fingers held up. Her mentaI condition was much as described on the 19th, but slightly duller. She was amiable; attempted.to be helpful; made no complaint whatever. The eyelids were hea.vy, and tended to close at any pause in the examination : but a s il~

was fairly continuous there was no opportunity of observ- ing any talking to herself. The reflexes were as already observed. No stiffness of the neck; no decided knee-exten- sion resistance, though a slight degree of it could not be absolutely excluded. Ir certa.inly provoked no pain. Eea'lier in the da.y her sense of orientation appears to have been defective ina.smuch as she thought she had her ha~ and ~-eil on, or perhaps this was a simple par~esthesia. Dr. O'Carroll suggested that the case wa.s one of encephaliti~ lethargica, and advised spinal puncture for the purpose both of diagnosis and treatment. With regard to prognosis he was hopeful, basing his optimism on his experience in the very grave hospital case of Mrs. G., and on the mor- tality record of about 20 per cent. as given in the English Local Government Report, abstracted in the Britisk Medical Journal of January l l t h . He did not see the case after this visit. The medical attendant 's note continues the history.

Janua.ry 21st.--Some stiffness of the neck and left leg. Very sleepy. Pulse and temperature as before. Twitch- ings of face and arms. Lumbar puncture ; clear fluid under considerable pressure, and several drachms.

January 2 '2nd. . Rigidity of left arm and leg and of neck ; increased mental confusion ; retention of urine with wetting

of bed. January 23rd.--No cha.nge. Lumbar puncture again; a

drachm or two ~'ith no pressure ; catheter necessary.

496 Some Recent Cases of E~wephalitis Lethargica.

Ja¡ 24.th.---Copious hmmorrhage in urine from this to the end. Temperature rose gradually to 105~ the pulse gra~lually failed, and the patient died comatose on the 26th of January. Kernig's knee extension sign was well marked towards the end. Plantar reflex remained normal; no pul- monary complications.

At the consultation on January 20th we had decided a gainst the use of hexamine, as the Br~tish M edical Journal ~bstract stated that it was supposed to be responsible for h.mmaturia in several of the English ca ses. At a subse- quent consultation with another physician ir was prescribed in 10-grain doses three times a day. Whether a s a mete sequence or a consequence, copious hmmorrhage occurred two days later. The doctor in eharge of the case is satis. fied that the case was so manifestly on the down grade that the hsematuria had no significance with regard to the fatal Issue.

CASE IV. ~']:r. D. M., aged sixty-eight, widower, was first seen by one of us (G. E. N.) on January 18th, 1919. He was in bed in his own borne, and complained that a few days previously he had developed intense pain of a tingling nature in three fingers of his right hand. tqe stayed in bed for a day, but the day before advice was sought he had been out as usual. In the evening he felt chilly, and took to befl again. He had always been a healthy man, though his family said he was inclined to be nervous and sometimes irritable. With the exception of a slight attack of in- fluenza last autumn, no history of definite illness could be, obtained. He complained of nothing except the pain in hi,~ fingers, which he said was then nearly gone, and he seemed inclined to consider a medical visit somewhat un- necessary. He had no headache, no cough, or othe~

By DR$. J. O'C~I~ROLL and G. NESBITT. 497

common symptom. On examination, his temperature was found to be 100.8 o, pulse 100, and rather low tensi£ (120 mm. Hg.). The urine of febrile type contained a trace of albumen, but the case was curiously nega tive as regards physical findings. His speech seemed, however, somewha.t thick and drawling, but when the attention of his family was drawn to this point they were not sure that t here was any definite alteration, t t is temperature fell the following morning to 98 z, but rose in the evening to 103 o, a.nd when seen the following day was 10], o. He was said r243 have slept a great deal in the interval, t t is hand had ceased to trouble him, and he complained of nothingMin fact, said he was very well. Ncxt day his tendency to sleep had become re- markable, so much so that his daughter jokingly remarked that " he must have sleeping sickness." This remark suddenly suggested a possible diagnosis. He lay in bed in

perfectly passive a ttitude, with his eyes closed and " mask-like " expression on his face. In addition, a slight tremor of the right hand made one think of paralysis agitans. On speaking to hito he was very easily roused, and answered questions quite intelligently and clearly, ex- cept that he still slurred his speech somewhat. Imme- diately one ceased to ta:lk to hito he relapsed into stupor. This condition of apparent stupor, from which he could be so easily roused only to re]apse again at once, presented remarkable and hitherto unfamiliar picture. That night, and to some extent during the previous one, he was de- cidedly delirriOus, though not at all violent, his nocturn~l

" O " �9 state contrastm~ forcibly with his a pathy during the day On January 2'2nd we saw him together, and examined him again very fully, t-Iis mental condition was unchanged~if anything more drowsy and lethargic. When roused he spoke quite sensibly, and denied a ny pain or other symptom.

498 Some Rece~~t Cases of Encephalitis Lethargica.

Though definite ptosis could hardly be said to be present, he opened his eyes but seldom, and never fully. The pupils were equal~somewhat contracted and reacting. Very small range of movement of the eyeballs could be elicited, though frequent attempts hito to look in various directions. mus. The visual fields seemed

were made to induce There was no strabis- normal. The facial

muscles appeared weak, and the expression was certainly " fixed," but no definite paralysis was present. There was some slight rigidity of the neek, but no pain on ttexing the head. The limbs were relaxed, but there was no paralysis. Knee-jerks just present; no Babinski of ankle elonus. Sensation seemed in abeyanee. He signified that he felt but did not resent painful stimuli. A non-painful Kernig was present. The bladder was normal, and the bowels had been made to aet with some difficulty. Cireulatory and respiratory systems showed nothing abnormaI. Tongue was dry and brownish, and teeth were septic.

lJumbar puneture was performed, and about 30 e.es. of elear fluid under eonsiderably inereased pressure were withdrawn. Subsequent examination of this fluid showed nothing abnormal--in faet, Dr. Polloek deseribed the fluid as " more normal than normal, with no exeess of pro- tein or lymphoeytes.

We agreed that the features of the case were remarkable were different from those of any eondition with which

we were familiar, a nd it was a noteworthy faet that a pre- eisely similar pieture had been eneountered by one of us (J. O'C.) two days before in the case deseribed above. We mad› a diagnosis of encephalitis lethargiea, and gave a guarded, though somewhat hopeful, prognosis in view of the published figures of mortality (20 per cent.).

The further progress of the case was uniformly bad. He

By DRS. J. O'CARROLL and G. ~N~ESBITT. 499

was again delirious that night, he began to pass under hito, and his bladder was distended when seen the next morning. On rousing him even then he was able to pass water at once, but did not empty the bladder, and the ca~heter was required. He was becoming more stuporous, and could be roused with greater difficulty. A few crackles could be detected at the base of the left lung. By evening his colour was greyish, his pulse was quick (120) and feeble, and ir was evident that he would not last long. Next morning, after a night during which he was less delirious but more comatose than the previous one, he was in profound stupor, and could not be roused. Lumbar puncture obtained a few c.cs. of clear fluid. He died a few hours later (January 24th), the acute part of bis illness having lasted almost exactly one week.

These cases seem to be undoubted examples of the disease which, on its appearance in England last February, was described as " Botulism" or " Infectious Ophthal- moplegia." The outbreak was very thoroughly investi- gated by the Local Government Board, the London County Council, and the Medical t~esearch Committee, working in conjunction, and the results were recently published in an exhaustive report, to which Drs. James, MacNalty, and McIntosh, and Professor Marinesco are the chief contri- butors.

They conclude that the disease has nothing to do with botulism--that it is the same condition ~ was described by Von Economo in Austria, and Professor Netter in Paris in 1917, under the name " Encephalitis Lethargica," and that, though ir presents some features resembling polio- encephalitis, i t i s " a disease sui generis ana.tomically and clinically distinct from analogous affections."

Ir is not possible at present to discuss the many interest-

500 Some Recent Cases o/E~wephalitis Lethargica.

ing points in this report, or to give even a r›233 of the mass of informa, tion detailed therein. An excellent summary will be found in the British Medical Journal of January l l t h , 1919 (page 45). The cases we have just described appear to be typical, and Dr. MacNaity sums up the diagnostic features as follows (page 31) :

" In the prodromal period. An initial catarrhal affec- tion, particularly conjunctivitis, muy be suggestive. A change in the patient 's mental attitude, taking the form of emotional changes, apathy, or extreme restlessness, pro- gressive lethargy, a nd drowsiness indicate the possibility of the disease. Ir these symptoms ate accompanied by head- ache, vertigo, asthenia., diplopia, and diminished visual activity, fl~e possibility is further strengthened.

"In the acute ilb~ess.--The initiaI period of i)yrexia, the characteristic attitude and mask-like face, the profound stupor, from which the patient can usually be aroused, and its alternation in the ea rly stages with delirium, the asthenia, the rigidity, the emotional characteristics, the speech changes, retention of urine, tremors, early vomit- ing, and obstinate constipation are typical of the disease. The occasional presence of transient rashes may be helpful. Transient remission periods in the disease should be re- membered."

In the types presenting tocalising nervous signs, the pro- gressive nature of the paralysis is most important. The elearing of one paralysis and the advent of a.nother is to be lookecl for, a.s is also the frequency of bilateral lesions whieh, however, are never truly symmetrical, being more marked on one side tha.n ano~her. The transient na~ure of cranial nerve pa.ralysis when present is almost conclusive. The frequency of' ptosis, paralysis of the

By Das. J. O'CARROr,r, and G. NESmTT. 501.

ocular muscles, diplopia, facial pa.ralysis ordination are of value.

When the rarity of bilateral facial

, and ocular inco-

pamlysis in other forros of nervous disease, and its frequent occurrence in encephaiitis are remembered, the presence of this sign ia ~n a dditional aid to diagnosis:

A negative sign of value is the absence of optic neuritis. Prognosis is said to be better than the ala.rming state of

the patient would suggest. Among 160 cases in EngIand there were 37 deaths.

Va luable pathological work was done in these cases by Professor Marinesco, who, ten years ago, himself described the changes in botulism. The naked-eye-findings a.re slight and consist mainly of minute h~emorrhages in the neigh- bourhood of the pons and fourth ventricle. MicroscopicalIy, chief fe~tures were perivascular infiltration with round cells, capilla.ry hmmorrha, ges, and thrombosis of small ~e.- .~sels, the changes being, in his opinion, infla mmatory in nature with a striking resemblance to those of sleeping sickness described by Mott in 1899.

Bacteriological examination has not yet given any definite positive results, though Von Economo states the finding of a, diplo-streptococcus in the cases examined by him.

Finally, tili the virus i~ discovered a.nd specific methods obtained, treatment is mainly symp~oma~ic. The use of hexamine in large doses is inadvisable on a ccount of its lia.bilitv to cause h~ematuria.

4 p