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coloured by other blood-derived pigments, such as

urobilin. Still more recently it has been recognisedthat the tissues may be stained by pigments moreremotely derived from the blood pigments in diseaseaffecting the spleen, the liver, sometimes associatedwith glycosuria; we occasionally see examples ofbronzed diabetes and of hasmachromatosis associatedwith certain types of splenomegaly. In addition, how-ever, to these pigmentations, which are capable of

explanation, there occur a series of disorders of pig-mentation in which the colouring material is notderived directly from the blood pigment, but appears tobe due to the formation of true melanin, the normalpigment of the body. A familiar example is the waxingand waning of pigmentation in certain parts of the

body during pregnancy, the chloasma uterinum. Butthe most remarkable cases of increase of pigmenta-tion occur in the course of Addison’s disease. Thenewly deposited pigment is apparently true melanin,and its increase seems to be the direct result of dis-order of the function of the suprarenal gland. It isknown that pigmentation of exactly the same typemay occur without the ordinary symptoms of Addison’sdisease. In a case under my own observation the

patient, a young woman, suffered from great ascites,was severely ill with loss of weight and strength ; theskin was widely pigmented, as in Addison’s disease. Theabdomen was opened, the abdominal fluid removed, andevidences of a mild, chronic peritonitis were observed.No opinion was formed as to the actual cause of the peri-tonitis. This patient, however, fortunately made anuninterrupted recovery and returned to her work as aschool teacher, and remained under observation for someyears. She gained strength, and at first gradually, thenmore rapidly, the abnormal pigmentation of the bodyvanished. It is very probable that some of the cases ofleucomelanodermia which come under observation fromtime to time are associated with disease or disorder ofthe abdominal viscera in the neighbourhood of the supra-renal gland. It is interesting to recall that, just as inthe case of xanthoma, in which there is reaction andovergrowth of tissue elements owing to irritation dueto metabolic error, so in the case of these abnormalpigmentations the affected parts may react and increasein thickness owing to the formation of a certainamount of new tissue. The remarkable disease knownas acanthosis nigricans, proved to be frequentlyassociated with organic disease of abdominal viscera,appears to be an example of this sequence of events.With regard to this remarkable series of pigmentarydiseases, the suggestion naturally arises in the mind,and is supported by a considerable body of clinical ’,observation, that alterations in the distribution andamount of melanin pigmentation is directly associatedwith disorders or disease of the suprarenal gland andcertain other glands producing " internal secretions."

Skin, Blood, and Lym,p7z(ttic glands.In a review, however short, of the relationships we

have been discussing, one cannot fail to refer to thechange in the skin associated with disease affecting thestructure of the blood and certain hitherto unknown ’,affections of the lymphatic glands. The two conditions, Ilymphatic leukasmia on the one hand and the lympho-granulomatosis known as Hodgkin’s disease, may be Itaken as examples. In both these conditions, differingso widely in many of their clinical symptoms, two setsof phenomena affect the skin. The skin in both mayshow tumours, lymphoid nodules in the case of leuksemia Ifand lympho-granulomata in the case of Hodgkin’sdisease. In addition they both show remarkablecutaneous reactions without definite tumour formation.The skin may become erythematous and thickened, Iwith symptoms of the most intense pruritus. Thereare few disorders of the skin so distressing as thepruriginous manifestations of both leuksemia and of

Hodgkin’s disease. They are, as is well known,frequently associated with characteristic fever. Theevidence seems to point strongly in both cases to theinfective origin of the classes of disease of which

lymphatic leuksemia and Hodgkin’s disease are

examples.

A LOCAL SURVEY OF

ENCEPHALITIS LETHARGICA,BASED ON 32 CASES OCCURRING IN MANCHESTER

DURING 1920.

BY W. ST. C. MCCLURE, M.R.C.S., L.R.C.P., D.P.H.,ASSISTANT TO THE MEDICAL OFFICER OF HEALTH, MANCHESTER.

IN view of the varying types of this disease whichhave been reported in different parts of the country, itseems desirable that some account of the incidence,distribution, and symptoms noted in a series of 32 casesoccurring in Manchester during 1920 should be recorded.The name encephalitis lethargica is apt to mislead,

because, although lethargy is present in many cases,yet it is not an essential symptom, and it may be that,on account of the use of this term, cases occurringwithout lethargy have remained unrecognised, andhave not, in consequence, been reported. During 1920and in the early weeks of 1921, 39 cases, in which thedate of onset of illness was in 1920, were reportedto be suffering or suspected to be suffering fromthis disease. After investigation and observation 32 wereaccepted as true cases, some other diagnosis being subse-quently arrived at in the other seven. Five of these sevencases ended fatally, and by post-mortem examinationor by positive findings in the cerebro-spinal fluid thecause of death was found to be cerebral abscess,cerebral tumour, cerebral haemorrhage, tubercularmeningitis, and cerebral softening. The symptomsin the other two were accounted for by influenza.There remain 32 cases in which the diagnosis wasaccepted as correct.The epidemiology and pathology of the disease are

known to a limited extent only, and up to the presenttime no causal organism has been isolated. Fromanalogy with similar diseases it seems likely that theillness is brought about by some infective micro-

organism. Nevertheless, there has not been inManchester any spread of infection from one personto another, nor has any connexion between the casesbeen discovered.

Seasonal and Local Incidence of the Disease.The cases were distributed over the year, according

to the dates of onset as follows : first quarter, 2 cases ;second quarter, 8 ; third quarter, 3 ; fourth quarter,19. In the second quarter 2 cases occurred in April,3 in May, and 3 in June; reported cases then becamefew until November, when there were 3, and in themonth of December the prevalence reached its

maximum, 16 cases coming to our notice.The cases were widely distributed over the city and

no connexion between them was traced, althoughcareful inquiry was made. The following figures showthe incidence on the various districts : Ancoats, 2 cases ;Central, 1; Cheetham, 3 ; Crumpsall, 3; Newton, 1 ;Clayton, 1; Ardwick, 1 ; Openshaw, 1 ; West Gorton, 3 ;Rusholme, 1; Chorlton-on-Medlock, 2 ; Moss Side, 2;Withington, 4; Gorton, 3 ; Levenshulme, 4. If thethree divisions of the city be taken, 3 cases occurred inManchester township, 8 in North Manchester, and 21 inSouth Manchester, the incidence rates being 0’30, 0’34,and 0’45 per 10,000 of the several populations. The16 cases in which the onset of the illness was inDecember occurred in 12 different districts.

J/6CMf!!/.The disease has shown no signs of infectivity-that

is to say, no connexion has been traced between thecases which were widespread over the city, nor didinfection spread to any of 138 family contacts. Nocommon source of infection was found. As regardsthe milk-supply, for instance, of the 32 persons affectedfour habitually consumed condensed milk, and theremainder obtained their milk from 28 different

sources ; nor does transference by means of otherfoods seem likely, though our investigation in thisdirection is incomplete. Housewives and workers havebeen attacked in about equa,l numbers, scholars and.infants have not escaped. It is certain that cases of’,encephalitis lethargica occur which remain unrecognised

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and escape investigation, and so connecting links maybe missed. Nevertheless, the conclusion may bededuced either that the disease is not infectious or thatthe infective material is widespread, and that thereexists amongst the majority of people a naturalimmunity to it.Cases of poliomyelitis and of cerebro-spinal fever

’crop up from time to time in a similar manner. These’two diseases are known to be due to infective micro-organisms, but no satisfactory explanation of theirmode of spread is forthcoming. It appears that theymay occur sporadically, or may, under certain unknown’circumstances, assume epidemic form. Until our

knowledge becomes more complete encephalitislethargica should be presumed to be infectious or

contagious and precautions taken accordingly.

Age- and Sex-Incidence.Table I. gives the age-groups and the sex of those

attacked and of those whose illness proved fatal. It

TABLE I.

will be noted that males and females were aboutequally affected and that adults were attacked ratherthan children.The question whether this disease is the same as, or

a variant form of, poliomyelitis has been studied by anumber of workers, and the conclusion arrived at onthe evidence so far obtained is that encephalitislethargica is a distinct entity. The data in the-Manchester series as regards seasonal incidence, age ofattack, and clinical manifestations tend to confirm thisconclusion, but the number of cases dealt with is smalland reliable inferences cannot safely be drawn. During-the year only 6 cases of poliomyelitis were reported,1 in July, 2 in August, 1 in September, and 2 in October.The entire absence of reported cases of poliomyelitis inNovember and December, when encephalitis lethargicareached its maximum prevalence, is a point to benoticed.

Occupational and Class Incidence.Of the 32 patients 4 were infants, 4 scholars, 10 were

women engaged in housework, and 14 were adults

employed, each in a different occupation. There isnothing to be learned, therefore, by further analysis.The social status of those attacked may be gatheredfrom a consideration of the size of house occupied by;them, and by the presence or absence of overcrowding.The figures are given in Table II.

’

TABLE II.

The greater number of cases occurred in houses withan average of one person or less per room, and theincidence is fairly well spread over the various socialgrades.

Syrnpt01ns.It is only by the collection and study of the symptoms

presented by a large number of cases that any reliable

classification can be made. The symptoms found inthe 32 cases under consideration and their relativefrequency are therefore recorded here without muchattempt to draw any general inferences.

General symptoms.-Most, but not all, began withsymptoms of an acute infection, fever, headache,vomiting, pains in the body and limbs. Fever was notconstant, and when present the temperature rarelyexceeded 103° F., more commonly it ranged between100° and 102°. In 11 cases it was absent altogether.This may be because the cases were not seen earlyenough but, in any event, the rise in temperature was,in many, a brief incident at the commencement of theillness. The absence of temperature is not necessarilyof good portent; of the 11 cases in which it was absent,6 died, 3 recovered, and 2 are yet ill. Headache wascomplained of by 16 patients, and 11 began withvomiting. Both headache and vomiting disappearedwithin a few days as a rule. In a few, headache waspersistent throughout and in one case in which thediagnosis is still in doubt, vomiting has continued forseveral weeks. Pain in the limbs and body occurredin about half the cases as an initial symptom, andin rather less than this number pains of a more

localised character, and probably nervous in origin,have been a marked feature in the later phases of theillness. General asthenia, becoming more pronouncedas the disease progressed, but without any markedwasting, occurred in all our cases.Duration of symptoms of onset.-The period elapsing

between the appearance of the first symptom and theonset of prostration can be stated approximately asfollows: 1 to 3 days-14 cases; 4 to 7 days-8 cases ;8 to 14 days-7 cases ; 15 to 24 days-3 cases. It is not,therefore, generally speaking, a disease of sudden onset.as is the case with cerebro-spinal fever, and as a rulewith poliomyelitis.

Nervoussymptoms.-Lethargy, which became extremeat some stage of the illness, was a prominent symptomin 29 cases. In the remaining 3, although there wassome hebetude of body, there was no inclination to sleep.Paralyses.-Fifteen cases were associated with

cranial nerve paralysis, and, in addition, 5 others

complained of diplopia at some time during theirillness. There were also cases in which the musclesof the face were relaxed and expressionless, due

apparently to general asthenia. The various nerveswere involved as follows: third, 4 cases; third and

sixth, 2 cases; sixth, 1 case; sixth and seventh,2 cases; seventh, 4 cases; seventh and ninth, 1 case;and possibly the fifth in 1 case. Paralysis of the thirdnerves was seldom complete. Squint or diplopiaoccurred in 13 cases, or in rather less than half ofthe total. Nystagmus of a coarse kind was present in3 cases. The condition of the pupils and the pupillaryreactions were found to vary at different stages of theillness, and gave no aid to diagnosis. The fundus oculiwas examined in 17 cases and was unchanged in 11;the retinal veins were congested in 4, and in 2 therewere signs of commencing optic neuritis.Limb paralyses.-In no instance was there paralysis

of the limbs, but in 2 cases the left arm was foundweaker than the right, and in 1 case there wastemporary paresis of the arm and leg on one side.

Positive nervous symptozr2s.-These symptoms did notpredominate in our series. Convulsions ushered in theillness in 2 instances, bilateral twitchings of thelower face muscles occurred in 2, of the jaw musclesin 1, of a group of muscles in the upper arm in 3, andspasms of both arms in 1 case. Persistent headacheor pains in some part of the body, usually the shouldersor back, were recorded in 8 cases.

Other symptoms and signs.-Hiccough was the initialsymptom in 2 cases; buzzing in the ear was the firstsign of illness in 1. Swelling and redness of one side ofthe face was noticed twice, and swelling of one legonce. Bowels were commonly constipated. Incontin-ence of urine was noted in 7 cases and retention in 3 :

paralysis of the sphincter ani was present in 5 cases.Skin eruption was seen only in 1 case, and in thatinstance it was of an acneiform character on the back.The condition of certain reflexes was recorded in 20

cases as follows :-Patellar reflexes : about normal 10,

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increased 2, absent 8. Plantar reflex : normal 16,extensor response 2, absent 2. Ankle clonus : presentin 1. Kernig’s sign : present in 5.

Res1llts of Illness.Of the 32 cases, 17, or about 53 per cent., proved fatal.

The duration of illness in the fatal cases was as

follows : Under 1 week, 5 cases ; 1 to 2 weeks, 4 cases ;2 to 3 weeks, 2 cases : over 3 weeks, 6 cases. One wasill for 170 days, one for 74. and one for 57 days. Of the

remaining 15 cases, 2 made a complete recovery, 7 havebeen ill for a few weeks and are still ill. The conditionof the other 6 may be stated briefly :-CASE 7.-M., 50. Condition nine months after onset: Face

expressionless, head and shoulders bowed, limbs stiff,shntfiing gait.CASE 8.-F., 20. Condition nine months after onset:

Mental depression, head and shoulders bowed, arms bent,stiff, and " sticky," paresis left shoulder muscles.CASE 15.-F., 45. Condition three months after onset:

General asthenia, paresis right arm and forearm.CASE 17.-M., 22. Condition two months after onset:

General asthenia, mental dullness, right partial ptosis.CASE 24.-F., 42. Condition two months after onset:

General asthenia, paresis right forearm.CASE 32.-M., 17. Condition nine weeks after onset:

General asthenia, mental dullness, and noises in ear.

Pathological Examinations.The blood of two patients was examined for Wassermann

reaction, with a negative result in one and a doubtful resultin the other. Cerebro-spinal fluid was examined from12 patients. In all it was clear; in one Staphylococcusaureus was said to be present; in the remainder noorganisms were found. In one instance there were

159 lymphocytes per c.mm., in another 30. In theremainder there were either no cells or very few.

Post-mortem Examinations.

In two cases a post-mortem examination was made.CASE A.-M., 28. Onset of illness, May 24th, 1920; date

of death, June 10th. Illness began with hiccough, followedby headache and drowsiness progressing to extremelethargy. Ptosis and left internal strabismus were

present.The following is a copy of a report upon the

examination of the brain by Dr. G. D. Dawson, aworker in Professor S. Delepine’s laboratory. Thebrain was sent for examination by Dr. T. E. Dickinson,acting superintendent of Monsall Hospital :-" A brain, weight 1315 grammes, shape normal. There is

general congestion of superficial blood-vessels. No evidenceof meningitis. On section, the grey and white mattereverywhere showed numerous small, dilated blood-vessels,the congestion is most pronounced in the pons and perhapsin the occipital lobes. No haemorrhages or other lesionsare visible to the naked eye. The ventricles are of normalsize and do not contain any excess of fluid."

Microscopical Examination.A. Transverse section througlt mitldle of pons.-" There is no

evidence of meningitis. The most noticeable feature is thepresence, especially in the grey matter, of numerous con-gested blood-vessels, mostly of small size. In most casesthe perivascular spaces are distinctly enlarged: some arefilled with small round cells, others contain a few extra-vasated red cells. Some haemorrhages are present, but theyare small and few. There is no clear evidence of anyconsiderable degree of chromatolysis."B. Section through part of left occipital lobe.-"The

appearances are similar to those of section A, but lesspronounced."CASE B.-Male, 39 years; onset of illness, Nov. 14th, 1920,

date of death, Jan. 26th, 1921. The illness began with painsin the " stomach " and vomiting. No headache, but painsin shoulders and back. Three weeks later there were

diplopia and blurring of vision; ptosis of the left eyelid andleft internal strabismus subsequently developed. Therewas little or no lethargy, but progressive asthenia ended indeath.

A post-mortem examination was made. There wasno evidence of meningitis, no deformity, no adhesionsor thickening of the membranes. On section, no gross i

lesions were seen, though the posterior half of thebrain was decidedly congested. The microscopicalexamination has not yet been completed.

I am indebted to those medical practitioners who ’,allowed me to see their patients.

A CASE OF OSTEITIS DEFORMANS.

BY DOROTHY C. HARE, C.B.E., M.D.LOND.,M.R.C.P. LOND.,

ASSISTANT PHYSICIAN, ELIZABETH GARRETT ANDERSON HOSPITAL.

With X Ray ReportBY C. C. BERNARD, M.A., L.M.S.S.A.,

HONORARY RADIOLOGIST TO THE ABOVE HOSPITAL.

THE patient, an unmarried woman, aged 47, is a.

native of Rangoon. Her mother was Armenian, herfather Eurasian; she was healthy, though not robust,as a child and young woman. At the age of 26 she hadboth ovaries removed for uterine fibroid at Madras,

Maternity Hospital by Sir Arthur Branfoot, after whichshe is said to have had fair health ; but between the.ages of 30 and 40 she had attacks of " kidney trouble "and recurrent fever diagnosed as malaria. At about,the age of 42 she was told that her mitral valve wasaffected. The present affection of the bones was first.noticed about June, 1917, when a nurse, who wasmassaging the patient, discovered that her righthumerus and right femur were bent. The patient at thistime complained of pains in the back, ribs, and ankles,and of general tenderness in the limbs. She went to theGeneral Hospital, Madras, in October, 1917, where thedisease was diagnosed as osteo-malacia. She wastreated with calcium lactate, and during the next fewmonths the pains and tenderness lessened, and havenever returned so acutely since. She has, however,complained increasingly of pain in the lower part ofthe spine, relieved by lying down. She has beenunable to walk far and is easily tired by exertion.The patient’s height has diminished progressively,

and she is said to have lost at least 7 inches. The onlywritten record is that in 1918 she measured 4 ft. 9 in. inher stockings ; her present height is 4 ft. 7 in. Theweight does not seem to have varied much, being 102 lb.in January, 1918, and 93 lb. in July, 1920. The headhas gradually enlarged; the patient says that theincrease in size was first noticed by her friends in thelatter part of 1917, and that in 1919 it measured 23g in.in circumference; the present measurement is 24 in.During 1918 there was a return of kidney trouble, andsmall quantities of blood and pus were passed in theurine, which contained at times a red sediment. Thepatient says that she has suffered frequently fromintestinal flatulence, but on the whole her generalhealth has remained good.

Dietetic Habits.Full notes on the patient’s customary diet are

recorded in view of the possibility that this diseasemay one day be brought into line with other bonediseases due to food deficiencies. The patient hasalways had plenty of eggs and milk. She is fond ofmeat and usually eats it twice a day. She has nevereaten much vegetable, and would go for weeks withouttaking green vegetables, roots, or potatoes ; but she hasalways eaten some fruit daily, such as mangoes,mangosteens, bananas, or plantains ; apples, pears, orgrapes have been eaten occasionally. She eats verylittle bread and does not care for sugar or sweets. Shenever takes meat fat, and very little butter ; bacon hasonly been eaten recently. The patient has always beencareful of her diet on account of indigestion, but madeno alteration in her habits of diet before the onset ofthis illness. She suffered no shortage of any particulararticle of diet during the war.

Previoits Treatments.From October, 1917, for about six months the patient

was treated with large doses of calcium lactate, 30 to40 gr. daily. After that time the drug was stopped, asit was thought to be causing indigestion, but it has been

i taken at irregular intervals since. The tenderness ofthe bones disappeared whilst taking the drug. During1918 the patient was given pituitary extract in tabletform, 2 gr. daily for about three months, but it was nottaken with great regularity. The patient noticed noeffects. The kidney symptoms were treated with an

H 2