ltdfim J" P#dtat. 42: 101, 1975

MEASLES ENCEPHALITIS*

A Clinical Study o f 25 Cases USHA SHARMA, SHAKUNTALA SAXENA AND K.

aTaipur

DzsA]

Post-infectious viral encephalomyelit ides

are rare but do occur as a complication,

specially in measles. As there was a severe outbreak of the disease recently, a study of measles encephalitis has been done in detail. Measles encephalomyelit is was descrihed for the first t ime by Lucas in 1790 from England who described it as "an account of unknown symptoms following measles". The incidence of measles encephalitis can be surmised from the

study by Miller (1964) who included about

600 cases of serious complications after

measles in an epidemic covering about hal f a million no t i f ed cases. Comparable

figures for India are not available but it

can be surmised that in India the incidence may be a little higher as a large number of patients are malnourished and living

conditions are not healthy. An important factor is the superstitious belief that meas-

les is due to divine upsurge and the patients are not brought to the hospital at all.

The original pathological description of myelitis following measles was made by Barlow and Penrose in 1886. Since then several reports have appeared on various

aspects of measles encephalitis.

Clinically, encephalitis may start abruptly with convulsions followed by

coma, or gradual ly with a slow lapse into

*From the Department of Paediattlcs, S.M.S. Medical College, Jaipur, Rajasthan. Received on ~ptember 10, 1974,

stupor, drowsiness, irri tabili ty, headache,

vomiting and signs of meningeal irritation. Many cases begin with disturbances of

behaviour, restlessness and irri tabil i ty passing into delir ium.

A variety of neurological signs may be present including abnormal reflexes, involuntary movements, hemiplegia, ataxia, nystagmus, dysar thr ia and dysphasia, the E.E.G. always reveals some abnormali ty. However , no diagnostic pa t tern is known. Th e morta l i ty rate is about 20~ Most of the deaths take place in the first week o f illness.

Material and Methods

rwenty-f ive cases of measles encepha- litis admit ted to the Paediatr ic Ward of Th e S.M.S. Hospital, Ja ipur , were studied. Most of the patients were seen from April to August, 1973.

A thorough history was taken and

detailed examinat ion done. Th e diagnosis

of measles was made on clinical grounds and the following criteria formed the basis

of diagnosis of encephalitis: Symptoms of irri tabil i ty, drowsiness, convulsions, deli- r ium, meningeal irr i tat ion in addi t ion to

unconsciousness, semiconsciousness, cranial nerve palsy, paralysis and vomiting. A

change in sensorium was the sheet anchor o f diagnosis as no facilities for virological studies were available.

Rout ine examinat ion of the blood, urine, stool and C.S.F. was done.

107 INDIAN JOURNAL OF PEDIATRIC8

All the patients were t reated with tetracycline (Rever ine)10-15 mg./Kg, of body weight, steroids, I .V. fluids supple- mented with symptomatic and supportive t reatment , i.e. fluids to correct electrolyte

imbalance, anticonvulsive drugs, antipyre- tics and suction and oxygen therapy wherever needed.

Observat ions

There were 9 cases below 2 years of age, 12 between 2-5 years and 4 between 5-Syears. No child above 8yea r s of age

Boys exceeded girls in the ratio was seen. of 3:2.

The Table 1.

clinical features are shown in

C.S.F. examination was done in 21

cases only. 16 cases showed 10-200 cells/cu, ram. predominant ly lymphocytes, and in 5 cases there were 5-10 lymphocytes/

cu. ram. Proteins, sugar, chloride and pressure were within normal limits in all

the samples. Tota l leucocyte count was between 4,000 to 6,000/cu. ram. with predominance of lymphocytes.

VOL. 42, No. 327

16 cases (64 ~/o) recovered completely.

Two (8%) recovered with residual sequelae. Tw o patients died. Five left against medical advice.

In 2 cases, signs of encephalitis appeared after 25 days of appearance of the rash. In one case, signs appeared after 1 month of appearance of the rash. In the remaining 22 cases, the interval was 3 to 15 days.

Discuss ion

Th e largest number of patients was less than 5 years of age. None was above 8

years of age. This finding is in concordance

with the observations by Srivastava and Garg (1968) and M a t h u r t t a l . (1969) but differs from La Boccetta and Tornay (1964) who reported ~/o of patients between the age of 5 to 7 years and 6.5~/o cases above 8

years. Most of the eases reported by

Karel i tz and Eiseuberg (1961) were 5 to 10 years of age.

Males were seen more than females, Th e ratio in our series was 3:2 which is slightly higer than that repor ted by others,

T a b l e 1. ,Symptoms ana s~gn~.

Symptoms Sign.~

No. of cases % No. of cases o/ /o

Fever

Convulsions

Irr i tabi l i ty

Headache

Vomiting

25 100 Meningism 7 28

21 84 Hemiparesis 7 28

11 44 Absent knee jerks 3 12

11 44 Brisk knee jerks 7 28

11 44 Extensor plantar 7 28

SHARMA ET A L . ~ M E A S L E S E N C E P H A L I T I S 103

Mathur etal . (1960), however, reported

that females were affected more in comparison to males (8:5). No reasons

were assigned for this.

In 22 cases encephalitis developed within 3 to 15 days of appearance of the rash and in the remaining 3, C.N.S. symptoms appeared after 25 days of the rash. In one case symptoms could be

appreciated only after 1 month. It has been reported in the l i terature that in nearly all cases encephalitis occurs within

7 days of appearance of the rash

C.S.F. examination could be done only in 21 cases. I t revealed normal chemistry but the cell counts varied from 10 to 200/cu. mm. (all lymphocytes) in 16 cases (64%) and in only 5 cases (20%) the counts were borderline, 5 to l0 lymphocytes/ cu. mm. Srivastava ~t al. (1968) reported 10 or more lymphocytes in 71.4% and

protein content over 45 rag. % in 42.0% of cases in his series. La Boccetta and Tornay (1964) found over I0 cells/cu, mm. in 85% of cases, proteins above 45 mg. (range 48-240 mg.) in 47% of patients on the first day and in 66 to 100% over the next five

days. They reported a sigmficant relation- ship between tile presence of coma and elevated C.S.F. glucose level but this corre-

lation has not been found in our series. In our series 8% of the cases expired.

20% of the cases left against medical advice in a moribund condition; they were seriously ill at the time of discharge. The remaining (72%) cases recovered com- pletely. Clinical lbllow up showed that only 2 cases had regression of intellectual milestones while the remaining ones were free from any residual sequelae. The I .Q . was not estimated.

Srivastava and Garg (1968) reported 28.5% mortali ty. In their series the

neurological sequelae were seen in 25% of cases in the form of hemiplegia, mental

deficiency, recurrent grand mal convulsions,

quadriplegia and athetosis. Th e high mortal i ty ra te and residual sequelae may

be due to the fact that a good number of patients were rushed to the hospital in a

moribund state as suggested by the obser-

vations that 50% of deaths occurred with- in 24 hours of admission. Ma thu r a al. (1969) repor ted a mortal i ty rate of 23.07%,

while no neurological sequelae persisted in survivors.

Sawchuk et al. (1949) reported a morta- lity of 32%, La Boccetta and Tornay (1964) 11.5% and Miller et al. (1964) 20%. No deaths occurred in 42 patients reported by Karel i tz and Eisenberg (1961) but 31% had neurological deficit.

The exact pathogenesis ol measles encephalitis is still debated. Various

theories put forward by various workers are: 1. Virus attacks the brain substance

directly.

2. Inflammation is due to an immunologi-

cal reaction. 3. Infective virus activates a latent neuro-

tropic virus.

4. Toxic theory.

The last one put forth by Carey (1944) is untenable and has been discarded.

The immunological theory is based on

the similarity between measles encephalitis and encephalitis accompanying vaccinia,

variola and rubella as well as reactions observed after rabies and pertussis infec- tion or immunization.

This has been fur ther substantiated by experimental sensitisation of animals with

homo or heterologous brain homogenate and producing comparable C.N.S. involve-

104 INDIAN JOURNAL OF PEDIATRICS VOL. 42, No. 327

ment (Rivers 1932, Kabat et al. 1947,

Morgan 1947). The direct invasion of the central nerv-

ous system by measles virus in the pathoge- nests of measles encephalitis is suggested by the following observations: Isolation of the virus from the brains of cases of measles encephalitis was reported by Scbafl'er et al. (1942). Histopathological examination of 20 cases revealed a characteristic intra- cytoplasmic and/or intranuclear inclusion in 15 cases and in 5 of these, giant cell syncytia were also present. The inclusions and syncytia were similar to those produced by measles virus in cells of tissue culture observed by Enders and Peebles (1954). Nearly all cases had evidence of classical pathological changes of perivascular in- filtration accompanied by demyelination. Clinical evidence that neurological signs and symptoms may precede the rash of

measles (Holliday 1950) also supports the direct virus invasion theory.

Webb et al. (1964) have suggested thal development of virus encephalitis depends both on virus infection of the brain and on the type of antibody response ot the host. They have put forward a hypothesis that if antibody reaches the brain at some critical

stage of viral multiplication, the union of antigen with antibody might give rise to an inflammatory reaction in the cerebral tissue. I f antibody reached the central nervous system eaIlier than usual, the risk of this might be increased. I t may be possible that measles encephalitiscould be due both to the invasicn of the brain by the virus, perhaps a fairly common event, and also an imml~nob~ical response such as unusually ear]y antibody response by the host. This has flarther gained support from the obser- vations tt~at perivenous demyelination can be produced in animals by injection of an emulsion of brain tissue.

A significant degree of pleocytosis in C.S.F. has been a common observation. In our series 6~% of cases revealed cell counts ranging between 10-200 cells/cu.mm. The association of disease with cell counts

within normal limits suggests that symptom- less disease of the nervous system may also occur in a small percentage of cases.

Electroencephalographic abnormalities have been reported by Gibbs et al. (1959). They have found abnormal slowing in all 37 patients with clinical evidence of encephalitis and in 51~/o other children suffering from uncomplicated measles. In the latter group of cases, the E.E.G. reverted to normal once the illness was over. Pampiglione (196~) reported moderate to slow activity in all cases in the prodromal

stage.

Karelitz and Eisenberg (1961) did not observe encephalitis in any patient who had received gammaglobulins. Greenberg et al. (1955) stated that gamma globulins modified measles may still be compli- cated by encephalitis thotlgh less frequently in comparison to unmodified measles. They concluded that there was no

difference in mortality and sequelae in treated cases. La Boccetto and Tornay (196~) reported a lower mortality of 11.5% in the treated group compared to 32~o in a previous series where gamma globulins were not used; on account of a smaller number of cases iu the study it was uon- conclusive. None of the cases in the

present study were given gamma globulins.

Appelbaum et al. (1956) reported pro- mising results of corticoid therapy in a

small series of cases. However, Swanson (1956) compared cortisone treated and nontreated cases and felt that the clinical course remained the same but sequelae

SHARMA ET AL. - - MEASLES ENCEPHALITIS I05

were less common after corticoid therapy.

Karelitz and Eisenberg (1961) did not agree with Swanson's findings and concluded that

cortisone administration did not prevent complications and survival can be attri-

buted to constant watch over the clinical

progress of the patient supplemented with timely and judicious supportive therapy.

Summary A detailed clinical study of 25 cases of

post-measles encephalitis has been presented. Male preponderance was evident, male: female ratio being 3:2. The Maximum num-

ber of patients (84~o) were below 5 years of

age. The sym~)toms of encephalitis were noticeable in 88% of cases between the 3rd to 15th day of appearance of the rash. The

mortality rate was 8% only but if 5 patients

who left against medical advice and were in a moribund condition, are included, it increases to 28~ which is quite significant. Residual sequelae developed in 8~/o of cases who were followed up for a few months.

R e f e r e n c e s

Appelabaum, E. and Abler, C. (1956). Treat- ment of measles encephailitis with cortiocotropin. Amer. 97. Dis. Child 92, 147.

Gibbs, F.A. and Gibbs, E.L., Carpenter, P.R. and Spie L H.W. (1959). Electroencephalographic abnorma- lity in uncomplicated childhood diseases. 97. Amer. ~d. Ass. 171, 1050.

Greenberg, M., Pellltteri, O. and Eisenstein, D.T. (1955). Measles encephalitis. Prophylactic effect of gamma globulin. ,7. Pe.diat. 46, 642.

Greenberg, M., Pellitteri, O. and Eisenstein, D..T

(1955). Measles encephalitis. Ibid. 46, 648. Holliday, R.B. Jr. (1950). Pre-eruptive neurologi-

cal complications of the common contagious diseases-- Rubella, rubeola, roseola and varicella. Ibid. 36, 185.

Kabat, E.A., Wolfe, A. and Bezer, H.E. (1947). The rapid production of acute disseminated encepha- lomyelitis in Rhesus monkey by injection of hetero- logous and homologous brain tissue with adjuvant 97. Exp. IVied. 85, 117.

Karelitz, S, and Eisenberg, M. (1961). Measles encephalitis: evaluation of treatment with adreno- corticotropin and adrenal corticosteroids. Pediatrics, 36, 351.

La Boccetta, A.C, and Tornay, A.S. (1964).

Measles encephalitis. Amer. 97. Dis. Child. 107, ~47. Mathur, .S., Dave, D.S. and Dhawan, S.K.

(1969). Measles encephalitis. Arch, Chld. Hlth. 11, 156.

Miller, D.L. (1964). Frequency of complications of measles. Brit. reed..7. 2, 75.

Morgan, I.M. (1947). Allergic encephalomyelitis in monkey in response to injection of normal monkey nervous tissue. 97. Exp. Meal 85, 131.

Pampiglione, G. (1964). Prodromal phase of measles. Some neurological studies. Brit. reed. ,7.

2, 1296. Rivers, M.A. (1932). Quoted by Srivastava and

Garg (1968). Sawchuk, S L., La Boccetta, A.C., Tornay, A.,

Silverstein, A. and Peale, A.R. (1949). Ara~r. 97. Dis. Child. 78, 844.

Schaffer, M.F., Rake, G.K. and Hodgcs, H.L. (1942). Amer. "7. Dis. Child. 64, 815.

Srivastava, J.R. and Garg, B.K. (1968). Measles encephalitis. Indian Pediat. 5, 29.

Swanson, B.E. (1956). Measles meningo-encepha- litis. Amer. 97. Dis. Chilh. 92, 272.

Webb. H.E. and Gordon, Smith, C.F. (1914). Neuroparalytic accidents with poliovaccine. Brit. reed. ,7. 2, 569.