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ENTEROVIRAL

MENINGITIS

IN VERY

YOUNG

INFANTS

Alan G. Nogen, M.D., and Martha L. Lepow, M.D.

From the Department of Pediatrics, Cleveland Metropolitan General Hospital, and

Wertern Reserve University School of Medicine, Cleveland, Ohio

(Submitted March 20; revision accepted May 24, 1967.)

This investigation was supported in part by Public Health Service Research Grant Number 5 RO1

A105770, from the National Institute of Allergy and Infectious Diseases.

ADDRESS FOR REPRINTS: Department of Pediatrics, Cleveland Metropolitan General Hospital, 3395

Scranton Road, Cleveland, Ohio 44109.

PEDIATRICS, Vol. 40, No. 4, Part I, October 1967

T

lIE syn(lrome of enteroviral meningitis

has rarely been recognized in infants

less than 6 weeks of age. Most published

reports of enteroviral disease in this age

group have described severe systemic

ill-ness involving multiple organ systems and

frequently culminating in death.

This report describes five cases of

entero-viral meningitis in young infants with

isola-tion of virus from cerebrospinal fluid

(CSF ). Four of the patients were treated at

the Cleveland Metropolitan General

Hos-pital (CMGH) during the period from Au-gust through October 1966. A fifth case

oc-curred iii 196:3 at the Babies and Childrens

Hospital, Cleveland, Ohio, and was studied

by one of the authors (MLL). The

experi-ence with suspected enteroviral meningitis

in infants less than 6 weeks of age at

CMCH during the 10-year period from

1956 to 1966 will be reviewed.

MATERIALS

AND

METHODS

Collection of Specimens

The specimens obtained for viral studies

included throat and rectal swabs

(

which

were placed in 2 ml of neutral Hank’s solu-tion with 0.5% bovine serum albumin, pen-icillin 1,000 units/ml and streptomycin 10

&g/m1), CSF, and acute and convalescent

sera. All specimens for virus isolation were

processed within 12 to 24 hours and

inocu-lated into tissue cultures.

Viral Studies

Examinations for enterovirus in stool,

throat, and CSF were performed in monkey

kidney and HEP-2 cells, according to the

previously described standard methods

em-plowed by the virus laboratory of CMGH.’

Viruses were identified by neutralization in

tissue culture, using specific hperimmune

monkey antisera produced in this

labora-tory.

Serologic Tests

Neutralizing antibody titers were

deter-mined in sul)jects sera as follows : mixtures

of twofold dilutions of serum and 100 TCD,#{176} of the virus isolated from

pa-tients’ cerebrospinal fluids were inoculated

into stationary cultures of African green

monkey kidney tissue. The highest dilution

of seruii preventing cytopathic effect was

considered to represent the actual titer and results are ex1)ressed as the reciprocal of the serum dilution.

CASE REPORTS

Patient 1

A 3,540 gm, white male vas born at University

Hospitals of Cleveland to a 29-year-old multipara

in August 1963 following an uncomplicated

preg-nancy. A few (lays prior to the mother’s

confine-nient two children at home were noted to have

“flu-like” illnesses with fevers of 39#{176}Cand

respira-tory and gastrointestinal symptoms. The infant

appeared normal at birth, but at 5 days of age

he was noted to be febrile (38.4#{176}C), anorectic,

lethargic, and mildly jaundiced (bilirubin + 7.9

mg/100 ml). Because of the possibility of bacterial

infection the infant was given 80 mg of

strepto-mvcin and 100,000 units of aqueous procaine

peni-cillin intramuscularl and transferred from the

obstetrical division to the pediatric service.

Pulse was 170 and the respiratory rate was 60.

The fontanelle was soft, but otherwise the 1)hySical

examination was normal. CSF examination revealed

#{176}TCD, is that dilution of virus which will

cause cytopathic effect in 50% of the inoculated

(2)

618

23 cells, 5 of which were polymorphonuclear

leukocytes, 12 were mononuclear cells, and 6 were

red blood cells. The protein was 71 mg/i#{174} ml

and the glucose was 53 mg/100 ml. Twenty-four

hours later the CSF cell count had risen to 129

cells, of which 25 were red blood cells, 98 were

mononuclear, and 6 were polymorphonuclear

leu-kocytes; the protein content was 71 mg/100 ml,

and glucose was 51 mg/100 ml. Treatment was

begun with 150,000 units of penicillin and 100

mg/kg of chioramphenicol intramuscularly every

12 hours for 4 days. Except for three short apneic

spells on the second day, the infant improved,

became afebrile, and was discharged on the fifth

day. Bacterial cultures of blood, throat, urine, and

CSF were negative.

Urine examination for cytomegalic inclusion

bodies was negative; x-ray films of the skull re-vealed no intracranial calcifications. Viral cultures

of the stool and throat were negative; Coxsackie

virus Group B, Type 3 was isolated from the CSF.

The baby’s development has been entirely normal

since discharge.

Patient 2

This 14-day-old, Negro male, the product of

a normal pregnancy and delivery, was delivered

of a 24-year-old multipara on August 11, 1966.

The infant was in good health until 2 days prior

to admission when a pustule, which drained the

following day, appeared on the left groin. At this

time the infant became increasingly irritable,

trem-ulous, anorectic, and warm. These symptoms

per-sisted and he was admitted to the hospital with

the diagnosis of suspected bacterial meningitis. There was no family illness.

The temperature on admission was 38.2#{176}C

(rectally), pulse was 180, and the respiratory rate

was 34. Examination of the left groin revealed a

2 x 2 cm lesion, which was no longer draining

pus. The infant was alert and tremulous, and he

was found to have bilateral sustained clonus of

both lower extremities and increased muscle tone.

The Moro, tonic neck, walking, and sucking

re-flexes were all normal.

The white blood count was 22,700, of which

40% were polymorphonuclear leukocytes, 1% were

bands, 47% were lymphocytes, and 12% were

mono-cytes; the hematocrit was 43%. Urinalysis and

x-ray films of the chest were negative. Admission

electrolyte values, including calcium and glucose,

were normal. The CSF obtained at time of

admis-sion revealed 20 red blood cells and 2,450 white

blood cells (of which 89% were mononuclear), a

protein content of 112 mg/100 ml, and glucose

of 43 mg!100 ml (blood glucose 72 mg/100 ml).

No organisms were seen on Gram’s stain. Because

of the possibility of bacterial meningitis, the child

was treated with methicilhin (200 mg/kg/day

in-travenously), colistin sulfate (10 mg/kg/day

intra-muscularly), and chloramphenicol (50 mg/kg/day).

Anticonvulsants were added because of the extreme

tremulousness. A repeat lumbar puncture 24 hours

after admission was traumatic, but the CSF was

again cultured for both bacteria and viruses. By

the second day after admission the tremulousness

had decreased. A third cerebrospinal fluid

exam-ination 4 days after admission revealed 240 white

blood cells, of which 99% were mononuclear; the

protein was 1 18 mg/100 ml, and glucose was 40

mg/100 ml. A final lumbar puncture on the

eigh-teenth day of hospitalization revealed 62 cells, of

which 61 were mononuclear. The clinical status of the infant remained stable during hospitalization.

Blood, throat, urine, and CSF cultures were

consistently negative for bacteria. Culture of the

skin lesion yielded proteus and Staphylococcus

aureus.

Coxsackie virus Group B, Type 5 was isolated

from the first and second CSF samples and the

stool specimen.

Patient 3

This Negro male was born at CMCH on July

15, 1966, to a 19-year-old primipara who had not

had any prenatal care. Two minutes prior to

delivery the fetal heart rate was 80, but the infant

was considered to be normal at birth.

He did well until 6 weeks of age when he was

brought to the hospital with a 1-day history of

irritability, fever, and a single, loose, yellow stool.

There was no other illness in the family.

On admission, the temperature was 38.5#{176}C

(rectally), pulse was 140, and respiratory rate was

52. Physical examination was normal except for

otitis media of the right ear and a diaper rash.

White blood count was 9,670 with a normal

dif-ferential; urinalysis and x-ray examination of the

chest were negative. Cerebrospinal fluid findings

revealed 35 white blood cells, of which 27 were

mononuclear and 8 were polymorphonuclear

leu-kocytes. Protein and glucose determinations were

not done. A second lumbar puncture was done 2

hours later; CSF examination revealed 42 cells

with a protein content of 35 mg/100 ml and

glucose of 62 mg/100 ml.

The infant was treated with sulfisoxazole for

the otitis media. Bacterial cultures of blood, stool,

and CSF were negative. He became afebrile on

the third hospital day and was discharged

asymp-tomatic on the fifth day.

ECHO virus Type 9 was isolated from the CSF

and rectal swab of this patient.

Patient 4

This 6-week-old, Negro male was born August

4, 1966, to a 21-year-old multipara following a

full-term, uncomplicated pregnancy; he weighed

(3)

the child developed a fine, erythematous, papular

rash over the arms and upper trunk which lasted

5 days. On the day before hospitalization the

in-fant’s temperature rose to 40#{176}C(rectally).

He was admitted to the hospital in September

with a temperature of 39.5#{176}C(rectally). The pulse

was 168, and respiratory rate was 66. Except for

somewhat increased tremulousness, the physical

examination was within normal limits. White blood

cell count was 13,350 with 86% lymphocytes. X-ray

film of the chest, urinalysis, and an intermediate

strength tuberculin skin test were negative. The

initial lumbar puncture at the time of admission

was slightly traumatic and examination of the CSF

revealed 437 white blood cells (all of which were

mononuclear), a protein of 63 mg/100 ml, and a

glucose of 44 mg/100 ml. A repeat lumbar

punc-ture was done 2 days later and the CSF contained

19 mononuclear cells, 15 red blood cells, protein

of 65 mg/100 ml, and a glucose of 54 mg/100 ml.

The child became afebrile within 24 hours after

admission and made an uneventful recovery.

Cul-tures of stool, blood, urine, and CSF were negative

for bacteria.

Coxsackie virus Group B, Type 5 was isolated

from the rectal swab and CSF specimen.

Patient 5

A 3,560 gm Negro, male was born in September

1966. He was the product of a normal pregnancy

and delivery and was well until 4 weeks of age

when he evidenced a non-specific erythematous

papular rash on the face and scalp. A week later he

was brought to the hospital because of fever and

ir-ritability for one day. The temperature was 38.9#{176}C

(rectally), pulse was 140, and respiratory rate was

40. Physical examination was entirely normal

ex-cept for the rash noted about the face and scalp.

White blood cell count was 15,000 with a normal differential; urinalysis and x-ray film of the chest were normal.

CSF examination revealed 440 white blood cells,

of which 96% were mononuclear and 4% were

polymorphonuclear leukocytes. Spinal fluid protein

was 48 mg/100 ml, and the glucose was 70 mg/

100 ml. The child was treated for 2 days with

methicillin (200 mg/kg intravenously) and received

2 doses of kanamycin (30 mg and 15 mg

intra-muscularly).

Bacteriologic cultures of stool, throat, blood, and

cerebrospinal fluid were negative, and

chemother-apy was discontinued. He became afebrile on the

third day of illness and was discharged

asymptom-atic on the fifth day of hospitalization. Coxsackie

virus, Group B, Type 5, was isolated from the

rectal and throat swabs and the CSF.

Three days after discharge a very fine,

papu-lovesicular eruption appeared on the chest and

back. Viral cultures obtained from these lesions

were negative.

CLINICAL FEATURES

During the 10-year period from 1956 to 1966 there have been at least 12 suspected cases of enteroviral meningitis in infants less than 6 weeks of age at CMGH. In eight of these babies the diagnosis has been made by exclusion of bacterial processes,

and recognizable viral lesions, since no

vi-ruses were isolated. In four of the patients

whose case histories are described in this

report, the diagnosis has been firmly estab-lished by the isolation of an enterovirus from the CSF. An additional case has been included of an infant hospitalized at an-other institution in Cleveland from whom Coxsackie, Group B, Type 3 was recovered in the CSF.

Description of the Patients

The age at onset of the syndrome varied

from 5 days to 6 weeks of age, but half of these infants became ill between the fourth to sixth week. As is the case with bacterial infections in the newborn, the male sex pre-dominated

(

10 males to 3 females

).

All but one of the patients were Negro, which reflects the major population treated at

CMGH. Birth weights varied from 2,340 gm to 3,720 gm. Those infants from whom enterovirus was recovered from the CSF were ill during the months of September or October.

Signs and Symptoms

Unexplained fever and irritability were often the only abnormal findings, as shown

iiiTable I.

Twelve patients were febrile with tem-peratures ranging from 38.2#{176}C to 39.5#{176}C

(rectally) ; 2 of the 12 had temperatures of 39#{176}C

(

rectally

)

or greater. Of the 13 cases

studied, 10 were noted to be irritable while

two were lethargic. Irritability in two was accompanied by tremulousness present during sleep.

The most common gastrointestinal symp-toms were anorexia and vomiting. Anorexia

was present in three of the infants while

(4)

620

not diarrhea. Five infants manifested skin

lesions. The face and trunk of one infant

had small pustules which were sterile on

bacterial cultures, while another had pe-techiae on the forearms. Three patients

had non-specific, erythematous,

maculo-papular rashes on the face and trunk. Neurologic evaluation performed on

ad-mission to the hospital was described as

within normal limits in eight of the cases.

Five infants were noted to have

exaggerat-ed s’Ioro and deep tendon reflexes, and one

of these

(

Patient 2

)

was noted to have in-creased muscle tone in both lower

extremi-ties with tremulousness. No abnormalities

of head circumference were noted. The

an-tenor fontanelle was normal in 12 infants.

Because of the difficulty in assessing

neuro-logical impairment at this age, long-term

follow-up is necessary. The longest follow-up in a child with a virus recovered from the CSF has been 3 years.

Laboratory Data

The white blood cell count was variable, but in most infants it was either normal or

increased. The most important diagnostic

procedure was an examination of the CSF. Lumbar puncturesf were performed on

all patients the day of admission. In some

cases a repeat examination of the CSF was

made several hours after admission

(

Table

II

)

. Over half of the infants had from 10 to

250 cells/mm in the CSF, and only one

child had more than 1,000 cells/mm’. Gen-erahly, the cell count returned to normal

values before the CSF protein.

The differential cell count of the CSF

re-vealed that none of these infants had less

than 25 mononuclear cells; the majority had over 50% mononuclear cells.

Protein levels in the spinal fluid were

ob-f A standard pediatric text lists up to 10

mono-nuclear cell/mm3 and a protein up to 120 mg/lOO

cc as normal.2 A spinal fluid glucose of 40 mg/100

ml or one-half of the blood glucose was considered

normal. Recognizing the variability of opinions,’

the foregoing criteria were utilized (except in the

premature infant in whom a CSF protein may be

up to 200 mg/100 ml until 1 week of age).’

tamed in 11 patients and 10 of these were within normal limits. In two additional

pa-tients the Pandy testy indicated a 2+ value.

In one of the patients the sPinal tap was traumatic.

None of the spinal fluid glucose

deter-minations performed on 10 patients was

less than 40 mg/100 ml. In six infants the

glucose was between 40 mg/100 ml and 60 mg/100 ml. In four additional neonates a five-tube reduction test, utilizing

Ben-edict’s qualitative solution, was performed.

In three instances there was reduction in four tubes; in one, three tubes showed re-duction.

VIRAL

STUDIES

Virus Isolation

Of the 13 infants studied, the CSF was received for viral culture from 10 and an enterovirus was isolated from 5, as is shown in Table III. Seven stool specimens were examined and an enterovirus was isolated from five. Seven pharyngeal swabs were

tested for virus, but only two positive

cul-hires were obtained. ECHO virus, Type 9 was isolated from the rectal swab and CSF sample of Patient 3, and Coxsackie virus Group B, Type 5 was isolated from both the CSF and stool in Patients 2, 4, and 5. Coxsackie virus Group B, Type 3 was iso-hated only from the CSF of Patient 1, but throat and rectal swabs were negative.

Serologic Studies

In an effort to determine whether any

in-fants with virus in the CSF were infected in

utero, blood specimens were obtained from mother and infant

(

Table III ).

Unfortu-nately, all the sera were not obtained early

in the course of illness. Since enteroviral infection is usually followed by an immu-nologic response, previous maternal infec-tion could be documented by the presence of neutralizing antibodies in the sera and

recent infection in mothers or infants by a

(5)

TABLE I

Pinsicti. Fisis IN 3 YOUNG INFANTS

. . ?Stnnber of

Findings

I alien/s

Sign

Fever U

38-38.5#{176}C 4

38.6-39#{176}C 6

over 39#{176}C

Irrital)ility 10

Lethargy

Anorexia S

Vomiting

Rash* 3

‘seurolo)gi( Examination

Normal 8

‘Freniulousiiess 3

Nuehal rigidity 1

Increased muscle tone 1

Exaggerated deep tendon reflexes

Exaggerated Moro response 3

* Included is a transient rash 7 days prior to

adniis-sion.

mother had low or absent antibody titers at

tIlC time of onset of illness in the infant, she

might have experienced infection (luring childhood with a decline of antibody below detectable levels, or she might be

undergo-ing concurrent infection. A second serum

sample, obtained from the mother several weeks later, could provide an answer to the

(lue5ti0I of recent infection. If the mother

had a low antibody titer at delivery, then

the infant would be susceptible to infection

at birth and would presumably have

ac-1uirel his infection either from his mother at the time of delivery or from the family contact at home. No serologic studies were performed on Patient 1. Patient 2 and his mother had antibody levels of 64 or greater to Coxsackie virus Group B, Type 5 in all sera tested, so that the time of onset of in-fection could not be determined. No acute serum samples were obtained from either the mother or the baby. Patient 5

demon-strated similar features. Patient 3 showed a

rise from less than 4 to 8 against ECHO

virus Type 9 during that period, indicating

an infant susceptible at birth who probably acquired his disease in the household. Pa-tient 4 and his mother were apparently

both infected simultaneously during a

family outbreak and both developed a

significant antibody titer to Coxsackie virus

Group B, Type 5 within 2 weeks after the

onset of illness. Rectal swabs obtained from

other family members at the time the infant

was admitted to the hospital yielded the same enterovirus.

COMMENT

Five young infants with enteroviral

men-ingitis, proven by virus isolation from the

CSF, and eight additional infants suspected

of having this disease have been described.

It is apparent from the findings in these

pa-tients that signs of meningeal irritation are

frequently lacking and symptoms are

non-specific. More frequently the diagnosis of enteroviral meningitis is made by exclusion of a bacterial etiology. It is quite likely that enteroviral meningitis occurs much more

frequently in infants less than 6 weeks of

age than has been previously appreciated.

A summary of some of the recent reports

of enteroviral disease with central nervous

system involvement in neonatal infants is shown in Table IV. Many Coxsackie and

ECHO viruses have been incriminated, in-chiding Coxsackie Types A-4,5 A-16,

B-i-5,10-22 and ECHO Types 7,23.s 9. and

15.1 1The majority of the reports emphasize

fatal illnesses. It is quite evident that in some fatal cases widespread pathologic changes occur. The findings in the brain include petechial hemorrhage in white matter,12 I)erivascular infiltrate,10 lympho-histiocytic arachnoiditis,hs and focal non-inflammatory necrosis of cerebral white matter.13 Other investigators have de-scribed grey matter lesions.11 Occasional-ly, infants have died showing little histolog-ic evidence of inflammation, but virus has been present in many organs.5’

(6)

Patient Age at Onset W1?(’/mm3

%

Mononuclear

1 5da 7 70

! 14 (III t,4.5() 89

S 6wk 35 78

4 6wk 437 100

5 4 wk 440 96

(; 18 (lit 13 .55

7 6 uk ‘306 80

S ‘34 wk 99 37

9 6wk 2I 67

11) 4 uk 720

11 10 dii 75 55

U 6wk 60 40

13 6wk 750 85

* Paucly test (lone.

t Benedict’s reducing solution used.

% Poly-morjihonuciear

Protein

(mg/100 iii!) (iiil/ /(1() iii!)

30 71 .53

U IU 43

U 35 6

0 63 44

4 48 70

45 37

0 - 4/St

63 5 43

33 40 61

74 So 4/St

45 +* 3/St

60 4/St

15 172 56

622

and ECHO 9 have previously been

re-covered in the CSF of young infants with only mild illness.’27

The infant may be infected in utero, from his mother during or after birth, or by family contact. Several investigators30’31 have reported in utero enteroviral infections with Group B Coxsackie virus. In these cases the infants became ill between the second and third day of life with fever and succumbed in congestive failure from 3

days to 1 week later. The importance of the

mother as an environmental contact has been emphasized previously.1 Coxsackie Group B, Type 2 was isolated from the CSF of a 1-week-old infant who manifested a meningoencephalitis at postmortem ex-amination and whose mother developed pleurodynia four days postpartum.

In Patients 2 and 5 antibody titers to the infecting virus in all sera tested from both mother and infant were greater than 64,

and it was not possible to establish if in

utero infection occurred. Serologic studies

in Patients 3 and 4 indicated that the moth-ers lacked antibodies at delivery and that their infants probably acquired their infec-tions from members of the household. Fecal samples obtained from other members of

the family of Patient 4 were found to con-tam Coxsackie virus Group B, Type 5, but none of these persons was symptomatic. No sera were available from the first patient or his mother, but it might be speculated that

the baby acquired the virus from the

mother.

The presence of maternally acquired an-tibody in the infant’s serum at birth does not always assure his protection.32 It is quite possible that the titer of antibody, passively acquired, may determine whether or not active infection can take place. It has certainly been well documented with vac-cine strains of pohioviruses that low levels of circulating, neutralizing antibody, pas-sively acquired, will not prevent intestinal infection.’ Although usually maternal and cord blood antibody titers are comparable, in a few cases neutralizing antibodies to Coxsackie viruses have been found in

ma-temal serum without being present in the cord blood.3 It is important to note that the neonatal infants in the present series, as well as those of others,21,2731 demonstrated immunologic competence with the develop-ment of neutralizing antibodies following enteroviral infections.

Previous investigators have stressed the

TABLE II

(7)

.1ge at

Sno/eel

Onset

I’iral (‘ul/i,re

Stool Throat (‘SF

Day Sera

Sample Neutralizing

f)btained 1ntibody

(After Titer*

Onset)

Patient I 4 dii

Patient t 14 dii

Mother ‘2

Patient 3 6 uk

Mother 3

Patient 4 6 wk

Mother 4

Sibling 4

Father 4

Patient 5 4 uk

Mother 5

(-)

Coxsaekie Group

B, TypeS

NT

EChO Type 9

Coxsackie Group

B, TypeS

Coxsackie Group

B, Type S

(‘oxsackie Group

B, Type 5

Coxsackie Group

B, Type 5

Coxsackie Group

B, Type 5

NT

(-)

NT

NT

NT

(‘oxsackie Group

B, TypeS

Coxsackie Group

B, Type 5

(-)

(-)

NT

(‘oxsackie Group

B, Type 3

(‘oxsackie Group

B, Type 5

NT

EChO ‘l’ype 9

Coxsackie Group

B, Type 5

Coxsackie Group

B, Type 5

NT

NTt

64 or > 64 or >

64 or >

64 or >

<4 8

<4

<4

<4 64 or>

<4

16

64 or > 64 or >

64 or >

64 or >

38

16 38

4 33

21 33

1 14

1

14

7 39

7

39

* Expressed as reciprocal of the serum dilution.

t Not tested.

TABLE III

Viuocooic AND SEROLOGIC FINDINGS IN FIvE PATIENTS WIT!! ENTEROVIRUSES IN CEREBROSPINAL Fiuin AND SOME FAMILY MEMBERS

ubiquity of enteroviruses and the

impor-tance of family spread.35’3#{176} Seasonal varia-tion is important, since enteroviral infec-tions are most prevalent from August 15 to October 15 in the Northern United States. The five infants whose CSF samples yield-ed an enterovirus were

ill

during these months.

The presence of enteroviruses in the feces only in patients with non-bacterial

meningitis must be interpreted cautiously,

since up to 10% of normal infants may har-bor such viruses at various times of the year.37 Isolation of virus directly from the cerebrospinal fluids is far more significant.

(8)

TABLE IV

REI’ORTED CASES OF \OUNG INFANT ENTEROVIRUS

1)ISEcSE ASSOCIATED VITI1 CENTRAL NERVOUS

SYSTEM INVOLl’EMENT

Oirotip

A A

B

B

B B

B 624

Serolype 1801(itiOfl Reference1 ReportedYear AgeChildof

(ozoackie

4 Brain 8 1961 18 da

16 Heart.

intestine 9 1963 7 wk

I Brain 13 1963 9 du

(‘SF 11 1960 1 mo

3 Brain l 1936 9do

4 Brain 1961 ?

3 CSF l 1961 tinder I mo

ECho

CSF t)

7 CSF !

9 Brain 5

9 CSF 7

11 Stool 6

15 CSF 11

1960

19&1

1964

1966 1964

1960

1mo

I mo

lOda

6 do

Sda 6 wk

Group B, Type 5 had been isolated from many patients with non-bacterial meningi-tis in the Cleveland area since 1958. It might be postulated that a considerable res-ervoir of susceptible persons to these two enteroviruses existed in the population, in-cluding women of the child-bearing age.

The

association of exanthems with

entero-virus infections is well established.35’39 Of

the 13 infants in the present report, five had skin manifestations.

It is interesting to speculate as to the re-cent success of viral isolation from the

spi-nat fluid of the four young infants studied

during 1966. Some investigators have pro-posed that an inverse relationship exists be-tween the number of cells in the CSF and the isolation of virus.40 Perhaps interferon is released by these cells which prevents the virus from propagating in the spinal fluid.41 Other investigators, however, have chal-lenged this idea.42

Viral culture techniques have not changed significantly during this time and are an unlikely explanation for the increased success. Perhaps the metabolic require-ments of the enteroviruses have changed so that they can now exist in the

spi-nal fluid. Possibly the eradication of p-lioviruses has allowed other, less virulent

enteroviruses to infect the human host. It would seem that certain enteroviruses are more readily isolated from the cerebrospi-nal fluid than others, and isolation would be more likely in seasons when these vi-ruses are prevalent.

There have been no reported fatalities in infants from whose spinal fluid virus was isolated in vivo either in the present series or the literature. The paucity of reported

cases, unfortunately, makes this statement

less meaningful. It may be concluded,

how-ever, that the mortality rate of enteroviral meningitis in the neonatal infant is lower than that of bacterial meningitis.

A significant question presently

swered is whether or not there is any iieu-rologic damage associated with enteroviral neonatal meningitis. Infection d tiring preg-nancy with ECHO virus, Type 9 has not been shown to increase the incidence of congenital anomalies, or to lead to an in-creased rate of fetal loss.’ On the other hand, intra-uterine infection with Coxsackie Group B has been associated with wide-spread and frequently fatal infections.

Of the five patients with virus present in the cerebrospinal fluid, only one child is suspect of possible brain damage. Patient 2 was quite tremulous a month after hospital-ization and did not follow a light well. Close follow-up and repeated neurologic examinations will be conducted on all these infants in the future.

Viral studies are expensive and mans’

areas in the country do not have facilities

for them. In addition, it usually takes sever-al days before a virus is isolated from the

CSF, making it an unimportant immediate diagnostic tool. It would seem, however, that in larger communities enough viral laboratories exist which could he used if the

diagnosis is suspected. It remains for the

(9)

SUMMARY

Enteroviral meningitis was studied in five

infants less than 6 weeks of age.

Eight additional cases of suspected

en-teroviral meningitis from the Cleveland

Metropolitan General Hospital were

re-ViCWC(l with regard to symptoms, CSF

findings, neurologic examination, prognosis, and epidemiology.

The entity of enteroviral meningitis

should be considered in and viral cultures

obtained from any young infant when

cx-amination of the CSF reveals a pleocytosis,

normal glucose, and absence of organisms

on Cram’s stain and culture.

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Acknowledgment

The authors wish to thank Drs. Alfred D. Heggie

and Russell

J.

Eyrnan, Babies and Childrens

(11)

1967;40;617

Pediatrics

Alan G. Nogen and Martha L. Lepow

ENTEROVIRAL MENINGITIS IN VERY YOUNG INFANTS

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Alan G. Nogen and Martha L. Lepow

ENTEROVIRAL MENINGITIS IN VERY YOUNG INFANTS

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