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Jornal de Pediatria - Vol. 76, Nº3, 2000 237
CASE REPORT
237
0021-7557/00/76-03/237
Jornal de Pediatria
Copyright
©
2000 by Sociedade Brasileira de Pediatria
Abstract
Objective: to present the case of a girl who was previously healthy but had fatal evolution due to
Coxsackie B2 viral meningoencephalitis.
Methods: the authors describe the case of a female child with fatal meningoencephalitis caused by
Coxsackie B2 virus and present a review of the literature (Medline and Lilacs).
Results: the girl was eight years old when she presented meningoencephalitis with bad evolution,
leading to death on the 32nd day of internation. The exams showed positive serologic reaction to Coxsackie
B2. The virus taken from two stool samples was isolated. The CRF exam showed an increase four times
higher on Coxsackie B2 titulation.
Conclusion: the death of healthy patients with enteroviral encephalitis, as described here, is rarely dealt
with in the medical literature, perhaps because of lack of clinic suspicion. This case tries to drive attention
to the importance of an early etiologic diagnosis in the meningoencephalities and the search for specific
etiological treatment.
J Pediatr (Rio J) 2000; 76(3): 237-40: meningitis, meningoencephalitis, coxsackieviruses, enterovirus.
Coxsackie B2 virus fatal meningoencephalitis in a student
Eduardo S. Carvalho,
1
Marcelo Abramczyk,
2
Antonio U. Brezolin,
3
Denise F.C. Souza,
4
Lilian A. Inocêncio,
4
Terezinha M. Paiva
5
1. Associate Professor of Pediatric Infectology, Escola Paulista de Medicina
- UNIFESP. Chife, Nosocomial Infection Service, Pronto Socorro Infantil
Sabará.
2. Graduate Student, Escola Paulista de Medicina - UNIFESP.
3. Neuropediatrician, Pronto Socorro Infantil Sabará and Instituto de
Infectologia Emilio Ribas.
4. Biologist, Enteric and Respiratory Virus Section, Instituto Adolfo Lutz.
5. Investigator, Biologist, Enteric and Respiratory Virus Section, Instituto
Adolfo Lutz.
Introduction
Enteroviral infections of the central nervous system are
important causes of morbidity among adults and children.
1
Enteroviruses may cause aseptic meningitis, paralysis,
encephalitis, and myalgic encephalomyelitis. Death or
sequels are more frequent among newborns
2,3
and
immunodepressed
4
people. Regarding the pathogenicity of
enteroviral infections of the central nervous system
5,6
no
significant alterations were observed in revisions of articles
published in 1978 and in 1984.
Enteroviruses are the main etiologic agents of aseptic
meningitis
7-9
and they are sometimes identified in
encephalitis.
10,11
It is important to distinguish the diagnoses
of enteroviral encephalitis from herpetic encephalitis.
The prognosis for enteroviral encephalitis is benign;
sequels or death rarely occur in patients who are not
included in the risk group.
The objective of this study is to present the case of a
previously healthy child who died due to
meningoencephalitis caused by Coxsackie B2 virus.
238 Jornal de Pediatria - Vol. 76, Nº3, 2000
Case report
NFL, 8 years old, female, started history of cephalea,
fever, and auricular pain in December, 21, 1995; in the same
date, she looked for medical assistance, and was admitted to
a hospital. On the 2nd day of hospitalization, she underwent
a cerebrospinal fluid (CSF) drainage, which presented
normal result. She remained in the hospital, and on her 3rd
in-patient day, she presented tonic-clonic convulsive crises,
making the use of anticonvulsant drugs become necessary.
She was transferred to our service in São Paulo on December,
26.
The initial examination indicated evident meningeal
signs, intense agitation, and oropharyngeal hyperemia.
During the hospitalization time, the patient presented fever,
sparse convulsive crises, and a progressive deterioration of
her neurological state. On the 14th day of hospitalization,
she went into deep coma, scored on Glasgow scale by 4.
From the 8th to the 10th day of hospitalization, she
presented semi-liquid evacuations, with dehydration.
CSF examinations carried out during the hospitalization
period presented discrete pleocytosis with normal
proteinorrhachia and glycorrhachia (Table 1).
acute phase and after 15 days, it was verified that serology
presented a four-time higher increase in the CSF titration
for Coxsackie B2, and serum titer of 1:512 on the last two
samples (Tables 2 and 3). Coxsackie B2 was isolated in two
fecal swab samples. Paired serologies for adenovirus,
respiratory syncytial virus, parainfluenza, and influenza A
and B have also been carried out, showing no alterations.
12/22/95 12/26/95 01/01/96
Cellularity (number) 6 51 73
Polymorphonuclear cells (%) 62 47
Lymphomononuclear cells (%) 38 53
Glucose (mg/l) 64 44 53
Protein (mg/l) 19 20 24
Table 1 - Cell count and glucose and protein dosage in the
CSF
Table 2 - Serology for enterovirus performed in paired blood
samples
1st sample 2nd sample
Coxsackie B 1 <1 : 8 <1 : 8
Coxsackie B 2 1 : 512 1 : 512
Coxsackie B 3 <1 : 8 <1 : 8
Coxsackie B 4 <1 : 8 <1 : 8
Coxsackie B 5 1 : 16 1 : 16
Coxsackie B 6 <1 : 8 <1 : 8
ECHO 6 <1 : 8 <1 : 8
ECHO 7 <1 : 8 <1 : 8
Poliovirus I 1 : 16 1 : 16
Polioviírus II 1 : 252 1 : 252
Polioviírus III 1 : 32 1 : 32
Table 3 - Titrations for enterovirus performed in CSF
1st sample 2nd sample
Coxsackie B 1 <1 : 8 <1 : 8
Coxsackie B 2 <1 : 8 1 : 128
Coxsackie B 3 <1 : 8 <1 : 8
Coxsackie B 4 <1 : 8 <1 : 8
Coxsackie B 5 <1 : 8 <1 : 8
Coxsackie B 6 <1 : 8 <1 : 8
ECHO 6 <1 : 8 <1 : 8
ECHO 7 <1 : 8 <1 : 8
Poliovirus I <1 : 8 <1 : 8
Poliovirus II <1 : 8 1 : 128
Poliovirus III <1 : 8 <1 : 8
Cranial computerized tomographies were performed on
the 4th and 7th days of evolution, with normal results. On
the 6th day, the electroencephalogram (EEG) presented
cerebral damaging to the right hemisphere and to the front-
parietal region. On the 12th day of evolution, the child was
submitted to a cranial magnetic nuclear resonance, with a
normal result. The EEG examination presented signs of
diffuse cerebral damaging and a severe decrease in activity
in the right cerebral hemisphere. The EEG was performed
2 days later and was considered isoelectric. The child
presented Glasgow score at 14 on the 6th day, at 6 on the
12th day, and at 3 on the 14th day.
No bacteria were identified in blood and CSF cultures,
an the agglutination in latex was not reagent for
meningococcus, pneumococcus, or Haemophilus influenzae
B. Using neutralization tests for enterovirus carried out at
Instituto Adolfo Lutz (São Paulo), performed during the
There was also an increase in the CSF titration for
poliovirus II, from 1:8 to 1:128, with no alteration in the
titration for poliovirus I and III. The serum titration on both
samples was 1:256 for poliovirus II, whereas for poliovirus
I and III, it was 1:16 and 1:32, respectively. Hemograms
performed during the evolution of the process are presented
on Table 4.
The child continued in deep coma, score on Glasgow
scale by 3, and died on the 32nd day of hospitalization.
Coxsackie B2 virus fatal meningoencephalitis... - Carvalho ES
et alii
Jornal de Pediatria - Vol. 76, Nº3, 2000 239
12/22/95 12/26/95 12/28/95 01/05/96
Hemoglobin 12.5 12.1 12.3 11.3
Hematocrit 40 37 37 34
Leukocytes 20,900 19,400 29,700 29,500
Polymorphonuclear
cells* 86% 93% 91% 83%
Lymphomononuclear
cells 13% 6% 8% 17%
Platelets 268,000 418,000 456,000
Table 4 - Results of sequential hemograms performed during
hospitalization
* No deviations to the left in any of the four examinations
Discussion
Enteroviruses form the main group of the Picornaviridae
family. Poliovirus subgroups (3 serotypes), Coxsackie A
virus (23 serotypes), Coxsackie B virus (6 serotypes),
echovirus (31 serotypes), and enterovirus (5 serotypes)12
were analyzed.
Enteroviruses are responsible for several diseases, such
as aseptic meningitis, encephalitis, cerebral ataxia, paralysis,
exanthemas, respiratory diseases, conjunctivitis,
myocarditis, pancreatitis, and hepatitis.
5
Nowadays, nonpolio enteroviruses are responsible for
80 to 92% of the cases of aseptic meningitis with identified
etiologic agent,13 and for 8 to 10% of the encephalitis
10,11
cases, with a clinical status similar to that of herpetic
encephalitis, including the sequels.
14,15
Enteroviral infections usually present a benign evolution.
Fatal cases are described in medical literature mainly among
newborns
2,3
immunodepressed people
4
or in cases of
patients affected by myocarditis;16 cases of death are
reported in enteroviral meningoencephalitis
17-19
with
unusual identification of the Coxsackie B2 virus after the
neonatal period.
17,18
The identification of the CSF Coxsackie B2 virus, in
cellular cultures, establishes the gold standard for
meningoencephalitis diagnosis; however, its identification
is rare due to the technical difficulty and to the small
quantity of virus verified in the CSF.
11
The identification of the fecal swab virus, associated
with a four-time or higher increase in the titer of antibodies
in liquor and/or serum paired samples in the acute phase and
during convalescence is indicative of acute infection.
12
The
early diagnosis of enteroviral encephalitis may be performed
through the polymerase chain reaction
20-22
which is
important to distinguish between bacterial meningitis and
herpetic meningoencephalitis diagnoses.
13
There is not any specific treatment for enteroviral
infections; the use of intravenous gammaglobulin seems to
produce good results among newborns and patients with
agammaglobulinemia and chronic meningoencephalitis. Its
indication, however, is controversial.
2,4,23
This case presents
particular clinical and laboratory characteristics, which
deserve special attention.
Leukocytosis and lymphocytosis, with possible initial
neutrophilia, normally characterize viral infection
hemograms. In the reported case, it was observed that
during the whole process of evolution, hemograms presented
leukocytosis and neutrophilia, which are more frequently
associated with bacterial infections. No deviation to the left
was verified in the examinations performed. These findings
stress the difficulty in the interpretation of hemograms, and
show that etiologic suspicions generated by their results
may lead to diagnostic errors.
Anemia, represented by hemoglobin and hematocrit
decrease, is often verified in serious infections. It was not
observed at any moment during the evolution.
In viral infections of the central nervous system, the CSF
presents an increase of cellularity, often with an initial
predominance of polymorphonuclear cells, and a posterior
increase of lymphomononuclear cells after 24 to 48 hours,
with normal or discretely altered glycorrhachia and
proteinorrhachia. In the reported case, it is interesting to
notice the predominance of polymorphonuclear cells until
the 4th day of evolution of this disease, a result usually
observed in bacterial infections.
Combining the high serum titration for Coxsackie B2
and the fecal identification of Coxsackie B2, we may affirm
that there was infection by the Coxsackie B2 virus. The
four-time or higher increase in the CSF titration and the
cytological alterations previously reported suggest that
probably an infection of the central nervous system occurred,
and was caused by Coxsackie B2. The increase of the CSF
titration could also be interpreted by the passage of serum
antibodies through the rupture of the hematoencephalic
barrier, due to the unfavorable neurological evolution.
The increase in the CSF titration for poliovirus II may be
explained by the high serum titration, probably due to
vaccination, together with the rupture of the
hematoencephalic barrier, while the levels of antibodies for
poliovirus I and II were insufficient to promote an increase
in CSF titration. No polioviruses were found in the feces.
According to the reported case, the occurrence of death
to healthy patients who presented enteroviral encephalitis is
little referred to in medical literature, maybe due to the lack
of clinical suspicions. This case demonstrates the importance
of an early etiological diagnosis of meningoencephalitis, as
well as the need for specific etiological treatment.
Coxsackie B2 virus fatal meningoencephalitis... - Carvalho ES
et alii
240 Jornal de Pediatria - Vol. 76, Nº3, 2000
Correspondence:
Dr. Eduardo da Silva Carvalho
Rua Eng. Teixeira Soares, 296
CEP 05505-030 – São Paulo, SP, Brazil
Phones: + 55 11 571.2944 / + 55 11 576.4325
Fax: + 55 11 575.6928
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et alii
