doi:10.1016/S1090-3798(03)00016-3
European Journal of Paediatric Neurology 2003; 7: 73–75

CASE STUDY

Transient cerebral arteriopathy in infancy associated
with enteroviral infection
PASCALE RIBAI,1 CORINNE LIESNARD,2 GEORGES RODESCH,3 SANDA GIURGEA,4
DENIS VERHEULPEN,1 PHILIPPE DAVID,3 PATRICK VAN BOGAERT1
1

Department of Paediatric Neurology; 2Department of Virology; 3Department of Neuroradiology; Université Libre de
Bruxelles, Hôpital Erasme, Brussels Belgium; 4Department of Neurology, Centre Hospitalier Universita de Tivoli,
La Louvière, Belgium

We report the case of an 18-month-old boy who presented aphasia and right hemiplegia of acute onset. The
neurological deficit completely resolved after a few hours, but identical transient neurological deficits and seizures
occurred during the following days. Imaging showed proximal stenosis of the medial cerebral artery and deep
ischaemic lesions in the territory of this artery. Analysis of the cerebrospinal fluid showed pleocytosis and an active
enteroviral infection with positive RNA detection. The evolution was consistent with transient cerebral arteriopathy
of childhood as magnetic resonance angiography showed normalization of the arterial lesions. This is the first
report of an enteroviral infection associated with this entity. We want to stress the importance of performing a
cerebrospinal fluid analysis when an ischaemic stroke of unclear aetiology occurs in a child.
Keywords: Stroke. Childhood. Virus. Enterovirus. Arteriopathy. Infection.

Introduction

Case report

One-third to one-half of childhood ischaemic
strokes occur without any predisposing factors.1,2
A subgroup of these patients presents with a relatively homogenous clinico-radiological picture
characterized by subcortical infarcts and angiographic abnormalities of the basal arteries of the
carotid system. Because these lesions of the arterial
walls stabilize or regress after weeks or months,
this entity has been called ‘transient cerebral
arteriopathy’.3 Viral infections, and more specifically varicella-zoster virus (VZV) infection, are
incriminated in the pathophysiology of this entity.
This hypothesis is supported by epidemiological
data showing that VZV infection occurs significantly more frequently in the months preceding
the stroke in these children than in age-matched
controls4 and by the identification of IgG against
VZV in the cerebrospinal fluid (CSF) in some
patients.5,6 We report a case of this so-called transient cerebral arteriopathy where active enteroviral
infection was demonstrated in the patient.

VD, an 18-month-old boy, suddenly developed
right hemiplegia and global aphasia. Both symptoms completely regressed after 1 hour. A second
transient episode of right hemiplegia and aphasia
occurred on the same day. The child was then
admitted. The only relevant feature in his past history was a transient skin rash 1 month previously.
His clinical examination on admission was completely normal; he was apyretic and there were no
dermatological or digestive signs. Brain computerized tomography (CT) scan was normal. Electroencephalogram (EEG) did not show any
epileptiform activity, making a diagnosis of epilepsy unlikely. However, on the next day, he presented several tonic-clonic seizures which were
successfully treated with intravenous phenytoin.
The neurological examination remained normal. A
lumbar puncture showed 29 nucleated cells per
mm3 with 78% lymphocytes; glucose and proteins
were within the normal range. Two days after
admission, he presented a third episode of right

Received 5.8.02. Revised 15.1.03. Accepted 16.1.03.
Correspondence: Dr P Van Bogaert, Department of Pediatric Neurology, ULB-Hôpital Erasme, 808 route de Lennik, B-1070 Brussels, Belgium;
Tel: þ 32-2555-4364; Fax: þ 32-2555-3942; e-mail: pvanboga@ulb.ac.be

1090-3798/03/07/0073+3 $35.00

Q 2003 European Paediatric Neurology Society

74
hemiplegia and aphasia. An intravenous anticoagulation treatment was then initiated, considering
the possibility of recurrent embolisms. Again he
completely recovered his deficits after 72 hours.
Cardiac ultrasonography was normal and heparin
was stopped after 7 days. Cranial magnetic resonance imaging (MRI) and angiography (MRA), performed respectively 2 and 9 days after the onset,
showed a hypersignal lesion on T2-weighted
images, likely to reflect an ischaemic lesion of
the basal ganglia (Fig. 1a) and probable thrombosis
of the left medial cerebral artery in its distal
portion.
A search for viral infection was performed
and included detection of viral material in the
CSF using polymerase chain reaction (PCR) techniques and detection of antibodies in early and
late sera. Enterovirus RNA was detected in the
CSF using reverse transcriptase (RT)-PCR. PCR
for herpes simplex virus (HSV) and VZV were
negative. Determination of serum VZV antibodies indicated past contact with the virus
(IgG 1/32– IgM 0). Early and late assessment of
serum complement fixation antibodies toward
an enteroviral antigenic pool and the six Coxsackie B antigens showed a significant rise of
these antibodies from a titer of 1/2 in an early
sample to 1/256 after 2 months, compatible
with a recent enteroviral infection, most probably
due to a Coxsackie B2 virus. Assessment for
recent infection due to HSV, cytomegalovirus,
Borrelia burgdorferi, Epstein – Barr virus, toxoplasm
and measles was negative. Other blood tests
including dosage of resistance to activated protein C, protein C, protein S, antithrombin type
III, antiphospholipid antibodies, homocystein
and lactic acid, were within the normal ranges.
Profiles of plasma amino acids and urine organic
acids were normal. Funduscopy and slit lamp
examination were normal.
Conventional arteriography performed 2 months
after the onset showed narrowing of the left medial
cerebral artery (Fig. 1b). The 2-year follow-up did
not indicate any residual disability nor recurrence.
MRA controlled after 1 year was completely
normal.

Discussion

Case study: P Ribaı̈ et al.

Fig. 1. (a) T2-weighted MR image showing hypersignal
of the left lenticular nucleus. (b) Angiography after selective catheterism of the left internal carotid artery showing
narrowing of the M1 segment of the sylvian artery
(arrow).

(1)
(2)

We report a case of ischaemic stroke which fulfills
the criteria for the so-called ‘transient cerebral arteriopathy’ as defined by Chabrier et al.3 These
include:

localization of the infarcts in basal ganglia and
internal capsule;
angiographic aspect characterized by the presence of multiple lesions (narrowing, occlusion) which are often unilateral and concern
mainly the initial parts of basal arteries of the
carotid system;

Case study: Transient cerebral arteriopathy in infancy associated with enteroviral infection
(3)

stabilization or regression of the lesions on
angiographic follow-up: this discrete entity
has been reported in children with ischaemic
stroke, with an average age at onset of
5 years.3,6 – 11

Some cases of transient arteriopathy have been
related to a VZV infection.3,6,9 – 13 Our patient had
evidence of previous VZV infection. However, the
stroke was probably related to an enteroviral infection. Indeed, enteroviral RNA was identified in the
CSF using RT-PCR and seroconversion against a
Coxsackie B virus was documented. This is, to our
knowledge, the first reported case of transient cerebral arteriopathy clearly associated with an enteroviral infection. Two previous reports of transient
neurological deficits associated with an entoviral
infection documented by positive RT-PCR and
pleocytosis in the CSF are reported in the literature,
but in none of them are available neuroradiological
data to support a diagnosis of transient cerebral
arteriopathy.14,15
The mechanisms by which viral infections
induce stroke are likely to be an inflammatory process of the arterial wall, as suggested by the angiographic findings. In the cases of VZV-associated
stroke, reactivation of latent infection in the trigeminal ganglion and viral invasion of the blood
vessels via the trigeminal axons has been
proposed.13,16 Other possible mechanisms are
immune reactions secondary to distant infection
or transient deficiency of protein S and protein C
due to circulating auto-antibodies and immune
complex formation.17
Pleocytosis in the CSF was observed in our
patient. This further supports the viral aetiopathogenic hypothesis of this entity. Among 25 children
with presumed VZV-associated ischaemic stroke,
results of CSF analysis were mentioned in nine
cases and an increase of cell count was observed
in four cases.3,6,9 – 13 As CSF analysis is not routinely performed in children with stroke, we would
like to stress the need for performing an extensive
infectious evaluation including cell count in the
CSF, serum and CSF viral antibody research,
and PCR for various possible viral pathogens of
the central nervous system when the cause of the
stroke remains unexplained.

75

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