Journal of Clinical Neuroscience xxx (2014) xxx–xxx

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Journal of Clinical Neuroscience
journal homepage: www.elsevier.com/locate/jocn

Case Report

Primary herpes virus infection and ischemic stroke in childhood: A new
association?
Vito Terlizzi a,⇑, Federica Improta a, Teresa Di Fraia b, Eduardo Sanguigno b, Alessandra D’Amico c,
Salvatore Buono d, Valeria Raia a, Gabriella Boccia b
a

Department of Translational Medical Sciences, University of Naples Federico II, Via Sergio Pansini 5, 80131 Naples, Italy
Department of Pediatrics, S. Maria delle Grazie Pozzuoli Hospital, Naples, Italy
Unit of Neuroradiology, Department of Advanced Biomedical Sciences, University of Naples, Federico II, Italy
d
Neuroscience Department, ‘‘Santobono-Pausilipon’’ Children’s Hospital, Naples, Italy
b
c

a r t i c l e

i n f o

Article history:
Received 8 September 2013
Accepted 19 December 2013
Available online xxxx
Keywords:
Acyclovir
Children
Herpes virus
Infection
Stroke
Therapy
Vascular narrowing

a b s t r a c t
We describe, to our knowledge, the first case of arterial ischemic stroke after primary herpes simplex
virus type 1 (HSV1) infection in a previously healthy child, without signs of encephalitis. A 10-year-old
previously healthy girl was admitted to our hospital with acute left-sided hemiparesis which involved
the lower half of her face. Submandibular lymphadenitis and oral vesicular lesions were present. MRI
confirmed the suspicion of an acute ischemic stroke. Immunoglobulin M antibodies to HSV1 were
detected. Cerebrospinal fluid polymerase chain reaction for herpes virus was negative. She was treated
with aspirin (3 mg/kg) and intravenous acyclovir (10 mg/kg every 8 hours) for 21 days. Immunoglobulin
G antibodies to HSV1 appeared 16 days after admission. Twelve months after her hospitalization the
patient’s examination was normal. Stroke should be considered a possible complication of HSV1 primary
infection. Guidelines for the management of acute stroke in children are needed.
Ó 2014 Elsevier Ltd. All rights reserved.

1. Case report
A 10-year-old previously healthy girl was admitted to our hospital with acute left-sided hemiparesis which involved the lower
half of her face. Her parents reported the sudden onset of rightsided headache with hypotonia and walking difficulty. A drop of
the left corner of the mouth and a divergent squint subsequently
appeared before hospitalization.
At admission vital parameters were normal. The patient was
apyretic, alert, oriented and able to describe the event. She could
frown and close both her eyes but she could not balance. The neurological examination showed a positive Babinski sign, hyposthenia and hyperreflexia of her left arm and leg. Submandibular
lymphadenitis and oral vesicular lesions were present. There were
no other neurological or physical abnormalities, and no nuchal
rigidity. Cerebral CT scan was normal.
Four days after the acute event, MRI of the brain was performed
on a 1.5 Tesla scanner and supplemented with axial diffusionweighted imaging (DWI) and time-of-flight MR angiography
(MRA) with maximum intensity projection reconstructions. DWI
⇑ Corresponding author. Tel.: +39 081 746 3273.
E-mail address: terlizzivito@libero.it (V. Terlizzi).

showed three areas of hyperintensity, located on the right side of
the brain at the inferior frontal gyrus, the posterior internal capsule
and the corona radiata, correlating with restricted water diffusion
and a typical arterial territory. Apparent diffusion coefficient map
confirmed the presence of cytotoxic edema, showing hypointense
signal of the same areas, confirming the suspicions of an acute
ischemic stroke (Fig. 1A). MRA showed a mild stenosis of the right
proximal middle cerebral artery and of the ipsilateral carotid
siphon (Fig. 1B).
Heart disease, hematological disorders, vasculitis, infection,
trauma, metabolic disorder and drug abuse were ruled out. Immunoglobulin M antibodies to herpes simplex virus type 1 (HSV1)
were detected in the patient’s serum, indicating a primary infection. No other cross-reactions were demonstrated for the most
common viral infections. Two days later she underwent lumbar
puncture [1]. Cerebrospinal fluid (CSF) analysis showed leucocyte
count 20 cells/ll (normal range: 0–5 cells/ll), total protein
25 mg/dl (normal range: 20–35 mg/dl) and glucose 54 mg/dl
(normal range: 40–70 mg/dl). CSF polymerase chain reaction
(PCR) for herpes virus was negative. She was treated with aspirin
(3 mg/kg) and intravenous acyclovir (10 mg/kg every 8 hours) for
21 days [2]. Her neurological examination improved significantly
after about 15 days. Immunoglobulin G antibodies to HSV1

http://dx.doi.org/10.1016/j.jocn.2013.12.023
0967-5868/Ó 2014 Elsevier Ltd. All rights reserved.

Please cite this article in press as: Terlizzi V et al. Primary herpes virus infection and ischemic stroke in childhood: A new association? J Clin Neurosci
(2014), http://dx.doi.org/10.1016/j.jocn.2013.12.023

2

Case Report / Journal of Clinical Neuroscience xxx (2014) xxx–xxx

Fig. 1. (A) Axial apparent diffusion coefficient map showing two of the three right hypointense lesions in the frontal and capsular regions, and (B) time-of-flight MR
angiography showing narrowing of the right carotid siphon and M1 segment of the middle cerebral artery.

appeared 16 days after the patient’s admission. After 20 months of
follow-up the girl had completely recovered.

2. Discussion
Stroke is an important cause of acquired brain injury in
children. It is associated with a high mortality rate and neurologic
sequelae in more than 50% of cases [3].
Data in the literature confirm an association between stroke
and varicella zoster virus (VZV) infection. In the vessel wall, VZV
may induce a noncytolytic infection of smooth muscle cells,
functional damage of the vascular endothelium and thrombosis.
Moreover it promotes subendothelial proliferation of smooth
muscle cells, fibroblasts, and collagen [4].
Recently a 36-year-old woman with cerebral vasculitis and
ischemic stroke secondary to HSV infection was reported [5]. In
regard to the pediatric population, a 3-year-old child with an occipital ischemic stroke has been reported during HSV1 encephalitis [6].
We describe to our knowledge the first case of arterial ischemic
stroke after primary HSV1 infection in a previously healthy child,
without signs of encephalitis. In our patient CSF PCR for herpes
virus was negative; however it is known that a negative CSF PCR
does not exclude an acute HSV infection when it is performed
between 3 and 14 days after symptoms onset [7]. HSV immunoglobulin M has a relatively high specificity and positive predictive
value, therefore it can be very useful if the result is positive. The
seroconversion to immunoglobulin G makes the correlation stronger. This patient suggests we should perform HSV serology more
often, and not only PCR.
Herpes simplex is one of the fastest replicating viruses that infects human beings; a delay in treatment greatly increases axonal
spread of the infection [7,8]. On the basis of oral vesicles and early
MRI/MRA vascular changes, we immediately started treatment
with intravenous acyclovir even though CSF PCR was negative. In
our patient this treatment was continued for 21 days, according

to Infectious Diseases Society of America guidelines [2] and it
was sufficient to avoid severe neurological sequelae.
This patient highlights the need to consider stroke as a possible
complication of HSV1 primary infection and to take into account
this etiology in children with acute onset of neurological symptoms and vascular narrowing on MRI and MRA. Vascular narrowing
is also typical of intracranial dissection in young people, nevertheless specific features of dissection are sometimes lacking on
imaging.
Further studies are necessary in order to confirm this possible
association.
Conflicts of Interest/Disclosures
The authors declare that they have no financial or other
conflicts of interest in relation to this research and its publication.
References
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Please cite this article in press as: Terlizzi V et al. Primary herpes virus infection and ischemic stroke in childhood: A new association? J Clin Neurosci
(2014), http://dx.doi.org/10.1016/j.jocn.2013.12.023