ILLUSTRATIVE CASE

Influenza A(H1N1)YAssociated Ischemic Stroke
in a 9-Month-Old Child
Raphaele Honorat, MD,* Camille Tison, MD,Þ Annick Sevely, MD,þ Emmanuel Cheuret, MD,Þ
Yves Chaix, MD, PhD,Þ and Isabelle Claudet, MD, MSc*

Aim: This study aimed to report a rare clinical course of pandemic influenza A(H1N1) infection, ischemic stroke, in a 9 month-old child.

Case: A 9-month-old girl with no previous medical problem presented
to our pediatric emergency department with high fever (39-C/102-F)
lasting for 48 hours. Soon after admission, she started generalized tonicclonic seizures that ceased after 2 injections of diazepam. Six hours later,
she presented 2 short episodes of partial clonic seizures of the right arm
followed by monoplegia. Lumbar puncture was normal. Noncontrast computed tomographic imaging of the brain was performed and revealed an
acute infarct in the left middle cerebral artery territory with no mass
effect. Electroencephalogram revealed important slowing in the left
hemisphere. A magnetic resonance imaging was performed the next day
and confirmed an ischemic stroke in the left posterior middle cerebral
artery region. Nasal swab polymerase chain reaction was positive for
influenza A(H1N1) and polymerase chain reaction detection negative in
cerebrospinal fluid. She fully recovered her right-arm function on day 3
and was discharged on day 10 without sequelae.
Comments: Seasonal influenza is known to cause neurological complications in children. Influenza increases the stroke risk especially in
adults at high risk. This is a rare event in childhood, and we believe this is
the first report associated with H1N1 new variant.
Conclusions: Acute viral infection, notably influenza, is associated
with increased susceptibility to stroke, and vaccination against influenza
may reduce the risk of stroke.
Key Words: influenza A, H1N1, stroke
(Pediatr Emer Care 2012;28: 368Y369)

CASE
A 9-month-old girl with no previous medical problems
presented in our pediatric emergency department with high fever
(39-C/102-F) lasting for 48 hours and associated with shivering
and episodes of lips cyanosis. On arrival, her vital signs were
as follows: temperature, 38-C (100-F); heart rate, 155 beats per
minute; respiratory rate, 32 breaths per minute; blood pressure,
107/80 mm Hg; and 100% finger probe pulse oximetry. As she
was installed in the waiting area, she started generalized tonicclonic seizures that ceased after 2 rectal injections of diazepam
(0.5 mg/kg). Examination during the postictal period revealed a
Glasgow Coma Scale score of 9, normal reactive pupils, absence
of peripheral motor impairment, normal peripheral reflexes, and
stertorous respiration. Laboratory investigations including a complete blood cell count and basic metabolic panel were significant
for hyponatremia (125 mmol/L). Lumbar puncture was normal.
She was treated with isotonic saline infusion. Her postictal neuFrom the Departments of *Pediatric Emergency, †Pediatric Neurology, and
‡Neuroradiology, Children Hospital, Toulouse, France.
Disclosure: The authors declare no conflict of interest.
Reprints: Isabelle Claudet, MD, MSc, Department of Pediatric Emergency,
Children Hospital, 330, Great Britain Ave, TSA 70034, 31059 Toulouse
Cedex 09-France (e-mail: claudet.i@chu-toulouse.fr).
Copyright * 2012 by Lippincott Williams & Wilkins
ISSN: 0749-5161

368

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rological status improved shortly with a Glasgow Coma Scale score
of 15. Six hours later, she had 2 short episodes of partial clonic
seizures of the right arm followed by monoplegia. Intravenous
antiviral therapy (acyclovir 500 mg/m2 per 8 hours) was started.
Initial hyponatremia was corrected after intravenous treatment.
Noncontrast computed tomographic (CT) imaging of the brain
was performed and revealed an acute infarct in the left middle
cerebral artery territory with no mass effect. Electroencephalogram revealed important slowing in the left hemisphere. A
magnetic resonance imaging (MRI) was performed the next day
and confirmed an ischemic stroke of the left posterior middle
cerebral artery region (Figs. 1Y3) without any sign of stenosis or
parietal irregularities of the artery on the magnetic resonance
angiography. Nasal swab polymerase chain reaction was positive
for influenza A(H1N1) and negative for respiratory syncytial
virus. Polymerase chain reaction detection for H1N1 and herpes
simplex virus was negative in the cerebrospinal fluid (CSF). She
has not been vaccinated for seasonal or H1N1 influenza. Evaluation for potential stroke factors revealed no family history,
normal level of antithrombin III activity, homocysteine, absence
of antiphospholipid antibodies, antinuclear antibodies, and factor V Leiden mutation. Protein C and S activities were equal to
52% and 62%, respectively. Serology panel (cytomegalovirus,
parvovirus B19, herpes simplex virus, varicella zoster virus,
Epstein-Barr virus, and Borrelia burgdorferi) showed previous
immunization. Electrocardiogram, echocardiography, and Doppler
ultrasound of the neck vessels were also normal. Her treatment was
completed by a 5-day course of oseltamivir and aspirin (5 mg/kg per
day); clonazepam was progressively replaced by carbamazepine
(15 mg/kg per day). Under this regimen, she fully recovered her
right-arm function on day 3. She was discharged on day 10 with
carbamazepine and aspirin treatment. Follow-up appointment
for cerebral MRI scheduled within the next 3 months showed a
discrete cortical residual atrophy.

COMMENTS
The role of infectious and inflammatory causes of stroke is
much more significant in children than in adults. Viruses may
produce transient ischemic attacks and stroke. The most wellstudied viruses are varicella zoster virus, cytomegalovirus, and
human immunodeficiency virus.1 The etiology of neurological
complications in influenza infection is unclear. Different pathophysiological mechanisms have been implicated in the resulting vasculitis: a direct infection of cerebral arteries, the product
of transient autoantibodies to phospholipids and coagulation
proteins (indirect autoimmune reactivity).1 Influenza virus proteins
influence hemostasis; influenza infection has a prothrombotic
effect by activating procoagulant pathway and inhibiting anticoagulant pathways. Proinflammatory cytokines are particularly
involved; they reduce the expression of thrombomodulin and,
in association with C-reactive protein, induce tissue factor expression by monocytes and macrophages.2 Only rarely is influenza virus detected in CSF, suggesting that neurological
manifestations might be an indirect effect of influenza respiratory
Pediatric Emergency Care

& Volume 28, Number 4, April 2012

Copyright © 2012 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Pediatric Emergency Care

& Volume 28, Number 4, April 2012

FIGURE 1. CT scan and axial diffusion-weighted MRI (with apparent
diffusion coefficient map) showing hypodensity and diffusion
restriction (arrows) in the left middle cerebral artery territory.

tract infection. Seasonal influenza is known to cause neurological
complications in children, including seizures, encephalopathy,
acute encephalitis, myositis, transverse myelitis, Guillain-Barre
syndrome, Reye syndrome, and acute necrotizing encephalitis.3
Influenza AYassociated stroke was reported in 2003 in a 4-year-old
boy. His MRI showed a subacute infarct of the left middle cerebral artery, and he fully recovered without sequelae.4 As in the
present case, the child did not have any evidence of direct central
nervous system invasion of the virus as shown by normal CSF
analysis. As with other reports of virus-related stroke in a pediatric population, neurological involvement was limited to the
middle cerebral artery.1 At that time, it was the first description
of a pediatric clinical presentation. Since 2003, similar pediatric
case reports have not been published. For H1N1 influenza in
2009, the description of neurological complications is emerging.5
The most common neurological manifestations were seizures
(60%Y70%) and encephalopathy (25%Y50%).6Y8 Seasonal influenza A or B reported rate for neurological complications is 8.5%.
Reported rates for pH1N1 hospitalized children were between 6%
and 19%, and most of the patients with neurological complica-

Influenza A(H1N1)YAssociated Stroke in an Infant

FIGURE 3. CT scan and axial diffusion-weighted MRI (with apparent
diffusion coefficient map) showing hypodensity and diffusion
restriction (arrows) in the left middle cerebral artery territory.

tions had underlying neurological conditions. The delay from
onset of respiratory tract symptoms to neurological symptoms
was short and was within the first 48 hours for seizures, meningitis, encephalitis, myelitis, or acute encephalopathy. The potential effects of antiviral medications on the development of
neurological symptoms has not been proven in pediatric H1N1
cohorts mainly because neurological complications occurred
shortly after respiratory symptoms and before any antiviral
treatment was started. In adults, oseltamivir seems to reduce the
stroke risk especially those with cardiovascular risk factors.1,2

CONCLUSIONS
Acute viral infection, notably influenza, is associated with
increased susceptibility to stroke, and vaccination against influenza may reduce the risk of stroke, particularly in children
already at high risk. Clinicians should remain aware of the potential for severe neurological sequelae associated with seasonal
or novel influenza A(H1N1) virus infection.
ACKNOWLEDGMENT
The authors thank Ms Claire Walker for her help in the
translation of the manuscript.
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FIGURE 2. CT scan and axial diffusion-weighted MRI (with apparent
diffusion coefficient map) showing hypodensity and diffusion
restriction (arrows) in the left middle cerebral artery territory.
* 2012 Lippincott Williams & Wilkins

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pandemic influenza A (H1N1) virus infection. Acta Paediatr.
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