Illustrative Teaching Case

Section Editors: Daniel Strbian, MD, PhD, and Sophia Sundararajan, MD, PhD

Acute Ischemic Stroke in Pediatric Patients

Shivam Om Mittal, MD; Sreenath ThatiGanganna, MD; Benjamin Kuhns, MS;
Daniel Strbian, MD, PhD; Sophia Sundararajan, MD, PhD

A 17-year-old boy with Down’s syndrome was last known

normal at 11 pm and found with right-sided weakness and
facial droop at 1 am. In the local hospital, stroke was suspected
up to three fourths of children with ischemic stroke and an
even greater percentage in children with hemorrhagic stroke.
Only 10% to 25% of childhood strokes remain cryptogenic.
and he was flown to a tertiary care center with MRI and neuro- Although high rates of childhood obesity and associated tradi-
logical expertise available 24 hours a day. On arrival, his National tional stroke risk factors, such as hypertension, diabetes melli-
Institutes of Health Stroke Scale was 12. He had a right partial tus, and hyperlipidemia, have led to increased pediatric stroke
hemianopia, severe right hemiparesis, moderate dysarthria and rates,1 additional factors, such as congenital heart disease,
aphasia. Emergent MRI demonstrated diffusion restriction in prothrombotic states, nonatherosclerotic arteriopathies, head
the left lentiform nucleus and a small area in the anterior tem- and neck trauma, and infection, are important contributors.1,2
poral lobe with apparent diffusion coefficient correlate sugges- Cardiac disease is identified in almost one third of pediatric
tive of acute ischemia. Magnetic resonance angiography (MRA) stroke patients. Major cardiac risk factors include congenital
revealed left middle cerebral artery bifurcation occlusion, and heart disease, acquired heart disease, and patent foramen ovale.2
a perfusion scan showed a large perfusion/diffusion mismatch In addition, evaluation and treatment of cardiac disease via
(Figure [A] and [B]). Consent was obtained from the parents and surgery and catheterization account for one fourth of ischemic
intravenous tissue-type plasminogen activator (tPA) adminis- strokes in this group of patients. Extracorporeal membrane oxy-
tered. In addition, the patient was immediately taken for endovas- genation and the use of left ventricular assist devices are also
cular thrombectomy. Conventional angiogram confirmed distal potential causes.2 Paradoxical embolism through a patent fora-
middle cerebral artery occlusion, and a Solitaire stent retriever men ovale or atrial septal defect may allow right to left shunt and
was used to recanalize the left middle cerebral artery (Figure [C] are the most common cause of stroke in congenital cardiac and
and [D]). The patient improved dramatically over the next few vascular malformations. Cyanotic heart disease leads to polycy-
hours and was discharged with an National Institutes of Health themia, further increasing the risk of thrombosis and ischemia.
Stroke Scale of 4. The patient had an atrial septal defect, which The incidence of prothrombotic conditions in children with
had previously been repaired. Echocardiography showed a right ischemic stroke is reported to be as high as 5% to 13%,1,2
to left shunt on bubble study, and he subsequently had this closed much higher than found in adult patients (4%). The most
using the Amplatzer device. The rest of his work-up was negative. common reported prothrombotic conditions include protein
Note: for the purposes of this discussion, we define pediat- C, protein S, plasminogen and antithrombin III deficiencies,
ric patients as aged <18 years although in some countries this antiphospholipid antibodies, homocystinuria, factor V leiden,
might be defined differently. and prothrombin G20210A mutations.2 Most patients with a
prothrombotic state have a single cause, but in 23% of cases,
Stroke in Pediatric Patients multiple prothrombotic risk factors are identified.1 Unlike
Although not as prevalent in pediatric populations as in adults, adults, in whom the vast majority of events related to throm-
stroke is an important cause of mortality and disability in bophilias are venous, there seems to be an equal incidence of
children. It is among the top 10 causes of mortality in chil- arterial and venous events in children.2
dren aged 5 to 25 years. Improved neuroimaging has led to Sickle cell disease is an important cause of pediatric stroke.
increased detection of childhood ischemic stroke, and the cur- Children, especially those <15 years, tend to have a high risk
rent estimated incidence of childhood arterial ischemic stroke of cerebral ischemia, whereas adults with sickle cell disease
is 1.6 per 100 000 children/y.1 are at increased risk for hemorrhage. High velocity on tran-
scranial Doppler ultrasonography (>200 cm/s) indicates ste-
Causes of Stroke in Children nosis and can be used to predict which children are at high
Causes of stroke in children are varied and differ from those risk for stroke and should receive prophylactic transfusions
seen in adults. One or more risk factors can be identified in to reduce the percentage of hemoglobin S, thereby lowering

Received November 6, 2014; final revision received November 6, 2014; accepted November 7, 2014.
From the Neurological Institute, University Hospitals Case Medical Center, Cleveland, OH (S.O.M., S.T., B.K., S.S.); and Departments of Neurology
and Stroke Unit, Helsinki University Central Hospital, Helsinki, Finland (D.S.).
Correspondence to Sophia Sundararajan, MD, PhD, Neurological Institute, University Hospitals/Case Medical Center, 11100 Euclid, Ave, Cleveland,
OH 44106. E-mail [email protected]
(Stroke. 2015;46:e32-e34. DOI: 10.1161/STROKEAHA.114.007681.)
© 2014 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org DOI: 10.1161/STROKEAHA.114.007681

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 Mittal et al   Acute Ischemic Stroke in Pediatric Patients    e33

physical examination alone cannot reliably distinguish stroke

and mimics. Neuroimaging, usually MRI, is required to diag-
nose stroke in children definitively. A prospective, consecutive
cohort study found that 30 of 143 (21%) patients had condi-
tions other than cerebrovascular disease. Of these 30 patients,
37% had benign diagnoses, including complicated migraine,
psychogenic weakness, and musculoskeletal abnormalities.
The remaining 67% of patients with stroke mimics had more
serious conditions, such as acute disseminated encephalomy-
elitis, intracranial hypertension, postictal paralysis, acute cer-
ebellitis, and intracranial abscess.4 In contrast, only 4% to 9%
of adult patients with an admission diagnosis of stroke were
found to have an alternate diagnosis.4

Reperfusion Strategies in Children

The only Food and Drug Administration–approved therapy for
acute ischemic stroke in adults is intravenous tPA. tPA has not
been rigorously studied in children age <18 years, and poten-
tial benefits remain unproven. The American Heart Association
Stroke Council outlined guidelines for management of pedi-
atric patients with acute ischemic stroke and did not recom-
mend the use of the intravenous tPA use outside clinical trials
(class III, level of evidence C). Unfortunately, clinical trials
of pediatric patients have proved difficult because of the low
enrollment and are unlikely to provide definitive evidence on
Figure. MRI shows a small area of diffusion restriction (A) with reperfusion strategies in children.
a large perfusion deficit seen with mean transit time (B) sugges- Although individual case reports suggest benefit, prospec-
tive of acute ischemia with a large penumbra. Digital subtrac- tive registries and clinical trials have not confirmed this. Case
tion angiography of the left internal carotid artery showed a left
middle cerebral artery occlusion (C), which was successfully reports from 17 children treated with intravenous thromboly-
recanalized with a stent retriever (D). sis (n=6), intra-arterial thrombolysis (n=10), or mechani-
cal thrombolysis (n=1) found no symptomatic intracranial
hemorrhages. Sixteen children (94%) survived and 12 (71%)
their risk.3 These children are also at risk for arteriopathies,
had a good outcome (modified Rankin Scale score 0 or 1),
such as moyamoya.
suggesting a possible beneficial role of reperfusion strategies
Arteriopathies are the most common sources of stroke in chil-
in pediatric strokes.5 On the contrary, a retrospective review
dren.2 Vasculitis of the intracranial vessels secondary to menin-
of 9257 children showed that only 0.7% of pediatric stroke
gitis, collagen vascular disease (systemic lupus erythematosus,
patients received thrombolysis. These patients had increased
rheumatoid arthritis, Behcet disease), intravenous drug abuse
mortality and intracerebral hemorrhage rates.6 A national
(commonly cocaine and amphetamine), and primary vasculitic
study of 2904 children with ischemic strokes found that 1.6%
conditions such as polyarteritis nodosa and Wegner arteritis
received thrombolytic therapy. Those who received tPA were
can cause thrombotic occlusion resulting in ischemic stroke.
less likely to be discharged home and had higher rates of death
Ischemic infarction because of intracranial focal arteriopathy
and dependency.7 Importantly, these studies did not control
after varicella infection and herpes zoster ophthalmicus are also
for stroke severity, the strongest predictors of outcome. The
important causes of stroke in children. Traumatic arterial dis-
International Pediatric Stroke Study, a multicenter, prospec-
section and subsequent embolization, secondary to sports inju-
tive registry included 687 children with acute ischemic stroke.
ries or motor vehicle accidents in children and adolescents are
Only 2% received tPA (9 received intravenous tPA, whereas
relatively common causes of stroke in this age group.1
6 received intra-arterial tPA). Children receiving tPA were
Moyamoya disease is a chronic noninflammatory vascu-
younger, more likely to receive tPA outside the established
lopathy of the head and neck vessels, which causes progressive adult time frame, and tended to have poorer neurological out-
stenosis and occlusion of the distal internal carotid arteries/prox- comes than children in previously published case reports. It
imal middle cerebral arteries. This inherited disease is one of the should be noted that there was a low number of patients in the
more common vasculaopathies causing stroke in children and International Pediatric Stroke Study, and the findings did not
is associated with Down’s syndrome, neurofibromatosis type I, reach statistical significance.8
and sickle cell disease. Surgical procedures, such as encephalo- The Thrombolysis in Pediatric Stroke trial attempted to test
duroarteriosynangiosis, can provide additional blood flow.2 the safety and feasibility of intravenous tPA in children with
acute ischemic stroke. This open-label, prospective, 5-year
Stroke Mimics multicenter international safety and dose-finding study was
The diagnosis of stroke is particularly challenging in chil- designed to determine the maximal safe dose of intravenous
dren because of the prevalence of stroke mimics. History and tPA (0.75, 0.9, or 1.0 mg/kg) for children aged 2 to 17 years

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e34  Stroke  February 2015

within 4.5 hours from symptom onset. Unfortunately, poor Disclosures

enrollment forced premature study termination.9 None.
Although data on the use of intravenous tPA are sparse, evi-
dence for endovascular therapy is even sketchier. Mechanical References
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STROKEAHA.108.529560.
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remain unproven in children
Key Words: thrombectomy ◼ thrombolytic therapy

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 Acute Ischemic Stroke in Pediatric Patients
Shivam Om Mittal, Sreenath ThatiGanganna, Benjamin Kuhns, Daniel Strbian and Sophia
Sundararajan

Stroke. 2015;46:e32-e34; originally published online December 11, 2014;

doi: 10.1161/STROKEAHA.114.007681
Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 2014 American Heart Association, Inc. All rights reserved.
Print ISSN: 0039-2499. Online ISSN: 1524-4628

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