ACUTE ISCHEMIC STROKE
IN CHILDREN
A BRIEF OVERVIEW
Tammy Hennika, M.D.
CHILDHOOD STROKE ACTIVATIONS
 What
neuroimaging?
 What labs?
 What is the treatment?
 Can we give tPA?
 If not a stroke, what could it be?
 If it is a stroke, what is the prognosis?
 Will it reoccur?
ARTERIAL ISCHEMIC STROKE (AIS)
More common in adults
 Also occurs in neonates, infants, children,
and young adults
 Result in significant morbidity and
mortality
 Incidence 0.6 to 7.9/100,000 children per
year
 More common in boys than girls

AIS ETIOLOGY AND RISK FACTORS
Older adults:
 Hypertension
 Smoking
 Diabetes
 Hypercholesterolemia
AIS ETIOLOGIES AND RISK FACTORS
Children:
 Cardiac abnormalities
 Vascular lesions
 Genetic conditions
 Hematologic abnormalities (such as sickle
cell disease)
 Infection
AIS ETIOLOGIES AND RISK FACTORS
Young adults:
 Vasculopathy (such as arterial dissection)
 Recent pregnancy and other
hypercoagulable states
 Smoking, drug use
 Premature atherosclerosis
 Hypertension
 Possibly migraine
INTERNATIONAL PEDIATRIC
STROKE STUDY (2010)
 Multi-center
report
 >600 children (age 29 days to 18 years)
with AIS
Most frequent conditions:
 Arteriopathy (53%)
 Cardiac disorders (31%)
 Infection (24%)
AIS RISK FACTORS
 Cardiac
Abnormalities:
 Congenital heart disease is a risk factor
for cardioembolic stroke
 Acquired cardiac lesions such as
endocarditis, cardiomyopathy, and
prosthetic valve placement
AIS RISK FACTORS
 Hematologic
abnormalities
 Sickle cell disease
 ~300 times higher than that seen in
children without SCD
 Other inherited or acquired prothrombotic
disorders such as:
 Anemia (particularly iron deficiency)
 Antiphospholipid syndrome
 Factor V Leiden mutation
AIS RISK FACTORS
 Vasculopathy
 Abnormalities
of the cerebral vasculature
 Inherited or acquired
 Pediatric
Stroke Study :
 525 children (ages 29 days to 19 years)
with arterial ischemic stroke
 Vascular imaging found arteriopathy in
277 (53%)
In the 277 cases with arteriopathy:
 Focal cerebral arteriopathy of childhood
(25%)
 Primary or secondary moyamoya (22%)
 Dissection (20%)
 Vasculitis (12%)
 Sickle cell disease arteriopathy (8%)
 Postvaricella arteriopathy (7%)
 Miscellaneous types (4%)
 Unspecified (3%)
FOCAL CEREBRAL ARTERIOPATHY (FCA)
OF CHILDHOOD
 Term
used by the International Pediatric
Stroke Study
 Unexplained focal arterial stenosis in a
child with arterial ischemic stroke
FOCAL CEREBRAL ARTERIOPATHY (FCA)
OF CHILDHOOD
 Etiology
unknown, probably multifactorial
 Possible causes:
 Inflammation and vasculitis due to
infection (eg antecedent varicella
infection) or autoimmune disease
 Thromboembolic arterial occlusion or
stenosis
 Intracranial dissection
 Arterial spasm
 Prothrombotic factors
MOYAMOYA SYNDROME
 Progressive
stenosis of the internal
carotid arteries and formation of collateral
vessels
 Name moyamoya means “puff of smoke”
in Japanese and describes the look of the
tangle of tiny vessels formed to
compensate for the blockage
ARTERIAL DISSECTION
 Definite
or probable trauma is identified
in some cases
 Spontaneous dissection also occurs
 Connective tissue disorders such as
vascular Ehlers- Danlos syndrome and
Marfan syndrome can predispose to
dissection
VASCULITIS
 Inflammatory
changes in the cerebral
vessels
 Primary

Kawasaki disease
 Secondary


Collagen vascular diseases (such as
Lupus)
Infections (bacterial meningitis, viral
infections)
OTHER ABNORMITIES OF VESSEL
STRUCTURE
 Arterial
tortuosity syndrome
 Vasospasms
resulting from subarachnoid
hemorrhage
 Fibromuscular
dysplasia
METABOLIC DISORDERS
 Several
metabolic conditions associated
with arterial ischemic stroke
 Generally through effects on the vessel
wall
 CADASIL
 MELAS
CADASIL
 Cerebral
Autosomal-Dominant
Arteriopathy with Subcortical Infarcts
and Leukoencephalopathy
Mutation in the Notch3 gene, short arm of
chromosome 19
 Progressive degeneration of smooth
muscle cells in the vessel wall
 May present with migraine, TIA, or
ischemic stroke in late childhood or early
adulthood

MELAS
 Mitochondrial
Encephalopathy with Lactic
Acidosis and Stroke-like episodes
Mutations of mitochondrial DNA
 Metabolic stroke rather arterial stroke
 Occurrence of stroke-like episodes: temporary
muscle weakness on one side of the body
(hemiparesis)
 Other features: focal or generalized seizures,
recurrent migraine-like headaches, vomiting,
short stature, hearing loss and muscle
weakness, dementia

MELAS
 Diagnostic
criteria:
 Stroke-like episodes
 Encephalopathy characterized by seizures
or dementia
 Blood lactic acidosis or
 Presence of ragged red fibers in skeletal
muscle biopsy
INGESTION
 Cocaine
and methamphetamine
 Can stroke due to hypertension,
vasospasm, or vasculitis
CLINICAL PRESENTATION
 Infants
with stroke:
 Seizures, altered mental status, or focal
weakness
 Children
with stroke:
 Hemiparesis or other focal neurologic
signs such as aphasia, visual disturbance,
or cerebellar signs
 Although seizures, headache and lethargy
are not uncommon
IF NOT A STROKE, WHAT COULD IT BE?
 Broad
differential diagnosis
 Extended in young children because
stroke may present with nonspecific signs
such as seizures or lethargy
 Vascular
abnormalities can present much
like AIS:
 Intracranial hemorrhage
 Aneurysms
 Arteriovenous malformation
 Cerebral venous thrombosis
NONVASCULAR CONDITIONS THAT MIMIC
STROKE IN CHILDREN:

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




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Tumors and other structural brain lesions
Prolonged postictal paresis (Todd’s)
Complicated migraine
Familial alternating hemiplegia
Posterior reversible encephalopathy syndrome (PRES)
Metabolic stroke
Intracranial infection (brain abscess or
meningoencephalitis)
Demyelinating conditions (ADEM)
Idiopathic intracranial hypertension
Drug toxicity
Post infectious cerebellitis
Psychogenic conditions
WHAT NEUROIMAGING?
 Neuroimaging
in children with suspected
stroke:
 Brain MRI
 Head CT can be substituted of MRI is not
tolerated or will not be available within 48
hours
 Also consider  MRA head and neck to evaluate arteries
 Axial T1 MRI neck to evaluate for
dissection
WHAT LABS?
 EKG,
ECHO, O2 saturation
 Laboratory studies:
 CBC, BMP, glucose, pt, ptt,
 Toxicology, blood alcohol, pregnancy test
 Hypercoagulable evaluation
 Vasculitis evaluation (angiography, ESR,
CRP, ANA, varicella titers, HIV, RPR)
 MELAS suspected, lactate level from
serum and CSF, molecular genetic testing,
muscle biopsy
CAN WE GIVE TPA?
 Initial
treatment of children with acute
arterial ischemic stroke :
 Recombinant
tissue plasminogen activator
(tPA) is NOT approved in the United
States by the FDA for the use in children
<18 years of age with ischemic stroke
 The
effectiveness, safety and dose of tPA
for the treatment of children with arterial
ischemic stroke have not been established
 Consensus
guidelines recommend NOT
using thrombolysis or mechanical
thrombectomy outside the of specific
research protocols or clinical trails
 Initial
antithrombotic treatment:
 No
randomized controlled trials
examining the effectiveness of antiplatelet
or anticoagulation therapy
 Limited
data suggests that
anticoagualtion therapy in children has
an acceptable safety profile, although
efficacy remains uncertain
WHAT IS THE TREATMENT?
 Ischemic
stroke of unknown etiology:
 Aspirin 3 to 5mg/kg per day rather than
anticoagulation as initial therapy
 High
clinical suspicion for either
dissection or cardioembolism:
 Short-term anticoagulation with LMWH
or unfractionated heparin until vascular
imaging and echocardiography are
obtained
 Anticoagulation
should be stopped and
aspirin initiated if no indication (eg, a
confirmed cardioemboilc source or arterial
dissection)
 Confirmed
cardioemboilc source, arterial
dissection, or hypercoagulable state:
 Initial
anticoagulation treatment (rather
than aspirin)
 IV unfractionated heparin (goal ptt 60-85) or
subcutaneous LMWH (eg, enoxaparin) for 5-7
days
 Followed by treatment with LMWH or
warfarin
 Aspirin (3 to 5mg/kg day) should be given if
there is a contraindication to anticoagulation
 AIS
Resulting from sickle cell disease:
 Urgent intravenous hydration
 Urgent exchange transfusion (goal
hemoglobin S fraction <30% of total
hemoglobin)
IF IT IS A STROKE, WHAT IS THE
PROGNOSIS?
 Prognosis:
 In
hospital mortality after ischemic stroke
in children ages 1 to 17 years – 3.4%
 Disability:
Despite neural plasticity,
majority have persistent disability
WILL IT REOCCUR?
 Recurrent
ischemia, including stroke and
TIA:
 Common after childhood arterial ischemic
stroke
 Recurrence ranging from 6.6 to 20%
 Presence of vasculopathy may be an
important risk factor for recurrent stroke
in children with later childhood stroke
 Cohort
study with cerebrovascualr
imaging available for 52 children with
later childhood stroke
 5-year stroke recurrence rate for children
with abnormal vascular imaging was 66%
 While children with normal vascular
imaging had no recurrences
CONCLUSION
 Childhood
arterial ischemic stroke differs
from adult stroke in risk factors,
etiologies, and outcomes
 Secondary stroke prevention with
antiplatelets or anticoagulation are
adapted from adult stroke management
 Little is known about the safety and
efficacy of acute thrombolytic therapy in
various age groups
 Further
study is greatly needed for a
better understanding of the pathogenesis,
management, and outcomes in childhood
arterial ischemic stroke
REFERENCES
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and children: a scientific statement from a Special Writing Group of the
American Heart Association Stroke Council and the Council on
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Monagle, P, Chan AK, Golenberg NA, et al. Antithrombotic therapy in
neonates and children; Antithrombotic Therapy and Prevention of
Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based
Clinical Preactice Guidleline. Chest 2012; 141:e737S.
Pediatric Stroke Working Group. Stroke in childhood: Clinicial guidelines
for diagnosis, management and rehabilitation. November 2004.
www.rcplondon.ac.uk/pubs/books/chidstroke (accessed on January 14,
2011).
Smith, S, Ischemic stroke in children: Ischemic stroke in children and
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