Topical Review

Section Editors: Mathew Reeves, PhD, and Amanda Thrift, PhD

Outcome in Childhood Stroke

Mardee Greenham, PGDipPsych; Anne Gordon, PhD; Vicki Anderson, PhD; Mark T. Mackay, MBBS

C ontrary to commonly held views, children do not recover

better than adults after a stroke.1 The lifelong individual,
family, and societal burden of stroke is likely to be greater than
in adults because infants and children surviving stroke face
many more years living with disability. The key difference
between children and adults is that childhood stroke (occurring
during the perinatal period and beyond) results primarily in a
changed ability to achieve, rather than lose, functional indepen-
dence. The extent and severity of deficits across motor, sensory,
cognitive, social, and behavioral domains may not be apparent
in the short-term after stroke, particularly in newborns and pre-
school children, who typically grow into their deficits.2,3
The World Health Organization’s International
Classification of Functioning (ICF), Disability, and Health can
be applied to childhood stroke to describe its impact across
health domains, including impairment in body structures and
functions, activity limitations and participation restrictions
at individual, institutional and social levels. This review will
focus on childhood stroke, defined as stroke from 1 month to
18 years of age, and where possible use the ICF framework
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disorders, which has an increased risk of mortality. It may
also be because modifiable risk factors such as hypertension,
smoking, and hyperlipidemia do not play important roles in
pathogenesis in childhood stroke.
Risk Factors and Causes
A diverse range of risk factors have been identified in asso-
ciation with childhood stroke. In AIS, there is increasing evi-
dence for factors, such as vasculopathy, infection,8 trauma,8
cardiac9 and hematologic disorders10 from case–control and
cohort-based studies. Contrasting with adults, atherosclerosis
is a rare cause for childhood AIS. Chronic diseases of child-
hood frequently underlie childhood AIS; however, approxi-
mately half of the children are previously healthy.11 Multiple
risk factors converge in >50% of children with AIS12 but at
least 10% remain idiopathic.
The common causes of nontraumatic HS are arteriovenous
malformation, hematologic abnormalities, and brain tumor,
with other pathogeneses, including cavernous hemangioma,
vasculopathy, vasculitis, and infections.13

to describe outcome after arterial ischemic stroke (AIS) and

hemorrhagic stroke (HS).
Body Structures and Functions
Mortality After Childhood Stroke
Stroke is among the top 10 causes of death in the pediatric
population. The reported mortality for AIS ranges from 7% to
28%1,4 and from 6% to 54% for HS.5 In the US study reporting
stroke mortality during a 10-year period from 1979 to 1998,
4881 deaths could be attributed to childhood stroke, giving
average annual mortality rates of 0.09 per 100 000 person-
years for AIS 0.14 for intracerebral hemorrhage and 0.11
for subarachnoid hemorrhage.6 Risk of death was higher in
infants, males, blacks, and children living in the South-Eastern
Stroke belt States.6,7 Declining mortality rates have been
observed in childhood HS, possibly related to improvements
in critical care, but there have been much smaller decreases
in AIS mortality rates.6 This may be partially because of the
underlying risk factors associated with AIS, such as heart
Stroke Recurrence
Rates of recurrent AIS ranges from 6% to 35%.1,4,14 Population-
based data suggest 5-year recurrence rates approach 50%.4,15
Presence of arteriopathy is the most important predictor of
recurrent AIS with rates of >65% reported.4,14,15 Other fac-
tors associated with increased risk of recurrence or reinfarc-
tion include genetic thrombophilia,14,16 previous TIA, bilateral
infarction, immunodeficiency, and leukocytosis.14
The relative efficacy of various secondary stroke preven-
tion interventions is unknown because of a lack of random-
ized controlled trials. There are however, some data to support
specific interventions in conditions associated with high
recurrence risk. In addition to primary prevention of stroke
in children with an abnormal transcranial doppler,17 regular
transfusions to reduce hemoglobin S to <20% to 30% pro-
tect against cerebrovascular events in children sickle cell
disease and radiological evidence of silent cerebral infarc-
tion.18 Surgical revascularization procedures are successful at
improving perfusion and reducing recurrent stroke or transient

Received September 28, 2015; final revision received February 7, 2016; accepted February 18, 2016.
From the Clinical Sciences, Murdoch Childrens Research Institute, Melbourne, Australia (M.G., V.A., M.T.M.); School of Psychological Sciences
(M.G., V.A.) and Department of Paediatrics (M.T.M), University of Melbourne, Melbourne, Australia; Department of Paediatric Neuroscience, Evelina
London Children’s Hospital, London, United Kingdom (A.G.); Institute of Psychology, Psychiatry, and Neuroscience, Kings College London, London,
United Kingdom (A.G.); and Department of Psychology (V.A.) and Neurology (M.T.M.), Royal Children’s Hospital, Melbourne, Australia.
Correspondence to Mardee Greenham, PGDipPsych, Clinical Sciences, Murdoch Childrens Research Institute, Flemington Rd, Parkville, Victoria 3052,
Australia. E-mail mardee.greenham@mcri.edu.au
(Stroke. 2016;47:1159-1164. DOI: 10.1161/STROKEAHA.115.011622.)
© 2016 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org DOI: 10.1161/STROKEAHA.115.011622

1159
 1160  Stroke  April 2016
ischemic attacks in children with Moyamoya disease.19 In con-
trast, a randomized controlled secondary prevention trial in
children with complex congenital heart disease undergoing
the Fontan procedure found no difference in the frequency of
thrombotic events between those treated with anticoagulant or
antiplatelet therapy. The study however, was not designed to
identify asymptomatic cerebrovascular events.20
There are less data on risk factors for recurrent HS in chil-
dren. In a population-based cohort study of 2.3 million chil-
dren, 116 cases of nontraumatic HS were identified during
11 years with a 5-year cumulative recurrence rate of 10%.21
Almost two thirds of bleeds occurred within the first 6 months
of diagnosis. No child with idiopathic HS had a recurrent
event, whereas 13% of children with structural abnormalities
such as AVMs or tumors and medical pathogeneses such as
thrombocytopenia or hypertension had recurrent events.
Post Stroke Epilepsy
Post stroke epilepsy occurs in ≈15% to 20% of children with
childhood AIS4 and ≤17% of HS.5 Larger cortical lesions
are associated with higher risk of developing seizures.4,22
Emerging data from the International Pediatric Stroke study
suggest that the incidence of a first remote seizure is 1% per
month, with a cumulative 13% incidence of active epilepsy
by 1 year after childhood AIS.23 Younger age, multifocal or
cortical infarction, involvement of the middle cerebral artery
territory, presence of focal cerebral arteriopathy, presence and
duration of symptomatic seizures at the time of diagnosis are
associated with increased risk of epilepsy.24,25 Children with
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epilepsy complicating AIS have poorer cognitive outcomes26
and quality of life27 than those who do not.
Neurological, Motor, and Speech Impairments
After Childhood Ischemic Stroke
A recent Swiss population-based study comparing long-term
neurological outcomes in children and young adults with AIS
found almost half of the children had long-term neurologi-
cal impairments. Mortality, disability, psychosocial impair-
ments, and quality of life outcomes did not differ for children
and young adults with the exceptions of behavioral problems
(more common in children) and impaired daily living skills
(more common in adults). Long-term outcome in children
was predicted by initial stroke severity.1 Another recent study
investigating recovery across multiple domains of health,
reported significant motor impairments in children at both
1- and 6-month post-AIS, in addition to deficits in adaptive
behavior at 6 months.2 A large multinational observational
study of 612 children with AIS found that almost 3 quarters
of children had neurological deficits at the time of discharge.
Poorer neurological outcomes were more common in children
with altered consciousness at presentation, bilateral infarction,
and presence of arteriopathies on brain imaging.28 Moderate
or severe neurological deficits were observed in >40% of chil-
dren and mild deficits in 20% of children in another Canadian
study.4 Independent predictors of poor neurological outcome
include AIS subtype, associated neurological disorders, and
need for rehabilitation. Few studies reporting neurological
impairments after childhood stroke have stratified outcome
by pathogenic subgroup. Arteriopathy was associated with
increased odds of adverse early outcome, defined as death or
neurological deficit at discharge, in a large international mul-
ticentre study,28 cardiac disease, and Moyamoya were associ-
ated with higher rates of neurological impairment in another
French study.29 In contrast, other studies from the United
Kingdom,30 Canada,4 and Switzerland1,31 found no associa-
tion between specific risk factors or pathogeneses and poorer
outcomes.
Physical and motor impairment are common after child-
hood AIS. Cross-sectional follow-up studies report motor
impairments ranging from mild clumsiness to significant
hemiparesis in 50% to 80% of children.4,26,30 Hemiplegia is
reported in 3 quarters of children.4 Infarcts involving >10% of
the supratentorial intracranial volume are typically associated
with poor outcome.30 Different patterns of motor recovery in
neonates compared with older children suggest age-dependent
vulnerability of brain structures or varying capacity for corti-
comotor reorganization. However, trajectories of motor recov-
ery from acute phase through to long-term remain unknown.
Speech and language impairments have not been widely
reported, but 1 study described language deficits in 30% of
children 12 months after AIS.32 Language impairment is most
common in left hemisphere strokes, but this may depend on
age at onset. A study investigating long-term language out-
comes in children with left subcortical AIS reported deficits in
6 of 9 patients, including naming difficulties, reduced fluency,
repetition difficulties, and written language difficulties.33 They
found posteriorly located lesions and younger age at stroke
were associated with poorer language outcomes. Another
study comparing children with left and right basal ganglia
infarcts found no difference between the groups, but did
note greater variation in performance of the patients with left
hemispheric stroke.34 Further examination showed language
deficits were associated with abnormalities in left hemisphere
cortical language areas remote from the lesion site.
Cognitive Function After Childhood AIS
Studies investigating intellectual function after childhood AIS
have found intelligence quotient scores are skewed toward
the lower end of average and significantly lower than control
groups and standardized test norms.35–37 Some studies report
weaknesses in complex cognitive skills, including attention,36
executive function,36 visuoconstructive skills,37 processing
speed, and working memory.3,37 Rates of cognitive impairment
are not frequently reported, but 1 study found attention and
executive function deficits in 30% to 67%.36
Larger lesion volume3,35 and infarcts affecting cortical and
subcortical regions3,37 are associated with poorer cognitive
outcomes. The effect of lesion laterality is unclear, with some
studies reporting better neuropsychological outcomes after
right hemisphere AIS38 and other studies demonstrating no
laterality effects.3,36 Age at AIS also affects cognitive outcome,
with possible periods of vulnerability and plasticity related to
growth spurts within the brain.37 Earlier age at onset (before
1 years of age) has been found to be associated with poorer
cognition in some studies,3,38 whereas others report poorer
outcomes in later-onset AIS, when brain maturity is more
 Greenham et al   Outcome in Childhood Stroke    1161
advanced.38 Cognitive outcomes vary widely between studies,
possibly because of large cross-sectional design and differing
methodology, such as varying age range of cohorts and wide
range in time since diagnosis.
The majority of studies reporting cognitive26,39,40 and func-
tional41,42 outcomes after childhood stroke have not assessed
the influence of risk factors or pathogenesis on outcome. A
recent Swiss multicentre study, however, found no association
between risk factors and cognition.37
Neurological and Cognitive Impairments After HS
HS has received less attention despite accounting for almost
half of childhood strokes.43 Poor outcomes were reported
in 25% to 52% of children after HS in a retrospective case
series.5,44,45 Specific outcomes are usually not defined, but
a recent US study of 19 children described mild to moder-
ate neurological impairments and significantly lower quality
of life than normative means in the majority of survivors.44
Predictors of poorer neurological outcomes include younger
age,45 depressed conscious state at presentation in some,45 but
not other studies,44 intracerebral hemorrhage volume44 and
presence of vascular anomaly.44
A Dutch study describing long-term outcome in 31 sur-
vivors of childhood HS found that over half had physical
impairments with paresis or cerebellar ataxia with a similar
proportion, showing cognitive deficits when compared with
premorbid academic functioning.5 These findings are consis-
tent with an earlier US study of 26 patients, which reported
motor and cognitive deficits in 38% and 50% of survivors,
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respectively.46
Activity Limitations and Participation
Restrictions
Most activity limitations and participation restrictions after
childhood stroke occur in motor function, self-care skills,
communication, educational problems, and social isolation.41
Reductions in family and school participation have been
identified via self- and parent report.26,41,42 One study found
that, 12 years after childhood stroke, despite a high level of
employment and college attendance, financial independence
and independent living were relatively low.42
A recent review of functioning and disability after child-
hood stroke found an imbalance between the evaluation of
impairment versus participation and activity.47 Cognitive func-
tion (intelligence quotient, memory, and attention) was the
most consistently measured outcome domain, and few studies
explored the relationship between these impairments and the
child’s learning abilities or academic progress.47 The sever-
ity of motor deficits varies, but most children gain or regain
independent mobility30 However, even mild motor impairment
may limit a child’s ability to participate in activities and affect
self-confidence. Task-based hand use has received limited
attention, but 1 study reported bimanual tasks, such as eating
and dressing, were a significant concern for parents.48 Findings
from studies exploring adaptive behavior vary widely, with
some reporting that most children attain age-appropriate inde-
pendence, whereas others document poor outcomes in 60%
of children.47
Attention deficit/hyperactivity disorder symptoms (learning
difficulties, attention problems, anxiety, and impulsivity) have
been reported in 50% of children,49 externalizing behaviors in
44%31 and emotional problems in 25%.41,50 One study found
59% of children with stroke developed psychiatric disorders
compared with only 14% of controls.51 Few studies have
explored specific components of social function, but there is
a trend toward reduced overall social function, lower levels
of participation, and reduced peer acceptance.52 Associations
have been reported between poorer psychosocial outcome and
lesions in the ventral putamen and attention deficit/hyperactiv-
ity disorder symptoms and between lesions in the medial and
orbital prefrontal correct and inattentive symptoms.53 Others,
using less specific measures, report no link between psycho-
logical problems and lesion characteristics.41,49
Impact of Childhood Stroke on Quality of Life
Quality of life has been investigated in several studies, all
reporting reduced levels of well-being across a variety of
domains.32,41,42,50 Severity of neurological impairment, sex
(girls rate their quality of life lower than boys), younger age
at stroke onset, cognitive function, self-esteem, and family
factors, including parent well-being and family functioning
have all (separately) been associated with poorer quality of
life.32,41,50
Environmental Factors
The ICF includes consideration of the impact of environmental
factors (physical, social, and attitudinal) that may act as barri-
ers or facilitators for effective daily living, but this area remains
largely unexplored in childhood stroke outcome studies. The
economic burden of childhood stroke on families and health
services has, however, been reported. Higher stroke costs cor-
relate with more impairment and poorer quality of life.54 A
recent retrospective study estimated the 5-year direct medical
cost of neonatal and childhood stroke to be $110 921,55 repre-
senting a 15-fold cost increase compared with controls. Costs
were higher for childhood stroke ($135 611) than for neonatal
stroke ($51 719) and higher for HS than AIS. Families experi-
ence substantial out of pocket expenses, related to lost wages,
transportation and nonreimbursed health care.
Outcome Measures for Childhood Stroke
The childhood stroke literature uses measures and describes
outcomes that focus predominantly on the domain of impair-
ments in body structures and functions. There is currently no
gold standard outcome measure for childhood stroke, and
recent reviews have shown a wide variety of measures that have
been used across studies.47,56 Many of the measures are author
derived, and the majority of the standardized measures used
are validated for use in children with other medical conditions,
such as cerebral palsy and head trauma, and not appropriately
sensitive to detect the focal and often mild deficits of child-
hood stroke.4 Many standardized, stroke-specific measures,
such as the modified Rankin Scale and Barthel Index, have
been developed for adults and rely on self-report and indepen-
dence of daily living, making them inappropriate for young
children.4 The Pediatric Stroke Outcome Measure is the only
 1162  Stroke  April 2016

validated disease-specific measure for the childhood stroke Table.  Factors Influencing Outcome in Childhood Arterial
population. The Pediatric Stroke Outcome Measure evalu- Ischemic Stroke
ates neurological impairment across sensorimotor, language, Neuro
cognitive, and behavioral domains.57 High inter-rater reli- Outcomes Death Recurrent Stroke Impairment
ability and construct validity of the Pediatric Stroke Outcome
Reported rates 7%–28% 6%–35% 50%–80%
Measure has been found with excellent agreement for pro-
spective and retrospective scoring. The Stroke Recovery and Association Yes No Yes No Yes No
Recurrence questionnaire, derived from the Pediatric Stroke Demographics
Outcome Measure for use as a telephone questionnaire, also  Age ✓14,59 ✓30,31 ✓1,28
demonstrates good agreement between total scores across
 Sex ✓7 ✓6 ✓59 ✓1
both measures in a recent validation study.58
 SES
Limitations of the Current Literature and  Ethnicity ✓6,7 ✓60 ✓14
Priorities for Future Research Pathogenesis
The infrequent occurrence of childhood stroke means that
 Risk factors ✓29,59
most studies reporting outcomes consist of single-center
cross-sectional or retrospective cohorts with variable dura-  Associated ✓4 ✓1,31
tion of follow-up, thus limiting the strength of evidence. neurological
disorder
There is also limited reporting of the clinical, radiologi-
cal, and environmental factors that may influence outcome  All arteriopathy ✓14–16,59 ✓28
(Table). As highlighted in a recent review, relatively few  Moyamoya ✓14,29 ✓29
studies have explored outcome beyond body structure and
 SSD ✓28
function (as classified using the ICF-CY).47 Therefore, our
knowledge of outcomes and contributing factors remains lim-  Cardiac ✓29
ited. Few studies provide details of which specific domains disease
are affected, and use of terminology including impairments,  Infection ✓16 ✓59
outcome, and function vary widely. Standardized outcome  Prothrombotic ✓14
measures are not always used, making it difficult to compare disorder
results,56 and only a small proportion of studies address daily
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 Type of ✓16,21,59
life abilities of those affected by childhood stroke, instead antithrombotic
focusing on specific domains of impaired body functions.47 Rx
These substantial gaps in knowledge mean there is little con- Infarct characteristics
sensus to assist in guiding rehabilitation. Larger, prospective
multicentre studies are required, using consistent diagnos-  Bilateral ✓59 ✓1,28
infarcts
tic definitions and adequate outcome measures, to gener-
ate better outcome data.61 Future research should compare  Circulation ✓28
neurological and functional outcomes in children with cryp-  Location ✓31
togenic stroke, to those with preexisting conditions such as
 Hemorrhagic
congenital heart disease or sickle cell disease, to guide the change
development of targeted interventions to improve outcomes.
 Size ✓14
Further investigation of other variables that potentially influ-
ence outcomes such as age and lesion characteristics may This table summarizes the findings in the literature to date. Cross-
study comparison is limited by large variation in study methodology,
also assist in identifying children most at risk. In addition,
cohort characteristics, and time to assessment after stroke. SES indicates
longitudinal studies are essential, particularly in infants and socioeconomic status; and SSD, sickle cell disease.
younger children where it is more difficult to predict out-
come and neurological deficits are not immediately apparent
It is therefore difficult to provide clear recommendations to
at the time of diagnosis.
clinicians about the optimal rehabilitation and long-term care
of children affected by stroke. A recent Delphi Consensus
Conclusions Process surveyed parents of children with AIS to identify
Stroke is among the top 10 causes of death in children and
the most important and acceptable research outcomes from a
is a significant cause of childhood disability. Most children
will experience long-term neurological, motor, and cogni- community perspective. The consensus from parents was that
tive impairments. Using the ICF classification, research to studies focusing on assessment of motor, cognitive, and com-
date has largely focused on body structures and functions, munication outcomes were of most interest.62 It is important
with little attention given to activity limitations and partici- that outcome research is informed by the expressed needs
pation restrictions. Studies focusing on quality of life, psy- of the children, young people, and families, with an antici-
chosocial functioning, and daily living have begun to emerge pation of the change in needs over time as a young person
in recent years but further research is required in these areas. grows and matures. This needs to be undertaken alongside the
 Greenham et al   Outcome in Childhood Stroke    1163
development of service delivery models that can provide flex-
ible, targeted, and effective intervention and support.
Sources of Funding
This study was supported by the Murdoch Children’s Research
Institute, Melbourne, Australia and the National Stroke Foundation
of Australia.
Disclosures
None.
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Key Words: child ◼ cognition ◼ infant ◼ quality of life ◼ stroke