The epidemiology of childhood stroke

doi:10.1016/j.ejpn.2009.09.006

European Journal of Paediatric Neurology

Volume 14, Issue 3, May 2010, Pages 197-205

https://doi.org/10.1016/j.ejpn.2009.09.006 Get rights and content

Abstract

This paper reviews the epidemiology of childhood stroke. Stroke is an important condition in children. It is one of the top ten causes of childhood death and there is a high risk of serious morbidity for the survivors. Epidemiological data are an integral part of disease understanding and high quality studies are required to ensure that this data is robust. Incidence rates from population-based studies vary from 1.3 per 100,000 to 13.0 per 100,000. Factors found to influence incidence rates include age, gender, and ethnicity but there are also many inherent differences between studies. Temporal analysis of mortality rates from childhood stroke shows falling rates but there has been little long-term study of changes in incidence rates. Improved epidemiological data should be a goal of the national and international collaborative networks that are studying childhood stroke.

Introduction

Stroke is defined by the World Health Organisation as “rapidly developing clinical signs of focal (or global) disturbance of cerebral function, with symptoms lasting 24 h or longer, or leading to death, with no apparent cause other than of vascular origin”.¹ This definition includes both ischaemic stroke and haemorrhagic stroke. Arterial ischaemic stroke (AIS) and cerebral venous thrombosis (CVT) are both subtypes of ischaemic stroke. Strictly, the WHO definition excludes cases of subarachnoid haemorrhage (SAH) without disturbance of cerebral function but most investigators include SAH as a subtype of haemorrhagic stroke.²

Stroke is the second most frequent cause of death in adults worldwide, responsible for over 5 million deaths per year.³ As befits the importance of stroke, its epidemiology in adults has been extensively studied.4, 5, 6 However, stroke is also an important disease in children. Childhood stroke is one of the top ten causes of death in US children,⁷ has a high risk of serious morbidity for survivors⁸ and has high financial cost implications for healthcare services.⁹ Epidemiological data are important as they quantify the scale of a disease, provide aetiological insights and provide data to inform other studies such as clinical trials. This paper reviews the epidemiology of childhood stroke and considers whether the quality of the epidemiological data currently available corresponds to the importance of this condition.

Section snippets

Incidence

There have been various population-based studies of the incidence of childhood stroke published over the last 30 years (Table 1). Some studies have only estimated the incidence of ischaemic stroke whereas others also included haemorrhagic stroke. Studies also vary regarding the inclusion of cases of CVT and SAH, although for a number of studies it was not possible to ascertain whether CVT and SAH were included. There is considerable variation in the reported incidence rates (for clarity always

Mortality

The US National Centre for Health Statistics reports mortality rates from cerebrovascular diseases as 3.1 per 100,000 for children aged under 1 year, 0.4 per 100,000 for children aged 1–4 years and 0.2 per 100,000 for children aged 5–14 years.²⁹

There have been two studies that have specifically investigated mortality from childhood stroke30, 31 although a number of other studies have reported case fatality rates of patient series.18, 20, 32 Both of the mortality studies used national death

Age

There is considerable variation in the risk of childhood stroke according to age. Five of the 6 studies with the largest number of cases published the age distribution of cases.13, 16, 17, 18, 32, 34 In all of these studies the greatest risk of childhood stroke is for children aged less than 1 year. In studies that analysed neonates (aged under 1 month) separately, this group was found to be at particularly high risk, responsible for between 8%³² and 35%¹⁷ of all cases of childhood stroke. The

Gender

It is well known that age-specific stroke rates are higher in adult men than women.47, 48 Most of the population-based studies of childhood stroke have reported the male to female ratio. Kleindorfer et al.²⁰ reported a male to female ratio of 0.8. Satoh et al.¹² and Zahuranec et al.⁴⁹ both reported equal numbers of males and females. The other 9 studies all found an increased risk for males with a male to female ratio of between 1.15 and 4.0 (see Table 1). The International Pediatric Stroke

Ethnicity and geography

The epidemiology of childhood stroke has not been extensively studied outside of highly developed nations with only two of the studies listed in Table 1 being within less economically developed countries. The studies in developed nations are almost all of relatively homogenous, predominantly white Caucasian populations. The notable exceptions are the studies by Satoh et al.¹² and Chung and Wong¹⁵ which studied populations that are almost exclusively (>98%) Japanese and Chinese respectively. The

Temporal trends

It has been suggested that the incidence of childhood stroke is increasing with time.75, 76, 77 In support of this suggestion it is noted34, 76 that the reported incidence of childhood stroke increases from the study by Schoenberg et al.²⁸ (1965–1974), to that of Broderick et al.⁷⁸ (1988–1989) and finally to that of Giroud et al.¹¹ (1985–1993) or deVeber¹⁸ (1992–1998). However, this progression does not robustly support the hypothesis that childhood stroke incidence is rising. As discussed,

Summary

Robust and comprehensive epidemiological data are an important aspect of the understanding of a disease. Stroke is a significant cause of childhood mortality and morbidity.8, 29 The mortality rate of childhood stroke is falling although there are suggestions that the incidence may be rising. Epidemiological studies of childhood stroke have shown that the greatest risk is in infancy, that males are at increased risk compared to females and that there are ethnic and geographical differences in

Acknowledgements

Both of the authors are contributors to a prospective study of childhood stroke funded by the Stroke Association (UK). The funding source had no involvement in study design; in the collection, analysis, or interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.

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Management of Pediatric Stroke - Challenges and Perspectives from Resource-limited Settings
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According to a study by Shack et al the organization and implementation of institutional acute stroke protocols can facilitate more timely access to diagnosis and management of children with acute stroke.24 Childhood stroke is an emergency and early interventions are critical and can impact on the associated morbidity and mortality.1,3,5 Intravenous thrombolysis improves outcomes for adults presenting with ischemic stroke when administered within 4.5 hours of stroke onset.25,26
Childhood stroke is not as common as adult stroke, but it is underrecognized the world over. Diagnosis is often delayed due to lack of awareness not only by the lay public but also by emergency and front-line health care workers. Despite the relative rarity of childhood stroke, the impact on morbidity, mortality and the economic burden for families and society is high, especially in poorly resourced settings. The risk factors for stroke in children differ from the adult population where lifestyle factors play a more important role. The developmental aspects of the pediatric cerebral vasculature and hematological maturational biology affects the clinical presentation, investigation, management and outcomes of childhood stroke in a different way compared to adults. The management of childhood stroke is currently based on expert guidelines and evidence extrapolated from adult studies. Hyperacute therapies that have revolutionized the treatment of stroke in adults cannot be easily applied to children at this stage due to the diagnostic delays, diverse risk factors and developmental considerations mentioned above. Much has been achieved in the understanding of genetic, acquired, preventable and recurrent stroke risk factors in the past decade through international collaborative efforts like the International Pediatric Stroke Study. Evidence for the prevention and treatment of childhood stroke remains elusive. Even more elusive are relevant and achievable management guidelines for pediatric stroke in resource-limited settings. This narrative review focusses on the current management practices globally, emphasizing the challenges, and gaps in knowledge of pediatric stroke in low- and middle-income countries and other areas with limited resources. Priorities and some potential solutions at national and local level are suggested for these settings.
Quality of life and psychosocial functioning in childhood stroke
2021, Factors Affecting Neurodevelopment: Genetics, Neurology, Behavior, and Diet
Stroke in childhood is rare but can have long-lasting significant consequences. This chapter shows that approximately three quarters of children with stroke have resulting functional and physical disabilities. Physical and psychosocial problems have been ranked by young people who have experienced childhood stroke as the biggest source of impairment, while parents have indicated that the emotional domain is the most affected. Approximately 50% of children with stroke have a psychological, behavioral, or psychiatric diagnosis (most commonly attention deficit hyperactivity disorder, anxiety or mood disorders), and one in five receive more than one diagnosis. A significant proportion of children with stroke have long-term difficulties in many psychosocial domains, and an estimated 50% require additional educational assistance. Childhood stroke is associated with higher levels of emotional, behavioral, and social problems, and fatigue is also commonly reported. Health-related quality of life (HR-QoL) is often significantly reduced following childhood stroke. Parental well-being and sibling HR-QoL can also be affected. Clinical assessment of psychosocial difficulties in children with stroke is vital, to develop tailored interventions and improve HR-QoL for children with stroke and their families.
Neuropsychological outcomes following childhood stroke
2021, Factors Affecting Neurodevelopment: Genetics, Neurology, Behavior, and Diet
Childhood stroke is rare but an increasingly recognized cause of childhood disability. Childhood stroke has an incidence rate of 13 per 100,000 children. Approximately 75% of children have residual functional difficulties following stroke in childhood. A significant number of children experience difficulties in a wide range of neuropsychological domains, and approximately half require extra educational supports due to academic challenges. Following stroke, children’s performance on assessments of general intellectual functioning is often lower than normative population samples or matched controls. Significant impairments are observed in attention, including sustained and divided attention, response inhibition, speed of information processing, and executive functions, including working memory, cognitive flexibility, switching, and emotional regulation. These difficulties in attention and executive function are associated with behavioral and academic challenges for children with stroke. Careful neuropsychological assessment and follow-up is required for children who experience stroke, as some difficulties may only become apparent with increased environmental, cognitive, social, and academic demands over time.
Targeted re-sequencing in pediatric and perinatal stroke
2020, European Journal of Medical Genetics
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Stroke and cerebrovascular disorders are an important cause of morbidity and mortality not only in elderly but also in children, being among the top 10 causes of death in the pediatric population, with a reported mortality ranging from 7% to 28%. Pediatric arterial ischemic stroke (AIS) occurs after one month of age, with an incidence of 1–2 cases per 100,000 children per year (deVeber, 2003; Tsze and Valente, 2011; Mallick and O'Callaghan, 2010; Numis and Fox, 2014). Of note, 6–35% of affected children experience recurrent stroke episodes, and up to 75% lives with persistent neurological deficits or develop epilepsy (deVeber, 2003; Tsze and Valente, 2011; Kolk et al., 2011; Numis and Fox, 2014; deVeber et al., 2017; Beslow et al., 2018).
Pediatric and perinatal stroke can present as an early symptom in undiagnosed syndromes characterized by simple Mendelian inheritance. In order to diagnose those patients affected with a monogenic disorder in which an arterial cerebrovascular event or arteriopathy may have preceded any other specific symptom, we aimed to establish and validate a targeted gene panel, and to determine its diagnostic yield and clinical utility. To this end, thirty-eight patients were selected with heterogeneous cryptogenic stroke phenotypes, mostly including multiple and recurrent ischemic or hemorrhagic arterial strokes and porencephalies, variably associated with calcifications, intracranial or systemic steno-occlusive arteriopathies, positive family history, and syndromic conditions. Clinical and neuroradiological data were collected for every patient enrolled in the study, and DNA samples were tested by means of a customized gene panel including 15 genes associated with known genetic diseases related to pediatric stroke. In four patients (10.5%) the analyses unraveled pathogenetic variants in ABCC6 and COL4A1 genes, leading to a definite genetic diagnosis with a great beneficial impact on patients management, while results were null in the remaining patients. These findings suggest a high complexity and variability of the included stroke phenotypes, that could not be fully accounted for by the genes tested in the present study. A wider gene panel or an unbiased genomic approach may be better suited and advisable to explain a greater proportion of pediatric and perinatal stroke events.
Language and cognitive outcomes after childhood stroke: Theoretical implications for hemispheric specialization
2019, Cortex
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Childhood stroke, defined as an ischemic or hemorrhagic stroke occurring during childhood outside the perinatal period, i.e., beyond the first month of life (Felling, Sun, Maxwell, Goldenberg, & Bernard, 2017; Fullerton, Wu, Zhao, & Johnston, 2003; Greenham, Gordon, Anderson, & Mackay, 2016), is a relatively rare condition. The reported incidence of childhood arterial ischemic stroke ranges from .2 to 7.9 per 100000 person-years (Agrawal, Johnston, Wu, Sidney, & Fullerton, 2009; Giroud et al., 1995; Mallick et al., 2014; Mallick & O'Callaghan, 2010). The relative proportions of ischemic and hemorrhagic strokes are comparable in childhood (Mallick & O'Callaghan, 2010).
The purpose of this study was to investigate language and cognitive outcomes following severe childhood stroke, and the role of age at stroke according to lesion lateralization.
We retrospectively included children consecutively admitted to a physical medicine and rehabilitation department between 1992 and 2015 following childhood stroke (age at stroke 1 month to15 years). Data collection included demographic and clinical information, results of cognitive assessments on the Wechsler Intelligence scales, detailed language assessments by speech and language therapists, and long-term academic outcome.
Overall, 184 children (52% boys; mean age at assessment = 8.5 years, range .7–15.4 years) were hospitalized following ischemic (n = 79) or hemorrhagic (n = 105) stroke. After a median time since stroke of 4 months (n = 135), mean Full-Scale, Verbal, and Performance Intellectual Quotient (FSIQ, VIQ and PIQ) were 85 (SD = 19), 93 (SD = 22), and 85 (SD = 20), respectively. In language tests (n = 130) assessing lexical and syntactic expression and comprehension, 26%–53% of the children exhibited impairments (scores <2SD). After a median follow-up of 40 months, only 27% of the children were following a normal curriculum without adaptations or delay, and 27% were attending special education programs. School situation was strongly associated with language and FSIQ scores. Language and verbal IQ scores were significantly lower (p < .01) among patients with lesions in the left hemisphere as opposed to the right. After a left hemisphere lesion, language skills were not associated with age at stroke, but for right hemisphere lesions, language was more impaired among children who were younger at stroke onset. PIQ tended to correlate positively with age at stroke in left hemisphere lesions (poorer PIQ in early lesions) and negatively for right hemisphere lesions (poorer PIQ in late lesions).
These findings, discussed in the light of the brain vulnerability and plasticity hypotheses, are in favor of a developmental view of hemispheric specialization.
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2020, Revue Neurologique
Pediatric arterial ischemic stroke (AIS) is a severe condition, with long-lasting devastating consequences on motor and cognitive abilities, academic and social inclusion, and global life projects. Awareness about initial symptoms, implementation of pediatric stroke code protocols using MRI first and only and adapted management in the acute phase, individually tailored recanalization treatment strategies, and multidisciplinary rehabilitation programs with specific goal-centered actions are the key elements to improve pediatric AIS management and outcomes. The main cause of pediatric AIS is focal cerebral arteriopathy, a condition with unilateral focal stenosis and time-limited course requiring specific management. Sickle cell disease and moyamoya angiopathy patients need adapted screening and therapeutics.

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Review articleThe epidemiology of childhood stroke

Abstract

Introduction

Section snippets

Incidence

Mortality

Age

Gender

Ethnicity and geography

Temporal trends

Summary

Acknowledgements

Lancet Neurol

Lancet Neurol

J Clin Epidemiol

Brain Dev

Semin Pediatr Neurol

Vaccine

Lancet Neurol

Best Pract Res Clin Endocrinol Metab

J Biol Chem

Pediatr Neurol

Brain Dev

Lancet

Pediatr Neurol

Cerebrovascular disease in the community: results of a WHO collaborative study

Bull World Health Organ

Comparing stroke incidence worldwide: what makes studies comparable?

Stroke

The global burden of disease 2004 update

Epidemiology of stroke

Lancet

Heart disease and stroke statistics – 2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee

Circulation

Outcome after ischaemic stroke in childhood

Dev Med Child Neurol

The cost of pediatric stroke care and rehabilitation

Stroke

Stroke in children and sickle-cell disease: Baltimore–Washington Cooperative Young Stroke Study

Neurology

Clinical survey of ischemic cerebrovascular disease in children in a district of Japan

Stroke

Risk of stroke in children: ethnic and gender disparities

Neurology

Cerebral sinovenous thrombosis in children

N Engl J Med

Pediatric stroke among Hong Kong Chinese subjects

Pediatrics

Cerebrovascular disease/stroke and like illness

The first three years of the Swiss Neuropaediatric Stroke Registry (SNPSR): a population-based study of incidence, symptoms and risk factors

Neuropediatrics

The Canadian Pediatric Ischemic Stroke Study Group: Canadian Paediatric Ischemic Stroke Registry: analysis of children with arterial ischemic stroke

Ann Neurol

Epidemiological investigation of cerebrovascular disease in Iceland, 1958–1968 (ages 0–35 years): a total population survey

Stroke

Temporal trends in the incidence and case fatality of stroke in children and adolescents

J Child Neurol

Time lag to diagnosis of stroke in children

Pediatrics

Delays in investigation and management of acute arterial ischaemic stroke in children

Dev Med Child Neurol

Delay to diagnosis in acute pediatric arterial ischemic stroke

Stroke

Diagnostic pitfalls in paediatric ischaemic stroke

Dev Med Child Neurol

Studies of disease occurrence

Stroke in children. Clinical characteristics and prognosis

Acta Paediatr Scand

Cerebrovascular disease in infants and children: a study of incidence, clinical features, and survival

Neurology

Deaths from stroke in US children, 1979 to 1998

Neurology

Arterial ischaemic stroke in children

J Paediatr Child Health

Cardiovascular diseases

Ischemic perinatal stroke: summary of a workshop sponsored by the National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke

Pediatrics

Acutely and retrospectively diagnosed perinatal stroke: a population-based study

Stroke

The changing epidemiology of meningococcal disease in the United States, 1992–1996

Review article
The epidemiology of childhood stroke