PURPOSE—Much has transpired since the last scientific statement on pediatric stroke was published 10 years ago. Although stroke has long been recognized as an adult health problem causing substantial ...morbidity and mortality, it is also an important cause of acquired brain injury in young patients, occurring most commonly in the neonate and throughout childhood. This scientific statement represents a synthesis of data and a consensus of the leading experts in childhood cardiovascular disease and stroke.
METHODS—Members of the writing group were appointed by the American Heart Association Stroke Council’s Scientific Statement Oversight Committee and the American Heart Association’s Manuscript Oversight Committee and were chosen to reflect the expertise of the subject matter. The writers used systematic literature reviews, references to published clinical and epidemiology studies, morbidity and mortality reports, clinical and public health guidelines, authoritative statements, personal files, and expert opinion to summarize existing evidence and to indicate gaps in current knowledge. This scientific statement is based on expert consensus considerations for clinical practice.
RESULTS—Annualized pediatric stroke incidence rates, including both neonatal and later childhood stroke and both ischemic and hemorrhagic stroke, range from 3 to 25 per 100 000 children in developed countries. Newborns have the highest risk ratio1 in 4000 live births. Stroke is a clinical syndrome. Delays in diagnosis are common in both perinatal and childhood stroke but for different reasons. To develop new strategies for prevention and treatment, disease processes and risk factors that lead to pediatric stroke are discussed here to aid the clinician in rapid diagnosis and treatment. The many important differences that affect the pathophysiology and treatment of childhood stroke are discussed in each section.
CONCLUSIONS—Here we provide updates on perinatal and childhood stroke with a focus on the subtypes, including arterial ischemic, venous thrombotic, and hemorrhagic stroke, and updates in regard to areas of childhood stroke that have not received close attention such as sickle cell disease. Each section is highlighted with considerations for clinical practice, attendant controversies, and knowledge gaps. This statement provides the practicing provider with much-needed updated information in this field.
Summary Background For childhood-onset arterial ischaemic stroke (AIS), treatment trials are lacking and practices vary from country to country and centre to centre. We aimed to describe frequencies ...and predictors of acute treatments and early outcomes in the International Pediatric Stroke Study (IPSS), a large international series of childhood AIS. Methods The IPSS has 33 centres enrolling children with stroke. Data for children aged 28 days to 19 years with AIS from Jan 1, 2003, to Oct 1, 2007, were collected with standardised case-report forms and analysed to identify factors associated with stroke treatment and early prognosis. Findings Among 661 children with AIS (640 with acute treatment data, 612 with morbidity data, and 643 with mortality data), acute treatments included anticoagulation alone in 171 patients (27%), antiplatelet therapy alone in 177 (28%), antiplatelet and anticoagulation in 103 (16%), and no antithrombotic treatment in 189 (30%). After adjustment for significant covariates, subtypes associated with any use of anticoagulation were dissection (odds ratio 14·09, 95% CI 5·78–37·01; p<0·0001) and cardiac disease (1·87, 1·20–2·92; p=0·01). Factors associated with non-use of anticoagulation included sickle-cell disease subtype (0·12, 0·02–0·95; p=0·04) and the enrolment centre being located in the USA (0·56, 0·39–0·80; p=0·002). By contrast, antiplatelet use was associated with moyamoya (4·88, 2·13–11·12; p=0·0002), whereas non-use was associated with dissection (0·47, 0·22–0·99; p=0·047), low level of consciousness (0·45, 0·31–0·64; p<0·0001), and bilateral ischaemia (0·32, 0·20–0·52; p<0·0001). Outcomes at hospital discharge included neurological deficits in 453 (74%) patients and death in 22 (3%). In multivariate analysis, arteriopathy, bilateral ischaemia, and decreased consciousness at presentation were prognostic of adverse outcome. Interpretation Acute anticoagulation is commonly prescribed in acute childhood-onset AIS although practice varies with AIS subtype and geographical region. Several factors are prognostic of adverse early outcome, and clinical trials are needed to determine the best treatment strategies. Funding Canadian Stroke Network; Auxilium Foundation; NIH NCRR; NIH NHLBI.
OBJECTIVES:To determine incidence rates and risk factors of remote seizure after perinatal arterial ischemic stroke.
METHODS:We retrospectively identified a population-based cohort of children with ...perinatal arterial ischemic stroke (presenting acutely or in a delayed fashion) from a large Northern Californian integrated health care system. We determined incidence and predictors of a remote seizure (unprovoked seizure after neonatal period, defined as 28 days of life) by survival analyses, and measured epilepsy severity in those with active epilepsy (≥1 remote seizure and maintenance anticonvulsant treatment) at last follow-up.
RESULTS:Among 87 children with perinatal stroke, 40 (46%) had a seizure in the neonatal period. During a median follow-up of 7.1 years (interquartile range 3.2–10.5), 37 children had ≥1 remote seizure. Remote seizure risk was highest during the first year of life, with a 20% (95% confidence interval CI 13%–30%) cumulative incidence by 1 year of age, 46% (CI 35%–58%) by 5 years, and 54% (CI 41%–67%) by 10 years. Neonatal seizures increased the risk of a remote seizure (hazard ratio 2.8, CI 1.3–5.8). Children with neonatal seizures had a 69% (CI 48%–87%) cumulative incidence of remote seizure by age 10 years. Among the 24 children with active epilepsy at last follow-up, 8 (33%) were having monthly seizures despite an anticonvulsant and 7 (29%) were on more than one anticonvulsant.
CONCLUSIONS:Remote seizures and epilepsy, including medically refractory epilepsy, are common after perinatal stroke. Neonatal seizures are associated with nearly 3-fold increased remote seizure risk.
BACKGROUND AND PURPOSE—Prior annualized estimates of pediatric ischemic stroke incidence have ranged from 0.54 to 1.2 per 100 000 US children but relied purely on diagnostic code searches to identify ...cases. We sought to obtain a new estimate using both diagnostic code searches and searches of radiology reports and to assess the relative value of these 2 strategies.
METHODS—Using the population of 2.3 million children (<20 years old) enrolled in a Northern Californian managed care plan (1993 to 2003), we performed electronic searches of (1) inpatient and outpatient diagnoses for International Classification of Diseases, 9th Revision codes suggestive of stroke and cerebral palsy; and (2) radiology reports for key words suggestive of infarction. Cases were confirmed through chart review. We calculated sensitivities and positive predictive values for the 2 search strategies.
RESULTS—We identified 1307 potential cases from the International Classification of Diseases, 9th Revision code search and 510 from the radiology search. A total of 205 ischemic stroke cases were confirmed, yielding an ischemic stroke incidence of 2.4 per 100 000 person-years. The radiology search had a higher sensitivity (83%) than the International Classification of Diseases, 9th Revision code search (39%), although both had low positive predictive values. For perinatal stroke, the sensitivity of the stroke International Classification of Diseases, 9th Revision codes alone was 12% versus 57% for stroke and cerebral palsy codes combined; the radiology search was again the most sensitive (87%).
CONCLUSIONS—Our incidence estimate doubles that of prior US reports, a difference at least partially explained by our use of radiology searches for case identification. Studies relying purely on International Classification of Diseases, 9th Revision code searches may underestimate childhood ischemic stroke rates, particularly for neonates.
Arteriovenous malformations (AVMs) have recently been reported to have a high incidence of somatic KRAS mutations suggesting potential for treatment with mitogen-activated protein kinase inhibitors. ...In this case report, we describe genotype-targeted treatment of a KRAS mutant metameric AVM in a patient with Cobb syndrome using the mitogen-activated protein kinase inhibitor trametinib. Therapeutic response was monitored with phase-contrast magnetic resonance angiography to quantify AVM arterial inflow as an imaging biomarker. Treatment with trametinib resulted in a substantial decrease in blood flow to the AVM, with a >75% reduction in arterial inflow after 6 months of trametinib therapy.
IMPORTANCE: Arterial ischemic stroke (AIS) incidence has decreased overall in recent decades yet has increased in young adults. The potential associations with atherosclerotic risk factors (ARFs) ...remain unknown. OBJECTIVE: To assess the ages at which ARFs may be risk factors associated with AIS. DESIGN, SETTING, AND PARTICIPANTS: A nested case-control study was conducted within Kaiser Permanente Northern California (KPNC) from January 1, 2000, through December 31, 2014. Data were analyzed from 2019 to 2022. Cases were identified using diagnostic codes and radiology reports. A total of 2 to 3 controls per case, matched on age and enrollment dates, were randomly identified and confirmed as stroke-free by medical record review. Only ARFs documented prior to stroke diagnosis (or the same date in controls) were considered to ensure the same period of observation. Comparisons were stratified by decade of life. Cases and controls were selected from the KPNC population (4.7 million children and 7.5 million young adults). Medical record review was conducted of all children (aged 29 days to 19 years) and a sample of young adults (aged 20-49 years) with International Classification of Diseases, Ninth Revision code or radiology text string search suggestive of AIS. Stroke-free controls were randomly selected. EXPOSURES: Hypertension, hyperlipidemia, diabetes, obesity, and smoking history. MAIN OUTCOMES AND MEASURES: Odds of AIS. In all analyses, cases and controls were compared using logistic regression. RESULTS: A total of 141 pediatric cases (69 48.9% aged 29 days to 9 years; 72 51.1% aged 10-19 years) and 364 pediatric controls (168 46.2% aged 0-9 years; 196 53.8% aged 10-19 years) and 455 young adult cases (71 15.6% aged 20-29 years; 144 31.6% aged 30-39 years; and 240 52.7% aged 40-49 years) and 1018 young adult controls (121 11.9% aged 20-29 years; 298 29.3% aged 30-39 years; and 599 58.8% aged 40-49 years) were identified. The percent of the cases that were male or female did not differ from the percent in the control group. The odds ratio (OR) of having any ARFs on AIS was 1.87 (95% CI, 0.72-4.88) for age range 0 to 9 years; OR, 1.00 (95% CI, 0.51-1.99) for age range 10 to 19 years; OR, 2.3 (95% CI, 1.17- 4.51) for age range 20 to 29 years; OR, 3.57 (95% CI, 2.34-5.45) for age range 30 to 39 years; and OR, 4.91 (95% CI, 3.52-6.86) for age range 40 to 49 years. The risk associated with multiple ARFs was OR, 5.29 (95% CI, 0.47-59.4) for age range 0 to 9 years; OR, 2.75 (95% CI, 0.77-9.87) for age range 10 to 19 years; OR, 7.33 (95% CI, 1.92-27.9) for age range 20 to 29 years; OR, 9.86 (95% CI, 4.96-19.6) for age range 30 to 39 years; and OR, 9.35 (95% CI, 6.31-13.8) for age range 40 to 49 years. The ARF findings by both definitions were significant in all young adult groups. Atherosclerosis was the presumed etiology in 0% of cases in the age group 0 to 9 years, 1.4% in the age group 10 to 19 years, 8.5% in the age group 20 to 29 years, 21.5% in the age group 30 to 39 years, and 42.5% in the age group 40 to 49 years. CONCLUSIONS AND RELEVANCE: Although atherosclerosis may not be a common cause of AIS in children or in early young adulthood, findings of this study suggest that ARFs associated with stroke in older adults are present in childhood and increase with age. Efforts to reduce these risk factors should begin as early as possible.
Few data exist regarding rates and predictors of recurrence after childhood arterial ischemic stroke. We sought to establish such rates within a large, multiethnic population and determine whether ...clinical vascular imaging predicts recurrence.
In a population-based cohort study, we collected data on all documented cases of arterial ischemic stroke among 2.3 million children (<20 years old) enrolled in a northern Californian managed care plan from January 1993 to December 2004. Perinatal strokes were those that occurred by 28 days of life. Data on cerebrovascular imaging (conventional or magnetic resonance angiography), including presence of vascular abnormalities, were abstracted from official radiology reports. We used Kaplan-Meier survival-analysis techniques to determine rates and predictors of recurrent stroke.
Among 181 incident childhood stroke cases (84 perinatal; 97 later childhood), there were 16 recurrent strokes (1 after a perinatal stroke) at a median of 2.7 months. The 5-year cumulative recurrence rates were 1.2% after perinatal stroke and 19% after later childhood stroke. Of the 97 children with later childhood strokes, 52 received cerebrovascular imaging, predominantly magnetic resonance angiography (n = 36) and conventional angiography (n = 26). Although there were no recurrences among children with normal vascular imaging, children with a vascular abnormality had a 5-year cumulative recurrence rate of 66%.
Strokes recur in one fifth of cases of later childhood arterial ischemic stroke but are rare after perinatal stroke. Among the later childhood cases, cerebrovascular imaging identifies those at highest risk for recurrence.
BACKGROUND AND PURPOSE—A better understanding of the stroke risk factors in children with congenital heart disease (CHD) could inform stroke prevention strategies. We analyzed pediatric stroke ...associated with CHD in a large community-based case–control study.
METHODS—From 2.5 million children (aged <20 years) enrolled in a Northern California integrated healthcare plan, we identified children with ischemic and hemorrhagic strokes and randomly selected age- and facility-matched stroke-free controls (3 per case). We determined exposure to CHD (diagnosed before stroke) and used conditional logistic regression to analyze stroke risk factors.
RESULTS—CHD was identified in 15 of 412 cases (4%) versus 7 of 1236 controls (0.6%). Cases of childhood stroke (occurring between ages 29 days to 20 years) with CHD had 19-fold (odds ratio, 19; 95% confidence interval 4.2–83) increased stroke risk compared to controls. History of CHD surgery was associated with >30-fold (odds ratio, 31; confidence interval 4–241) increased risk of stroke in children with CHD when compared with controls. After excluding perioperative strokes, the history of CHD surgery still increased the childhood stroke risk (odds ratio, 13; confidence interval 1.5–114). The majority of children with stroke and CHD were outpatients at the time of stroke, and almost half the cases who underwent cardiac surgery had their stroke >5 years after the most recent procedure. An estimated 7% of ischemic and 2% of hemorrhagic childhood strokes in the population were attributable to CHD.
CONCLUSIONS—CHD is an important childhood stroke risk factor. Children who undergo CHD surgery remain at elevated risk outside the perioperative period and would benefit from optimized long-term stroke prevention strategies.
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