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ObjectiveHealthcare disparities are widely described in adults, but barriers affecting access to care for pediatric patients with moyamoya disease (MMD) are unknown. Understanding socioeconomic factors impacting hospital access and outcomes is necessary to address pediatric healthcare disparities.MethodsIn this cross-sectional observational study, the Kids' Inpatient Database was used to identify patients admitted with a primary diagnosis of MMD from 2003 to 2016. Patients ≤ 18 years with a primary diagnosis of MMD based on International Classification of Diseases (ICD) codes were included. Hospital admissions were queried for use of cerebral revascularization based on ICD procedure codes.ResultsQuery of the KID yielded 1449 MMD hospitalizations. After multivariable regression, Hispanic ethnicity (OR 0.52 [95% CI 0.33-0.81], p = 0.004) was associated with lack of surgical revascularization. Private insurance (OR 1.56 [95% CI 1.15-2.13], p = 0.004), admissions at medium- and high-volume centers (OR 2.01 [95% CI 1.42-2.83], p < 0.001 and OR 2.84 [95% CI 1.95-4.14], p < 0.001, respectively), and elective hospitalization (OR 3.37 [95% CI 2.46-4.64], p < 0.001) were positively associated with revascularization. Compared with Caucasian race, Hispanic ethnicity was associated with increased mean (± SEM) length of stay by 2.01 ± 0.70 days (p = 0.004) and increased hospital charges by $24,333.61 ± $7918.20 (p = 0.002), despite the decreased utilization of surgical revascularization. Private insurance was associated with elective admission (OR 1.50 [95% CI 1.10-2.05], p = 0.01) and admission to high-volume centers (OR 1.90 [95% CI 1.26-2.88], p = 0.002). African American race was associated with the development of in-hospital complications (OR 2.52 [95% CI 1.38-4.59], p = 0.003).ConclusionsAmong pediatric MMD hospitalizations, multiple socioeconomic factors were associated with access to care, whether surgical treatment is provided, and whether in-hospital complications occur. These results suggest that socioeconomic factors are important drivers of healthcare disparities in children with MMD and warrant further study.

ObjectivePediatric brain arteriovenous malformations (AVMs) are the leading cause of spontaneous intracranial hemorrhage (SICH) in children. Although the incidence of SICH is low in pediatric populations, such events cause substantial morbidity. The recently created Ruptured Arteriovenous Malformation Grading Scale (RAGS) is proposed as a reliable and novel grading system to specifically serve as a predictor of clinical outcomes in patients following AVM rupture, similar to the Hunt and Hess (HH) grade for ruptured aneurysms. While these data are promising, pediatric patients were notably absent from the original study validating the RAGS. Therefore, correlation of the RAGS score with clinical outcomes following AVM rupture in individuals younger than 18 years of age using the RAGS score is needed. The objective of this study was to validate the RAGS in a cohort of pediatric patients with AVMs who presented with hemorrhage, thereby demonstrating the score's generalizability, and expanding its external validity.MethodsA cohort of children with ruptured AVMs were retrospectively reviewed. Using disability, measured by the modified Rankin Scale (mRS), as the response variable, the area under the receiver operating characteristic curve (AUROC) was calculated for patients based on their RAGS scores for three time periods. The AUROC values were then compared with those generated by two commonly used clinical grading systems, the HH classification and Glasgow Coma Scale.ResultsA total of 81 children who presented with ruptured AVMs were included in the study, with a mean follow-up duration of 4 years. The RAGS score outperformed other clinical grading scales in predicting mRS scores, with AUROC values of 0.81, 0.82, and 0.81 at three distinct follow-up periods.ConclusionsThe RAGS score correlated well with the clinical outcome after AVM rupture in pediatric patients. Additional validation studies across multiple treatment centers are needed to further demonstrate the generalizability of the scoring system.

Background and objectivesSeizure incidence rates related to Familial Cerebral Cavernous Malformation (FCCM) are not well described, especially for children. To measure the seizure incidence rate, examine seizure predictors and characterize epilepsy severity, we studied a cohort of children and adults with FCCM enrolled in the Brain Vascular Malformation Consortium (BVMC).MethodsSeizure data were collected from participants with FCCM in the BVMC at enrollment and during follow-up. We estimated seizure probability by age, and tested whether cerebral cavernous malformation (CCM) counts or genotype were associated with earlier seizure onset.ResultsThe study cohort included 479 FCCM cases. Median age at enrollment was 42.5 years (Interquartile Range [IQR] 22.5-55.0) and 19% were children (

BACKGROUNDThe authors recently reported a series of children with vertebral artery (VA) compression during head turning who presented with recurrent posterior circulation stroke. Whether VA compression occurs during head positioning for cranial surgery is unknown.OBSERVATIONSThe authors report a case of a child with incidental rotational occlusion of the VA observed during surgical head positioning for treatment of an intracranial arteriovenous fistula. Intraoperative angiography showed dynamic V3 occlusion at the level of C2 with distal reconstitution via a muscular branch “jump” collateral, supplying reduced flow to the V4 segment. She had no clinical history or imaging suggesting acute or prior stroke. Sequential postoperative magnetic resonance imaging scans demonstrated signal abnormality of the left rectus capitus muscle, suggesting ischemic edema.LESSONSThis report demonstrates that rotational VA compression during neurosurgical head positioning can occur in children but may be asymptomatic due to the presence of muscular VA–VA “jump” collaterals and contralateral VA flow. Although unilateral VA compression may be tolerated by children with codominant VAs, diligence when rotating the head away from a dominant VA is prudent during patient positioning to avoid posterior circulation ischemia or thromboembolism.

ObjectiveTo describe a pediatric stroke syndrome with chronic focal vertebral arteriopathy adjacent to cervical abnormalities.MethodsAt a single pediatric stroke center, we identified consecutive children with stroke and vertebral arteriopathy of the V3 segment with adjacent cervical bony or soft tissue abnormalities. We abstracted clinical presentation, treatment, and follow-up data from medical charts.ResultsFrom 2005 to 2019, 10 children (all boys, ages 6-16 years) presented with posterior circulation strokes and vertebral arteriopathy with adjacent cervical pathology. Two children had bony abnormalities: one had a congenital arcuate foramen and one had os odontoideum with cervical instability. In children without bony pathology, vertebral artery narrowing during contralateral head rotation was visualized by digital subtraction angiography. Eight boys had recurrent ischemic events despite anti-thrombotic treatment (including 5 with multiple recurrences) and were treated surgically to prevent additional stroke. Procedures included vertebral artery decompression (n = 6), endovascular stent and spinal fusion (n = 1), and vertebral artery endovascular occlusion (n = 1). In boys treated with decompression, cervical soft tissue abnormalities (ruptured atlantoaxial bursa, ruptured joint capsule, or connective tissue scarring) were directly visualized during open surgery. No other etiology for stroke or dissection was found in any of the cases. Two boys without recurrent stroke were treated with activity restriction and antithrombotics. At a median follow-up of 51 months (range 17-84), there have been no additional recurrences.ConclusionsChildren with V3 segmental vertebral arteriopathy frequently have stroke recurrence despite antithrombotics. Cervical bone imaging and angiography with neck rotation can identify underlying pathology.

Moyamoya is a progressive cerebrovascular arteriopathy that affects children of any age. The goal of this study was to determine imaging and clinical outcomes as well as complication rates in a pediatric cohort undergoing either a combined direct/indirect or indirect-only revascularization approach. Patients with moyamoya disease or syndrome ≤ 18 years of age at the time of initial surgery were identified, and clinical data were collected retrospectively. Over a 12-year period, 26 patients underwent revascularization procedures on 49 hemispheres with a median follow-up of 2.6 years from surgery. Median age at surgery was 7.3 years (range 1.4-18.0 years). Thirty-three hemispheres (67.3%) underwent combined revascularization with a direct bypass and encephalomyosynangiosis, and sixteen hemispheres (32.7%) underwent indirect-only revascularization. The rate of 30-day perioperative complication was 10.2%, and the rate of postoperative clinical stroke by end of follow-up was 10.2% by hemisphere. There was a 5.7% rate of intraoperative bypass failure requiring conversion to an indirect revascularization approach. On follow-up imaging, 96.9% of direct bypasses remained patent. On multivariate analysis, higher preoperative Pediatric Stroke Outcome Measure (PSOM) scores were associated with lower rates of good clinical outcome on follow-up (unit OR 0.03; p = 0.03). Patients with age

OBJECTIVE:Brain arteriovenous malformations (AVMs) consist of dysplastic blood vessels with direct arteriovenous shunts that can hemorrhage spontaneously. In children, a higher lifetime hemorrhage risk must be balanced with treatment-related morbidity. The authors describe a collaborative, multimodal strategy resulting in effective and safe treatment of pediatric AVMs. METHODS:A retrospective analysis of a prospectively maintained database was performed in children with treated and nontreated pediatric AVMs at the University of California, San Francisco, from 1998 to 2017. Inclusion criteria were age ≤ 18 years at time of diagnosis and an AVM confirmed by a catheter angiogram. RESULTS:The authors evaluated 189 pediatric patients with AVMs over the study period, including 119 ruptured (63%) and 70 unruptured (37%) AVMs. The mean age at diagnosis was 11.6 ± 4.3 years. With respect to Spetzler-Martin (SM) grade, there were 38 (20.1%) grade I, 40 (21.2%) grade II, 62 (32.8%) grade III, 40 (21.2%) grade IV, and 9 (4.8%) grade V lesions. Six patients were managed conservatively, and 183 patients underwent treatment, including 120 resections, 82 stereotactic radiosurgery (SRS), and 37 endovascular embolizations. Forty-four of 49 (89.8%) high-grade AVMs (SM grade IV or V) were treated. Multiple treatment modalities were used in 29.5% of low-grade and 27.3% of high-grade AVMs. Complete angiographic obliteration was obtained in 73.4% of low-grade lesions (SM grade I-III) and in 45.2% of high-grade lesions. A periprocedural stroke occurred in a single patient (0.5%), and there was 1 treatment-related death. The mean clinical follow-up for the cohort was 4.1 ± 4.6 years, and 96.6% and 84.3% of patients neurologically improved or remained unchanged in the ruptured and unruptured AVM groups following treatment, respectively. There were 16 bleeding events following initiation of AVM treatment (annual rate: 0.02 events per person-year). CONCLUSIONS:Coordinated multidisciplinary evaluation and individualized planning can result in safe and effective treatment of children with AVMs. In particular, it is possible to treat the majority of high-grade AVMs with an acceptable safety profile. Judicious use of multimodality therapy should be limited to appropriately selected patients after thorough team-based discussions to avoid additive morbidity. Future multicenter studies are required to better design predictive models to aid with patient selection for multimodal pediatric care, especially with high-grade AVMs.

ObjectiveTo compare risk factors, clinical presentation, and outcomes after posterior circulation arterial ischemic stroke (PCAIS) and anterior circulation arterial ischemic stroke (ACAIS) in neonates and children.MethodsIn this international multicenter observational study including neonates and children up to 18 years of age with arterial ischemic stroke (AIS), we compared clinical and radiologic features according to stroke location.ResultsOf 2,768 AIS cases, 507 (18%) were located in the posterior circulation, 1,931 (70%) in the anterior circulation, and 330 (12%) involved both. PCAIS was less frequent in neonates compared to children (8.8% vs 22%, p < 0.001). Children with PCAIS were older than children with ACAIS (median age 7.8 [interquartile range (IQR) 3.1-14] vs 5.1 [IQR 1.5-12] years, p < 0.001), and more often presented with headache (54% vs 32%, p < 0.001) and a lower Pediatric NIH Stroke Scale score (4 [IQR 2-8] vs 8 [IQR 3-13], p = 0.001). Cervicocephalic artery dissections (CCAD) were more frequent (20% vs 8.5%, p < 0.001), while cardioembolic strokes were less frequent (19% vs 32%, p < 0.001) in PCAIS. Case fatality rates were equal in both groups (2.9%). PCAIS survivors had a better outcome (normal neurologic examination at hospital discharge in 29% vs 21%, p = 0.002) than ACAIS survivors, although this trend was only observed in children and not in neonates.ConclusionPCAIS is less common than ACAIS in both neonates and children. Children with PCAIS are older and have a higher rate of CCAD, lower clinical stroke severity, and better outcome than children with ACAIS.

Background Epilepsy is a common complication of pediatric stroke. Aim In this study, we aim to measure the association between epilepsy and neurologic outcome after childhood arterial ischemic stroke. Methods Prospective cohort study of children (29 days-19 years) enrolled after an acute arterial ischemic stroke at 21 international pediatric stroke centers and followed to identify epilepsy. One year post-stroke, outcomes were scored using the examination-based Pediatric Stroke Outcome Measure (range = 0-10); higher values reflect greater disability. Ordinal logistic regression was used to measure the association of Pediatric Stroke Outcome Measure scores (categorized as 0-1, 1.5-3, 3.5-6, 6.5-10) with epilepsy. Results Investigators enrolled 86 children (median age = 6.1 years, interquartile range (IQR) = 1.4-12.2 years) with acute stroke. At 1 year, 18/80 (23%) remained on an anticonvulsant including 8/80 (10%) with epilepsy. Among the 70 with Pediatric Stroke Outcome Measure scored, the median was 0.5 (IQR = 0-1.5) for children without epilepsy ( n = 63), and 6 (IQR = 0.5-10) for children with epilepsy ( n = 7). In univariable analyses, poorer 1-year outcome was associated with middle cerebral artery stroke, cortical infarcts, hemorrhagic transformation, hospital disposition not to home, and epilepsy. In multivariable analysis, middle cerebral artery stroke (odds ratio (OR) = 4.9, 95% confidence intervals (CI) = 1.1-21.3) and epilepsy (OR = 24.1, CI = 1.5-380) remained associated with poorer outcome. Conclusions Children who developed epilepsy during the first year post-stroke had poorer neurologic outcomes than those without epilepsy.

ObjectiveTo determine whether lower socioeconomic status (SES) is associated with worse 1-year neurologic outcomes and reduced access to rehabilitation services in children with arterial ischemic stroke (AIS).MethodsFrom 2010 to 2014, the Vascular effects of Infection in Pediatric Stroke (VIPS) observational study prospectively enrolled and confirmed 355 children (age 29 days-18 years) with AIS at 37 international centers. SES markers measured via parental interview included annual household income (US dollars) at the time of enrollment, maternal education level, and rural/suburban/urban residence. Receipt of rehabilitation services was measured by parental report. Pediatric Stroke Outcome Measure scores were categorized as 0 to 1, 1.5 to 3, 3.5 to 6, and 6.5 to 10. Univariate and multivariable ordinal logistic regression models examined potential predictors of outcome.ResultsAt 12 ± 3 months after stroke, 320 children had documented outcome measurements, including 15 who had died. In univariate analysis, very low income (p = 0.004). In multivariable analysis, including adjustment for stroke etiology, this association persisted (OR 3.17, 95% CI 1.18-8.47, p = 0.02). Income did not correlate with receiving rehabilitation services at 1 year after stroke; however, quality and quantity of services were not assessed.ConclusionsIn a large, multinational, prospective cohort of children with AIS, low income was associated with worse neurologic outcomes compared to higher income levels. This difference was not explained by stroke type, neurologic comorbidities, or reported use of rehabilitation services. The root causes of this disparity are not clear and warrant further investigation.

ObjectiveTo quantify the incidence, timing, and risk of ischemic stroke after trauma in a population-based young cohort.MethodsWe electronically identified trauma patients (

AimTo determine epilepsy risk factors after pediatric stroke.MethodA cohort of children with arterial ischemic stroke (birth-18y) was enrolled at 21 centers and followed for 1 year. Acute seizures (≤7d after stroke) and active epilepsy (at least one unprovoked remote seizure plus maintenance anticonvulsant at 1y) were identified. Predictors were determined using logistic regression.ResultsAmong 114 patients (28 neonates and 86 children) enrolled, 26 neonates (93%) and 32 children (37%) had an acute seizure. Acute seizures lasted longer than 5 minutes in 23 patients (40%) and were frequently recurrent: 33 (57%) had 2 to 10 seizures and 11 (19%) had more than 10. Among 109 patients with 1-year follow-up, 11 (10%) had active epilepsy. For each year younger, active epilepsy was 20% more likely (odds ratio [OR] 0.8, 95% confidence interval [CI] 0.6-0.99, p=0.041). Prolonged or recurrent acute seizures also increased epilepsy risk. Each additional 10 minutes of the longest acute seizure increased epilepsy risk fivefold (OR 4.7, 95% CI 1.7-13). Patients with more than 10 acute seizures had a 30-fold increased epilepsy risk (OR 30, 95% CI 2.9-305).InterpretationPediatric stroke survivors, especially younger children, have a high risk of epilepsy 1 year after stroke. Prolonged or recurrent acute seizures increase epilepsy risk in a dose-dependent manner.

Mutations in the smooth muscle-specific isoform of alpha actin (ACTA2) cause smooth muscle dysfunction in arteries. This rare loss-of-function mutation may cause a diffuse occlusive cerebral arteriopathy, resulting in stroke. While ACTA2 arteriopathy is often described as moyamoya-like, it has a distinct phenotype characterized by dilation of the proximal internal carotid artery (ICA) and occlusion of the terminal ICA and proximal middle cerebral artery. Intracranial arteries have an abnormally straight course, often with small aneurysms. There is limited experience with revascularization procedures for ACTA2 arteriopathy, and the safety and efficacy of these procedures are unknown. In this paper the authors present a symptomatic 6-year-old patient with ACTA2 cerebral arteriopathy who underwent both indirect revascularization and direct cerebrovascular bypass. Postoperatively, the patient suffered an ischemic infarct in a neighboring vascular territory. While direct cerebrovascular bypass is technically feasible, patients with ACTA2 arteriopathy may be at increased risk for perioperative stroke compared with patients with moyamoya disease.

Background and purposeAmong children with arterial ischemic stroke (AIS), those with arteriopathy have the highest recurrence risk. We hypothesized that arteriopathy progression is an inflammatory process and that inflammatory biomarkers would predict recurrent AIS.MethodsIn an international study of childhood AIS, we selected cases classified into 1 of the 3 most common childhood AIS causes: definite arteriopathic (n=103), cardioembolic (n=55), or idiopathic (n=78). We measured serum concentrations of high-sensitivity C-reactive protein, serum amyloid A, myeloperoxidase, and tumor necrosis factor-α. We used linear regression to compare analyte concentrations across the subtypes and Cox proportional hazards models to determine predictors of recurrent AIS.ResultsMedian age at index stroke was 8.2 years (interquartile range, 3.6-14.3); serum samples were collected at median 5.5 days post stroke (interquartile range, 3-10 days). In adjusted models (including age, infarct volume, and time to sample collection) with idiopathic as the reference, the cardioembolic (but not arteriopathic) group had higher concentrations of high-sensitivity C-reactive protein and myeloperoxidase, whereas both cardioembolic and arteriopathic groups had higher serum amyloid A. In the arteriopathic (but not cardioembolic) group, higher high-sensitivity C-reactive protein and serum amyloid A predicted recurrent AIS. Children with progressive arteriopathies on follow-up imaging had higher recurrence rates, and a trend toward higher high-sensitivity C-reactive protein and serum amyloid A, compared with children with stable or improved arteriopathies.ConclusionsAmong children with AIS, specific inflammatory biomarkers correlate with cause and-in the arteriopathy group-risk of stroke recurrence. Interventions targeting inflammation should be considered for pediatric secondary stroke prevention trials.

ObjectivesTo determine incidence rates and risk factors of remote seizure after perinatal arterial ischemic stroke.MethodsWe 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.ResultsAmong 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.ConclusionsRemote 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 purposePublished cohorts of children with arterial ischemic stroke (AIS) in the 1990s to early 2000s reported 5-year cumulative recurrence rates approaching 20%. Since then, utilization of antithrombotic agents for secondary stroke prevention in children has increased. We sought to determine rates and predictors of recurrent stroke in the current era.MethodsThe Vascular Effects of Infection in Pediatric Stroke (VIPS) study enrolled 355 children with AIS at 37 international centers from 2009 to 2014 and followed them prospectively for recurrent stroke. Index and recurrent strokes underwent central review and confirmation, as well as central classification of causes of stroke, including arteriopathies. Other predictors were measured via parental interview or chart review.ResultsOf the 355 children, 354 survived their acute index stroke, and 308 (87%) were treated with an antithrombotic medication. During a median follow-up of 2.0 years (interquartile range, 1.0-3.0), 40 children had a recurrent AIS, and none had a hemorrhagic stroke. The cumulative stroke recurrence rate was 6.8% (95% confidence interval, 4.6%-10%) at 1 month and 12% (8.5%-15%) at 1 year. The sole predictor of recurrence was the presence of an arteriopathy, which increased the risk of recurrence 5-fold when compared with an idiopathic AIS (hazard ratio, 5.0; 95% confidence interval, 1.8-14). The 1-year recurrence rate was 32% (95% confidence interval, 18%-51%) for moyamoya, 25% (12%-48%) for transient cerebral arteriopathy, and 19% (8.5%-40%) for arterial dissection.ConclusionsChildren with AIS, particularly those with arteriopathy, remain at high risk for recurrent AIS despite increased utilization of antithrombotic agents. Therapies directed at the arteriopathies themselves are needed.

Background and purposeA 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.MethodsFrom 2.5 million children (aged 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.ConclusionsCHD 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.

BackgroundCardiac disease is a leading cause of stroke in children, yet limited data support the current stroke prevention and treatment recommendations. A multidisciplinary panel of clinicians was convened in February 2014 by the International Pediatric Stroke Study group to identify knowledge gaps and prioritize clinical research efforts for children with cardiac disease and stroke.ResultsSignificant knowledge gaps exist, including a lack of data on stroke incidence, predictors, primary and secondary stroke prevention, hyperacute treatment, and outcome in children with cardiac disease. Commonly used diagnostic techniques including brain computed tomography and ultrasound have low rates of stroke detection, and diagnosis is frequently delayed. The challenges of research studies in this population include epidemiologic barriers to research such as small patient numbers, heterogeneity of cardiac disease, and coexistence of multiple risk factors. Based on stroke burden and study feasibility, studies involving mechanical circulatory support, single ventricle patients, early stroke detection strategies, and understanding secondary stroke risk factors and prevention are the highest research priorities over the next 5-10 years. The development of large-scale multicenter and multispecialty collaborative research is a critical next step. The designation of centers of expertise will assist in clinical care and research.ConclusionsThere is an urgent need for additional research to improve the quality of evidence in guideline recommendations for cardiogenic stroke in children. Although significant barriers to clinical research exist, multicenter and multispecialty collaboration is an important step toward advancing clinical care and research for children with cardiac disease and stroke.

Stroke is increasingly recognized as a significant cause of morbidity and mortality in children, and as a financial burden for families and society. Recent studies have identified and confirmed presumptive risk factors, and have identified novel associations with childhood arterial ischemic stroke. A better understanding of risk factors for stroke in children, which differ from the atherosclerotic risk factors in adults, is the first step needed to improve strategies for stroke prevention and intervention, and ultimately minimize the physical, mental, and financial burden of arterial ischemic stroke. Here, we discuss recent advances in research for selected childhood stroke risk factors, highlighting the progress made in our understanding of etiologic mechanisms and pathophysiology, and address the future directions for acute and long-term treatment strategies for pediatric stroke.

ObjectiveTo determine incidence rates and predictors of epilepsy after childhood stroke and compare these to published estimates of 3 to 5% cumulative epilepsy incidence by 5 years poststroke in adults.MethodsIn a retrospective population-based study of children with stroke (29 days-19 years) in an integrated health care system (1993-2007), poststroke seizures were identified through electronic searches and confirmed by chart review. Stroke and seizure characteristics were abstracted from medical records. Survival analysis was used to determine rates and predictors of remote seizures and active epilepsy (anticonvulsant treatment for remote seizure within prior 6 months) at last follow-up.ResultsFrom a population of 2.5 million children, we identified 305 stroke cases. Over a median follow-up of 4.1 years (interquartile range = 1.8-6.8), 49 children had a first unprovoked remote seizure. The average annual incidence rate of first remote seizure was 4.4% (95% confidence interval [CI] = 3.3-5.8) with a cumulative risk of 16% (95% CI = 12-21) at 5 years and 33% (95% CI = 23-46) at 10 years poststroke. The cumulative risk of active epilepsy was 13% (95% CI = 9-18) at 5 years and 30% (95% CI = 20-44) at 10 years. Acute seizures at the time of stroke predicted development of active epilepsy (hazard ratio = 4.2, 95% CI = 2.2-8.1). At last follow-up, ⅓ of the children with active epilepsy had a recent breakthrough seizure despite anticonvulsant usage.InterpretationUnlike adults, children are uniquely vulnerable to epilepsy after stroke. Children with acute seizures at the time of stroke are at particularly high risk.

ObjectivesTo measure intensive care unit (ICU) admission, intubation, decompressive craniotomy, and outcomes at discharge in a large population-based study of children with ischemic and hemorrhagic stroke.MethodsIn a retrospective study of all children enrolled in a Northern Californian integrated health care plan (1993-2003), we identified cases of symptomatic childhood stroke (age >28 days through 19 years) from inpatient and outpatient electronic diagnoses and radiology reports, and confirmed them through chart review. Data regarding stroke evaluation, management, and outcomes at discharge were abstracted. Intensive care unit (ICU) admission, intubation, and decompressive neurosurgery rates were measured, and multivariate logistic regression was used to identify predictors of critical care usage and outcomes at discharge.ResultsOf 256 cases (132 hemorrhagic and 124 ischemic), 61% were admitted to the ICU, 32% were intubated, and 11% were treated with a decompressive neurosurgery. Rates were particularly high among children with hemorrhagic stroke (73% admitted to the ICU, 42% intubated, and 19% received a decompressive neurosurgery). Altered mental status at presentation was the most robust predictor for all 3 measures of critical care utilization. Neurologic deficits at discharge were documented in 57%, and were less common after hemorrhagic than ischemic stroke: 48% vs 66% (odds ratio 0.5, 95% confidence interval 0.3-0.8). Case fatality was 4% overall, 7% among children admitted to the ICU, and was similar between ischemic and hemorrhagic stroke.ConclusionsICU admission is frequent after childhood stroke and appears to be justified by high rates of intubation and surgical decompression.

Although many underlying diseases have been reported in the setting of childhood arterial ischemic stroke, emerging research demonstrates that non-atherosclerotic intracerebral arteriopathies in otherwise healthy children are prevalent. Minor infections may play a role in arteriopathies that have no other apparent underlying cause. Although stroke in childhood differs in many aspects from adult stroke, few systematic studies specific to pediatrics are available to inform stroke management. Treatment trials of pediatric stroke are required to determine the best strategies for acute treatment and secondary stroke prevention. The high cost of pediatric stroke to children, families, and society demands further study of its risk factors, management, and outcomes. This review focuses on the recent findings in childhood arterial ischemic stroke.