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Background: Data from the early pandemic revealed that 0.62% of children hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had an acute arterial ischemic stroke (AIS). In a larger cohort from June 2020 to December 2020, we sought to determine whether our initial point estimate was stable as the pandemic continued and to understand radiographic and laboratory data that may clarify mechanisms of pediatric AIS in the setting of SARS-CoV-2. Methods: We surveyed international sites with pediatric stroke expertise to determine numbers of hospitalized SARS-CoV-2 patients Results: Sixty-one centers from 21 countries provided AIS data. Forty-eight centers (78.7%) provided SARS-CoV-2 hospitalization data. SARS-CoV-2 testing was performed in 335/373 acute AIS cases (89.8%) compared with 99/166 (59.6%) in March to May 2020, P P =0.78. Of the 22 of 23 AIS cases with SARS-CoV-2 in whom we could collect additional data, SARS-CoV-2 was the main stroke risk factor in 6 (3 with arteritis/vasculitis, 3 with focal cerebral arteriopathy), a contributory factor in 13, and incidental in 3. Elevated inflammatory markers were common, occurring in 17 (77.3%). From centers with SARS-CoV-2 hospitalization data, of 7231 pediatric patients hospitalized with SARS-CoV-2, 23 had AIS (0.32%) compared with 6/971 (0.62%) from March to May 2020, P =0.14. Conclusions: The risk of AIS among children hospitalized with SARS-CoV-2 appeared stable compared with our earlier estimate. Among children in whom SARS-CoV-2 was considered the main stroke risk factor, inflammatory arteriopathies were the stroke mechanism. more...

Background and Purpose: Recent studies using automated perfusion imaging software have identified adults most likely to benefit from reperfusion therapies in extended time windows. The time course of penumbral tissue is poorly characterized in childhood arterial ischemic stroke (AIS). We explore the feasibility of using automated perfusion-diffusion imaging software to characterize penumbra in childhood AIS. Methods: An observational cohort study of children with acute unilateral AIS presenting to our institution. Diffusion-weighted imaging and dynamic susceptibility contrast perfusion magnetic resonance imaging performed within 72 hours of symptom onset were necessary for inclusion. Perfusion-diffusion mismatch was estimated using RAPID software. Ischemic core was defined as apparent diffusion coefficient −6 mm 2 /s and hypoperfusion as Tmax >6 seconds. Favorable mismatch profile was defined as core volume Results: Twenty-nine children (median 8 years old, interquartile range, 4.4–14.6) were included (26 unilateral middle cerebral artery and 3 unilateral cerebellar infarcts). Median Pediatric National Institutes of Health Stroke Scale was 4 (interquartile range, 3–11). Most cases had cryptogenic (n=11) or focal cerebral arteriopathy (n=9) causes. Median time-to-imaging =13.7 hours (interquartile range, 7.5–25.3). RAPID detected an ischemic core in 19 (66%) patients. In the remaining cases, the mean apparent diffusion coefficient values were mostly higher than the threshold as the majority of these presentations were delayed (median >21 hours) and infarct volumes were small ( Conclusions: This study demonstrates it is feasible to rapidly assess perfusion-diffusion mismatch in childhood AIS using automated software. Favorable mismatch profiles, using adult-based parameters, persisted beyond the standard 4.5 hours window for thrombolysis, suggesting potential therapeutic benefit of RAPID use. Further work is required to determine the utility of perfusion-based imaging to guide clinical decision making, whether adult thresholds require modification in childhood AIS, and to investigate the effect of time-delay and cause on mismatch characteristics. more...

Background and Purpose: The aims of this study were to assess the prevalence of multidimensional fatigue symptoms 5 years after pediatric arterial ischemic stroke and identify factors associated with fatigue. Methods: Thirty-one children (19 males) with pediatric arterial ischemic stroke, participating in a larger prospective, longitudinal study, were recruited to this study at 5 years poststroke. Parent- and self-rated PedsQL Multidimensional Fatigue Scale scores were compared with published normative data. Associations between parent-rated PedsQL Multidimensional Fatigue Scale, demographics, stroke characteristics, and concurrent outcomes were examined. Results: Parent-rated total, general and cognitive fatigue were significantly poorer than population norms, with more than half of all parents reporting fatigue symptoms in their children. One-third of children also reported experiencing fatigue symptoms, but their ratings did not differ significantly from normative expectations, as such, all further analyses were on parent ratings of fatigue. Older age at stroke and larger lesion size predicted greater general fatigue; older age, female sex, and higher social risk predicted more sleep/rest fatigue. No significant predictors of cognitive fatigue were identified and only older age at stroke predicted total fatigue. Greater fatigue was associated with poorer adaptive functioning, motor skills, participation, quality of life, and behavior problems but not attention. Conclusions: Fatigue is a common problem following pediatric arterial ischemic stroke and is associated with the functional difficulties often seen in this population. This study highlights the importance of long-term monitoring following pediatric arterial ischemic stroke and the need for effective interventions to treat fatigue in children. more...

Background and Purpose: Childhood and adolescence coincide with rapid maturation of distributed brain networks supporting social cognition; however, little is known about the impact of early ischemic brain insult on the acquisition of these skills. This study aimed to examine the influence of arterial ischemic stroke (AIS) on facial emotion recognition and theory of mind (ToM) abilities of children and adolescents initially recruited to a single-center, prospective longitudinal study of recovery following AIS. Methods: The study involved 67 participants, including 30 children with AIS (mean time since stroke=5 years) and 37 age-matched typically developing controls who were assessed on measures of cognitive ToM, facial emotion recognition, and affective ToM. Acute clinical magnetic resonance imaging, including diffusion-weighted imaging sequences, were used to evaluate prospective structure-function relationships between acute lesion characteristics (size, location, and arterial territories affected) and long-term social cognitive abilities. Results: Relative to age-matched typically developing controls, children with AIS showed significantly worse performance on measures of basic facial emotion processing, cognitive ToM, and affective ToM. In univariate models, poorer ToM was associated with larger infarcts, combined cortical-subcortical pathology, and involvement of multiple arterial territories. In multivariate analyses, larger lesions and multiterritory infants were predictive of ToM processing but not facial emotion recognition. Poorer cognitive ToM predicted less frequent prosocial behavior and increased peer problems. Conclusions: Social cognitive skills appear vulnerable to disruption from early ischemic brain insult. In the first study to examine social cognition in a prospective cohort of children with AIS, our findings suggest that acute magnetic resonance imaging-based lesion characteristics may have predictive value for long-term social cognitive outcomes and may assist to identify children at elevated risk for social cognitive dysfunction. more...

Background: Maternal and newborn stroke occur during the same period when physiological and anatomic connections between mother and infant may provide a rationale for common pathogenetic mechanisms. The similarities and differences between maternal and newborn stroke remain poorly understood. We created the International Maternal Newborn Stroke Registry - the first database to explore these relationships. Methods: Eleven international sites participated; 9 enrolled cases for this analysis. Eligible cases were newborns (from 28 weeks gestation to 28 postnatal days) or mothers (peripartum or within 6 weeks postpartum) diagnosed with stroke (ischemic, hemorrhagic, cerebral sinovenous thrombosis). Preterm infants (< 28 weeks gestation) and neonates with germinal matrix/intraventricular hemorrhage were excluded. Descriptive statistics were performed to compare stroke sub-types, demographic and pregnancy-related risk factors. Results: We enrolled 103 cases, 69 newborn and 34 maternal. Median maternal age was 29 years (IQR 25-36) for the maternal group and 32 years (IQR 30-36) for the neonatal group. Women with maternal strokes were more likely to have pre-eclampsia (15%) and migraine (44%). Compared to maternal strokes, newborn strokes occurred more often in women from urban locations, were ischemic, and were less likely to be associated with alcohol use and pre-eclampsia during pregnancy (Table). Conclusion: In this novel registry, we describe factors that impact both maternal and newborn stroke. Urban area of residence and maternal age > 30 were associated with newborn strokes, while migraine and pre-eclampsia were strongly associated with maternal strokes. Differing mechanisms and stroke subtypes may explain these differences. In addition, lack of access to healthcare in certain geographical locations may lead to under-identification. Further research is needed to determine if these results are consistent when applied to a larger sample size. more...

Background: In adults, time since stroke onset correlates with efficacy and risk of recanalization therapies; beyond this temporal window there is increased risk of adverse events in particular hemorrhage with thrombolysis and decreased benefit of recanalization due to irreversible tissue injury. In adults the appearance of fluid attenuated inversion recovery (FLAIR) signal is a proxy for time, and is typically present by 6 hours. The time to FLAIR signal hyperintensity in childhood stroke is unknown but is of interest with potential utility due to the often greater uncertainty as to timing symptom onset. Methods: Time to FLAIR signal hyperintensity on brain MRI performed on children within 24 hours of stroke onset was studied with logistic regression. Results: A total of 68 MRIs with FLAIR imaging were available from 54 children (27 female), age 0.8 to 17.9 years, median 12.0 years. Seventy-four percent (40/54) of children and 72% (49/68) of scans had anterior circulation stroke. Interquartile range for time to FLAIR presence was 7.8 to 19.1 hours. The 90% probability of FLAIR change was reached at 11.2 hours for all strokes (Figure, dotted line; 80% highest density interval (HDI): 1.2-11.2 hours), and 9.3 hours for anterior circulation only strokes (Figure, solid line; 80% HDI: 3.3-9.3 hours), though nearly all had FLAIR change by 6 hours. FLAIR change was absent in 4 children after 6 hours, two with anterior circulation stroke (16 year-old at 6.1 hours, 10 year-old at 7.0 hours) and 2 with posterior circulation stroke (15 year-old at 7.3 hours, 9 month-old at 18.2 hours). Conclusion: Similar to adults, FLAIR hyperintensity can be used to estimate time since stroke ictus in childhood stroke. Children may have somewhat delayed time to FLAIR signal change compared with adults, suggesting that they may have a longer window for effective recanalization therapies. more...

Background and Purpose— Focal cerebral arteriopathy (FCA)—a common cause of arterial ischemic stroke in previously healthy children—often progresses over days to weeks, increasing the risk of recurrent stroke. We developed a novel severity scoring system designed to quantify FCA progression and correlate with clinical outcomes. Methods— The VIPS study (Vascular Effects of Infection in Pediatric Stroke) prospectively enrolled 355 children with arterial ischemic stroke (2010–2014), including 41 with centrally confirmed FCA. Two neuroradiologists independently reviewed FCA cerebrovascular imaging, assigning a graded severity score of zero (no involvement) to 4 (occlusion) to individual arterial segments. The FCA severity score (FCASS) was the unweighted sum. In an iterative process, we modeled scores derived from different combinations of arterial segments to identify the model that optimized correlation with clinical outcome, simplicity, and reliability. Results— The optimal FCASS summed scores from 5 arterial segments: supraclinoid internal carotid artery, A1, A2, M1, and M2. The median (interquartile range) baseline FCASS was 4 (2–6). Of 33 children with follow-up imaging, the maximum FCASS (at any time point) was 7 (5–9). Twenty-four (73%) had FCA progression on follow-up with their maximum FCASS at a median of 8 (5–35.5) days poststroke; their median FCASS increase was 4 (2.5–6). FCASS did not correlate with recurrent arterial ischemic stroke. Maximum (but not baseline) FCASS correlated with 1-year pediatric stroke outcome measures ( P =0.037). Conclusions— Our novel scoring system for FCA severity correlates with neurological outcomes in the VIPS cohort and provides a tool for FCA treatment trials under development. more...

Background and Purpose— Focal cerebral arteriopathy accounts for up to 35% of arterial ischemic stroke (AIS) in children and is the most important predictor of stroke recurrence. The study objective was to compare outcomes for children with focal cerebral arteriopathy treated with combined corticosteroid antithrombotic treatment (CAT) to those receiving antithrombotic treatment (AT) alone. Methods— This multicenter retrospective Swiss/Australian cohort study analyzed consecutive children, aged 1 month to 18 years, presenting with first AIS because of a focal cerebral arteriopathy from 2000 to 2014. Children with CAT were compared with those treated with AT. Primary outcome was the presence of neurological deficits at 6 months post–AIS as measured by the Pediatric Stroke Outcome Measure. Secondary outcomes included resolution of stenosis and stroke recurrence. Analysis of covariance was used to adjust for potential confounders (baseline pediatric National Institute of Health Stroke Scale and concomitant acyclovir use). Results— A total of 73 children (51% males) were identified, 21 (29%) of whom received CAT. Mean (SD) age at stroke for the entire group was 7.9 years (4.7). Median (interquartile range) pediatric National Institute of Health Stroke Scale was 3 (2.0–8.0) in the CAT group and 5 (3.0–9.0) in the AT group ( P =0.098). Median (interquartile range) Pediatric Stroke Outcome Measure 6 months post-AIS was 0.5 (0–1.5) in the CAT group compared with 1.0 (0.5–2.0) in the AT group ( P =0.035), the finding was sustained after adjusting for potential confounders. Complete resolution of stenosis at last MRI was noted in 17 (81%) in the CAT group compared with 24 (59%) in the AT group ( P =0.197). Stroke recurrence occurred in 1 patient in each group. Conclusions— Corticosteroid treatment may provide additional benefit over AT for improved neurological outcome in childhood AIS because of focal cerebral arteriopathy. Larger prospective studies are warranted to further investigate these differences and understand mechanisms by which steroids modify outcome. more...

Objectives: To investigate correlations between infarct topography on acute diffusion weighted MRI, using voxel-based lesion-symptom mapping (VLSM), and later development of cerebral palsy (CP) and neurological impairments, in neonatal arterial ischaemic stroke (AIS). Methods: Newborns were recruited from prospective Australian and Swiss pediatric stroke registries. CP diagnosis was based on clinical examination. Language or cognitive-behavioural impairments were assessed using the Pediatric Stroke Outcome Measure dichotomized to good (0-0.5) or poor (≥1), at ≥18 months of age. Infarcts were manually segmented using axial DWI images, and coregistered to the Melbourne Children’s Regional Infant Brain 2.0 atlas. All lesions were projected to the left hemisphere to obtain binary union masks. VLSM was conducted using MATLAB SPM12 toolbox. A generalised linear model was used to correlate the lesion mask with outcomes. Voxel-wise t test statistics were calculated, and corrected for multiple comparisons using family-wise error rate (FWE). Results: 85 newborns (55 male) met inclusion criteria. Infarct lateralization was left hemisphere in 62%, right in 8% and bilateral in 29%. At median age 2.1 years (IQR1.9-2.6), 34% developed CP and 42% had neurological impairments. 54 ROIs were correlated with CP (t>4.33; FWE Conclusions: Cerebral palsy following neonatal AIS correlates predominantly with regions of acute infarction directly involved in motor control, or in functionally connected regions. Brain regions associated with language or cognitive-behavioural impairment are less clear. more...

Background and Purpose— Data regarding the safety and efficacy of intravenous tPA (tissue-type plasminogen activator) in childhood acute arterial ischemic stroke are inadequate. The TIPS trial (Thrombolysis in Pediatric Stroke; National Institutes of Health grant R01NS065848)—a prospective safety and dose-finding trial of intravenous tPA in acute childhood stroke—was closed for lack of accrual. TIPS sites have subsequently treated children with acute stroke in accordance with established institutional protocols supporting data collection on outcomes. Methods— Data on children treated with intravenous tPA for neuroimaging-confirmed arterial ischemic stroke were collected retrospectively from 16 former TIPS sites to establish preliminary safety data. Participating sites were required to report all children who were treated with intravenous tPA to minimize reporting bias. Symptomatic intracranial hemorrhage (SICH) was defined as ECASS (European Cooperative Acute Stroke Study) II parenchymal hematoma type 2 or any intracranial hemorrhage associated with neurological deterioration within 36 following tPA administration. A Bayesian beta-binomial model for risk of SICH following intravenous tPA was fit using a prior distribution based on the risk level in young adults (1.7%); to test for robustness, the model was also fit with uninformative and conservative priors. Results— Twenty-six children (age range, 1.1–17 years; median, 14 years; 12 boys) with stroke and a median pediatric National Institutes of Health Stroke Scale score of 14 were treated with intravenous tPA within 2 to 4.5 hours (median, 3.0 hours) after stroke onset. No patient had SICH. Two children developed epistaxis. Conclusions— The estimated risk of SICH after tPA in children is 2.1% (95% highest posterior density interval, 0.0%–6.7%; mode, 0.9%). Regardless of prior assumption, there is at least a 98% chance that the risk is more...

Contrary 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 independence. 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 preschool 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 to describe outcome after arterial ischemic stroke (AIS) and hemorrhagic stroke (HS). ### 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 … more...

Background and Objectives: Recent studies have used automated perfusion imaging software to identify adults most likely to benefit from reperfusion therapies in extended time windows. The time course of penumbral evolution in childhood arterial ischemic stroke (AIS) is poorly characterised. We investigated the utility of automated perfusion imaging software in childhood AIS and explored the relationship between time to imaging and perfusion-diffusion mismatch. Methods: Convenience population of children with acute AIS, presenting to the Royal Children’s Hospital Melbourne from 2005-2014, where diffusion and dynamic susceptibility contrast MRI were performed -6 mm2/s and hypoperfusion as Tmax>6s. Favourable mismatch profile was defined as core Results: Twenty-nine children (median age 8, IQR 4.4-14.6) met eligibility criteria (26 unilateral MCA and 3 unilateral cerebellar infarcts). Median PedNIHSS was 4.5. Etiologies included focal cerebral arteriopathy (n=9), cryptogenic (n=12), cardioembolic (n=5), other (n=3). Median time from onset to imaging was 13.7 hours (IQR 7.5-25.3). The visible diffusion lesion was not below ADC Conclusions: RAPID failed to segment the ischaemic core in cases with delayed imaging. Favourable mismatch profiles persisted beyond the standard 4.5 hours window for thrombolysis. Further work is required to investigate the effect of time-delay and aetiology on mismatch characteristics in childhood AIS. Figure: 22-month child with acute left MCA occlusion. Diffusion (left) and Tmax perfusion (right) MRI at 3.75 hours post-onset demonstrating a favourable mismatch profile. more...

Background: There is evidence that male neonates have higher incidences of ischemic stroke and associated limitations in brain repair compared to female neonates. We used data from the International Maternal Newborn Stroke Registry (IMNSR) to further explore neonatal sex differences in demographics, birth characteristics, stroke onset, and maternal factors. Methods: Eleven international sites participated; 8 entered data for this analysis. Eligible participants with newborn (28 weeks gestation to 28 postnatal days) ischemic or hemorrhagic stroke or cerebral venous thrombosis were identified prospectively and retrospectively and enrolled. Preterm infants born before 28 weeks and neonates with germinal matrix intraventricular hemorrhage were excluded. We collected APGAR scores at 1 and 5 minutes, resuscitation status, demographics, stroke type, maternal and gestational age at birth, and mother’s health conditions at birth. Descriptive statistics were performed to identify differences in female versus male neonate cases related to demographics, pregnancy-related factors, and birth-related factors. Results: We analyzed 68 cases, 38 males and 30 females. Median maternal age for all cases was 31 y (IQR 29-34). Compared to females, males were more likely to have a lower APGAR 1 score and receive resuscitation, and more likely to have a stroke onset within the first week of life. This data set did not show significant gender-related differences in stroke type, or maternal health concerns during pregnancy (Table). Conclusions: We found that males with newborn strokes had more complications at birth and were more likely to have strokes present in the first week of life than females. Further research on the reasons for these sex differences is needed. more...

Introduction: Treatment trials under development for Focal Cerebral Arteriopathy (FCA)—a unilateral anterior circulation arteriopathy that causes childhood arterial ischemic stroke—require a validated metric for FCA severity. The FCA Severity Score (FCASS) quantifies disease severity and extent. In the derivation cohort, FCASS peaked at 1-4 weeks post-stroke, and maximum FCASS correlated with infarct size and one-year Pediatric Stroke Outcome Measures (PSOM). The goal of the current study was to validate this score in an independent cohort. Methods: We used banked neuroimaging and previously acquired 6-month PSOM scores for 32 children with FCA in the Swiss Neuro-Paediatric Stroke Registry (SNPSR). A pediatric neuroradiologist applied FCASS to all available vascular imaging. FCASS sums the individual severity scores (from 0 for no involvement, to 4 for occlusion) for 5 arterial segments (supraclinoid ICA, M1, M2, A1, A2). The same neuroradiologist measured Pediatric ASPECTS scores, a measure of infarct volume (higher scores representing greater volumes, with a maximum possible score of 30). Results: Of 32 cases, 6 had only acute vascular imaging (≤1 day post-stroke), and 2 had only delayed vascular imaging (>3 months post-stroke). Including all 32 cases, the maximum FCASS score at any time was a median of 9 (range 3, 15; IQR 6, 12). Maximum FCASS correlated with Pediatric ASPECTS (Spearman’s rho=0.616, p=0.0002; Figure). The median PSOM was 0.5 (range 0 [no deficit], 3 [moderate deficit]; IQR 0, 1.5). Although Pediatric ASPECTS correlated with PSOM (Spearman’s rho=0.623, p=0.0002), there was no direct correlation between maximum FCASS and PSOM (rho=0.25, p=0.185). Conclusion: Limitations include a small sample size and missing imaging during the peak FCASS window for 8 of 32 cases. Regardless, in this independent validation cohort, higher maximum FCASS correlated with greater infarct volume scores that also correlated with worse neurological outcomes. more...

Introduction: Cerebral arteriopathies are frequently identified in children with arterial ischemic stroke (AIS), and are distinguished by high stroke recurrence. However, the clinical and neuroimaging profiles of AIS due to cerebral arteriopathy versus non- arteriopathy have not been compared. Hypothesis: We hypothesized that children with AIS due to arteriopathy would differ in their demographic, clinical, and radiographic presentation from those without arteriopathy. Methods: We report a large, prospective, multicentre cohort of children, 1 month - 17 years, with AIS, enrolled in the International Pediatric Stroke Study, 2003-2014. Those with arteriopathy including focal cerebral arteriopathy, dissection, moyamoya, vasculitis and non-specific arteriopathies, were compared to those with non-arteriopathic stroke etiologies. Results: Of 2127 children with AIS, 725(34%) had arteriopathy (58% male, mean age 8.1years). The remaining 1402(66%) had non-arteriopathic AIS. Arteriopathy was associated with older age, but not a specific gender or ethnicity. Geographic differences were observed. Children with arteriopathy were likely to present with hemiparesis, dysarthria, ataxia, headache, preceding/concurrent thromboembolic events and without seizures. Risk factors associated with arteriopathy included sickle anemia, head/neck trauma and lack of acute systemic disease. Radiological associations with arteriopathy included right sided unilateral or bilateral stroke, multiple infarcts and relative reduction in occurrence of intracranial hemorrhage. On multivariate analysis, headache (p=0.006), additional thromboembolic events (p=0.007), multiple infarcts (p=0.002) and lack of seizures (p=0.001) were independently associated with arteriopathy. Conclusions: Specific clinical profiles are associated with arteriopathy in children with AIS and may guide the clinician in early diagnostic evaluations and management. more...

Introduction: Stroke is reported among the top 10 causes of death in children in the US. In the Kids’ Inpatient Database, older age and Hispanic ethnicity were risk factors for mortality after pediatric ICH. Limited data is available regarding risk factors for death after pediatric arterial ischemic stroke (AIS). Objective: To identify predictors of in-hospital mortality in pediatric patients hospitalized with AIS. Methods: Neonates (0-28 days) and children (29 days- Results: Fourteen of 915 neonates (1.5%) and 74/2,285 children (3.2%) died during hospitalization. Of 54 cases with reported causes of death, 32 (59%) were related to AIS (herniation 2, brain death 10, ICH/hemorrhagic transformation 5, care withdrawal due to stroke severity 15), with the remaining deaths attributed to underlying medical disease. Of 356 children with Pediatric NIH Stroke Scale (PedNIHSS) scores, median PedNIHSS was 19 (IQR 14-27) among the 13 children who died and 7 (IQR 3-12) among the 343 children who did not die. In multivariable analysis, congenital heart disease (OR 4.1, 95%CI 1.3-13, p=0.018) and posterior plus anterior circulation stroke (OR 4.3, 95%CI 1.3-14, p=0.017) were associated with in-hospital mortality for neonates, while higher PedNIHSS [OR 1.11 (per 1 point PedNIHSS increase), 95%CI 1.03-1.19, p=0.004], Hispanic ethnicity (OR 7.6, 95%CI 1.8-32.3, p=0.006), and cardiac disease (OR 7.5, 95%CI 1.5-38.6, p=0.015) were associated with in-hospital mortality for children. Conclusions: In-hospital mortality occurred in about 2% of pediatric AIS cases with nearly 60% attributable to stroke. Risk factors for in-hospital mortality included cardiac disease and stroke severity, factors also associated with mortality in adults. Hispanic ethnicity, a factor associated with mortality in childhood ICH, was also associated with mortality after childhood AIS; the underlying reasons are unclear. Additional information is needed on stroke-related deaths after hospitalization. more...

Background and Purpose— Although arteriopathies are the most common cause of childhood arterial ischemic stroke, and the strongest predictor of recurrent stroke, they are difficult to diagnose. We studied the role of clinical data and follow-up imaging in diagnosing cerebral and cervical arteriopathy in children with arterial ischemic stroke. Methods— Vascular effects of infection in pediatric stroke, an international prospective study, enrolled 355 cases of arterial ischemic stroke (age, 29 days to 18 years) at 39 centers. A neuroradiologist and stroke neurologist independently reviewed vascular imaging of the brain (mandatory for inclusion) and neck to establish a diagnosis of arteriopathy (definite, possible, or absent) in 3 steps: (1) baseline imaging alone; (2) plus clinical data; (3) plus follow-up imaging. A 4-person committee, including a second neuroradiologist and stroke neurologist, adjudicated disagreements. Using the final diagnosis as the gold standard, we calculated the sensitivity and specificity of each step. Results— Cases were aged median 7.6 years (interquartile range, 2.8–14 years); 56% boys. The majority (52%) was previously healthy; 41% had follow-up vascular imaging. Only 56 (16%) required adjudication. The gold standard diagnosis was definite arteriopathy in 127 (36%), possible in 34 (9.6%), and absent in 194 (55%). Sensitivity was 79% at step 1, 90% at step 2, and 94% at step 3; specificity was high throughout (99%, 100%, and 100%), as was agreement between reviewers (κ=0.77, 0.81, and 0.78). Conclusions— Clinical data and follow-up imaging help, yet uncertainty in the diagnosis of childhood arteriopathy remains. This presents a challenge to better understanding the mechanisms underlying these arteriopathies and designing strategies for prevention of childhood arterial ischemic stroke. more...

Introduction: Childhood cerebral arteriopathies are heterogeneous and difficult to classify. Our goal was to identify clinical and imaging biomarkers associated with subtypes of childhood arteriopathy in order to facilitate their diagnosis and classification in both research and clinical settings. Methods: From 2009-2014, the VIPS study enrolled 355 children (age 29d-18y) with arterial ischemic stroke. A neuroradiologist and pediatric vascular neurologist independently reviewed vascular imaging and clinical data to diagnose arteriopathy (none, possible, definite), and then classify arteriopathy subtype: arterial dissection, transient cerebral arteriopathy (TCA), moyamoya, and secondary vasculitis. Disagreements were resolved through discussion by a panel of two neuroradiologists and two pediatric vascular neurologists. We constructed multivariable logistic regression models to identify characteristics independently associated with each subtype. Results: Of 127 cases with definite arteriopathy, 109 received a single arteriopathy subtype diagnosis (26 dissection, 25 TCA, 34 moyamoya, 15 secondary vasculitis, and 9 “other”), while 18 were of indeterminate subtype. There were no cases of primary vasculitis. Independent predictors of arteriopathy subtype are shown (Table). The association between black race and moyamoya is explained by sickle cell anemia. A banding pattern on the vascular imaging was pathognomonic of TCA. Moyamoya and vasculitis secondary to meningitis had similar distal internal carotid artery abnormalities, but lenticulostriate collaterals suggested moyamoya, and a decreased level of consciousness predicted secondary vasculitis. Conclusions: The different subtypes of childhood arteriopathies are associated with typical clinical, parenchymal and vascular imaging features that can help narrow the differential diagnosis in pediatric stroke patients with vascular abnormalities. more...

Introduction: New imaging markers employing sophisticated models of tissue microstructure may lead to better understanding of neurobiological substrates in childhood arterial ischemic stroke. Methods: Four children with acute unilateral MCA territory ischemic stroke were retrospectively included [two males, age range 2 -16 years]. Parameters of two complementary diffusion modeling techniques: Neurite Orientation Dispersion and Density Imaging (NODDI), and Spherical Mean Technique (SMT) were estimated using two-shell diffusion data acquired at presentation ( b- values = 1000 and 3000 s/mm 2 ). For comparison, diffusion tensor imaging (DTI) parameters were also estimated. Parameter estimates were derived from the acute infarct-affected gray matter, the reconstructed pyramidal tract and the contra-hemispheric homologs. Contrast-to-noise ratios (CNRs) were calculated for each pair of homologous brain regions. Results: In both the acute infarct-affected gray matter, and pyramidal tracts, the multi-shell parameter estimates demonstrated increased intra-cellular volume fraction (F icvf and INVF in figure), predominant reduced extra-cellular microscopic diffusivity (ENMMD and ENTMD in figure), and increased orientation dispersion of the infarct-affected axonal fibers (ODI in figure). These findings were consistent with respective acute stroke histopathological features of cytotoxic edema, narrowed extracellular spaces, and axonal swelling. The CNRs were associated with stroke severity and motor function outcome at follow-up. Conclusion: The parameter estimates derived from multi-shell diffusion data produces robust infarct contrast, and provides histopathologically plausible imaging biomarkers representing brain microstructural changes in acute childhood stroke. Routine clinical introduction of this imaging technique requires further elucidations of its prognostic values in predicting stroke severity and/or motor outcomes. more...

Objectives: Access to acute stroke interventions in the emergency department (ED) relies on correct clinical diagnosis. Our aims were to determine the accuracy and reliability of pediatric ED physician diagnosis of childhood stroke and other conditions presenting with brain attack symptoms. Methods: Prospective study of consecutive children aged one month-18 years presenting to the ED from June 2009-December 2010 with focal neurological deficits. Accuracy (sensitivity, specificity, receiver operator characteristic curves (ROCs)), and inter-rater agreement (kappa (κ )) were determined, between ED physician diagnoses, as recorded in the electronic hospital administrative software system, and final neurological diagnosis, following completion of diagnostic work-up. Results: Two-hundred-eighty seven children with 301 consecutive presentations were recruited. The most common final brain attack diagnoses included migraine in 84 children, first seizure in 48, Bell’s palsy in 29, stroke in 21, and conversion disorders in 18 children. Sensitivity of ED physician stroke diagnosis was 62% and specificity was 98% (ROC 0.8). Inter-rater agreement for ED physician and final stroke diagnosis was substantial (κ 0.61). ED physician diagnostic accuracy and reliability was highest for Bell’s palsy (ROC 0.98, κ 0.96), and lowest for CNS demyelination (ROC 0.5, κ -0.01) and cerebellitis (ROC 0.50, κ 0.50). Conclusions: ED physician diagnostic accuracy and reliability varies considerably across disorders presenting with brain attack symptoms. Clinical recognition tools are required to assist pediatric ED physicians with diagnosis of stroke and other serious neurological disorders. more...

Objective: Migraine, a typically benign disorder, is the most common stroke mimic in children presenting with brain attacks. We aimed to identify clinical features which discriminate childhood arterial ischaemic stroke (AIS) from migraine. Methods: Fifty-five consecutive children with AIS, presenting to a tertiary pediatric emergency department (ED), prospectively/retrospectively recruited from 2003-2010, were compared to 84 children with migraine, prospectively recruited from 2009-2010. Results: Health professional referral, (odds ratio (OR), 5.71, 95% confidence intervals 2.54-12.81), ambulance transport (OR 2.95, 1.45-5.97), high triage category assignment (OR 2.41, 1.06-5.49), sudden onset (OR 2.74, 1.18-6.39), symptoms of focal weakness (OR 6.96, 3.24-14.93), seizures (OR 7.44, 1.99-27.81), speech disturbance (OR 3.06, 1.48-6.32), and ataxia (OR 4.88, 1.63-14.65) were significantly associated with increased odds of AIS diagnosis. Signs of face (OR 155.37, 20.03-1205.33), arm (OR 15.58, 6.41-37.84), or leg weakness (OR 15.40, 5.75-41.27), inability to walk (OR 14.18, 3.07-65.41), dysarthria (OR 47.21, 6.07-367.13), dysphasia (OR 12.76, 1.52-106.97) and altered consciousness (OR 2.45, 1.03-5.85) were also significantly associated with increased odds of AIS diagnosis, In contrast, vomiting (OR 0.23, 0.10-0.53), visual symptoms (OR 0.24, 0.10-0.57), other symptoms (OR 0.06, 0.01-0.48) and absence of neurological signs on ED physician assessment (OR 0.05, 0.01-0.17) were associated with decreased odds of AIS diagnosis. Conclusion: Differing presenting symptoms and signs allow discrimination of childhood AIS from migraine. These findings can inform decisions about urgency and type of diagnostic neuroimaging in the ED for children presenting with brain attack symptoms. more...

Background and Purpose— Access to acute stroke interventions in the emergency department (ED) relies on correct clinical diagnosis. Our aims were to determine the accuracy and reliability of pediatric ED physician diagnosis of childhood stroke and other conditions presenting with brain attack symptoms. Methods— Prospective study of consecutive children aged 1 month to 18 years presenting to the ED from June 2009 to December 2010 with focal neurological deficits. Accuracy (sensitivity, specificity, and receiver operator characteristic curves [ROCs]) and interrater agreement (κ) were determined, between ED physician diagnoses, as recorded in the electronic hospital administrative software system, and final neurological diagnosis, after completion of diagnostic work-up. Results— Two-hundred eighty-seven children with 301 consecutive presentations were recruited. The most common final brain attack diagnoses included migraine in 84 children, first seizure in 48, Bell’s palsy in 29, stroke in 21, and conversion disorders in 18 children. Sensitivity of ED physician stroke diagnosis was 62%, and specificity was 98% (ROC, 0.8). Inter-rater agreement for ED physician and final stroke diagnosis was substantial (κ=0.61). ED physician diagnostic accuracy and reliability was highest for Bell’s palsy (ROC=0.98; κ=0.96), and lowest for central nervous system demyelination (ROC=0.5; κ=−0.01) and cerebellitis (ROC=0.50; κ=0.50). Conclusions— ED physician diagnostic accuracy and reliability varies considerably across disorders presenting with brain attack symptoms. Clinical recognition tools are required to assist pediatric ED physicians with diagnosis of stroke and other serious neurological disorders. more...

Background and Purpose— Immediately calling an ambulance is the key factor in reducing time to hospital presentation for adult stroke. Little is known about prehospital care in childhood arterial ischemic stroke (AIS). We aimed to determine emergency medical services call-taker and paramedic diagnostic sensitivity and to describe timelines of care in childhood AIS. Methods— This is a retrospective study of ambulance-transported children aged Results— Twenty-three children were identified; 4 with unavailable ambulance records were excluded. Nineteen children were included in the study. Median age was 8 years (interquartile range, 3–14); median Pediatric National Institutes of Stroke Severity Scale score was 8 (interquartile range, 3–16). Emergency medical services call-taker diagnosis was stroke in 4 children (21%). Priority code 1 (lights and sirens) ambulances were dispatched for 13 children (68%). Paramedic diagnosis was stroke in 5 children (26%), hospital prenotification occurred in 8 children (42%), and 13 children (68%) were transported to primary stroke centers. Median prehospital timelines were onset to emergency medical services contact 13 minutes, call to scene 12 minutes, time at scene 14 minutes, transport time 43 minutes, and total prehospital time 71 minutes (interquartile range, 60–85). Conclusions— Emergency medical services call-taker and paramedic diagnostic sensitivity and prenotification rates are low in childhood AIS. more...

Background and Purpose— Taking appropriate action in the prehospital setting is important for rapid stroke diagnosis in adults. Data are lacking for children. We aimed to describe parental care–seeking behavior and prehospital timelines of care in childhood arterial ischemic stroke. Methods— A structured questionnaire was developed, using value-focused event-driven conceptual modeling techniques, to interview parents of children presenting to the emergency department with arterial ischemic stroke from 2008 to 2014. Results— Twenty-five parents (median age 41 years, interquartile range 36–45) were interviewed. Twenty-four children were awake, and 1 child was asleep at stroke onset; 23 had sudden onset symptoms. Location at stroke onset included home (72%), school (8%), or other setting (20%). Carergivers present included parent (76%), another child (8%), teacher (4%), or alone (8%). Eighty-four percent of parents thought symptoms were serious, and 83% thought immediate action was required, but only 48% considered the possibility of stroke. Initial actions included calling an ambulance (36%), wait and see (24%), calling a general practitioner (16%) or family member (8%), and driving to the emergency department or family physician (both 8%). Median time from onset to emergency department arrival was 76 minutes (interquartile range 53–187), being shorter for ambulance-transported patients. Conclusions— Stroke recognition and care-seeking behavior are suboptimal, with less than half the parents considering stroke or calling an ambulance. Initiatives are required to educate parents about appropriate actions to facilitate time-critical interventions. more...

Introduction and objectives: Ambulance usage is the most important factor resulting in shorter time to hospital arrival in adult stroke. Prenotification and bypass to stroke centres are associated with increased thrombolysis rates. Sensitivity of paramedic stroke identification in adults varies from 44-66% but there are no published data in children. Hypotheses and aims: We hypothesised that emergency medical services call-taker (EMSDCT) and paramedic identification of childhood arterial ischemic stroke (AIS) is suboptimal and contributes to prehospital delays. Our aims were to determine sensitivity of EMSCT and paramedic diagnosis, and to describe patterns and timelines of paramedic care in childhood AIS. Methods: Retrospective study of ambulance transported children Results: Ambulance records were reviewed for 19 children. Four children were excluded because records were unavailable. 58% were female, median age was 8 years (IQR 3-14) and median PedNIHSS score was 8 (IQR 3-16). EMSCT diagnosis was stroke in 21% of children and Code 1 (lights and sirens) ambulance were dispatched for 72% of children. Paramedic diagnosis was stroke in 26% of children. Prenotification occurred in 42% of children and 64% were transported to adult (6) or pediatric (6) hospitals meeting criteria for primary stroke centres. Median prehospital timelines were: onset to 911 call 13 minutes, call to scene 12 minutes, time at scene 14 minutes, call to ED arrival 54 minutes, and total pre-hospital lag time 71 minutes (IQR 60-85). In contrast post-arrival lag time to radiological confirmation of diagnosis was 568 minutes (IQR 144-799). Conclusion: Sensitivity of EMSCT and paramedic childhood AIS diagnosis and pre-notification rates are much lower than those reported in adults. However prehospital factors contribute less to delayed diagnosis than in hospital factors, representing an important difference to adult stroke. more...

Introduction: Stroke is among the top 10 causes of death in children. Survivors face many potential years of disability but few studies have explored factors which contribute to poor outcome. Our aims were to describe factors associated with mortality, neurological disability and recurrence in a population of Australian children with arterial ischaemic stroke (AIS). Methods: Prospective consecutive single centre cohort study of children 1 month-18 years with AIS, from 2003-2013, who underwent standardised diagnostic work up. The NINDS common data element framework was used to select risk factors, laboratory and radiological variables of interest. The Paediatric Stroke Outcome Measure (PSOM) was used to classify neurological outcome at 12 months and the CASCADE system was used to classify aetiology. Recurrence was defined as clinical (completed stroke/TIA) or radiological event with new infarction. Chi 2 analyses were used to identify risk factors for poor outcome. Results: A total of 126 cases of childhood AIS were identified. 6% of children died, 27% had recurrent events (21 clinical, 5 radiological strokes, 9 TIAs). 63% of children had poor neurological outcome (total PSOM≥2) with motor disability (53%) being most common. Male gender, prothrombotic disorders and cortical infarct location were significantly associated with mortality (P Conclusion: The economic and social costs of childhood AIS are likely substantial because long term neurological deficits are common. The finding that arteriopathies are a risk factor for recurrence is consistent with data from overseas. These findings will inform development of longitudinal multicentre Australian studies of childhood AIS. more...

BACKGROUND: Cardiac disease is identified in up to 30% of children with stroke, with almost one quarter occurring in the perioperative period. This has potentially devastating implications for long term neurodevelopmental outcomes. The aim of the study was to investigate risk factors of peri-procedural stroke in children with cardiac disease. METHODS AND PATIENTS: We performed a retrospective case-control study of all children under RESULTS: A total of 52 children with AIS were identified. Univariable analysis identified post-procedural infection (OR 7.3, CI 2.0-26, p=0.002) and length of ICU stay (OR 4.7, CI 1.9-12, p Conclusion: Although the study is limited to a single center cohort, length of ICU stay and post procedural infection were identified as risk factors for AIS. These findings demonstrate these factors to be important areas to focus attention for stroke prevention in children with cardiac disease. more...

Objective: Bedside stroke recognition tools improve diagnostic accuracy in adult stroke. Our aim was to assess the diagnostic utility of the CPSS and ROSIER tools in children presenting to the emergency department (ED) with brain attack symptoms. Methods: The Cincinnati Prehospital Stroke Scale (CPSS ) and the Recognition of Stroke in the Emergency Room (ROSIER) tool were retrospectively applied to 101 consecutive children with stroke, presenting from 2003-2010, and 279 children with mimics, presenting to the ED from 2009-2010. A positive CPSS was defined as ≥1 positive sign (face or arm weakness, speech disturbance). A positive ROSIER was defined as a score of ≥1. Diagnostic accuracy of the tools in determining the patients’ true status were estimated for arterial (AIS), hemorrhagic (HS) and combined stroke subtypes versus mimics. Results: The CPSS and ROSIER tools correctly discriminated combined stroke subtypes from mimics (diagnostic odds ratio (DOR) 5.6 and 4.7 respectively) and AIS from mimics (DOR 15.1 and 13.4 respectively) but not HS from mimics (DOR 1.2 for both tools). CPSS and ROSIER accuracy were fair for AIS versus mimics (ROC 0.79 and 0.77 respectively), fair to poor for combined stroke subtypes versus mimics (ROC 0.70 and 0.68 respectively) and failed for HS versus mimics (ROC 0.51 and 0.52 respectively). Reasons for limited accuracy include different spectrum of mimics, lower overall prevalence, higher proportion of HS subtype and common seizure occurrence in childhood stroke. Conclusions: Adult stroke recognition tools correctly discriminate combined stroke types and AIS subtype from mimics but their limited accuracy suggest further modifications are required to improve diagnostic utility for identification of childhood stroke in the ED. more...

Objective: Recognizing stroke symptoms and taking appropriate action are vital first steps in stroke care in adults but data are lacking in children. Our objective was to describe stroke knowledge and care seeking behaviour in parents of children presenting to the Emergency Room with stroke. Methods: Structured parental interview to determine stroke symptom knowledge. Event driven process modeling and value focused engineering were used to select questions with the fundamental objectives being correct recognition of stroke symptoms and correct action (call 911). The Stroke Action Test (STAT), a validated instrument with stroke scenarios was used to determine care seeking behaviour; 21 items are stroke specific. The correct response is to call 911. Results: A total of 34 parents were interviewed. The most common unprompted stroke symptoms given were limb (94%) or face weakness (78%) and speech disturbance (66%). 14 (41%) of parents remembered at least one item of the Face Arm Speech Time (FAST) acronym. 8 (24%) could remember all 4 items. Prompted recognition of AHA SUDDENS symptoms (yes I would think of stroke) included face (88%) or limb (77%) numbness/weakness, confusion/speech problems (77%), trouble walking/incoordination (47%), visual symptoms (35%) and headache (38%). 26 (77%) of parents knew of stroke treatments; 37% were aware of anti-thrombotic treatments but only 12% were aware of thrombolysis. Median STAT score was 10 (IQR 6-14), meaning parents called 911 for 48% of stroke scenarios. Questions with >1 symptom (focal weakness and speech disturbance) had highest correct responses (84%) and visual disturbance or dizziness had the lowest correct responses (12.5%). Conclusions: Parental knowledge varies across stroke symptoms and care seeking behaviour is suboptimal. Few parents are aware of thrombolysis. Initiatives to link knowledge to appropriate action are urgently needed if children are to receive the benefits of hyper-acute therapies. more...

Objective: Timely recognition of stroke in the pediatric emergency room (ER) is critical to improving access to hyper-acute therapies. We aimed to identify key clinical features which discriminate between stroke and non-stroke brain attacks (mimics). Methods: Two-hundred and eighty consecutive children presenting to the ER with non-stroke brain attacks, prospectively recruited over 18 months in 2009-2010, were compared to 104 children with stroke, prospectively/retrospectively recruited from 2003-2010. Brain attack was defined as acute onset focal brain dysfunction with ongoing symptoms or signs on arrival to the ER. Exclusion criteria included known epilepsy, hydrocephalus, head trauma and isolated headache. Results: Stroke diagnoses included arterial ischemic stroke (AIS) (55), hemorrhagic stroke (HS) (37), TIA (10) and sinovenous thrombosis (2). The most common mimic diagnoses included migraine (87), first seizure (46), Bell’s palsy (29) and conversion disorder (18). Children with stroke were more likely to have sudden onset of symptoms (85% vs. 71%), arrive by ambulance (63% vs. 33%) and receive higher triage category (43% vs. 23%) than mimics (p Conclusions: Focal weakness and speech disturbance predict stroke diagnosis in children with brain attack symptoms, findings which are similar to adults. These findings will inform the development of pediatric bedside stroke recognition tools to improve rapid recognition of stroke by emergency physicians. more...

Objective: Taking appropriate action in the pre-hospital setting is important for rapid stroke diagnosis in adults but data are lacking for children. Our objectives were to describe help seeking behaviour and pathways to hospital in pediatric arterial ischemic stroke. Methods: A structured interview was performed to determine carer actions and pathway to hospital. Event driven process modeling techniques were used to develop questions with fundamental objectives being timely and correct recognition of stroke in the pre-hospital setting. Results: Parents of 28 children (61% female) were interviewed. 27 children (96%) were awake at stroke ictus and 26 (93%) had sudden onset symptoms. Child’s location at stroke onset included home 19 (68%), school 3 (11%) or other setting 6 (21%). Carers present included parent 21 (75%), teacher 2 (7%), other adult 4 (14%) or alone 1 (4%). 24 (89%) parents thought symptoms were serious but only 10 (36%) considered the possibility of stroke. Symptoms of most concern to parents included face weakness 14 (54%), speech disturbance 9 (32%), incoordination or difficulty walking 6 (21%), headache 5 (18%) and weakness 4 (14%). Initial actions included calling 911 in 10 (36%), wait and see 6 (21%), calling family member 1 (4%), private transport to emergency room (ER) 7 (25%) or family physician 4 (14%). 22 (85%) carers thought urgent action was required but only 14 (54%) ultimately called 911. First heath professional contact included paramedic 13 (46%), ER physician 8 (29%) or family physician 7 (25%). Median time from onset to ER arrival was 1.8 hours (IQR 0.75-7). Conclusions: Only one-third of carers considered stroke as a possible cause for their child’s neurological symptoms and less than half called 911. Initiatives are required to educate parents about taking appropriate action to improve access to time critical interventions. more...

Background and Purpose— Limited data exist on childhood posterior circulation arterial ischemic stroke (PCAIS). We describe clinical and radiological features of childhood PCAIS to determine whether there are differences in infarct topography, vascular abnormalities, risk factors, and stroke subtypes when compared to adults. Methods— Children with radiologically confirmed PCAIS were prospectively identified from August 2002 to February 2008. Infarcts were divided into proximal, middle, and distal posterior circulation segments utilizing an adult topographical classification system. Vascular abnormalities were described in terms of location, severity, and evolution over time. A pediatric modification of the TOAST classification system was used to define stroke subtypes. Results— Twenty seven (37%) of 73 children recruited to our registry had 34 radiologically confirmed PCAIS events. Infarct location was distal (25), middle (2), proximal (1), and multiple segments (6). Fourteen events were associated with single infarcts and 20 were associated with multiple infarcts. Magnetic resonance angiography was abnormal in 16 of 25 children with PCAIS at presentation with stenosis (8) or occlusion (8). Vascular lesions progressed (5), transiently worsened before stabilizing (2), remained stable or improved (8), or normalized (1) over 12 months. Stroke subtypes included nonprogressive steno-occlusive cerebral arteriopathy (9), cardioembolic (4), dissection (3), Moyamoya syndrome (3), other determined (4), probable (1), and undetermined etiology (3). Fifty-two percent of children had recurrent posterior (6) or anterior (8) strokes. Conclusions— Nonprogressive arteriopathies are the most common cause of childhood PCAIS, usually affecting distal segments. Atherosclerosis-related risk factors do not play an important role in stroke causation. PCAIS is frequently associated with recurrent events. more...