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Background: Our team designed an innovative, observation-based motor impairment measure-the Pediatric Stroke Hemiplegic Motor Impairment Scale (Pedi HEMIs). Here we present the results of a survey describing common practices in the pediatric stroke community and the initial psychometric properties of the upper extremity subscale of the Pedi HEMIs (Pedi HEMIs-UE)., Methods: This is a cross-sectional study whereby participants completed a battery of assessments including the novel Pedi HEMIs-UE. Internal consistency was measured via Cronbach alpha (α). Intraclass correlation (ICC) was used to assess inter-rater reliability (IRR). Concurrent validity was investigated using Pearson or polychoric correlations and simple linear regressions., Results: The study sample consisted of 18 children aged 1.08 to 15 years. Two participants completed two sets of evaluations, totaling 20 data sets. Cronbach α, a measure of internal consistency, was on average 0.91 (range: 0.89 to 0.92). IRR was excellent with the six raters in almost perfect agreement (ICC = 0.91; 95% confidence interval [CI]: 0.83 to 0.96). Pearson correlation coefficient between the Pedi HEMIs-UE and logit Assisting Hand Assessment (AHA)/mini-AHA was -0.938 (95% CI: -0.979 to -0.827, P < 0.001), indicating excellent concurrent validity., Conclusions: We found excellent feasibility, reliability, and validity of the Pedi HEMIs-UE in a convenience sample of youth with hemiparesis after stroke., Competing Interests: Declaration of competing interest Dr. Suskauer serves on the Scientific Advisory Board role for Myomo. Dr. Sun receives funding from the American Heart Association (Career Development Award [850044]) and the D.C. Women's Board., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Neurological morbidity is common after pediatric stroke, with moderate to severe deficits that can significantly impact education and social function. Care and recovery occur in phases distinguished by the time interval after stroke onset. These phases include the hyperacute and acute periods in which the focus is on cerebral reperfusion and prevention of neurological deterioration, followed by the subacute and chronic phases in which the focus is on secondary stroke prevention and mitigation of disability through rehabilitation, adaptation, and reintegration into the community. In this article, a multidisciplinary group of pediatric stroke experts review the stages of recovery after pediatric stroke with an emphasis on critical assessment time points. Our goal is to encourage increased standardization of outcome assessment to facilitate future clinical trials comparing various treatment and intervention options and advance optimized care for children with stroke., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Following a pediatric stroke, outcome measures selected for monitoring functional recovery and development vary widely. We sought to develop a toolkit of outcome measures that are currently available to clinicians, possess strong psychometric properties, and are feasible for use within clinical settings. A multidisciplinary group of clinicians and scientists from the International Pediatric Stroke Organization comprehensively reviewed the quality of measures in multiple domains described in pediatric stroke populations including global performance, motor and cognitive function, language, quality of life, and behavior and adaptive functioning. The quality of each measure was evaluated using guidelines focused on responsiveness and sensitivity, reliability, validity, feasibility, and predictive utility. A total of 48 outcome measures were included and were rated by experts based on the available evidence within the literature supporting the strengths of their psychometric properties and practical use. Only three measures were found to be validated for use in pediatric stroke: the Pediatric Stroke Outcome Measure, the Pediatric Stroke Recurrence and Recovery Questionnaire, and the Pediatric Stroke Quality of Life Measure. However, multiple additional measures were deemed to have good psychometric properties and acceptable utility for assessing pediatric stroke outcomes. Strengths and weaknesses of commonly used measures including feasibility are highlighted to guide evidence-based and practicable outcome measure selection. Improving the coherence of outcome assessment will facilitate comparison of studies and enhance research and clinical care in children with stroke. Further work is urgently needed to close the gap and validate measures across all clinically significant domains in the pediatric stroke population., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Pediatric stroke results in life-long morbidity for many patients, but the outcomes can vary depending on factors such as age of injury, or mechanism, size, and location of stroke. In this review, we summarize the current understanding of outcomes in different neurological domains (eg, motor, cognitive, language) for children with stroke of different mechanisms (ie, arterial ischemic stroke, cerebral sinus venous thrombosis, and hemorrhagic stroke), but with a focus on World Health Organization International Classification for Functioning, Disability, and Health (ICF-CY) framework for measuring health and disability for children and youth. We describe outcomes for the population as a whole and certain factors that may further refine prognostication., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Childhood stroke is rare, and diagnosis is frequently delayed. The use of pediatric stroke teams has the potential to decrease time to neurology evaluation and imaging, hastening appropriate diagnosis and treatment for acute neurologic presentations in children., Methods: We performed a retrospective analysis of our institutional pediatric stroke or "brain attack" team (pedsBAT) activations from October 2014 to July 2017. Clinical characteristics and timing parameters were compared between pedsBAT activations in the inpatient vs emergency department (ED) / outpatient settings as well as between pediatric and adult BAT activations in the same time period., Results: We identified 120 pedsBAT activations (75% in the ED/outpatient setting) during the study time period. Inpatient pedsBAT activations were more likely than outpatient activations to have heart disease as a risk factor for ischemic stroke and presented more frequently with altered mental status, but there were no differences in the proportion of cerebrovascular diagnoses or timing parameters between the 2 groups. When compared with adult BAT activations, outpatient pedsBAT activations had a longer time from symptom discovery to arrival at the ED, and inpatient pedsBAT activations had longer time from symptom discovery to BAT activation., Conclusions: Compared with adults, the interval leading up to stroke team activation was longer in children, suggesting delays in symptom recognition. Future interventions should be aimed at reducing these delays in presentation to care and stroke alert activation in pediatric patients.

Objective: To characterize predictors of recovery and outcome following pediatric arterial ischemic stroke, hypothesizing that age influences recovery after stroke., Methods: We studied children enrolled in the International Pediatric Stroke Study between January 1, 2003 and July 31, 2014 with 2-year follow-up after arterial ischemic stroke. Outcomes were defined at discharge by clinician grading and at 2 years by the Pediatric Stroke Outcome Measure. Demographic, clinical, and radiologic outcome predictors were examined. We defined changes in outcome from discharge to 2 years as recovery (improved outcome), emerging deficit (worse outcome), or no change., Results: Our population consisted of 587 patients, including 174 with neonatal stroke and 413 with childhood stroke, with recurrent stroke in 8.2% of childhood patients. Moderate to severe neurological impairment was present in 9.4% of neonates versus 48.8% of children at discharge compared to 8.0% versus 24.7% after 2 years. Predictors of poor outcome included age between 28 days and 1 year (compared to neonates, odds ratio [OR] = 3.58, p < 0.05), underlying chronic disorder (OR = 2.23, p < 0.05), and involvement of both small and large vascular territories (OR = 2.84, p < 0.05). Recovery patterns differed, with emerging deficits more common in children <1 year of age (p < 0.05)., Interpretation: Outcomes after pediatric stroke are generally favorable, but moderate to severe neurological impairments are still common. Age between 28 days and 1 year appears to be a particularly vulnerable period. Understanding the timing and predictors of recovery will allow us to better counsel families and target therapies to improve outcomes after pediatric stroke. ANN NEUROL 2020;87:840-852., (© 2020 American Neurological Association.)

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 <15% and at least a 93% chance that the risk is <10%. These results suggest that the overall risk of SICH after intravenous tPA in children with acute arterial ischemic stroke, when given within 4.5 hours after symptom onset, is low.

Pediatric stroke causes significant morbidity for children resulting in lifelong neurological disability. Although hyperacute recanalization therapies are available for pediatric patients, most patients are ineligible for these treatments. Therefore the mainstay for pediatric stroke treatment relies on rehabilitation to improve outcomes. Little is known about the ideal rehabilitation therapies for pediatric patients with stroke and the unique interplay between the developing brain and our models of stroke recovery. In this review, we first discuss the consequences of pediatric stroke. Second, we examine the scientific evidence that exists between the mechanisms of recovery and how they are different in the pediatric developing brain. Finally, we evaluate potential interventions that could improve outcomes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Mechanical thrombectomy has emerged as a standard of care for acute stroke from large vessel occlusion in adults but remains controversial in children. Cerebral vessels are nearly adult size by 5 years of age but the technical feasibility of achieving recanalization in younger and smaller children with current endovascular tools remains unclear., Objective: To systematically review the literature on mechanical thrombectomy for stroke in children less than 5 years of age., Results: Mechanical thrombectomy for acute stroke has been reported in 11 children under the age of 5 years (range 9 months to 4 years). The mean time from symptom onset to groin puncture was 12 hours (range 4-50 hours). Complete recanalization was achieved in 7/12 (58%) vessels attempted, and partial recanalization in 4/12 (33%). Two procedure related complications were reported, with small vessel size felt to be contributory to basilar vasospasm in one case. Favorable neurological outcomes were reported in 7 cases (64%)., Conclusions: Our review of the literature demonstrates that mechanical thrombectomy for acute ischemic stroke may be feasible in carefully selected infants and young children less than 5 years of age using currently available devices. Efficacy in promoting better neurologic outcomes remains unproven, and other questions persist, including whether complications such as vasospasm occur more frequently in young children compared with adults. Further study is needed to determine the safety and efficacy of pediatric mechanical thrombectomy. These data suggest that young children should not be excluded from future studies or clinical treatment on the basis of age alone., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose of Review: After decades of hype, cell-based therapies are emerging into the clinical arena for the purposes of promoting recovery after stroke. In this review, we discuss the most recent science behind the role of cell-based therapies in ischemic stroke and the efforts to translate these therapies into human clinical trials., Recent Findings: Preclinical data support numerous beneficial effects of cell-based therapies in both small and large animal models of ischemic stroke. These benefits are driven by multifaceted mechanisms promoting brain repair through immunomodulation, trophic support, circuit reorganization, and cell replacement. Cell-based therapies offer tremendous potential for improving outcomes after stroke through multimodal support of brain repair. Based on recent clinical trials, cell-based therapies appear both feasible and safe in all phases of stroke. Ongoing translational research and clinical trials will further refine these therapies and have the potential to transform the approach to stroke recovery and rehabilitation.

Pediatric arterial ischemic stroke (AIS) is an uncommon but important cause of neurologic morbidity in neonates and children, with consequences including hemiparesis, intellectual disabilities, and epilepsy. The causes of pediatric AIS are unique to those typically associated with stroke in adults. Familiarity with the risk factors for AIS in children will help with efficient diagnosis, which is unfortunately frequently delayed. Here we review the epidemiology and risk factors for AIS in neonates and children. We also outline consensus-based practices in the evaluation and management of pediatric AIS. Finally we discuss the outcomes observed in this population. While much has been learned in recent decades, many uncertainties sill persist in regard to pediatric AIS. The ongoing development of specialized centers and investigators dedicated to pediatric stroke will continue to answer such questions and improve our ability to effectively care for these patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: This article was written to provide clinicians and researchers with an overview of a number of advanced neuroimaging techniques in an effort to promote increased utility and the design of future studies using advanced neuroimaging in childhood stroke. The current capabilities of advanced magnetic resonance imaging techniques provide the opportunity to build on our knowledge of the consequences of stroke on the developing brain. These capabilities include providing information about the physiology, metabolism, structure, and function of the brain that are not routinely evaluated in the clinical setting., Methods: During the Proceedings of the Stroke Imaging Laboratory for Children Workshop in Toronto in June 2015, a subgroup of clinicians and imaging researchers discussed how the application of advanced neuroimaging techniques could further our understanding of the mechanisms of stroke injury and repair in the pediatric population. This subgroup was established based on their interest and commitment to design collaborative, advanced neuroimaging studies in the pediatric stroke population., Results: In working toward this goal, we first sought to describe here the magnetic resonance imaging techniques that are currently available for use, and how they have been applied in other stroke populations (e.g., adult and perinatal stroke)., Conclusions: With the continued improvement in advanced neuroimaging techniques, including shorter acquisition times, there is an opportunity to apply these techniques to their full potential in the research setting and learn more about the effects of stroke in the developing brain., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To identify perinatal risk factors that can distinguish arterial ischemic stroke from hypoxic-ischemic encephalopathy at birth., Methods: This is a cohort study of all neonates born at 35 weeks of gestation or greater admitted to our neonatal intensive care unit from January 1, 2010, to December 31, 2015, that compares neonates with stroke with those with hypoxic-ischemic encephalopathy undergoing whole-body hypothermia with abnormal brain magnetic resonance imaging., Results: During this 6-year period, there were 22 neonates with stroke and 47 with hypoxic-ischemic encephalopathy undergoing whole-body hypothermia with abnormal magnetic resonance imaging. Three neonates triaged to hypothermia initially thought to have hypoxic-ischemic encephalopathy were later diagnosed with stroke. All neonates with stroke had a negative thrombophilia workup. Neonates with stroke had a significantly higher incidence of seizures and increased initial platelet counts on univariate analysis. A multivariable model of variables with P<.1 on univariate analysis present within 6 hours of birth found significant increases in nonreassuring fetal heart rate tracings, sentinel events, low Apgar score at 5 minutes, and metabolic acidosis at birth with hypoxic-ischemic encephalopathy. Stroke was associated with a significantly increased initial platelet count., Conclusion: Stroke is associated with increased initial platelet counts and is not associated with cesarean delivery for nonreassuring fetal heart rate tracings, sentinel events, or perinatal metabolic acidosis. Stroke is a form of neonatal brain injury not associated with perinatal risk factors that allow early identification.

Ischemic stroke is a devastating brain injury and an important cause of neurologic disability worldwide and across the lifespan. Despite the physical, social, and economic burdens of this disease there is only a single approved medicine for the treatment of acute stroke, and its use is unfortunately limited to the small fraction of patients presenting within the narrow therapeutic window. Following stroke, there is a period of plasticity involving cell genesis, axon growth, and synaptic modulation that is essential to spontaneous recovery. Treatments focusing on neuroprotection and enhancing recovery have been the focus of intense preclinical studies, but translation of these treatments into clinical use has been disappointing thus far. The important role of epigenetic mechanisms in disease states is becoming increasingly apparent, including in ischemic stroke. These regulators of gene expression are poised to be critical mediators of recovery following stroke. In this review we discuss evidence for the role of epigenetics in neuroplasticity and the implications for stroke recovery., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Each year hundreds of thousands of people must cope with the severe neurological consequences of a stroke. Current therapeutic strategies for stroke focus on acute treatment and neuroprotection. Unfortunately, these practices do little to reduce the long-term morbidity associated with the injury. To develop effective therapies that promote regeneration, we must have an understanding of the cellular and molecular events involved in the recovery from an insult. Neural stem and progenitor cells are likely to be affected during this period. Here we review how the proliferation, migration, and maturation of these precursors are affected by ischemia. Furthermore, we summarize data available on the underlying mechanisms and the therapeutic implications of these studies. The studies that we review provide compelling evidence that neural precursors resident in the brain initiate a compensatory response to stroke that results in the production of new neurons. Moreover, administration of growth factors can enhance this compensatory response. Based on these encouraging results, we may eventually be able to manipulate these precursors to improve recovery of function in individuals afflicted by this devastating injury., (Copyright 2003 Wiley-Liss, Inc.)