Neuromonitoring During ECMO Support in Children.

Extracorporeal membrane oxygenation is a potentially lifesaving intervention for children with severe cardiac or respiratory failure. It is used with increasing frequency and in increasingly more complex and severe diseases. Neurological injuries are important causes of morbidity and mortality in children treated with extracorporeal membrane oxygenation and include ischemic stroke, intracranial hemorrhage, hypoxic-ischemic injury, and seizures. In this review, we discuss the epidemiology and pathophysiology of neurological injury in patients supported with extracorporeal membrane oxygenation, and we review the current state of knowledge for available modalities of monitoring neurological function in these children. These include structural imaging with computed tomography and ultrasound, cerebral blood flow monitoring with near-infrared spectroscopy and transcranial Doppler ultrasound, and physiological monitoring with electroencephalography and plasma biomarkers. We highlight areas of need and emerging advances that will improve our understanding of neurological injury related to extracorporeal membrane oxygenation and help to reduce the burden of neurological sequelae in these children.

Pediatric Ischemic Stroke: An Infrequent Complication of SARS-CoV-2.

OBJECTIVE: Severe complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) include arterial ischemic stroke (AIS) in adults and multisystem inflammatory syndrome in children. Whether stroke is a frequent complication of pediatric SARS-CoV-2 is unknown. This study aimed to determine the proportion of pediatric SARS-CoV-2 cases with ischemic stroke and the proportion of incident pediatric strokes with SARS-CoV-2 in the first 3 months of the pandemic in an international cohort. METHODS: We surveyed 61 international sites with pediatric stroke expertise. Survey questions included: numbers of hospitalized pediatric (≤ 18 years) patients with SARS-CoV-2; numbers of incident neonatal and childhood ischemic strokes; frequency of SARS-CoV-2 testing for pediatric patients with stroke; and numbers of stroke cases positive for SARS-CoV-2 from March 1 to May 31, 2020. RESULTS: Of 42 centers with SARS-CoV-2 hospitalization numbers, 8 of 971 (0.82%) pediatric patients with SARS-CoV-2 had ischemic strokes. Proportions of stroke cases positive for SARS-CoV-2 from March to May 2020 were: 1 of 108 with neonatal AIS (0.9%), 0 of 33 with neonatal cerebral sinovenous thrombosis (CSVT; 0%), 6 of 166 with childhood AIS (3.6%), and 1 of 54 with childhood CSVT (1.9%). However, only 30.5% of neonates and 60% of children with strokes were tested for SARS-CoV-2. Therefore, these proportions represent 2.9, 0, 6.1, and 3.0% of stroke cases tested for SARS-CoV-2. Seven of 8 patients with SARS-CoV-2 had additional established stroke risk factors. INTERPRETATION: As in adults, pediatric stroke is an infrequent complication of SARS-CoV-2, and SARS-CoV-2 was detected in only 4.6% of pediatric patients with ischemic stroke tested for the virus. However, < 50% of strokes were tested. To understand the role of SARS-CoV-2 in pediatric stroke better, SARS-CoV-2 testing should be considered in pediatric patients with stroke as the pandemic continues. ANN NEUROL 2021;89:657-665.

Pediatric ECMO: unfavorable outcomes are associated with inflammation and endothelial activation.

BACKGROUND: Inflammatory and endothelial activation responses during extracorporeal membrane oxygenation (ECMO) support in children are poorly understood. In this study, we aimed to determine if circulating inflammatory, endothelial activation, and fibrinolytic markers are associated with mortality and with neurologic outcomes in children on ECMO. METHODS: We conducted a secondary analysis of a two-center prospective observational study of 99 neonatal and pediatric ECMO patients. Inflammatory (interferon gamma [IFNγ], interleukin-6 [IL-6], IL-1ß, tumor necrosis factor alpha [TNFα]), endothelial activation (E-selectin, P-selectin, intercellular adhesion molecule-3 [ICAM-3], thrombomodulin [TM]), and fibrinolytic markers (tissue plasminogen activator [tPA], plasminogen activator inhibitor-1 [PAI-1]) were measured in plasma on days 1, 2, 3, 5, 7, and every third day thereafter during the ECMO course. RESULTS: All ECMO day 1 inflammatory biomarkers were significantly elevated in children with abnormal vs. normal neuroimaging. ECMO day 1 and peak levels of IL-6 and PAI-1 were significantly elevated in children who died compared to those who survived to hospital discharge. Tested biomarkers showed no significant association with long-term neurobehavioral outcomes measured using the Vineland Adaptive Behavioral Scales, Second Edition. CONCLUSIONS: High levels of circulating inflammatory, endothelial activation, and fibrinolytic markers are associated with mortality and abnormal neuroimaging in children on ECMO. IMPACT: The inflammatory, endothelial activation, and fibrinolytic profile of children on ECMO differs by primary indication for extracorporeal support. Proinflammatory biomarkers on ECMO day 1 are associated with abnormal neurologic imaging in children on ECMO in univariable but not multivariable models. In multivariable models, a pronounced proinflammatory and prothrombotic biomarker profile on ECMO day 1 and longitudinally was significantly associated with mortality. Further studies are needed to identify inflammatory, endothelial, and fibrinolytic profiles associated with increased risk for neurologic injury and mortality through potential mediation of bleeding and thrombosis.

Sex specific correlation between GABAergic disruption in the dorsal hippocampus and flurothyl seizure susceptibility after neonatal hypoxic-ischemic brain injury.

Since neonatal hypoxia-ischemia (HI) disrupts the hippocampal (Hp) GABAergic network in the mouse and Hp injury in this model correlates with flurothyl seizure susceptibility only in male mice, we hypothesized that GABAergic disruption correlates with flurothyl seizure susceptibility in a sex-specific manner. C57BL6 mice were exposed to HI (Vannucci model) versus sham procedures at P10, randomized to normothermia (NT) or therapeutic hypothermia (TH), and subsequently underwent flurothyl seizure testing at P18. Only in male mice, Hp atrophy correlated with seizure susceptibility. The number of Hp parvalbumin positive interneurons (PV+INs) decreased after HI in both sexes, but TH attenuated this deficit only in females. In males only, seizure susceptibility directly correlated with the number of PV+INs, but not somatostatin or calretinin expressing INs. Hp GABAB receptor subunit levels were decreased after HI, but unrelated to later seizure susceptibility. In contrast, Hp GABAA receptor α1 subunit (GABAARα1) levels were increased after HI. Adjusting the number of PV+ INs for their GABAARα1 expression strengthened the correlation with seizure susceptibility in male mice. Thus, we identified a novel Hp sex-specific GABA-mediated mechanism of compensation after HI that correlates with flurothyl seizure susceptibility warranting further study to better understand potential clinical translation.

Predicting Recovery and Outcome after Pediatric Stroke: Results from the International Pediatric Stroke Study.

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.

Intrathecal chemotherapy-associated cerebral vasospasm in children with hematologic malignancies.

BACKGROUND: Mechanisms of chemotherapy-associated neurotoxicity are poorly understood, and therefore, prevention strategies have not been developed. We hypothesized that a subgroup of children receiving intrathecal cytarabine develops subclinical vasospasm, which may contribute to long-term neurocognitive sequelae of cancer. METHODS: We used transcranial Doppler ultrasound to serially evaluate cerebral blood flow velocities in participants ≤25 years old receiving intrathecal cytarabine for hematologic malignancies. RESULTS: Four of 18 participants (22%) met the criteria for subclinical vasospasm within 4 days of intrathecal cytarabine administration. The distribution of oncologic diagnoses differed between the vasospasm and non-vasospasm groups (p = 0.02). Acute myeloid leukemia was identified as a potential risk factor for vasospasm. Children with vasospasm were more likely to have received intravenous cytarabine (75% versus 0%, p = 0.01) and less likely to have received steroids (25% versus 100%, p = 0.01). CONCLUSIONS: A subpopulation of children with hematologic malignancies develops subclinical vasospasm after intrathecal cytarabine treatment. Future research is needed to determine the long-term clinical consequences of cerebral vasospasm in this population. IMPACT: A subset of children with hematologic malignancies who receive intrathecal cytarabine experience subclinical cerebral vasospasm, as measured by transcranial Doppler ultrasound. Of children receiving intrathecal cytarabine, those who develop cerebral vasospasm are more likely to have diagnosis of acute myeloid leukemia, more likely to receive concurrent intravenous cytarabine, and less likely to receive steroids as part of their chemotherapy regimen, as compared with children without vasospasm. Future research is needed to determine if vasospasm during chemotherapy is associated with higher rates of neurocognitive dysfunction, and if so, to focus on prevention of these long-term sequelae of childhood cancer.

Risk of Intracranial Hemorrhage Following Intravenous tPA (Tissue-Type Plasminogen Activator) for Acute Stroke Is Low in Children.

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.

Seizure Susceptibility Correlates with Brain Injury in Male Mice Treated with Hypothermia after Neonatal Hypoxia-Ischemia.

Hypoxic-ischemic encephalopathy is a common neonatal brain injury associated with significant morbidity and mortality despite the administration of therapeutic hypothermia (TH). Neonatal seizures and subsequent chronic epilepsy are frequent in this patient population and current treatments are partially effective. We used a neonatal murine hypoxia-ischemia (HI) model to test whether the severity of hippocampal and cortical injury predicts seizure susceptibility 8 days after HI and whether TH mitigates this susceptibility. HI at postnatal day 10 (P10) caused hippocampal injury not mitigated by TH in male or female pups. TH did not confer protection against flurothyl seizure susceptibility at P18 in this model. Hippocampal (R2 = 0.33, p = 0.001) and cortical (R2 = 0.33, p = 0.003) injury directly correlated with seizure susceptibility in male but not female pups. Thus, there are sex-specific consequences of neonatal HI on flurothyl seizure susceptibility in a murine neonatal HI model. Further studies are necessary to elucidate the underlying mechanisms of sex dimorphism in seizure susceptibility after neonatal HI.

Promoting Brain Repair and Regeneration After Stroke: a Plea for Cell-Based Therapies.

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: Epidemiology, risk factors, and management.

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.

Astrocyte-produced leukemia inhibitory factor expands the neural stem/progenitor pool following perinatal hypoxia-ischemia.

Brain injuries, such as cerebral hypoxia-ischemia (H-I), induce a regenerative response from the neural stem/progenitors (NSPs) of the subventricular zone (SVZ); however, the mechanisms that regulate this expansion have not yet been fully elucidated. The Notch- Delta-Serrate-Lag2 (DSL) signaling pathway is considered essential for the maintenance of neural stem cells, but it is not known if it is necessary for the expansion of the NSPs subsequent to perinatal H-I injury. Therefore, the aim of this study was to investigate whether this pathway contributes to NSP expansion in the SVZ after H-I and, if so, to establish whether this pathway is directly induced by H-I or regulated by paracrine factors. Here we report that Notch1 receptor induction and one of its ligands, Delta-like 1, precedes NSP expansion after perinatal H-I in P6 rat pups and that this increase occurs specifically in the most medial cell layers of the SVZ where the stem cells reside. Pharmacologically inhibiting Notch signaling in vivo diminished NSP expansion. With an in vitro model of H-I, Notch1 was not induced directly by hypoxia, but was stimulated by soluble factors, specifically leukemia inhibitory factor, produced by astrocytes within the SVZ. These data confirm the importance both of the Notch-DSL signaling pathway in the expansion of NSPs after H-I and in the role of the support cells in their niche. They further support the body of evidence that indicates that leukemia inhibitory factor is a key injury-induced cytokine that is stimulating the regenerative response of the NSPs. © 2016 Wiley Periodicals, Inc.

Molecular features of neural stem cells enable their enrichment using pharmacological inhibitors of survival-promoting kinases.

Isolating a pure population of neural stem cells (NSCs) has been difficult since no exclusive surface markers have been identified for panning or FACS purification. Moreover, additional refinements for maintaining NSCs in culture are required, since NSCs generate a variety of neural precursors (NPs) as they proliferate. Here, we demonstrate that post-natal rat NPs express low levels of pro-apoptotic molecules and resist phosphatidylinositol 3'OH kinase and extracellular regulated kinase 1/2 inhibition as compared to late oligodendrocyte progenitors. Furthermore, maintaining subventricular zone precursors in LY294002 and PD98059, inhibitors of PI3K and ERK1/2 signaling, eliminated lineage-restricted precursors as revealed by enrichment for Nestin(+)/SOX-2(+) cells. The cells that survived formed neurospheres and 89% of these neurospheres were tripotential, generating neurons, astrocytes, and oligodendrocytes. Without this enrichment step, less than 50% of the NPs were Nestin(+)/SOX-2(+) and 42% of the neurospheres were tripotential. In addition, neurospheres enriched using this procedure produced 3-times more secondary neurospheres, supporting the conclusion that this procedure enriches for NSCs. A number of genes that enhance survival were more highly expressed in neurospheres compared to late oligodendrocyte progenitors. Altogether, these studies demonstrate that primitive neural precursors can be enriched using a relatively simple and inexpensive means that will facilitate cell replacement strategies using stem cells as well as other studies whose goal is to reveal the fundamental properties of primitive neural precursors.

Pediatric hemiplegic migraine: role of multiple MRI techniques in evaluation of reversible hypoperfusion.

BACKGROUND: Hemiplegic migraine (HM) is a rare type of migraine with aura that involves motor weakness. Data on conventional and advanced neuroimaging findings during prolonged attacks of HM are limited, particularly in children. CASE: A 13-year-old-female with a history of migraine had a typical attack of HM characterized by right-sided hemiplegia, deterioration of vigilance and paraphasia. MRI performed 3 hours after hemiplegia onset revealed normal diffusion tensor imaging (DTI) sequences, but perfusion weighted imaging (PWI) showed a large area of hypoperfusion within the left cerebral hemisphere and susceptibility weighted imaging (SWI) demonstrated a matching area with prominent, hypointense draining sulcal veins. Magnetic resonance angiography (MRA) revealed subtle narrowing of the left middle cerebral artery. The neuroimaging abnormalities completely resolved 24 hours after the attack onset. CONCLUSION: Multiple conventional and advanced MRI techniques including SWI play a key role in an HM attack to (1) exclude acute arterial ischemic stroke and (2) further understand the pathophysiology of HM.

Neuroimaging findings in children with Keutel syndrome.

BACKGROUND: Keutel syndrome is a rare autosomal-recessive condition characterized by abnormal cartilage calcification. Neuroimaging findings associated with this condition have been randomly described in the literature. OBJECTIVE: To systematically evaluate the neuroimaging findings in a series of children with Keutel syndrome to broaden our base of knowledge. MATERIALS AND METHODS: Four children with confirmed Keutel syndrome were reviewed for the brain, head and neck imaging findings. RESULTS: Three of the four children, all siblings, showed evidence of moyamoya syndrome. All four siblings had pinna cartilage calcification. CONCLUSION: We propose that Keutel syndrome be considered and included among the secondary causes of moyamoya syndrome. In children with petrified auricle and neurological symptoms, Keutel syndrome should be considered and brain MRI with MRA is required.

An Initial Psychometric Evaluation of a Novel Upper Extremity Pediatric Stroke Hemiplegic Motor Impairment Scale.

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.

Neuroimaging and Neurological Outcomes in Perinatal Arterial Ischemic Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: Prediction of outcomes in perinatal arterial ischemic stroke (PAIS) is challenging. We performed a systematic review and meta-analysis to determine whether infarct characteristics can predict outcomes in PAIS. METHODS: A systematic search was conducted using five databases in January 2023. Studies were included if the sample included children with neonatal or presumed PAIS; if infarct size, location, or laterality was indicated; and if at least one motor, cognitive, or language outcome was reported. The level of evidence and risk of bias were evaluated using the Risk of Bias in Non-Randomized Studies of Interventions tool. Meta-analyses were conducted comparing infarct size or location with neurological outcomes when at least three studies could be analyzed. RESULTS: Eighteen full-text articles were included in a systematic review with nine included in meta-analysis. Meta-analyses revealed that small strokes were associated with a lower risk of cerebral palsy/hemiplegia compared with large strokes (risk ratio [RR] = 0.263, P = 0.001) and a lower risk of epilepsy (RR = 0.182, P < 0.001). Middle cerebral artery (MCA) infarcts were not associated with a significantly different risk of cerebral palsy/hemiplegia compared with non-MCA strokes (RR = 1.220, P = 0.337). Bilateral infarcts were associated with a 48% risk of cerebral palsy/hemiplegia, a 26% risk of epilepsy, and a 58% risk of cognitive impairment. CONCLUSIONS: Larger stroke size was associated with worse outcomes across multiple domains. Widely heterogeneous reporting of infarct characteristics and outcomes limits the comparison of studies and the analysis of outcomes. More consistent reporting of infarct characteristics and outcomes will be important to advance research in this field.

In Vivo Formation and Tracking of π-Peptide Nanostructures.

The photophysics associated with the self-assembly of π-peptide molecules into 1-D nanostructures has been well-established, thus revealing the creation of nanoscale electronic conduits in aqueous media. Such materials have therapeutic potential in many biomedical applications. In this work, we report the in vivo deployment of these π-peptide nanostructures in brain tissue using photothrombotic stroke as a model application. A test peptide was used for brain injections, and the nanostructures formed were visualized with electron microscopy. A new peptide bearing a low-energy fluorescence dye was prepared to facilitate direct visualization of π-peptide localization in the brain cavity by way of fluorescence microscopy. This work demonstrates feasibility for in vivo application of π-peptide nanostructures toward pressing biomedical challenges.

Consensus-Based Evaluation of Outcome Measures in Pediatric Stroke Care: A Toolkit.

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.