Pediatric Stroke Research Articles

Abstract WP225: Changes in Hemoglobin Levels During Vascular Events in Moyamoya Arteriopathy

Background: Anemia is a well-established risk factor for stroke in many populations. Recent data suggest that in patients with moyamoya arteriopathy (MMA), decrease in hemoglobin is associated with perioperative stroke. Evaluating the role of anemia in stroke pathogenesis outside of the perioperative period in MMA could aid in risk stratification and stroke prevention. Hypothesis: We hypothesized that patients with MMA have lower hemoglobin levels in the setting of vascular events compared to their pre-event baseline. Methods: In this retrospective self-controlled case series, we abstracted demographic and clinical data from patients < 40 years old with MMA cared for in our institution’s pediatric or young adult stroke clinics between 2003 and 2023. Laboratory data for each vascular event (stroke or TIA) were collected. The most recent laboratory data preceding events were also collected (baseline). Perioperative events (those occurring ≤7 days after revascularization) were excluded. Pre- and post-revascularization events were analyzed together and separately. Paired T-tests were used to compare baseline and vascular event hemoglobin values. Results: Eighty-nine (89) participants met inclusion criteria. There were 32 vascular events with corresponding baseline data available. There was no significant difference in hemoglobin between event and baseline values (11.2 v 11.3 g/dL, p = 0.87). However, among only pre-surgical events (n=20), hemoglobin was lower during events compared to baseline (10.4 v 11.5 g/dL, p=0.03). For events that occurred >7 days post-revascularization (n=12), hemoglobin was higher during events compared with baseline (12.6 v 10.9 g/dL, p=0.008). Conclusions: In our cohort of children and young adults with MMA, hemoglobin was lower than baseline during presurgical vascular events and higher than baseline during post-revascularization vascular events. Though further exploration with multivariate models is necessary, these preliminary data suggest that while anemia and dehydration may both increase the risk of stroke in MMA, the relative contributions of these stroke risk factors differ based on surgical status.

Abstract TMP9: Flair Vascular Hyperintensities as Imaging Biomarker in Pediatric Arterial Ischemic Stroke

Background: FLAIR vascular hyperintensities (FVH) are high signal intensities on MRI resulting from sluggish flow through collateral vessels in patients with acute arterial ischemic stroke (AIS). Data from adults suggest they may be a marker of penumbra. In this first investigation of FVH in children, I measured the prevalence and identified risk factors for FVH in pediatric patients with AIS. Methods: Retrospective review of patients prospectively enrolled in the CHOP Stroke Registry from 2006-2022. Patients with AIS age 29 days to 18 years with MRI within 72 hours of last known well were included. Children with pre-existing strokes, vasculopathy, prior brain surgery, radiation, or vascular compression from intracranial mass were excluded. MRIs were assessed by a blinded reviewer and adjudicated by a neuroradiologist for presence of LVO, FVH score, modASPECTS score, and AIS lesion volume. Clinical data were abstracted from chart review. Independent sample t-test compared FVH score and LVO presence. Pearson's correlation assessed the relationship between total FVH score and age, stroke size, modASPECTS, and pedNIHSS scores. Multivariable logistic regression evaluated predictors of significant FVH (score >= 3) and included time to MRI, large vessel occlusion, modASPECTS, pedNIHSS, stroke size, and age as independent variables. Results: 83 patients met inclusion criteria. Median time to MRI was 26 hours (95% CI 26-33). FVH were present in 45 patients (54%). Mean FVH score was higher in patients with LVO (5.22 ± 0.64) compared to those without (1.21 ± 0.24; p = 0.00). There was a positive correlation between total FVH score and age (p < 0.05), stroke size (p < 0.0001), modASPECTS (p < 0.0000), and pedNIHSS (p < 0.0002). In the multivariate logistic regression, only older age (OR 1.50, 95% CI 1.12-2.01, p < 0.006) and presence of LVO (OR 0.002, 95% CI 4.85x10 -5 -0.08, p<0.001) were associated with significantly increased odds of high FVH burden. Conclusions: FVH are prevalent in children with AIS, with higher burden in older children. Similar to adults, large vessel occlusion and larger infarct size are associated with higher FVH burden. Further study is needed on whether FVH could be used to identify patients who would benefit from reperfusion therapies.

Abstract 109: Towards Individualised Prediction of Neurodevelopmental Outcomes After Neonatal Stroke: A Brain Lesion Network Mapping Study Leveraging Large-Scale Datasets

Introduction: Prediction of adverse neurodevelopmental outcomes after neonatal arterial ischemic stroke (NAIS) is challenging. We identified brain regions functionally connected to stroke lesions (lesion networks), and investigated whether such lesion networks are related to the development of cerebral palsy (CP) after NAIS. Methods: We performed a novel lesion network mapping approach, involving: 1. Creation of a normative connectome using the developing Human Connectome Project (dHCP) dataset. Resting state functional magnetic resonance imaging (MRI) scans of 518 neonates born at term (>36 weeks) from the dHCP were aligned to a template, built from T 2 -weighted scans of the same neonates; 2. Manual segmentation of lesions using diffusion MRI scans of 85 term-born neonates with NAIS, who were identified from Australian and Swiss pediatric stroke registries. Lesion masks were aligned to the template; 3. Construction of lesion network maps, by computing functional correlations between lesion masks and other brain grey matter regions, making use of the normative connectome; 4. Investigation of relationships between lesion networks and CP, diagnosed by clinical examination at least 18 months after NAIS. Lesion network maps were compared between those who did (n=28) and did not (n=57) develop CP after NAIS, with two sample t-tests. Results: In participants who developed CP after NAIS, lesions were more strongly functionally connected to the following regions: frontal (inferior and orbital frontal), temporal (pole, superior, and mesial temporal), insula, basal ganglia, thalamus and cerebellum (Figure 1). Conclusions: Leveraging large-scale datasets and innovative connectomic methods, we uncovered brain networks related to adverse outcomes after NAIS. This provided novel findings compared to past methods such as voxel-based lesion-symptom mapping. Our results point to differences in network vulnerabilities after stroke in neonates compared to adults.

Abstract WP220: Structural Connectivity Injury is Associated With Poor Language Outcomes in Perinatal Stroke

Introduction: Perinatal stroke refers to brain injury sustained between 28 weeks of gestational age (GA) and 28 days of life. Stroke risk in the newborn period is significantly higher relative to other life stages, and over half of all survivors endure lifelong neurological sequalae. Language deficits are observed in many patients, can emerge at any stage in development, and are difficult to predict. Lesion laterality and location are not sufficient to explain language outcomes in a rapidly developing brain with capacities for reassignment of functions to non-injured structures. Structural connectivity studies describe a “rich club” organization of the brain with 6 bilateral highly connected anatomical structures that form the information backbone for all networks. This organization has been found to exist as early as 30 weeks GA. The effects of injury to this rich club have been studied in adult stroke patients with respect to stroke severity and outcome. Given that language is a network function, we hypothesized that injury to rich club regions - a measure of structural network disruption - is associated with poor language outcomes in perinatal stroke. Methods: Retrospective study that identified perinatal stroke patients in a pediatric stroke clinic database. Clinical and imaging data retrieved included brain MRI scans and longitudinal scores of standardized neuropsychological tests. Multiple linear regression models were created for the following variables: age, sex, Autism Spectrum Disorder diagnosis, lesion volume (cm 3 ), and number of rich clubs affected by the stroke. All analyses were conducted using the computing environment R. Significance was set at p < 0.05. Results: Cohort of 75 patients was identified. Median time to follow up was 7 years, and median time between the first and last test was 30 months. Lesion volume significantly influenced receptive language outcomes at younger ages (beta = -0.446), however the number of rich clubs affected by the injury was the only significant variable associated with a poor expressive language outcome at follow-up (beta = -0.699). Discussion: Number of rich clubs affected by injury, as a global measure of structural network disruption in the neonatal period, can be used to inform language outcome prognostication.

Etiology and Risk Factors for Strokes in the Pediatric Population

Pediatric arterial ischemic stroke (AIS) and hemorrhagic stroke represent a relatively uncommon yet significant source of neurological challenges for neonates and children, resulting in outcomes such as hemiparesis, intellectual disabilities, and epilepsy. The etiology of pediatric strokes differs from the typical causes seen in adult stroke cases. Therefore, understanding the specific risk factors associated with strokes in children is crucial for facilitating early diagnosis, which regrettably remains frequently delayed. AIS incidence varies due to factors such as patient age, types of cerebral vascular diseases, other chronic conditions and geographic location. In this comprehensive review, we delve into the epidemiology, clinical manifestation and risk factors linked to arterial ischemic stroke and hemorrhagic stroke in neonates and children.

A Review of an Interfacility Transport Program Pediatric Stroke Clinical Practice Guideline.

Pediatric acute ischemic stroke is a rare diagnosis that requires timely recognition and definitive management to prevent morbidity and mortality. Children often present to primary care offices, urgent care clinics, and adult emergency departments for evaluation of symptoms that may be signs and symptoms of stroke. Currently, there are no published prehospital or transport protocols specific to pediatric acute ischemic stroke. The Children's Mercy Hospital Critical Care Transport Team (CMCCT) created a pediatric-specific clinical practice guideline (CPG) for suspected acute ischemic stroke. This retrospective, descriptive study reports pediatric patients aged younger than 18 years who met criteria for the pediatric stroke CPG and required interfacility transport by CMCCT over a 4- year period. Large vessel occlusion (LVO) scores used in adults were calculated retrospectively. Seventeen patients met inclusion criteria. Four (24%) of 17 had radiographic evidence of acute thrombus, 3 of whom received alteplase and/or endovascular clot retrieval. Median age of confirmed stroke was 83 months (interquartile range, 65-148) compared with 177 months for nonstroke (interquartile range, 169-191), P = 0.126. The most common presenting symptom was hemiplegia in the confirmed stroke group. The confirmed stroke group scored significantly lower on the Glasgow Coma Scale (median of 8 vs 15, P = 0.014), significantly higher on the Los Angeles Motor Scale LVO score (median 4 vs 0, P = 0.021), and significantly higher on the Rapid Arterial Occlusion Evaluation LVO (median 4 vs 0, P = 0.036). To our knowledge, the CMCCT CPG is the first pediatric transport protocol aimed at recognition and management of pediatric stroke described in the literature. Retrospective calculation of LVO scores show that they may be helpful in application to pediatric patients.

Systematic Review and Case of Thrombectomy for Pediatric Stroke Due to Myxoma Embolism

BackgroundStroke presentation secondary to a cardiac myxoma thromboembolism are rare in the pediatric population. Because of its rarity, the reported cases in the literature are primarily case reports. Additionally, general pediatric stroke management lacks evidence-based guidelines because of its low incidence and lack of clinical trials. In pediatric strokes identified from a cardiac myxoma, the incidence favors boys with classical presentation of unilateral weakness and aphasia. We present a pediatric patient who presented with stroke-like symptoms secondary to an intracranial embolus from a previously undiagnosed cardiac myxoma. MethodsWe performed a systematic review by searching PubMed, Google Scholar, Web of Science, and Embase databases for cases of pediatric myxoma causing stroke (n=2431) and identified 19 reported uses of surgical management in treating pediatric patients who present with stroke symptoms secondary to a cardiac myxoma thromboembolism. ResultsThe most common imaging modality was MRI in 42% of cases, CT in 36.8%, followed by CTA in 31.6% of cases. Of these 19 children treated with procedures, 36.8% of pediatric patients aged between 4 and 14 years underwent neurosurgery (n=7). ConclusionsWe describe an urgent mechanical thrombectomy, share preoperative and postoperative images and pathology slides confirming a stroke from myxoma origin. We provide added insight in the safe use of mechanical thrombectomy as treatment for pediatric strokes secondary to a thromboembolism.

A Review of Current Perspectives on Motoric Insufficiency Rehabilitation following Pediatric Stroke.

Pediatric stroke (PS) is an injury caused by the occlusion or rupture of a blood vessel in the central nervous system (CNS) of children, before or after birth. Hemiparesis is the most common motoric deficit associated with PS in children. Therefore, it is important to emphasize that PS is a significant challenge for rehabilitation, especially since the consequences may also appear during the child's growth and development, reducing functional capacity. The plasticity of the child's CNS is an important predecessor of recovery, but disruption of the neural network, specific to an immature brain, can have harmful and potentially devastating consequences. In this review, we summarize the complexity of the consequences associated with PS and the possibilities and role of modern rehabilitation. An analysis of the current literature reveals that Constraint-Induced Movement Therapy, forced-use therapy, repetitive transcranial magnetic stimulation, functional electrical stimulation and robot-assisted therapy have demonstrated at least partial improvements in motor domains related to hemiparesis or hemiplegia caused by PS, but they are supported with different levels of evidence. Due to the lack of randomized controlled studies, the optimal rehabilitation treatment is still debatable, and therefore, most recommendations are primarily based on expert consensuses, opinions and an insufficient level of evidence.

Factors Associated with Pathway-Concordant Neuroimaging for Pediatric Ischemic Stroke

ObjectiveTo determine factors associated with magnetic resonance imaging (MRI) and non-invasive diagnostic angiography among children presenting to the emergency department (ED) with acute ischemic stroke. Study DesignWe performed a cross-sectional study using data from >50 US children’s hospitals. We included children 29 days through 17 years old hospitalized from the ED with an International Classification of Disease, 10th revision, diagnosis code for acute ischemic stroke between October 1, 2015, and November 30, 2022. We excluded children with a principal diagnosis code of trauma/external injury, without neuroimaging on day of presentation, and into-ED transfers. Our outcomes were defined as acquisition of MRI (versus computed tomography only) and angiography (versus no angiography) on day of presentation. We performed generalized linear mixed modeling with hospital as a random effect to determine the association of demographics, known comorbidities, and treatment factors with each outcome. ResultsWe included 1,601 children. In multivariable analysis, younger age, mechanical ventilation, and Black race were associated with lower odds of MRI acquisition, while history of moyamoya disease and sickle cell disease were associated with higher odds. Younger age, mechanical ventilation, Hispanic ethnicity, Black race, other races, history of metabolic disease, and history of seizures were associated with lower odds of angiography. ConclusionsYounger and non-White children experienced lower odds of MRI and angiography, which may be driven by health system limitations or provider implicit biases or both. Our results expose risk factors for underdiagnosis of ischemic stroke and provide opportunities to tailor institutional pathways reflective of underlying pathophysiology.

Intravenous Thrombolysis for Pediatric Ischemic Stroke Secondary to Cancer Therapy-related Cardiac Dysfunction: A Case Report.

An 11-year-old boy developed cardioembolic stroke (CES) and cancer therapy-related cardiac dysfunction (CTRCD). He originally developed Ewing sarcoma and was treated with high-dose chemotherapy including doxorubicin. On admission, he had severe aphasia, and magnetic resonance imaging showed occlusion of the left middle cerebral artery M3 segment. Transthoracic echocardiography revealed severe left ventricular dysfunction and a mobile thrombus at the left ventricular apex. Intravenous thrombolysis was administered, and effective recanalization was achieved. The patient did not exhibit any neurological deficits during discharge. Reperfusion therapy for pediatric patients has not yet been established; however, it may be effective for CES secondary to CTRCD.

A scoping review of cerebral reperfusion therapies in childhood and adolescence with arterial ischemic stroke

AbstractBackgroundManagement of pediatric stroke is challenging because of the paucity of data supporting the efficacy of interventions. This scoping review details the treatments available for the acute phase of stroke in pediatric patients with arterial ischemic stroke.Summary of ReviewOverall, 68 relevant articles were published between 2001 and 2023. The primary study included 48 case reports (n = 48). Eleven articles reported the use of intravenous thrombolysis (IVT) with alteplase, eight used intra‐arterial (IA) alteplase, and 52 reported mechanical thrombectomy (MT). IVT was administered to 195 patients with a median of 5.5 h of stroke onset, and only four (2.0%) had intracranial hemorrhage after alteplase treatment. Of the 11 articles, nine used 0.9 mg/kg IVT administered as a 10% bolus, with the remaining 90% administered over one hour, and one study used 0.54 mg/kg. IA was performed in 17 patients with a median of 5.05 h of stroke onset, and three individuals (17.6%) had intracranial hemorrhage. Of the eight reports that document IA, two used 0.9 mg/kg; one each used 0.16 mg/kg, 0.1 mg/kg, 0.6 mg/kg, 100 mg/day, and 10 mg/day; and one article documented the use of urokinase 750 000 IU. MT was used in 434 and 215 individuals in a previous systematic review, with a median of 11.82 h of stroke onset, and only 2.9% had intracranial hemorrhage after the treatment. Stent retrievers were used in 33 reports (63.5%) and aspiration retrievers were mentioned in 15 articles (28.8%). Overall, the outcomes ranged from complete to moderate recovery for all modalities.ConclusionsIVT and MT are safer than IA; however, despite the lack of clinical trials, all modalities seem effective in improving clinical recovery. To guide clinical practice and determine better intervention modalities, clinicians should note the key messages from this review, such as using magnetic resonance imaging in the acute phase and identifying key risk factors and presenting symptoms.

Sickle Cell Disease and Other Risk Factors for Pediatric Arterial Ischemic Stroke: A Systematic Review and Meta-Analysis

Purpose: The incidence and mortality rates of arterial ischemic stroke (AIS) among pediatric patients have been frequently reported. While pediatric stroke can have multiple severe effects, its risk factors have not been methodically examined. This systematic review and meta-analysis were completed to summarize the existing evidence regarding risk factors for AIS in pediatric patients.Methods: To gather relevant articles published in the past 15 years, searches were conducted of PubMed and Scopus. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) were analyzed using Review Manager 5.4.Results: From the initial screening of 507 articles, five articles comprising a total of 1,423 participants were selected for qualitative analysis. Two of these additionally underwent quantitative analysis. Among the total participants, 1,108 children with AIS (77.9%) had arteriopathy as the underlying disease. Types of arteriopathy included moyamoya disease (24.28%), arterial dissection (23.29%), focal cerebral arteriopathy (16.16%), and vasculitis (14.71%). The meta-analysis revealed that being between 6 and 9 years of age (OR, 2.19; 95% CI, 1.76 to 2.73; <i>P</i><0.00001) and having sickle cell disease (OR, 3.46; 95% CI, 2.38 to 5.05; <i>P</i><0.00001) were associated with arteriopathy in pediatric AIS.Conclusion: Arteriopathy is the most common risk factor for AIS in pediatric patients, and in turn, an age of 6 to 9 years and sickle cell disease are risk factors for arteriopathy within this demographic.

Brain injury and neurodevelopmental outcomes in children undergoing surgery for congenital heart disease

ObjectivesBrain injury is commonly seen on magnetic resonance imaging in infants with complex congenital heart disease. The impact of perioperative brain injury on neurodevelopmental outcomes is not well understood. We evaluate the association of brain injury and other markers on neurodevelopmental outcomes in patients undergoing surgery for congenital heart surgery during infancy. MethodsTerm newborns with infant cardiac surgery performed between 2008 and 2019 at a single tertiary center, and both preoperative and postoperative brain magnetic resonance imaging were included. Those with underlying genetic conditions were excluded. Brain injury was characterized using an magnetic resonance imaging scoring system. Neurodevelopmental outcomes were assigned using the Pediatric Stroke Outcome Measure and Glasgow Outcome Scale Extended. Independent risk factors for poor neurodevelopmental outcomes were determined by multivariable Cox regression. ResultsA total of 122 patients were included. New or progressive postoperative brain injury was noted in 69 patients (57%). A total of 101 patients (83%) had at least 1 neurodevelopmental assessment (median age 36 months) with an early assessment (5-24 months) performed in 95 children. Multivariable Cox regression analysis of early neurodevelopmental outcomes identified new stroke on postoperative magnetic resonance imaging to be an independent predictor of poor neurodevelopmental outcome. Postoperative peak lactate was an independent predictor of poor outcome assessed by the Pediatric Stroke Outcome Measure and Glasgow Outcome Scale Extended. ConclusionsOur study reveals that evidence of new stroke on magnetic resonance imaging after infant congenital heart surgery is a predictor of poor neurodevelopmental outcomes in early childhood. Postoperative lactic acidosis is associated with poor neurodevelopmental outcome and may be a surrogate biomarker for ischemic brain injury.

Imaging of Vertebral Artery Dissection in Children: An Underrecognized Condition with High Risk of Recurrent Stroke.

Vertebral artery dissection (VAD) is a common cause of a rare condition, pediatric posterior circulation arterial ischemic stroke (PCAIS). VAD is clinically important due to the risk of multifocal and continuing infarcts from artery-to-artery thromboembolism, with the potential for occlusion of arteries that perfuse the brainstem. Early diagnosis is important, as recurrent stroke is a common effect of VAD in children. Although the relative efficacies of different treatment regimens for VAD in children remain unsettled, early initiation of treatment can mitigate the risk of delayed stroke. Clinical diagnosis of PCAIS may be delayed due to multiple factors, including nonspecific symptoms and the inability of younger patients to express symptoms. In fact, subacute or chronic infarcts are often present at initial imaging. Although the most common cause of isolated PCAIS is VAD, imaging of the cervical arteries has been historically underused in this setting. Cervical vascular imaging (MR angiography, CT angiography, and digital subtraction angiography) for VAD must be optimized to detect the sometimes subtle findings, which may be identified at initial or follow-up imaging. Osseous variants of the craniocervical junction and upper cervical spine and other extrinsic lesions that may directly injure the vertebral arteries or lead to altered biomechanics have been implicated in some cases. The authors review characteristic imaging features and optimized imaging of VAD and associated PCAIS and related clinical considerations. Identification of VAD has important implications for evaluation, treatment, and imaging follow-up, as this condition may result in progressive arteriopathy and recurrent stroke. © RSNA, 2023 Supplemental material is available for this article. Quiz questions for this article are available through the Online Learning Center.

Paediatric ischaemic stroke – recommended interventions and outcome markers

Paediatric ischaemic stroke – recommended interventions and outcome markers

Machine Learning Model for Predicting Mortality Risk in Pediatric Cerebral Venous Sinus Thrombosis

Introduction: Pediatric Cerebral Venous Sinus Thrombosis (CVST) is a rare but serious disorder with risk for neurologic sequelae and mortality. Prediction of health outcomes for risk stratification and tailored therapy is difficult based on available literature with single center studies and limited sample sizes. We sought to analyze the CVST data in Pediatric Health Information System (PHIS) database, a large, multicenter administrative database of pediatric inpatient data, to assess if supervised machine learning can assist in identifying pediatric CVST patients with increased risk of adverse outcomes. Methods: Patients 0 to 17 years of age with a diagnosis of CVST were identified in the PHIS database from 2011 to 2022. Demographic information, clinical characteristics, evaluation and management, and outcome data was extracted from diagnostic, imaging, procedure, and pharmaceutical billing codes. An XGBOOST model was fitted using 10-fold cross-validation with Bayesian optimization for hyperparameter tuning. The clinical parameters with values optimal for analysis from the “early era” (2011-2015) dataset were used to train for machine learning, and the test was applied to the “late era” (2016-2022) dataset. The final model was chosen based on the highest test set AUC score. The clinical parameters with significant SHAP values from the model were compared to published risk factors for mortality from an International Pediatric Stroke Study (IPSS) (RN Ichord, et al. Arch Dis Child 2015). Results: 6080 hospitalizations with CVST diagnosis (0.1% of all hospitalizations) were identified. The clinical parameters applied for machine learning included the following: age, gender, race, major complications (intracranial bleeding, hydrocephalus, coma), child opportunity index and ICU admission (Table 1.). The overall mortality rate at discharge was 4.2%. 2029 hospitalizations occurred in the early era and 4051 hospital admissions occurred in the late era. With the analyzable clinical parameters, the XGBOOST model could predict mortality with a probability of 0.7906. Of the clinical parameters used for machine learning (Figure 1), ICU admission, intracranial bleeding, hydrocephalus and coma had positive SHAP values indicating higher mortality risk prediction, whereas older age and being non-Hispanic white had negative SHAP values indicating lower mortality risk prediction. Similar risk associations for mortality were reported in the IPSS study, with patients with intracranial bleeding, younger age, and coma having higher mortality risk, consistent with our study finding. Conclusion: Our study in pediatric CVST, using machine learning, shows higher risk of mortality with ICU admission, and complications including intracranial bleeding, hydrocephalus, and coma; and lower risk of mortality with older age and non-Hispanic White status, which are consistent with IPSS study observations. Our study also illustrates how machine learning can be utilized by investigators to predict adverse clinical outcomes in pediatric CVST. In rare diseases which are difficult to study due to limited sample sizes like pediatric CVST, our study shows that data from large databases such as PHIS can be utilized for machine learning to predict health care outcomes, which can in turn inform future clinical practice to improve patient outcome.

Utilization of Early Intervention Among Children with Sickle Cell Disease

Background: The most prevalent monogenic disorder among children is sickle cell disease (SCD). SCD is the most common cause of pediatric stroke and is primarily inherited by people that identify as Black or of African descent. 1,2 Children with SCD have an elevated risk for delayed development and poor academic outcomes. 2 Our previous findings identified that 50% of children with SCD have a developmental delay, however, <5% were receiving therapy services. 3-5 Home-based programs have ameliorated cognitive and language delays in children with SCD. 6 In the United States, home-based therapy services (e.g., occupational, physical, and speech therapy) are provided through a federally mandated program called Early Intervention for free or reduced cost for children with developmental delay <3 years of age. 7 Unfortunately, this program is underutilized, especially in underserved and minoritized communities, with as few as 2% of eligible children receiving services. 8,9 Hematologists, who are tasked with providing ongoing medical care for young children with SCD, often lack the resources/tools needed to incorporate developmental screening into standard care. Thus, early indicators of developmental delay remain undetected and untreated, costing children and families precious time to intervene early. 6,10,11 This study aimed to assess the use of early intervention and determinants affecting participation in developmental screening and intervention among caregivers of children 0-4 years of age with SCD. Methods: We recruited caregivers with children under 4 years of age with SCD from clinics in St. Louis, Missouri and Memphis, Tennessee. Semi-structured interviews based on the Reach-Effectiveness-Adoption-Implementation-Maintenance (RE-AIM) framework were used to describe determinants for referral success and describe the mechanisms (barriers and facilitators) that influence early intervention program utilization. 12 Interviews included open-ended to address topics related to reach, perceived effectiveness, and likelihood of adoption of early intervention if recommended. Additional questions assessed caregiver knowledge of developmental delays in SCD and utilization of screening and intervention. Results: Among 127 caregivers identified as eligible, 47 consented and 20 completed an interview between September 2022 and February 2023. Similar to prior studies, over half of caregivers reported living in a low-income household, over half of children had hemoglobin SS and all participants identified as Black or African American. Interviews lasted between 15-75 minutes (mean = 34). Three themes emerged from the data including 1) Caregivers have not been informed about elevated risk for developmental delay, 2) Caregivers prioritize connecting with their provider and 3) Caregivers had not been adequately informed about early intervention services (Table 1). Conclusions: This study highlights the low utilization of early intervention services for young children with SCD. Caregivers expressed frustration with the lack of awareness regarding the elevated risk for developmental delays and prioritize that information coming from their specialty providers (e.g., sickle cell clinic). Additionally, inadequate information about available services contributes to underutilization. As healthcare providers, we are tasked with increasing awareness about the associated risks of SCD, integrating developmental screening into standard care, and providing caregivers with information that could improve developmental outcomes for children with SCD.

Tenecteplase in Pediatric Stroke: Ready or Not

BackgroundIntravenous thrombolysis with tissue plasminogen activator is used for off-label treatment of acute childhood stroke. Tenecteplase (TNK) is used to treat acute stroke in adults at many institutions, although there are extremely few data about TNK use in children. We aimed to characterize pediatric stroke experts’ experience and preferences with regard to TNK use in children with stroke. MethodsOnline survey distributed to members of the International Pediatric Stroke Organization in April 2023. ResultsWe received 33 responses. Most (81.2%) respondents reported only being “a little familiar” or “somewhat familiar” with TNK. Only six (18%) respondents reported being “familiar” or “very familiar” with TNK. Seventy percent of respondents were willing to treat pediatric stroke with TNK, at least in some situations. In a hypothetical scenario of a child in an outside emergency room with only TNK available, 81.8% would consider recommending treatment with TNK. However, only three (9.1%) respondents had TNK in their stroke protocol and seven (21.2%) had TNK on formulary at their hospital. Two respondents reported direct awareness of a child treated with TNK. ConclusionsThe majority of pediatric stroke neurologists responding to this survey reported a willingness to consider TNK use in children. However, data on TNK use in children, provider experience, and pediatric hospital preparedness are limited.

Abstract 17479: Angiographic Factors Influencing Treatment Decisions in Pediatric Brain Arteriovenous Malformation (pAVM): Insights From Cart Analysis

Introduction: Pediatric cerebral AVM (pAVM) are the most common cause of hemorrhagic stroke in children. Their optimal management approach remains controversial. Determining the angiographic factors that impact outcomes for the various treatment strategies is crucial. Hypothesis: To identify angiographic factors for modality-treatment decision-making Methods: Cross-sectional study of patients diagnosed with pAVM at a pediatric stroke center between 2016 and 2021. Patients’ demographics, angiographic characteristics (volume, location, nidal aneurysms, non-plexiform rapid fistulas, venous drainage, and nidus diffuseness), treatment, and clinical outcomes were collected. Classification and Regression Tree Analysis (CART) was used to identify impactful angiographic factors, multivariate regression was applied to evaluate their significance in treatment decision-making. Results: Thirty-seven consecutive patients were included, 25 were male, with a median age of 10.3 years (IQR 7.9-13.3). Median follow-up was 30.3 months (IQR 8.6-53.8). Twenty patients presented with a ruptured pAVM. Endovascular embolization was the most common treatment (19, 51.4%), followed by radiosurgery (14, 37.8%), and observation (8, 21.6%). Twenty-seven patients (81.8%) had improved or stable functional neurologic status at last follow-up, and six (18.2%) declined (none of them by more than one point on the mRS). Only one patient had post-treatment hemorrhage during follow-up.The angiographic features associated with specific treatments were: the presence of non-plexiform rapid fistulas (endovascular in 94.0% of patients p=0.01), basal ganglia or pons location (excluded from endovascular in 86% of patients p=0.30), absence of a nidal aneurysm (radiation in 98% p=0.03). CART did not identify other potentially impactful angiographic factors. Conclusions: Our study shows generally favorable outcomes and low complication rates in pAVM patients who underwent multimodal treatment. The presence of non-plexiform rapid fistulas and nidal aneurysms should be considered when determining the appropriate treatment approach. Further prospective confirmatory analyses are warranted.

1 Predictors of Neurocognitive Outcome in Pediatric Ischemic and Hemorrhagic Stroke

Objective:Neurocognitive deficits commonly occur following pediatric stroke and can impact many neuropsychological domains. Despite awareness of these deleterious effects, neurocognitive outcome after pediatric stroke, especially hemorrhagic stroke, is understudied. This clinical study aimed to elucidate the impact of eight factors identified in the scientific literature as possible predictors of neurocognitive outcome following pediatric stroke: age at stroke, stroke type (i.e., ischemic vs. hemorrhagic), lesion size, lesion location (i.e., brain region, structures impacted, and laterality), time since stroke, neurologic severity, seizures post-stroke, and socioeconomic status.Participants and Methods:Ninety-two patients, ages six to 25 and with a history of pediatric stroke, chose to participate in the study and were administered standardized neuropsychological tests assessing verbal reasoning, abstract reasoning, working memory, processing speed, attention, learning ability, long-term memory, and visuomotor integration. A standardized parent questionnaire provided an estimate of executive functioning. Statistical analyses included spline regressions to examine the impact of age at stroke and lesion size, further divided by stroke type; a series of one-way analysis of variance to examine differences in variables with three levels; Welch’s t-tests to examine dichotomous variables; and simple linear regressions for continuous variables.Results:Lesion size, stroke type, age at stroke, and socioeconomic status were identified as predictors of neurocognitive outcome in our sample. Large lesions were associated with worse neurocognitive outcomes compared to small to medium lesions across neurocognitive domains. Exploratory spline regressions suggested that ischemic stroke was associated with worse neurocognitive outcomes than hemorrhagic stroke. Based on patterns shown in graphs, age at stroke appeared to have an impact on outcome depending on the neurocognitive domain and stroke type, with U-shaped trends suggesting worse outcome across most domains when stroke occurred at approximately 5 to 10 years of age. Socioeconomic status positively predicted outcomes across most neurocognitive domains. Participants with seizures had more severe executive functioning impairments than youth without seizures. Youth with combined cortical-subcortical lesions scored lower on abstract reasoning than youth with cortical and youth with subcortical lesions, and lower on attention than youth with cortical lesions. Neurologic severity predicted scores on abstract reasoning, attention, processing speed, and visuomotor integration, depending on stroke type. There was no evidence of differences on outcome measures based on time since stroke, lesion laterality, or lesion region defined as supra-versus infratentorial.Conclusions:The current study contributed to the scientific literature by identifying lesion size, stroke type, age at stroke, and socioeconomic status as predictors of neurocognitive outcome following pediatric stroke. Future research should examine other possible predictors of neurocognitive outcome that remain unexplored. Multisite collaborations would provide larger sample sizes and allow teams to build models with better statistical power and more predictors. Enhancing understanding of neurocognitive outcomes following pediatric stroke is a first step towards improving appraisals of prognosis.Findings are clinically applicable as they provide professionals with information that can help assess individual expected patterns of recovery and thus refer patients to appropriate support services.