Long-term clinical and radiological trajectories of craniocervical vasculopathy in children with PHACE syndrome.

AIM: To describe the rates of stroke and craniocervical vasculopathy progression in children with posterior fossa malformations, hemangioma, arterial anomalies, coarctation of the aorta/cardiac defects, and eye abnormalities (PHACE) syndrome. METHOD: A single-center, retrospective natural history study of children with PHACE syndrome. Clinical and sequential neuroimaging data were reviewed to study the characteristics and progression of vasculopathy and calculate the rates of arterial ischemic stroke (AIS) and transient ischemic stroke (TIA). Vasculopathy progression was defined as worsening or new vascular findings on follow-up magnetic resonance angiography. RESULTS: Thirty-four children with cerebrovascular abnormalities at the PHACE syndrome diagnosis were studied (age range = 2 to 18 years, 85% females). Median age at the initial diagnosis was 5.5 months (interquartile range = 1-52 months); median age at the last follow-up was 8 years 6 months (range = 2-18 years). Overall, 10 (29%) patients had radiological progression of their vasculopathy, with a cumulative progression-free rate of 73% (95% confidence interval [CI] = 0.57-0.89), and a cumulative TIA-free and AIS-free rate of 87% (95% CI = 0.745-0.99). Vasculopathy was continuously progressive in six patients (18%) at the last follow-up. Three patients (9%) had TIA and all had progressive vasculopathy. One patient had presumed perinatal AIS at the initial PHACE diagnosis, while no other patient experienced an AIS during the follow-up. INTERPRETATION: In children with PHACE syndrome, craniocervical vasculopathy is non-progressive and asymptomatic in the majority of cases. The risk of ischemic stroke in these children is very low. Larger and prospective studies are necessary to confirm these findings.

Health Inequity and Time From Pediatric Stroke Onset to Arrival.

BACKGROUND: Time from stroke onset to hospital arrival determines treatment and impacts outcome. Structural, socioeconomic, and environmental factors are associated with health inequity and onset-to-arrival in adult stroke. We aimed to assess the association between health inequity and onset-to-arrival in a pediatric comprehensive stroke center. METHODS: A retrospective observational study was conducted on a consecutive cohort of children (>28 days-18 years) diagnosed with acute arterial ischemic stroke (AIS) between 2004 and 2019. Neighborhood-level material deprivation was derived from residential postal codes and used as a proxy measure for health inequity. Patients were stratified by level of neighborhood-level material deprivation, and onset-to-arrival was categorized into 3 groups: <6, 6 to 24, and >24 hours. Association between neighborhood-level material deprivation and onset-to-arrival was assessed in multivariable ordinal logistic regression analyses adjusting for sociodemographic and clinical factors. RESULTS: Two hundred and twenty-nine children were included (61% male; median age [interquartile range] at stroke diagnosis 5.8-years [1.1-11.3]). Over the 16-year study period, there was an increase in proportion of children diagnosed with AIS living in the most deprived neighborhoods and arriving at the emergency room within 6 hours (P=0.01). Among Asian patients, a higher proportion lived in the most deprived neighborhoods (P=0.02) and level of material deprivation was associated with AIS risk factors (P=0.001). CONCLUSIONS: Our study suggests an increase in pediatric stroke in deprived neighborhoods and certain communities, and earlier arrival times to the emergency room over time. However, whether these changes are due to an increase in incidence of childhood AIS or increased awareness and diagnosis is yet to be determined. The association between AIS risk factors and material deprivation highlights the intersectionality of clinical factors and social determinants of health. Finally, whether material deprivation impacts onset-to-arrival is likely complex and requires further examination.

The development of the pediatric stroke neuroimaging platform (PEDSNIP).

Childhood stroke occurs from birth to 18 years of age, ranks among the top ten childhood causes of death, and leaves lifelong neurological impairments. Arterial ischemic stroke in infancy and childhood occurs due to arterial occlusion in the brain, resulting in a focal lesion. Our understanding of mechanisms of injury and repair associated with focal injury in the developing brain remains rudimentary. Neuroimaging can reveal important insights into these mechanisms. In adult stroke population, multi-center neuroimaging studies are common and have accelerated the translation process leading to improvements in treatment and outcome. These studies are centered on the growing evidence that neuroimaging measures and other biomarkers (e.g., from blood and cerebrospinal fluid) can enhance our understanding of mechanisms of risk and injury and be used as complementary outcome markers. These factors have yet to be studied in pediatric stroke because most neuroimaging studies in this population have been conducted in single-centred, small cohorts. By pooling neuroimaging data across multiple sites, larger cohorts of patients can significantly boost study feasibility and power in elucidating mechanisms of brain injury, repair and outcomes. These aims are particularly relevant in pediatric stroke because of the decreased incidence rates and the lack of mechanism-targeted trials. Toward these aims, we developed the Pediatric Stroke Neuroimaging Platform (PEDSNIP) in 2015, funded by The Brain Canada Platform Support Grant, to focus on three identified neuroimaging priorities. These were: developing and harmonizing multisite clinical protocols, creating the infrastructure and methods to import, store and organize the large clinical neuroimaging dataset from multiple sites through the International Pediatric Stroke Study (IPSS), and enabling central searchability. To do this, developed a two-pronged approach that included building 1) A Clinical-MRI Data Repository (standard of care imaging) linked to clinical data and longitudinal outcomes and 2) A Research-MRI neuroimaging data set acquired through our extensive collaborative, multi-center, multidisciplinary network. This dataset was collected prospectively in eight North American centers to test the feasibility and implementation of harmonized advanced Research-MRI, with the addition of clinical information, genetic and proteomic studies, in a cohort of children presenting with acute ischemic stroke. Here we describe the process that enabled the development of PEDSNIP built to provide the infrastructure to support neuroimaging research priorities in pediatric stroke. Having built this Platform, we are now able to utilize the largest neuroimaging and clinical data pool on pediatric stroke data worldwide to conduct hypothesis-driven research. We are actively working on a bioinformatics approach to develop predictive models of risk, injury and repair and accelerate breakthrough discoveries leading to mechanism-targeted treatments that improve outcomes and minimize the burden following childhood stroke. This unique transformational resource for scientists and researchers has the potential to result in a paradigm shift in the management, outcomes and quality of life in children with stroke and their families, with far-reaching benefits for other brain conditions of people across the lifespan.

Early Discontinuation of Phenobarbital After Acute Symptomatic Neonatal Seizures in the Term Newborn.

Acute symptomatic seizures in the term newborn are often seen after perinatal brain injury. Common etiologies include hypoxic-ischemic encephalopathy, ischemic stroke, intracranial hemorrhage, metabolic derangements, and intracranial infections. Neonatal seizures are often treated with phenobarbital, which may cause sedation and may have significant long-term effects on brain development. Recent literature has suggested that phenobarbital may be safely discontinued in some patients before discharge from the neonatal intensive care unit. Optimizing a strategy for selective early phenobarbital discontinuation would be of great value. In this study, we present a unified framework for phenobarbital discontinuation after resolution of acute symptomatic seizures in the setting of brain injury of the newborn.

Roadmap for the Assessment and Management of Outcomes in Pediatric Stroke.

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.

Cerebral Venous Sinus Thrombosis in Preterm Infants.

BACKGROUND: Neonatal cerebral venous sinus thrombosis (CVST) can lead to brain injury and neurodevelopmental impairments. Previous studies of neonatal CVST have focused on term infants, and studies of preterm infants are lacking. In this study, we examined the clinical and radiological features, treatment and outcome of CVST in preterm infants. METHODS: This was a retrospective, consecutive cohort study of preterm infants (gestational age <37 weeks) with radiologically confirmed CVST. All magnetic resonance imaging/MRV and CT/CTV scans were re-reviewed to study thrombus characteristics and pattern of brain injury. Outcome was assessed by the validated pediatric stroke outcome measure at the most recent clinic visit. RESULTS: Twenty-six preterm infants with CVST were studied. Of these, 65% were moderate-late preterm (32-37 weeks), 27% very preterm (28-32 weeks), and 8% extreme preterm (<28 weeks). Most (73%) were symptomatic at presentation with seizures or abnormal exam. Transverse (85%) and superior sagittal (42%) sinuses were common sites of thrombosis. Parenchymal brain injury was predominantly periventricular (35%) and deep white matter (31%) in location. Intraventricular hemorrhage occurred in 46%. Most infants (69%) were treated with anticoagulation. No treated infant (including eleven with pretreatment hemorrhage) had new or worsening post-treatment hemorrhage. Outcomes ranged from no deficits (50%), mild-moderate (25%), and severe (25%) impairment. CONCLUSIONS: In our sample of preterm infants with CVST, more than one-quarter were asymptomatic. White matter brain lesions predominated and one-half had neurological deficits at follow-up. Anticoagulation of preterm CVST in this small cohort appeared to be safe. Larger studies of preterm CVST are needed.

Fronto-Parietal and White Matter Haemodynamics Predict Cognitive Outcome in Children with Moyamoya Independent of Stroke.

Moyamoya disease is a major arteriopathy characterised by progressive steno-occlusion of the arteries of the circle of Willis. Studies in adults with moyamoya suggest an association between abnormal fronto-parietal and white matter regional haemodynamics and cognitive impairments, even in the absence of focal infarction. However, these associations have not been investigated in children with moyamoya. We examined the relationship between regional haemodynamics and ratings of intellectual ability and executive function, using hypercapnic challenge blood oxygen level-dependent magnetic resonance imaging of cerebrovascular reactivity in a consecutive cohort of children with confirmed moyamoya. Thirty children were included in the final analysis (mean age: 12.55 ± 3.03 years, 17 females, 15 idiopathic moyamoya and 15 syndromic moyamoya). Frontal haemodynamics were abnormal in all regardless of stroke history and comorbidity, but occipital lobe haemodynamics were also abnormal in children with syndromic moyamoya. Executive function deficits were noted in both idiopathic and syndromic moyamoya, whereas intellectual ability was impaired in syndromic moyamoya, even in the absence of stroke. Analysis of the relative effect of regional abnormal haemodynamics on cognitive outcomes demonstrated that executive dysfunction was predominantly explained by right parietal and white matter haemodynamics independent of stroke and comorbidity, while posterior circulation haemodynamics predicted intellectual ability. These results suggest that parietal and posterior haemodynamics play a compensatory role in overcoming frontal vulnerability and cognitive impairment.

Exploring demographic, medical, and developmental determinants of adaptive behaviour in children with hemiplegic cerebral palsy.

Hemiplegic cerebral palsy (CP), the most common subtype, is characterized by high levels of mobility. Despite this, children with hemiplegic CP can face challenges functioning in and adapting to situations of everyday life. The purpose of this cross-sectional study (Hemi-NET database) was to identify factors associated with adaptive behaviour in 59 children with hemiplegic CP (ages 4-18; GMFCS I-IV). Using multivariate regression analyses, the relationship between demographic, medical, and developmental factors and adaptive behaviour (measured by the Adaptive Skills Composite score of the BASC-2) was explored. Results indicate that 34% of children had impaired adaptive skills. An autism diagnosis and lower communication functioning were significantly associated with poorer adaptive skills (R2 = 0.42, F(4, 43) = 7.87, p < 0.001), while factors such as IQ scores and GMFCS level were not. The results contribute to the growing literature that suggests that clinicians and researchers need to look beyond motor functioning when working with individuals with CP.

Gene-Targeted Therapies in Pediatric Neurology: Challenges and Opportunities in Diagnosis and Delivery.

BACKGROUND: Gene-targeted therapies are becoming a reality for infants and children with diseases of the nervous system. Rapid scientific advances have led to disease-modifying or even curative treatments. However, delays and gaps in diagnosis, inequitable delivery, and the need for long-term surveillance pose unresolved challenges. OBJECTIVE AND METHODS: The goal of the Child Neurology Society Research Committee was to evaluate and provide guidance on the obstacles, opportunities, and uncertainties in gene-targeted therapies for pediatric neurological disease. The Child Neurology Society Research Committee engaged in collaborative, iterative literature review and committee deliberations to prepare this consensus statement. RESULTS: We identified important challenges for gene-targeted therapies that require resource investments, infrastructure development, and strategic planning. Barriers include inequities in diagnosis and delivery of therapies, high costs, and a need for long-term surveillance of efficacy and safety, including systematic tracking of unanticipated effects. Key uncertainties regarding technical aspects and usage of gene-targeted therapies should be addressed, and characterization of new natural histories of diseases will be needed. Counterbalanced with these obstacles and uncertainties is the tremendous potential being demonstrated in treatments and clinical trials of gene-targeted therapies. CONCLUSIONS: Given that gene-targeted therapies for neurological diseases are in their earliest phase, the pediatric neurology community can play a vital role in their guidance and implementation. This role includes facilitating development of infrastructure and guidelines; ensuring efficient, equitable, and ethical implementation of treatments; and advocating for affordable and broad access for all children.

A Web-based System to Assist With Etiology Differential Diagnosis in Children With Arterial Ischemic Stroke.

BACKGROUND AND PURPOSE: The diagnosis of childhood arteriopathy is complex. We present a Web-based, evidence-backed classification system to return the most likely cause(s) of a pediatric arterial ischemic stroke. This tool incorporates a decision-making algorithm that considers a patient's clinical and imaging features before returning a differential diagnosis, including the likelihood of various arteriopathy subtypes. METHODS: The Vascular Effects of Infection in Pediatric Stroke study prospectively enrolled 355 children with arterial ischemic stroke (2010-2014). Previously, a central panel of experts classified the stroke etiology. To create this tool, we used the 174 patients with definite arteriopathy and spontaneous cardioembolic stroke as the "derivation cohort" and the 34 with "possible" arteriopathy as the "test cohort." Using logistic regression models of clinical and imaging characteristics associated with each arteriopathy subtype in the derivation cohort, we built a decision framework that we integrated into a Web interface specifically designed to create a probabilistic differential diagnosis. We applied the Web-based tool to the "test cohort." RESULTS: The differential diagnosis returned by our tool was in complete agreement with the experts' opinions in 20.6% of patients. We observed a partial agreement in 41.2% of patients and an overlap in 29.4% of patients. The tool disagreed with the experts on the diagnoses of 3 patients (8.8%). CONCLUSIONS: Our tool yielded an overlapping differential diagnosis in most patients that defied definitive classification by experts. Although it needs to be validated in an independent cohort, it helps facilitate high-quality, and timely diagnoses of arteriopathy in pediatric patients.

Hemorrhagic transformation and stroke recurrence in children with cardiac disease receiving antithrombotic therapy for secondary stroke prevention.

BACKGROUND: Antithrombotic therapy is currently recommended for stroke prevention in pediatric cardioembolic stroke where the recurrence risk is high; however, safety concerns remain. The primary objective of this study was to evaluate clinical and radiographic predictors of hemorrhagic transformation and stroke recurrence in children with cardiac disease to ascertain the safety and failure rates for secondary stroke prevention. METHODS: This was a single-center, retrospective analysis of a prospectively enrolled cohort of children with radiologically confirmed cardioembolic stroke from January 2003 to December 2017 treated with institutional guidelines. RESULTS: Eighty-two children met inclusion criteria (male 44 [54%]; neonates 23 [28%]; median age 0.43 years [0.08-4.23]). Hemorrhagic transformation occurred in 20 (24%) with the majority (75% of 20) being petechial and asymptomatic. One death (1%) was reported from hemorrhagic transformation. Four children (5%) had major extracranial hemorrhage. Most (95%) received antithrombic therapy, with anticoagulation being favored (82%). Greater stroke volume was associated with hemorrhagic transformation using the pediatric Alberta Stroke Program Early CT Score (6.1 ± 3.3 vs. 3.5 ± 2.3; p = .006). Stroke recurred in 11 (13%) children at a median 32 days (5.5-93) from the index event and the majority (90%) were on treatment at the time of recurrence. Children with univentricular physiology were less likely to have hemorrhagic transformation (RR 0.31; 95% CI 0.09-0.96, p = .04); however, they had higher rates of recurrent stroke before final palliative repair. CONCLUSIONS: In spite of the 24% hemorrhagic transformation rate, antithrombotic therapy has a positive risk-balance in certain cardioembolic stroke subgroups, particularly in those with single-ventricle physiology, when accounting for stroke volume.

Distinct Clinical and Radiographic Phenotypes in Pediatric Patients With Moyamoya.

BACKGROUND: Given the expanding evidence of clinico-radiological differences between moyamoya disease (MMD) and moyamoya syndrome (MMS), we compared the clinical and radiographic features of childhood MMD and MMS to identify predictors of ischemic event recurrence. METHODS: We reviewed a pediatric moyamoya cohort followed between 2003 and 2019. Clinical and radiographic characteristics at diagnosis and follow-up were abstracted. Comparisons between MMD and MMS as well as between MMD and two MMS subgroups (neurofibromatosis [MMS-NF1] and sickle cell disease [MMS-SCD]) were performed. RESULTS: A total of 111 patients were identified. Patients with MMD presented commonly with transient ischemic attacks (TIAs) (35 % MMD versus 13% MMS-NF1 versus 9.5% MMS-SCD; P = 0.047). Symptomatic stroke presentation (MMD 37% versus MMS-NF1 4% versus 33%; P = 0.0147) and bilateral disease at diagnosis (MMD 73% versus MMS-NF1 22 % versus MMS-SCD 67%; P = 0.0002) were uncommon in MMS-NF1. TIA recurrence was common in MMD (hazard ratio 2.86; P = 0.001). The ivy sign was absent on neuroimaging in a majority of patients with MMS-SCD (MMD 67% versus MMS-NF1 52% versus MMS-SCD 9.5%; P = 0.0002). Predictors of poor motor outcome included early age at diagnosis (odds ratio [OR] 8.45; P = 0.0014), symptomatic stroke presentation (OR 6.6; P = 0.019), and advanced Suzuki stage (OR 3.59; P = 0.019). CONCLUSIONS: Moyamoya exhibits different phenotypes based on underlying etiologies. Frequent TIAs is a common phenotype of MMD and symptomatic stroke presentation a common feature of MMD and MMS-SCD, whereas unilateral disease and low infarct burden are common in MMS-NF1. In addition, absence of ivy sign is a common phenotype in MMS-SCD.

Childhood arterial ischemic stroke due to mineralizing angiopathy: an 18-year single-center experience.

Mineralizing angiopathy is a unique, age-specific stroke syndrome characterized by basal ganglia infarction and lenticulostriate calcification after minor head injury in early childhood. There is limited understanding of the pathophysiology, course, and clinical outcome of this syndrome. We describe the clinical and radiographical phenotype of a single-center, consecutively enrolled cohort of children with mineralizing angiopathy from January 2002 to January 2020 and provide a comparative analysis to previously published literature. Fourteen children were identified. Previously unreported findings include: stroke onset in eight children older than 18 months; presence of basal ganglia hemorrhage in four; multifocal basal ganglia infarcts in three; presence of additional non-basal ganglia calcifications in three; and presence of thrombophilia in one. Seven children had moderate-to-severe neurological deficits. There was no symptomatic stroke recurrence (mean follow-up 3y 7mo, SD 1y 7mo). Our expanded phenotype highlights distinct characteristics of mineralizing angiopathy in children and has the potential to inform future research. What this paper adds Children with mineralizing angiopathy are often misdiagnosed as having a limb fracture despite normal x-rays. A magnetic resonance imaging-only approach may miss this entity. Non-contrast computed tomography, in addition to MRI is recommended to identify calcifications in idiopathic arterial ischemic stroke. Most children have moderate-to-severe neurological sequela.

Swallowing, Oral Motor, Motor Speech, and Language Impairments Following Acute Pediatric Ischemic Stroke.

BACKGROUND AND PURPOSE: Following adult stroke, dysphagia, dysarthria, and aphasia are common sequelae. Little is known about these impairments in pediatric stroke. We assessed frequencies, co-occurrence and associations of dysphagia, oral motor, motor speech, language impairment, and caregiver burden in pediatric stroke. METHODS: Consecutive acute patients from term birth-18 years, hospitalized for arterial ischemic stroke (AIS), and cerebral sinovenous thrombosis, from January 2013 to November 2018 were included. Two raters reviewed patient charts to detect documentation of in-hospital dysphagia, oral motor dysfunction, motor speech and language impairment, and caregiver burden, using a priori operational definitions for notation and assessment findings. Other variables abstracted included demographics, preexisting conditions, stroke characteristics, and discharge disposition. Impairment frequencies were obtained by univariate and bivariate analysis and associations by simple logistic regression. RESULTS: A total of 173 patients were stratified into neonates (N=67, mean age 2.9 days, 54 AIS, 15 cerebral sinovenous thrombosis) and children (N=106, mean age 6.5 years, 73 AIS, 35 cerebral sinovenous thrombosis). Derived frequencies of impairments included dysphagia (39% neonates, 41% children); oral motor (6% neonates, 41% children); motor speech (37% children); and language (31% children). Common overlapping impairments included oral motor and motor speech (24%) and dysphagia and motor speech (23%) in children. Associations were found only in children between stroke type (AIS over cerebral sinovenous thrombosis) and AIS severity (more severe deficit at presentation) for all impairments except feeding impairment alone. Caregiver burden was present in 58% patients. CONCLUSIONS: For the first time, we systematically report the frequencies and associations of dysphagia, oral motor, motor speech, and language impairment during acute presentation of pediatric stroke, ranging from 30% to 40% for each impairment. Further research is needed to determine long-term effects of these impairments and to design standardized age-specific assessment protocols for early recognition following stroke.

Neurologic complications of pediatric congenital heart disease.

Improved medical management and surgical outcomes have significantly decreased mortality in children with congenital heart disease; however, with increased survival, there is a greater lifetime exposure to neurologic complications with serious long-term neurodevelopmental consequences. Thus, recent focus has shifted to recognition and reduction of these extracardiac comorbidities. Vascular and infective complications, such as arterial ischemic stroke, infective endocarditis, and localization-related epilepsy are some of the most common neurologic comorbidities of congenital heart disease. In addition, it is now well recognized that congenital heart disease has an impact on overall brain development and contributes to adverse neurodevelopmental outcomes across multiple domains. The goal of this chapter is to summarize the most common neurologic comorbidities of congenital heart disease and its management.

Neurodevelopmental profiles of children with unilateral cerebral palsy associated with middle cerebral artery and periventricular venous infarctions.

AIM: To compare the neurodevelopment of children with unilateral cerebral palsy (CP) with middle cerebral artery (MCA) and periventricular venous infarctions (PVIs). METHOD: In this cross-sectional study, children with unilateral CP completed a neurological exam, unimanual Quality of Upper Extremity Skills Test, hand usage questionnaires, and IQ test. Neuroimaging was obtained from health records. RESULTS: Two hundred and forty-five participants with unilateral CP had neuroimaging (151 [61.9%] male, ages 2-18y, median=7y 6mo, interquartile range [IQR]=6y 7mo, with 93.6% in Gross Motor Function Classification System level I/II and 78.8% in Manual Ability Classification System level I/II). Ninety-seven (39.6%) had MCA injuries and 106 (43.3%) had periventricular white matter injuries, of which 48 (45.3%) were PVIs. Median Quality of Upper Extremity Skills Test for the MCA group was 49.2 (IQR=55.8), PVI 79.9 (IQR=23.6) (Mann-Whitney U=988.50, p<0.001). Bimanual hand usage (Children's Hand-use Experience Questionnaire) (Mann-Whitney U=425, p<0.001) and light touch (odds ratio=9.12, 95% confidence interval 1.28-400.76, Fisher's exact test p=0.017) were lower in the MCA compared to the PVI group. Full-scale IQ median centile score for the MCA group was 18.0 (IQR=35.5) and 50.0 (IQR=30.0) for the PVI group (Mann-Whitney U=382, p<0.001). INTERPRETATION: Children with unilateral CP and MCA injuries demonstrated lower hand function and usage, decreased light touch, and lower IQs compared to the PVI group. This study aids in defining rehabilitation needs informed by brain injury patterns.

The Pediatric Neurology 2020 Research Workforce Survey: Optimism in a Time of Challenge.

BACKGROUND: The past decades have seen a transformational shift in the understanding and treatment for neurological diseases affecting infants and children. These advances have been driven in part by the pediatric neurology physician-scientist workforce and its efforts. However, pediatric neurology research faces substantial challenges from internal and external forces including work-life balance demands, COVID-19 pandemic effects, and research funding. Understanding the impact of these challenges on the perceptions, planning, and careers of pediatric neurology physician-scientists is needed to guide the research mission. METHODS: Our objective was to survey the research challenges, goals, and priorities of pediatric neurologists. In 2020 we conducted a cross-sectional, 28-question survey emailed to 1,775 members of the Child Neurology Society. RESULTS: One hundred fifty-one individuals responded to the survey. Most respondents were grant investigators (52%) and conducted clinical research (69%). Research areas included epilepsy (23%), neurodevelopmental and autism (16%), neurocritical care and stroke (11%), neurogenetics and neurometabolics (9%), neonatal neurology (8%), and others. The most common funding source was the National Institutes of Health (37%). Shared major research concerns were funding, utilization of remote technology, overcoming disparities, natural history and multicenter studies, global neurology, and diversification of the research portfolio. Commitment to continuing and increasing research efforts was evident. CONCLUSIONS: Our survey demonstrates obstacles for physician-scientist researchers in pediatric neurology, but it also shows optimism about continued opportunity. Creative approaches to address challenges will benefit the research mission, maximize the current and future pool of researchers, and help improve the lives of children with neurological disorders.

Additional validation study and French cross-cultural adaptation of the Pediatric Stroke Outcome Measure-Summary of Impressions (PSOM-SOI).

BACKGROUND: The Pediatric Stroke Outcome Measure-Summary of Impressions (PSOM-SOI) measures neurological function across right and left sensorimotor domains (Item A), language production (Item B), language comprehension (Item C), and cognition/behaviour (Item D). OBJECTIVE: This study was a cross-cultural adaptation into French of the PSOM-SOI and an assessment of its reliability and limitations of use. MATERIAL AND METHODS: The translation and adaptation of the PSOM-SOI was followed by the assessment of its reliability in a cohort of 69 children with diagnosed acute neonatal arterial ischemic stroke. Three independent raters retrospectively scored the PSOM-SOI based on data from in-person neurological examination and results of standardized tests performed at age 7 in the cohort database. Comparison 1 (C1) involved a less experienced rater and an experienced rater and comparison 2 (C2) involved 2 experienced raters. Inter-rater reliability (IRR) was measured with Kappa coefficients. RESULTS: The cross-cultural adaptation was easily performed, and no rater had difficulties using the French PSOM-SOI. The IRR was better in C1 than C2. For Item A, the agreement in C1 (κ=0.47) and C2 (κ=0.44) was moderate. The C1 agreement was substantial for Items B (κ=0.71) and C (κ=0.70); the C2 agreement was fair for Item B (κ=0.23) and slight for Item C (κ=0.16). For Item D, the agreement was moderate in C1 (κ=0.52) and fair in C2 (κ=0.35). In all but one comparison, agreement or minor disagreement (≤0.5 points) was obtained for more than 90% of the item scores. Regarding the total score, agreement for normal function (≤0.5) versus abnormal function (>0.5) was achieved for 90% in C1 and 67% in C2. CONCLUSION: The IRR of the French PSOM-SOI gave variable results depending on the item and rater's experience, but the extent of disagreements was minor for individual items and total score. Additional prospective validation studies using the French PSOM-Short Neurological Exam to score the PSOM-SOI are needed. A dichotomised total score (cut-off≤0.5) could be used to define normal function versus poor outcome.

Pediatric Neurology Research in the Twenty-First Century: Status, Challenges, and Future Directions Post-COVID-19.

BACKGROUND: The year 2020 marked a fundamental shift in the pediatric neurology field. An impressive positive trajectory of advances in patient care and research faced sudden global disruptions by the coronavirus disease 2019 pandemic and by an international movement protesting racial, socioeconomic, and health disparities. The disruptions revealed obstacles and fragility within the pediatric neurology research mission. However, renewed commitment offers unique opportunities for the pediatric neurology research community to enhance and prioritize research directions for the coming decades. METHODS: The Research Committee of the Child Neurology Society evaluated the challenges and opportunities facing the pediatric neurology research field, including reviewing published literature, synthesizing publically available data, and conducting a survey of pediatric neurologists. RESULTS: We identified three priority domains for the research mission: funding levels, active guidance, and reducing disparities. Funding levels: to increase funding to match the burden of pediatric neurological disease; to tailor funding mechanisms and strategies to support clinical trial efforts unique to pediatric neurology; and to support investigators across their career trajectory. Active guidance: to optimize infrastructure and strategies, to leverage novel therapeutics, enhance data collection, and improve inclusion of children in clinical trials. Reducing disparities: to reduce health disparities in children with neurological disease, to develop proactive measures to enhance workforce diversity and inclusion, and increase avenues to balance work-life obligations for investigators. CONCLUSIONS: In this uniquely challenging epoch, the pediatric neurology research community has a timely and important mission to re-engage the public and government, advancing the health of children with neurological conditions.

Long-term cognitive outcomes after cerebral sinovenous thrombosis in childhood.

AIM: To assess long-term cognitive function in children after cerebral sinovenous thrombosis (CSVT). METHOD: Children with CSVT, who had neuropsychological testing for intellectual ability, executive function, attention, language, or behavior, were included in a prospective observational study. Outcomes were compared with normative means using one-sample t-tests. Predictors of abnormal function were examined using logistic regression. RESULTS: Fifty children with CSVT were included (median age at diagnosis 2y 10mo, interquartile range 7d-6y 10mo; 35 males, 15 females). The median follow-up time was 4 years 2 months (interquartile range 2y 8mo-6y 4mo). Compared with normative means, children with CSVT had lower mean (± standard deviation) full-scale IQ, working memory, and processing speed scores (93.3±16, p=0.01; 93.6±16, p=0.04; 93.7±15.3, p=0.02 respectively). They also had lower scores in executive function, attention, and language domains. Refractory seizure at presentation was associated with a trend in behavioral problems (odds ratio [OR] 6.3, 95% confidence interval [CI] 0.9-46, p=0.07). Females were less likely to experience processing speed difficulties (OR 0.22, 95% CI 0.04-1.3, p=0.09). Incomplete recanalization was associated with a greater risk of abnormal verbal comprehension (OR 5.3, 95% CI 0.93-30.5, p=0.059). INTERPRETATION: Children with CSVT as a group performed below age expectations on standardized neuropsychological tests, although there was variability across individuals and cognitive domains. Larger studies are needed to evaluate predictors of cognitive deficits in children with CSVT.