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There is an increased risk of stroke in adults with severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]) infection, but whether there is a similar association with stroke in children is unclear. Our objective was to determine whether there is a correlation between COVID-19 infection, multisystem inflammatory syndrome in children (MIS-C), and pediatric ischemic stroke.This was a retrospective, population-based cohort analysis between March 1, 2020, and June 30, 2021, conducted at a children's hospital. Pediatric patients with a diagnosis of ischemic stroke were identified using ICD-10 diagnoses of ischemic stroke, cerebrovascular accident, or cerebral infarction.We identified 16 patients, seven male and nine female, with ischemic stroke. Ages were 8 months to 17 years (median 11.5 years). More Asian (6%) and black (13%) patients had strokes compared with population prevalence (2% each, respectively). No patients had active COVID-19 infection. COVID-19 antibodies were identified in five of 11 patients tested (45%), of whom three were diagnosed with MIS-C. 82% of the strokes occurred between February and May 2021. The peak incidence was in February 2021, which was two months after peak incidence of pediatric cases of COVID-19 and one month after the peak of MIS-C cases.Our study suggests that prior COVID-19 infection, but not acute infection, is correlated with a risk for stroke in the pediatric population. The risk for stroke appears to be distinct from the risk for MIS-C.

Informed consent is crucial for participant understanding, engagement, and partnering for research. However, current written informed consents have significant limitations, particularly for complex topics such as genomics and biobanking. Our goal was to identify how participants visually conceptualize terminology used in genomics and biobanking research studies, which might provide a novel approach for informed consent. An online convenience sample was used from May to July 2020 to collect data. Participants were asked to draw 10 randomly chosen words out of 32 possible words commonly used in consent forms for genomics and biobanking research. An electronic application captured drawings that were downloaded into a qualitative software program for analysis. A total of 739 drawings by 269 participants were captured. Participants were mostly female (61.3%), eight different race/ethnicities were represented (15.6% Black, 13.8% Hispanic), and most had some college education (68.8%). Some words had consistent visual themes such as different types of risky activities for risk or consistent specific images such as a double helix for DNA. Several words were frequently misunderstood (e.g., ascend for assent), while others returned few submissions (e.g., phenotype or whole genome sequencing). We found that although some words used in genomics and biobanking research were visually conceptualized in a common fashion, but misunderstood or less well-known words had no, few, or mistaken drawings. Future research can explore the incorporation of visual images to improve participant comprehension during consent processes, and how to utilize visual imagery to address more challenging concepts.

Background: The leukodystrophy “Vanishing White Matter” (VWM) is an orphan disease with neurological decline and high mortality. Currently, VWM has no approved treatments, but advances in understanding pathophysiology have led to identification of promising therapies. Several investigational medicinal products are either in or about to enter clinical trial phase. Clinical trials in VWM pose serious challenges, as VWM has an episodic disease course; disease phenotype is highly heterogeneous and predictable only for early onset; and study power is limited by the small patient numbers. To address these challenges and accelerate therapy delivery, the VWM Consortium, a group of academic clinicians with expertise in VWM, decided to develop a core protocol to function as a template for trials, to improve trial design and facilitate sharing of control data, while permitting flexibility regarding other trial details. Overall aims of the core protocol are to collect safety, tolerability, and efficacy data for treatment assessment and marketing authorization. Methods: To develop the core protocol, the VWM Consortium designated a committee, including clinician members of the VWM consortium, family and patient group advocates, and experts in statistics, clinical trial design and alliancing with industries. We drafted three age-specific protocols, to stratify into more homogeneous patient groups, of ages ≥18 years, ≥6 to Discussion: The core protocol provides a shared uniformity across trials, enables a pool of shared controls, and reduces the total number of patients necessary per trial, limiting the number of patients on placebo. All VWM clinical trials are suggested to adhere to the core protocol. Other trial components such as choice of primary outcome, pharmacokinetics, pharmacodynamics, and biomarkers are flexible and unconstrained by the core protocol. Each sponsor is responsible for their trial execution, while the control data are handled by a shared research organization. This core protocol benefits the efficiency of parallel and consecutive trials in VWM, and we hope accelerates time to availability of treatments for VWM. Trial registration: NA

ObjectiveTo identify novel disease associated loci for amyotrophic lateral sclerosis (ALS), we used sequencing data and performed in vitro and in vivo experiments to demonstrate pathogenicity of mutations identified inTP73.MethodsWe analyzed exome sequences of 87 patients with sporadic ALS and 324 controls, with confirmatory sequencing in independent ALS cohorts of >2,800 patients. For the top hit,TP73, a regulator of apoptosis and differentiation and a binding partner and homolog of the tumor suppressor geneTP53, we assayed mutation effects using in vitro and in vivo experiments. C2C12 myoblast differentiation assays, characterization of myotube appearance, and immunoprecipitation of p53-p73 complexes were performed in vitro. In vivo, we used clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 targeting of zebrafishtp73to assay motor neuron number and axon morphology.ResultsFour heterozygous rare, nonsynonymous mutations inTP73were identified in our sporadic ALS cohort. In independent ALS cohorts, we identified an additional 19 rare, deleterious variants inTP73. PatientTP73mutations caused abnormal differentiation and increased apoptosis in the myoblast differentiation assay, with abnormal myotube appearance. Immunoprecipitation of mutant ΔN-p73 demonstrated that patient mutations hinder the ability of ΔN-p73 to bind p53. CRISPR/Cas9 knockout oftp73in zebrafish led to impaired motor neuron development and abnormal axonal morphology, concordant with ALS pathology.ConclusionTogether, these results strongly suggest that variants inTP73correlate with risk for ALS and indicate a role for apoptosis in ALS disease pathology.

Congenital myasthenic syndrome (CMS) is a group of 32 disorders involving genetic dysfunction at the neuromuscular junction resulting in skeletal muscle weakness that worsens with physical activity. Precise diagnosis and molecular subtype identification are critical for treatment as medication for one subtype may exacerbate disease in another (Engel et al.

Access to paediatric neurology care is complex, resulting in significant wait times and negative patient outcomes. The goal of the American Academy of Pediatrics National Coordinating Center for Epilepsy's project, Access Improvement and Management of Epilepsy with Telehealth (AIM-ET), was to identify access and management challenges in the deployment of telehealth technology. AIM-ET organised four paediatric neurology teams to partner with primary-care providers (PCP) and their multidisciplinary teams. Telehealth visits were conducted for paediatric epilepsy patients. A post-visit survey assessed access and satisfaction with the telehealth visit compared to an in-person visit. Pre/post surveys completed by PCPs and neurologists captured telehealth visit feasibility, functionality and provider satisfaction. A provider focus group assessed facilitators and barriers to telehealth. Sixty-one unique patients completed 75 telehealth visits. Paired t-test analysis demonstrated that telehealth enhanced access to epilepsy care. It reduced self-reported out-of-pocket costs ( p

Objective To examine disparities in the diagnosis of leukodystrophies including geographic factors and access to specialty centers. Study design Retrospective cohort study of pediatric patients admitted to Pediatric Health Information System hospitals. Patients with leukodystrophy were identified with International Classification of Diseases, Tenth Revision, Clinical Modification diagnostic codes for any of 4 leukodystrophies (X-linked adrenoleukodystrophy, Hurler disease, Krabbe disease, and metachromatic leukodystrophy). We used 3-level hierarchical generalized logistic modeling to predict diagnosis of a leukodystrophy based on distance traveled for hospital, neighborhood composition, urban/rural context, and access to specialty center. Results We identified 501 patients with leukodystrophy. Patients seen at a leukodystrophy center of excellence hospital were 1.73 times more likely to be diagnosed than patients at non-center of excellence hospitals. Patients who traveled farther were more likely to be diagnosed than those who traveled shorter. Patients living in a Health Professionals Shortage Area zip code were 0.86 times less likely to be diagnosed than those living in a non-Health Professionals Shortage Area zip code. Conclusions Geographic factors affect the diagnosis of leukodystrophies in pediatric patients, particularly in regard to access to a center with expertise in leukodystrophies. Our findings suggest a need for improving access to pediatric specialists and possibly deploying specialists or diagnostic testing more broadly.

Previous work has shown that children of Hispanic ethnicity have reduced likelihood to achieve seizure remission, but it was unknown why. The purpose of this study was to evaluate antiseizure medicine (ASM) refill characteristics, comparing Hispanic and non-Hispanic White pediatric patients.This was a retrospective population-based study in children between ages 6 months and 15 years. Epilepsy outcome was categorized as seizure free, treatment failure, or undetermined. ASM refill characteristics were determined from an insurance provider.247 patients were identified: 52 (21 %) were treatment failure; 181 (73 %) were seizure free; and 14 (5.7 %) were undetermined. ASM refill rates were similar in Hispanic and White patients (38.2, 32.1, respectively). Hispanic and White patients had similar numbers of different ASMs prescribed (2.1 and 2.4). There was not a significant difference in proportion of days covered between Hispanic and White patients (0.99 and 0.95).We found no differences between pediatric Hispanic and White epilepsy patients, for number of ASM refills, the number of ASMs prescribed, the choice of ASMs, the proportion of days covered, or the lateness of refills. Our findings suggest that the observation of reduced likelihood to achieve seizure remission in pediatric Hispanic patients is not associated with ASM refill patterns.

Objectives Cerebral X-linked adrenoleukodystrophy (cALD) is an inflammatory demyelination of the brain that can lead to death unless treated by hematopoietic stem cell transplantation. Survival and improved outcomes for cerebral adrenoleukodystrophy are associated with hematopoietic stem cell transplantation at earliest evidence of disease on magnetic resonance imaging (MRI). Our goal was to determine average duration between diagnosis of cALD and hematopoietic stem cell transplantation. Methods This was a retrospective review of data of patients aged 18 years or younger, using a nationwide administrative health care database (Pediatric Health Information System), with an International Classification of Diseases, Tenth Revision ( ICD-10) diagnosis of adrenoleukodystrophy. Time range was October 1, 2015, through June 30, 2021. We determined time to hematopoietic stem cell transplantation by duration between index brain MRI and a code for hematopoietic stem cell transplantation. Results We identified 27 patients with cerebral adrenoleukodystrophy. Total charges for the cohort was $53 million. Time to transplant averaged 97 days. For Hispanic patients, time to transplant was 117 days, compared with 80 days for White, non-Hispanic patients. Comparison of different hospitals showed significant variability in time to hematopoietic stem cell transplantation. Discussion We found that time to hematopoietic stem cell transplantation was >3 months for patients with cerebral adrenoleukodystrophy in the hospitals we evaluated. We noted differences in average time by race/ethnicity and by hospital. Our findings suggest opportunity to reduce time to transplant in cerebral adrenoleukodystrophy.

Item does not contain fulltext NOTCH1 belongs to the NOTCH family of proteins that regulate cell fate and inflammatory responses. Somatic and germline NOTCH1 variants have been implicated in cancer, Adams-Oliver syndrome, and cardiovascular defects. We describe 7 unrelated patients grouped by the presence of leukoencephalopathy with calcifications and heterozygous de novo gain-of-function variants in NOTCH1. Immunologic profiling showed upregulated CSF IP-10, a cytokine secreted downstream of NOTCH1 signaling. Autopsy revealed extensive leukoencephalopathy and microangiopathy with vascular calcifications. This evidence implicates that heterozygous gain-of-function variants in NOTCH1 lead to a chronic central nervous system (CNS) inflammatory response resulting in a calcifying microangiopathy with leukoencephalopathy. ANN NEUROL 2022;92:895-901.

A subset of boys with X-linked adrenoleukodystrophy (ALD) develop inflammatory demyelinating brain lesions. Risk factors are largely undefined. We used two independent cohorts to assess whether low vitamin D status predicts lesion development. In our first cohort, we measured 25-hydroxyvitamin D in 53 plasma samples from 20 pre-lesional ALD boys followed at two centers; half subsequently developed lesions. In our second cohort, we measured latitude (using home ZIP code) among 230 ALD boys in a database of 51 US pediatric hospitals; over half developed lesions. In regression models, low plasma vitamin D and northerly latitudes independently predicted ALD brain lesions.

Objective: The purpose of our study was to understand the healthcare burden and incidence of Krabbe disease (Krabbe). Methods: Retrospective analysis of Krabbe patients identified October 1, 2015 through December 31, 2020, ages birth through age 3, evaluated in two national databases. We estimated point prevalence and incidence from year 2016 data. Results: We identified 98 unique Krabbe patients with 736 visits including 260 were inpatient admissions. Total healthcare charges were $51.5 million dollars. We determined a point prevalence of 34 68 Krabbe patients in 2016 ages 0 3 years. This estimates a birth incidence of ~1 in 310,000 live births. Significance: Krabbe disease patients had over $51 million in health care charges and hundreds of hospitalizations. Estimated prevalence and birth incidence is similar to rates observed from newborn screening. Our findings show the tremendous health impacts of Krabbe disease, and provide guidance for efforts in screening and treatment planning.

Families of children with special health care needs may travel substantial distances to access specialized health care. However, it is not known how race/ethnicity, insurance status, and access to disease-specific specialty care affect travel distances. This analysis examines patients aged 18 years or younger who were discharged from a Pediatric Health Information System (PHIS) children's hospital (n = 52) with a diagnosis of an inherited leukodystrophy between October 1, 2015, and September 30, 2018 (n = 950 patients). Leukodystrophies are rare but very serious neurological illnesses, with elevated mortality and morbidity rates. Bivariate and hierarchical generalized linear models reveal that white children, privately insured children, and children visiting leukodystrophy specialist centers travel farther for children's hospital care. These findings indicate that socially privileged families travel greater distances to obtain specialized health care, which could affect clinical outcomes.

ObjectiveTo determine shared comorbidities and to identify underrecognized or unexpected morbidities in children with leukodystrophies using an unbiased phenome-wide association study (PheWAS) analysis of a nationwide pediatric clinical and financial database.MethodsData were extracted from the Pediatric Health Information System database. Patients with leukodystrophy were identified with International Classification of Diseases, 10th revision, clinical modification, diagnostic codes for any of 4 specific leukodystrophies (X-linked adrenoleukodystrophy (E71.52x), Hurler disease (E76.01), Krabbe disease (E75.23), and metachromatic leukodystrophy (E75.25)) over a 3-year time period. Confirmed leukodystrophy cases (n = 553) were matched with 1659 controls. A PheWAS analysis was performed on all available ICD diagnostic codes for cases and controls. Comparisons were performed for all 4 leukodystrophies as a group and individually.ResultsWe found 174 phecodes (grouped ICD codes) associated with leukodystrophies, including 28 codes with a rate difference (RD) > 20%. Known comorbidities of leukodystrophies including developmental delay, epilepsy, and adrenal insufficiency were identified. Unexpected associations identified included hypertension (RD 30%, OR 25), hearing loss (RD 28%, OR 15), and cardiac dysrhythmias (RD 27%, OR 9). Hurler disease had a greater number of unique disease conditions.ConclusionsPheWAS analysis from a national database demonstrates shared and unique features of leukodystrophies. Developmental delay, cardiac dysrhythmias, fluid and electrolyte disturbances, and respiratory issues were common to all 4 leukodystrophy diseases. Use of a PheWAS in leukodystrophies and other pediatric neurologic diseases offers a method for targeting improved care for patients by identification of morbidities.

Objective:The purpose of our study was to assess whether race/ethnicity was associated with seizure remission in pediatric epilepsy.Methods:This was a retrospective population-based cohort study of children who were evaluated for new-onset epilepsy in the clinic, emergency department, and/or hospital by a pediatric neurologist in an integrated health care delivery system. Children were between ages 6 months and 15 years at their initial presentation of epilepsy. The cohort, identified through an electronic database, was assembled over 6 years, with no less than 5 years of follow-up. All children were evaluated for race, ethnicity, insurance type, and socioeconomic background. Patient outcome was determined at the conclusion of the study period and categorized according to their epilepsy control as either drug resistant (pharmacoresistant and intractable) or drug responsive (controlled, probable remission, and terminal remission).Results:In the final cohort of 776 patients, 63% were drug responsive (control or seizure remission). After controlling for confounding socioeconomic and demographic factors, children of Hispanic ethnicity experienced reduced likelihood (hazard) of drug-responsive epilepsy (hazard ratio 0.6, P < .001), and had longer median time to remission (8 years; 95% CI 5.9-9.6 years) compared to white non-Hispanic patients (5.6 years; 95% CI 4.9-6.1 years). Among Hispanic patients, higher health care costs were associated with reduced likelihood of drug responsiveness.Significance:We found that Hispanic ethnicity is associated with a reduced likelihood of achieving seizure control and remission. This study suggests that factors associated with the race/ethnicity of patients contributes to their likelihood of achieving seizure freedom.

The clinical use of genomic analysis has expanded rapidly resulting in an increased availability and utility of genomic information in clinical care. We have developed an infrastructure utilizing informatics tools and clinical processes to facilitate the use of whole genome sequencing data for population health management across the healthcare system. Our resulting framework scaled well to multiple clinical domains in both pediatric and adult care, although there were domain specific challenges that arose. Our infrastructure was complementary to existing clinical processes and well-received by care providers and patients. Informatics solutions were critical to the successful deployment and scaling of this program. Implementation of genomics at the scale of population health utilizes complicated technologies and processes that for many health systems are not supported by current information systems or in existing clinical workflows. To scale such a system requires a substantial clinical framework backed by informatics tools to facilitate the flow and management of data. Our work represents an early model that has been successful in scaling to 29 different genes with associated genetic conditions in four clinical domains. Work is ongoing to optimize informatics tools; and to identify best practices for translation to smaller healthcare systems.

Leukodystrophies are a group of genetically determined disorders that affect development or maintenance of central nervous system myelin. Leukodystrophies have an incidence of at least 1 in 4700 live births and significant morbidity and elevated risk of early death. This report includes a discussion of the types of leukodystrophies; their prevalence, clinical presentation, symptoms, and diagnosis; and current and future treatments. Leukodystrophies can present at any age from infancy to adulthood, with variability in disease progression and clinical presentation, ranging from developmental delay to seizures to spasticity. Diagnosis is based on a combination of history, examination, and radiologic and laboratory findings, including genetic testing. Although there are few cures, there are significant opportunities for care and improvements in patient well-being. Rapid advances in imaging and diagnosis, the emergence of and requirement for timely treatments, and the addition of leukodystrophy screening to newborn screening, make an understanding of the leukodystrophies necessary for pediatricians and other care providers for children.

Zellweger spectrum disorder (ZSD) is the most severe peroxisomal biogenesis disorder (PBD). Why ZSD patients not only loose functional peroxisomes but also present with severe mitochondrial dysfunction was a long‐standing mystery. In this issue, Nuebel et al (2021) identified that loss of peroxisomes leads to re‐routing of peroxisomal proteins to mitochondria, thereby impairing mitochondrial structure and function. The findings provide the first molecular understanding of the mitochondrial‐peroxisomal link in ZSD., A study in this issue provides the first molecular understanding of the mitochondrial‐peroxisomal link in peroxisomal disorders.

Summary Leukodystrophies, genetic neurodevelopmental and/or neurodegenerative disorders of cerebral white matter, result from impaired myelin homeostasis and metabolism. Numerous genes have been implicated in these heterogeneous disorders; however, many individuals remain without a molecular diagnosis. Using whole-exome sequencing, biallelic variants in LSM7 were uncovered in two unrelated individuals, one with a leukodystrophy and the other who died in utero. LSM7 is part of the two principle LSM protein complexes in eukaryotes, namely LSM1-7 and LSM2-8. Here, we investigate the molecular and functional outcomes of these LSM7 biallelic variants in vitro and in vivo. Affinity purification-mass spectrometry of the LSM7 variants showed defects in the assembly of both LSM complexes. Lsm7 knockdown in zebrafish led to central nervous system defects, including impaired oligodendrocyte development and motor behavior. Our findings demonstrate that variants in LSM7 cause misassembly of the LSM complexes, impair neurodevelopment of the zebrafish, and may be implicated in human disease. The identification of more affected individuals is needed before the molecular mechanisms of mRNA decay and splicing regulation are added to the categories of biological dysfunctions implicated in leukodystrophies, neurodevelopmental and/or neurodegenerative diseases., Derksen et al. use molecular and functional studies to demonstrate that variants in LSM7 lead to defects in the assembly of LSM complexes, impair neurodevelopment in zebrafish, and might be implicated in human disease.

Rapid whole genome sequencing (rapid WGS) is a powerful diagnostic tool that is becoming increasingly practical for widespread clinical use. However, protocols for its use are challenging to implement. A significant obstacle to clinical adoption is that laboratory certification requires an initial research development phase, which is constrained by regulations from returning results. Regulations preventing return of results have ethical implications in cases which might impact patient outcomes. Here, we describe our experience with the development of a rapid WGS research protocol, that balanced the requirements for laboratory-validated test development with the ethical needs of clinically relevant return of results.

Context 4H or POLR3-related leukodystrophy is an autosomal recessive disorder typically characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, caused by biallelic pathogenic variants in POLR3A, POLR3B, POLR1C, and POLR3K. The endocrine and growth abnormalities associated with this disorder have not been thoroughly investigated to date. Objective To systematically characterize endocrine abnormalities of patients with 4H leukodystrophy. Design An international cross-sectional study was performed on 150 patients with genetically confirmed 4H leukodystrophy between 2015 and 2016. Endocrine and growth abnormalities were evaluated, and neurological and other non-neurological features were reviewed. Potential genotype/phenotype associations were also investigated. Setting This was a multicenter retrospective study using information collected from 3 predominant centers. Patients A total of 150 patients with 4H leukodystrophy and pathogenic variants in POLR3A, POLR3B, or POLR1C were included. Main Outcome Measures Variables used to evaluate endocrine and growth abnormalities included pubertal history, hormone levels (estradiol, testosterone, stimulated LH and FSH, stimulated GH, IGF-I, prolactin, ACTH, cortisol, TSH, and T4), and height and head circumference charts. Results The most common endocrine abnormalities were delayed puberty (57/74; 77% overall, 64% in males, 89% in females) and short stature (57/93; 61%), when evaluated according to physician assessment. Abnormal thyroid function was reported in 22% (13/59) of patients. Conclusions Our results confirm pubertal abnormalities and short stature are the most common endocrine features seen in 4H leukodystrophy. However, we noted that endocrine abnormalities are typically underinvestigated in this patient population. A prospective study is required to formulate evidence-based recommendations for management of the endocrine manifestations of this disorder., Canadian Institutes of Health Research [201610PJT-377869, MOP-G2-341146-159133-BRIDG]; Fondation Les Amis d'Elliot; Leuco-Action; Fondation Lueur d'Espoir pour Ayden; Fondation le Tout pour Loo; Reseau de Medecine Genetique Appliquee of the Fonds de Recherche du Quebec-Sante; Compute Canada; Fonds de Recherche du Quebec en Sante (FRQS) Doctoral Scholarship; Fondation du Grand defi Pierre Lavoie Doctoral Scholarship; McGill Faculty of Medicine F. S.B. Miller Fellowship; Research Institute of the McGill University Health Centre Desjardins Studentship in Child Health Research; Directorate of Higher Education Overseas Scholarship-Dikti Scholarship, Ministry of National Education, Republic of Indonesia; CIHR [201603PJT-148695]; BC Children's Hospital Foundation through its intramural Investigator Grant Award Program (IGAP); National Institute for Neurological Disorders and Stroke [R01NS082094]; Jakob Kamens Chair in Translational Neurotherapeutics; Fonds de Recherche du Quebec-Sante (FRQS); Canadian Institutes of Health Research; European Reference Network for Rare Neurological Disorders (ERN-RND) [739510], This study was supported by grants from the Canadian Institutes of Health Research (201610PJT-377869, MOP-G2-341146-159133-BRIDG), Fondation Les Amis d'Elliot, Leuco-Action, Fondation Lueur d'Espoir pour Ayden, Fondation le Tout pour Loo, and Reseau de Medecine Genetique Appliquee of the Fonds de Recherche du Quebec-Sante to G. Bernard. This research was enabled in part by support provided by Compute Canada (www.computecanada.ca).S.Perrier is supported by the Fonds de Recherche du Quebec en Sante (FRQS) Doctoral Scholarship, the Fondation du Grand defi Pierre Lavoie Doctoral Scholarship, the McGill Faculty of Medicine F. S.B. Miller Fellowship, and the Research Institute of the McGill University Health Centre Desjardins Studentship in Child Health Research. F. K.C. is a recipient of the Directorate of Higher Education Overseas Scholarship-Dikti Scholarship, Ministry of National Education, Republic of Indonesia. W.T. G. received funding from the CIHR (201603PJT-148695) and is supported by the BC Children's Hospital Foundation through its intramural Investigator Grant Award Program (IGAP). B.L. F. was supported by the National Institute for Neurological Disorders and Stroke (R01NS082094). A.V. receives funding from the Jakob Kamens Chair in Translational Neurotherapeutics. G. Bernard has received a Research Scholar Junior 1 award from the Fonds de Recherche du Quebec-Sante (FRQS) (2012-2016) and the New Investigator Salary Award from the Canadian Institutes of Health Research (2017-2022). I.K.M., M. Synofzik, D. Tonduti, B.P.v.d.W., M.S. V.d.K., and N.I.W. are members of the European Reference Network for Rare Neurological Disorders (ERN-RND), project ID 739510.

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.