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Background: To assess the effectiveness of a structured algorithm for pediatric positive airway pressure (PAP) initiation for the treatment of obstructive sleep apnea (OSA)., Methods: An algorithm was created to support pediatric PAP use and identify patients who could benefit from early behavioral consultation and education. Sleep providers implemented a unified introduction to PAP therapy with the PAP therapy toolkit. Through a collaborative approach with the medical equipment companies, pediatric patients were provided with PAP equipment before PAP titration studies and were allowed a gradual initiation of PAP therapy. PAP downloads were reviewed to determine improvements in compliance measured by percent of average days used and average minutes per night used., Results: Thirty-eight pediatric patients completed the PAP therapy algorithm. There was significant improvement in PAP compliance in percentage of days used (paired t test P value = 0.04), as well as an improvement (although not statistically significant) in average nightly use. Patients benefitted from close follow-up visits with the sleep advanced practice providers. Patients seen for the consultation with the pediatric behavioral psychologist showed statistically significant improvement in both percentage of days and average nightly use., Conclusions: Our pilot study shows that a behavioral and medical partnership using a structured algorithm was feasible and resulted in improved PAP compliance for our pediatric patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Emerging evidence suggests that endovascular thrombectomy is beneficial for treatment of childhood stroke, but the safety and effectiveness of endovascular thrombectomy has not been compared with best medical treatment. We aimed to prospectively analyse functional outcomes of endovascular thrombectomy versus best medical treatment in children with intracranial arterial occlusion stroke., Methods: In this prospective registry study, 45 centres in 12 countries across Asia and Australia, Europe, North America, and South America reported functional outcomes for children aged between 28 days and 18 years presenting with arterial ischaemic stroke caused by a large-vessel or medium-vessel occlusion who received either endovascular thrombectomy plus best medical practice or best medical treatment alone. Intravenous thrombolysis was considered part of best medical treatment and therefore permitted in both groups. The primary outcome was the difference in median modified Rankin Scale (mRS) score between baseline (pre-stroke) and 90 days (±10 days) post-stroke, assessed by the Wilcoxon rank test (α=0·05). Efficacy outcomes in the endovascular thrombectomy and best medical treatment groups were compared in sensitivity analyses using propensity score matching. The Save ChildS Pro study is registered at the German Clinical Trials Registry, DRKS00018960., Findings: Between Jan 1, 2020, and Aug 31, 2023, of the 241 patients in the Save ChildS Pro registry, 208 were included in the analysis (115 [55%] boys and 93 [45%] girls). 117 patients underwent endovascular thrombectomy (median age 11 years [IQR 6-14]), and 91 patients received best medical treatment (6 years [3-12]; p<0·0001). The median Pediatric National Institutes of Health Stroke Scale (PedNIHSS) score on admission was 14 (IQR 10-19) in the endovascular thrombectomy group and 9 (5-13) in the best medical treatment group (p<0·0001). Both treatment groups had a median pre-stroke mRS score of 0 (IQR 0-0) at baseline. The change in median mRS score between baseline and 90 days was 1 (IQR 0-2) in the endovascular thrombectomy group and 2 (1-3) in the best medical treatment group (p=0·020). One (1%) patient developed a symptomatic intracranial haemorrhage (this patient was in the endovascular thrombectomy group). Six (5%) patients in the endovascular thrombectomy group and four (5%) patients in the best medical treatment group had died by day 90 (p=0·89). After propensity score matching for age, sex, and PedNIHSS score at hospital admission (n=79 from each group), the change in median mRS score between baseline and 90 days was 1 (IQR 0-2) in the endovascular thrombectomy group and 2 (1-3) in the best medical treatment group (p=0·029). Regarding the primary outcome for patients with suspected focal cerebral arteriopathy, endovascular thrombectomy (n=18) and best medical treatment (n=33) showed no difference in 90-day median mRS scores (2 [IQR 1-3] vs 2 [1-4]; p=0·074)., Interpretation: Clinical centres tended to select children with more severe strokes (higher PedNIHSS score) for endovascular thrombectomy. Nevertheless, endovascular thrombectomy was associated with improved functional outcomes in paediatric patients with large-vessel or medium-vessel occlusions compared with best medical treatment. Future studies need to investigate whether the positive effect of endovascular thrombectomy is confined to older and more severely affected children., Funding: None., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Positional plagiocephaly (PP) is an asymmetric deformation of the skull as a consequence of external forces acting on a normal and pliable skull. The prevalence of PP ranges between 19.6% and 46.6%. Treatment options for PP include repositioning, physical therapy, and helmet orthoses. Consensus regarding the treatment of PP remains elusive due to the condition's imprecise natural history, dissimilar diagnostic strategies, and unreliable data asserting treatments' efficacy. Our aim was to conduct a systematic review of the tools used to diagnose, suggest treatment strategies, and assess outcomes for PP., Methods: We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to query a variety of databases. A total of 444 articles were imported into Covidence, a screening and data extraction tool for conducting systematic reviews., Results: After a series of screenings, 60 articles met inclusion criteria and were reviewed in detail. The information was entered into a data extraction list consisting of 16 variables in the categories of general information, diagnostic strategies, treatment modalities, and treatment outcomes. Most articles reported retrospective case series, which yielded level 4 evidence. Only one article reported the results of a randomized and blinded outcomes assessment trial. Such article yielded level 1 evidence and was rated as high quality for allocation, concealment, and blinding of personnel., Conclusion: The strategies used to diagnose and classify PP are a disparate list of measures most of which have no parallels making it impossible to offer treatment recommendations and generate generalizable knowledge., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to report., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Neonatal seizures (NS) represent an important clinical manifestation among critically ill infants and are often the first sign of underlying brain injury. Early recognition and treatment are essential to reduce morbidity and mortality. The present study investigated the NS management and treatment approaches employed by level II/III neonatal intensive care units (NICUs) across the United States to identify areas of consensus and variability., Methods: Personnel associated with level II/III NICUs were directly surveyed with an electronic questionnaire. Access to neurology specialists, on-site electroencephalography (EEG) monitoring, and use of antiseizure medications was directly queried. A total of 51 NICUs participated in this survey., Results: Twenty-five percent of the surveyed NICUs reported having an established clinical practice pathway available for treating NS. Twenty-four percent endorsed having written guidelines that provided a formal definition for the concept of "neonatal seizures." Although the majority of NICUs reported having phenobarbital available for rapid seizure management, most NICUs lacked access to additional antiseizure medications for treatment escalation. Twenty-four percent of the surveyed NICUs had no access to EEG monitoring available to them on-site. Daytime and overnight access to neurology consultants was limited and variable., Conclusions: Findings were consistent with a lack of equitable access for NS treatment. Areas of potential improvement include development and implementation of a protocol for rapidly treating NS that emphasizes enhanced access to EEG and rapid neurology consultation, acknowledging and improving upon resource limitations. These developments may eventually provide earlier detection, evaluation, and treatment of seizures in newborns, contributing to improved long-term outcomes., Competing Interests: Declaration of competing interest The authors declare no known conflicts of interest associated with this publication., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest.

Spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) is a rare autosomal recessive disorder due to mutations in the ASAH1 gene. SMA-PME is characterized by progressive muscle weakness from three to seven years of age, drug refractory epilepsy, and variable degree of cognitive decline. Nearly 50 cases have been reported worldwide so far. Here the authors present a case of 9-y-old boy affected by SMA-PME characterized by progressive proximal weakness, and lower motor neuron disease, as proven by muscle biopsy, electro diagnostic studies and whole exome sequencing (WES). WES revealed compound heterozygous missense variant in exon 12 of ASAH1 gene (chr8: g.18059385G>C) and exon 2 of ASAH1 gene (chr8: g.18075542T>C). Patient did not have cognitive decline and epilepsy and EEG record obtained was normal. In addition to reporting a novel variant in the ASAH1 gene causing SMA-PME disease, this paper discusses previous reports and literature of the disease., Competing Interests: Declarations Conflict of Interest None., (© 2023. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Stride velocity 95th centile (SV95C) is a wearable-derived endpoint representing the 5% fastest strides taken during everyday living. In July 2023, SV95C received European Medicines Agency (EMA) qualification for use as a primary endpoint in trials of patients with Duchenne muscular dystrophy (DMD) aged ≥ 4 years-becoming the first digital endpoint to receive such qualification. We present the data supporting this qualification, providing insights into the evidentiary basis of qualification as a digital clinical outcome assessment. Clinical trials, natural history studies, and patient surveys (ages 5 - 14 years) showed that SV95C is accurate, valid, reliable, sensitive, and clinically meaningful. SV95C significantly correlated with traditional DMD assessments, increased rapidly after steroid initiation (0.090 m/s 3 months post-treatment), and declined steadily in patients on stable steroid regimens. Compared with traditional assessments, SV95C demonstrated earlier sensitivity to disease progression (3 vs 9 months) and greater sensitivity at 12 months. Distribution- and anchor-based approaches revealed a change of - 0.10 to - 0.20 m/s as clinically meaningful. The EMA qualification of SV95C illustrates the willingness of regulators to accept novel digital endpoints for drug approval, setting an important precedent for the evidentiary basis of regulatory digital endpoint qualification that could transform clinical development in disorders affecting movement., Competing Interests: Declarations. Competing interests: L.S. is a member of scientific advisory boards for Novartis Gene Therapies (formerly AveXis), Biogen, Biophytis, Cytokinetics, Dynacure, F. Hoffmann-La Roche Ltd, GeneTx Biotherapeutics, REGENXBIO, Santhera Pharmaceuticals, and Sarepta Therapeutics, Inc., has consulted for Pfizer and Affinia, conducts research funded by Novartis Gene Therapies (formerly AveXis), Biogen, and F. Hoffmann-La Roche Ltd, holds part of the patent WO2017129890A1 with no financial interest, and has provided consultancy services to SYSNAV. P.S. is an employee of and hold stocks in F. Hoffmann-La Roche Ltd. M.P. reports no disclosures relevant to the manuscript. A.M. reports no disclosures relevant to the manuscript. N.B. reports no disclosures relevant to the manuscript. V.A.S. provides intellectual consultancies and teaching activities for Biogen, F. Hoffmann-La Roche Ltd, Novartis, Lupin, Dyne Therapeutics, and PTC Therapeutics. C.V. reports participation in scientific advisory boards for Novartis Gene Therapies (formerly AveXis), Biogen, PTC Therapeutics, F. Hoffmann-La Roche Ltd, Italfarmaco, and Sarepta Therapeutics, Inc., and is involved in research funded by Novartis Gene Therapies (formerly AveXis), Biogen, Sarepta Therapeutics, Inc., and F. Hoffmann-La Roche Ltd. U.S.S. is a member of scientific advisory boards for Novartis Gene Therapies (formerly AveXis), Biogen, F. Hoffmann-La Roche Ltd, Pfizer, Santhera Pharmaceuticals, Sarepta Therapeutics, Inc., Italfarmaco, and PTC Therapeutics, and has received honoraria for invited talks or chair positions in scientific symposia from Novartis Gene Therapies (formerly AveXis), Biogen, F. Hoffmann-La Roche Ltd, Pfizer, Santhera Pharmaceuticals, Sarepta Therapeutics, Inc., Italfarmaco, and PTC Therapeutics. M.S. has provided consultancy services for and received honoraria (as a member of scientific advisory boards) from Biogen, F. Hoffmann-La Roche Ltd, and Novartis Gene Therapies (formerly AveXis). A.M.S. reports no disclosures relevant to the manuscript. S.C.P. reports participation in scientific advisory boards for EspeRare Foundation, Wave Life Sciences Ltd, Argenx, and Sarepta Therapeutics, Inc., and has provided consultancy service for Alia Therapeutics and LSC Lifesciences. M.T. has participated in scientific advisory boards for Biogen, PTC Therapeutics, F. Hoffmann-La Roche Ltd, and Sarepta Therapeutics, Inc., and has received honoraria for invited lectures from Biogen, Sarepta Therapeutics, Inc., and PTC Therapeutics. A.N. reports participation in scientific advisory boards for Novartis Gene Therapies (formerly AveXis), Biogen, PTC Therapeutics, F. Hoffmann-La Roche Ltd, Italfarmaco, Pfizer, Dyne Therapeutics, and Sarepta Therapeutics, Inc., and is involved in research funded by Novartis Gene Therapies (formerly AveXis) and Biogen. P.F. reports no disclosures relevant to the manuscript. T. S. is an employee of Sarepta Therapeutics, Inc. and has stock and stock options. R.D.D. is Head of Clinical Development at Solid Biosciences, was previously employed at F. Hoffmann-La Roche Ltd, Santhera Pharmaceuticals, and Novartis, and has stock in Solid Biosciences and F. Hoffmann-La Roche Ltd. N.G. reports activities as a Data and Safety Monitoring Board member for Pfizer, Antisense Therapeutics, Wave Life Sciences Ltd, and Genethon. E.M. has served on clinical steering committees and/or as a consultant and received compensation from Italfarmaco, PTC Therapeutics, Sarepta Therapeutics, Inc., Santhera Pharmaceuticals, Pfizer Inc., F. Hoffmann-La Roche Ltd, Wave Life Sciences, NS Pharma, and Dyne Therapeutics, and is involved in research funded by Novartis Gene Therapies (formerly AveXis), Biogen, Sarepta Therapeutics, Inc., and F. Hoffmann-La Roche Ltd. V.S. has served on scientific advisory boards for Astellas Gene Therapies, Biogen, Edgewise Therapeutics, Ipsen, Kate Therapeutics, ML Bio Solutions, Novartis Gene Therapies, PepGen, F. Hoffmann-La Roche Ltd, Sanofi, Sarepta Therapeutics, Inc., Vertex Pharmaceuticals, and Wave Therapeutics, has received speaker honoraria from Pfizer, F. Hoffmann-La Roche Ltd, Sanofi, and Sarepta Therapeutics, Inc., has received grants for clinical research from Sarepta Therapeutics, Inc. and Sanofi, and has received support from the NIHR Newcastle Biomedical Research Centre. M.G.O. is an employee of and hold stocks in F. Hoffmann-La Roche Ltd. J.B. is an employee of and hold stocks in F. Hoffmann-La Roche Ltd. F.M. reports participation in scientific advisory boards for Novartis Gene Therapies (formerly AveXis), Biogen, F. Hoffmann-La Roche Ltd, Italfarmaco, Pfizer, Dyne Therapeutics, and Sarepta Therapeutics, Inc., and is involved in research funded by Novartis Gene Therapies (formerly AveXis), Biogen, Sarepta Therapeutics, Inc., and F. Hoffmann-La Roche Ltd. A.T. has nothing to disclose other than his employment at SYSNAV, a company that collaborated with the Institute of Myology to create ActiMyo®. M.A. was an employee of SYSNAV at the time that this manuscript was developed. D.E. has nothing to disclose other than his employment at SYSNAV, a company that collaborated with the Institute of Myology to create ActiMyo®., (© 2024. The Author(s).)

The interaction between basic science epilepsy researchers and clinical epileptologists is a longstanding issue. Efforts to provide opportunities for a dialogue between preclinical and clinical epilepsy professionals are crucial to reduce the knowledge gap between them and improve the translational success of neurobiology-based research. The International League Against Epilepsy (ILAE) Research and Innovation Task Force circulated a survey to investigate the need for an update on new clinical epilepsy concepts within the basic science community. The 336 respondents included basic scientists (BS), preclinical scientists (PCSs), and/or clinical scientists (CSs). The majority of the 237 BSs/PCSs were engaged in preclinical studies in translational epilepsy research and declared translational research as a priority research interest. Fewer respondents from low-middle-income countries than from upper-middle or high-income countries (40.7% vs 65%) considered translational research a critical aspect of their research. A broad understanding of both clinical and neurobiological aspects of epilepsy was declared by 48% of BSs/PCSs; 96% of CSs declared a superficial knowledge of neurobiology of epilepsy. Most BSs/PCSs were aware that epilepsy is a complex condition that should be investigated with the help of clinical epileptologists, even though concerns were expressed on the relationship with clinicians. A focused training program on emerging clinical epileptological aspects tailored for BSs/PCSs was recommended by 81% of the participants; the majority of respondents preferred either 1- or 2-week in-presence tutoring or continuous online training coordinated by ILAE at the regional/national level. The survey also underscored the value of educational programs on neurobiology of epilepsy targeting CSs and low-middle-income countries (LMIC) investigators., (© 2024 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Dravet syndrome (DS) is a severe genetic developmental and epileptic encephalopathy, primarily caused by SCN1A gene mutations. Historically, treatments like clobazam and valproate have been used without evidence from randomized controlled trials (RCTs). However, the therapeutic landscape of DS has evolved with multiple RCTs demonstrating the efficacy and safety of three antiseizure medications (ASMs): stiripentol, cannabidiol (CBD), and fenfluramine. In the absence of direct comparisons between these therapies, several network meta-analyses have been conducted to compare the ASMs, while expert consensus has independently been developed to formulate treatment guidelines. While these three ASMs show promise in reducing seizures, increasing awareness of non-seizure outcomes-such as cognitive development and quality of life-has shifted the focus of evaluation. Some recent real-world studies of these ASMs have reported improvements in these non-seizure outcomes, alongside sustained efficacy and safety. However, natural history studies continue to underscore persistent deficits in these areas and highlight suboptimal long-term seizure control despite the use of these therapies. This review addresses these gaps by first discussing network meta-analyses and treatment guidelines, along with the practical limitations of these approaches. It then examines the long-term efficacy, safety, non-seizure effects, and cost-effectiveness from real-world studies of these ASMs. Finally, emerging research on novel therapeutic approaches, including genetic and serotonergic modulation, is explored. By evaluating these developments, this review aims to guide clinical decision-making and propose future directions for optimizing DS care., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Parent training (PT) is an effective program for improving the parenting skills and mental health of parents of children with developmental disabilities (DD) and for improving children's behavioral problems. However, studies must substantiate the effectiveness of PT for the parents of adolescents with DD in improving parental mental health and children's problem behaviors with ample scientific evidence. This study is a retrospective observational study and has two objectives. The first is to examine the effectiveness of online adolescent PT (ON-APT), in which lectures on counseling skills are incorporated for the parents of adolescents with DD. The second aim is to examine the effects of different delivery conditions on community- and clinical-based ON-APT., Methods: Data from seven parents and children who participated in community-based ON-APT and 14 parents and 12 children who participated in clinical-based ON-APT were included in the analysis. Prior to the intervention (pre-test) and after the intervention (post-test), paired t -tests were conducted using the CBCL, BDI-II, and PATS scores to demonstrate the effectiveness of the ON-APT program. Second, a two-way repeated measures analysis of variance with aligned rank transform was conducted to assess the impact of varying ON-APT delivery conditions (clinical- versus community-based ON-APT) and time (pre- and post-tests) on the outcome variables., Results: ON-APT resulted in significant improvements in some children's problem behaviors (withdrawal). Community-based ON-APT resulted in improvements in some children's problem behaviors (total score, withdrawal, and social problems scales) compared with clinical-based ON-APT., Conclusion: This study shows the potential effectiveness of ON-APT, in which lectures on counseling skills are incorporated for parents of adolescents with DD. Further, a comparison between clinical-based and community-based ON-APT showed that integrating face-to-face consultations into ON-APT may improve children's problem behaviors. However, this study provides preliminary evidence for its potential efficacy, and future studies should demonstrate this efficacy through a validation design., Competing Interests: The authors declare no conflict of interest., (©2024 Tottori University Medical Press.)

Objective: To review the available literature concerning the definition of neonatal status epilepticus (SE) and/or seizure burden., Methods: The International League Against Epilepsy Neonatal Task Force performed a scoping review of the definitions of neonatal SE. Following a systematic literature review, articles were screened and data were abstracted regarding: (1) article characteristics (author identification, publication year, journal name, digital object identifier, title, objective, and study design); (2) cohort characteristics (sample size, gestational age, seizure etiology); (3) definition of SE and/or seizure burden; and (4) the method used to identify and classify SE, including routine EEG (EEG), continuous EEG monitoring (cEEG), amplitude-integrated EEG (aEEG), or clinical features., Results: The scoping review yielded 44 articles containing a definition of neonatal SE. Studies mainly included infants with hypoxic-ischemic encephalopathy or neonates considered at risk for seizures. SE identification and classification most often relied on cEEG. The majority of studies based the definition of SE on seizure duration, including summed duration of seizures comprising ≥50% of any 1-h epoch, recurrent seizures for >50% of the total recording time, or either electrographic seizures lasting >30 min and/or repeated electrographic seizures totaling >50% in any 1-h period. Seizure burden was reported in 20 studies, and the most commonly used approach assessed total seizure burden, defined as total duration of EEG seizures in minutes. Sixteen studies assessed the relationship between seizure burden and outcomes, and most identified a significant association between higher seizure burden and unfavorable outcomes., Significance: This scoping review demonstrates a substantial variation in neonatal SE definitions across the literature. The most common definitions were based around a 30-min seizure duration criterion, but evidence was insufficient to support that 30 min was a cutoff defining prolonged seizures or that seizures exceeding this burden were more likely to be pharmacoresistant or associated with worse outcomes. As a next step, the Neonatal Task Force intends to develop a standardized approach to assessing and describing neonatal seizure burden and defining neonatal SE., Plain Language Summary: Prolonged seizures are a neurologic emergency, if untreated, can lead to permanent injury or death. In adults and children, seizures lasting longer than 30 min are believed to cause brain damage. However, it is not clear if this definition can be applied to neonates. The International League Against Epilepsy Neonatal Taskforce performed a scoping literature review which identified 44 articles containing a definition of neonatal status epilepticus. In this article, the authors reviewed the current used definitions for prolonged seizures in neonates to establish a relationship between seizure duration and neurological outcome. As a next step, the Neonatal Task Force intends to develop a standardized approach to assessing and describing neonatal seizure burden and defining neonatal SE., (© 2024 The Author(s). Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

The diagnosis of epilepsy based on visual inspection of electroencephalogram (EEG) signals is inherently complex and prone to error, even for physicians, mainly due to the large number of signals involved and the variability between individuals. These same challenges make the development of portable epilepsy diagnostic systems for everyday use difficult. Key obstacles include the immense complexity of signal processing and the inherent ambiguity in accurately classifying disease. For these reasons, we propose in this paper the deployment of compressive sensing to condense EEG signals while preserving relevant information, allowing seizure classification based on systematically selected features of the reconstructed signals. Based on a dataset comprising EEG recordings from 13 epileptic patients with various seizure types, we explore the deployment of the discrete cosine transform (DCT) and random matrix multiplication for compression ratios ranging from 5% to 70%, balancing data reduction with signal fidelity. Following the extraction of relevant features, selection was performed based on mutual information and a correlation matrix to preserve only the most relevant features for analysis. For classification, following a comparison of adequate machine learning models, XGBoost is chosen as it realizes a classification accuracy of 98.78%. The CS method was implemented on an STM32 microcontroller and a Raspberry Pi for reconstruction and classification, to demonstrate feasibility as an embedded system. At 70% compression, significant improvements have been observed: 70% file size reduction, 84% decrease in transmission time (from 2518.532s to 400.392s), and substantial energy savings (e.g., from 11.5±0.707 mWh to 4.5±0.707 mWh for Patient 12). Thereby, the signal quality was maintained with PSNR of 16.15±3.98 and Pearson correlation coefficient of 0.68±0.15. The proposed system highlights the potential for efficient, portable, real-time epilepsy diagnosis systems that achieve precise and fully automated seizure classification., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Neonatal tone abnormalities can often be the first indication of cerebral palsy (CP) and need regular developmental assessments by a multidisciplinary team. The need for early diagnosis and treatment during the height of neural plasticity is crucial. Currently, the number of clinical practice guidelines and the quality of evidence for treatment of tone in neonates is insufficient. In this review, we discuss the physiology of tone abnormalities including structural-functional components of motor control and time-dependent etiology of injury. We provide a guideline for assessment of a neonate with concern for tone abnormalities including a discussion on available diagnostic and functionality rating scales. Lastly, we describe the importance of a multidisciplinary care team involving the patient's caregiver as well as non-pharmacological, pharmacological, and surgical treatment options for tone abnormalities. We stress the importance of regular, serial examinations for tone as these neonates get older to assess eligibility for additional interventions., Competing Interests: Declaration of competing interest None., (Published by Elsevier Ltd.)

Human inborn errors of thymic T cell tolerance underlie the production of autoantibodies (auto-Abs) neutralizing type I IFNs, which predispose to severe viral diseases. We analyze 131 female patients with X-linked dominant incontinentia pigmenti (IP), heterozygous for loss-of-function (LOF) NEMO variants, from 99 kindreds in 10 countries. Forty-seven of these patients (36%) have auto-Abs neutralizing IFN-α and/or IFN-ω, a proportion 23 times higher than that for age-matched female controls. This proportion remains stable from the age of 6 years onward. On imaging, female patients with IP have a small, abnormally structured thymus. Auto-Abs against type I IFNs confer a predisposition to life-threatening viral diseases. By contrast, patients with IP lacking auto-Abs against type I IFNs are at no particular risk of viral disease. These results suggest that IP accelerates thymic involution, thereby underlying the production of auto-Abs neutralizing type I IFNs in at least a third of female patients with IP, predisposing them to life-threatening viral diseases., (© 2024 Rosain et al.)

Objective: There is a growing number of monogenic disorders implicated in neurodevelopmental disorders (NDDs), including autism spectrum disorder and intellectual disability. Motor impairment is frequently seen in these disorders, although not clearly defined. We aimed to characterize the motor phenotype of genetic NDDs., Methods: We analyzed data from Simons Searchlight, collecting information on patients with genetic NDDs. Data analyzed included Vineland Adaptive Behavior Scales Second Edition (Vineland-II) motor standard scores, motor milestones and tone abnormalities., Results: In total, 959 patients with 57 genetic disorders were included. Disorders associated with Vineland-II motor standard score <56 included GRIN2B-related disorder (mean standard score = 53.5), HNRNPH2-related disorder (mean standard score = 55.8) and SCN2A-related disorder (mean standard score = 49.9). The only genetic condition with a mean age of sitting unsupported ≥18 months was GRIN1-related disorder (mean age = 26.3 months). Genetic conditions with a mean age of walking independently ≥36 months included CTNNB1-related disorder (mean age = 37.4 months) and HNRNPH2-related disorder (mean age = 41.9 months). Tone abnormalities included hypotonia in 83% (577/696), hypertonia in 16% (112/696), a diagnosis of cerebral palsy (CP) in 10% (73/696) and a diagnosis specifically of spastic CP in 3% (23/696)., Interpretation: Patients with genetic NDDs have a spectrum of motor impairment, which warrant further characterization., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Tuberous sclerosis Complex (TSC) is a genetic disorder characterized by multisystem involvement, with epilepsy affecting 80-90% of patients, often beginning in infancy. Early-life seizures in TSC are associated with poor neurodevelopmental outcomes, underscoring the importance of timely and effective management. This review explores the evolving treatment landscape for TSC-associated seizures in young children, focusing on three recently approved or license-expanded therapies: vigabatrin, everolimus, and cannabidiol. The efficacy and safety profiles of these treatments are examined based on clinical trials and real-world evidence, with a focus on their use in treating seizures in young children. The preemptive use of vigabatrin in clinical studies has also been carefully reviewed. A treatment algorithm is proposed, emphasizing early diagnosis, prompt initiation of appropriate therapy, and a stepwise approach to managing both infantile spasms and focal seizures. The algorithm incorporates these newer therapies alongside traditional antiseizure medications and non-pharmacological approaches. Challenges in optimizing treatment strategies, minimizing side effects, and improving long-term outcomes are discussed. This review aims to guide clinicians in navigating the complex landscape of early-life seizures associated with TSC, ultimately striving for improved seizure control and better developmental outcomes in this vulnerable population., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Debopam Samanta collected the data, analyzed and interpreted them, and drafted and revised the manuscript for intellectual content.He declares no potential conflicts of interest with respect to this article's research, authorship, and/or publication.]., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Objectives: Data on hypersensitivity reactions (HR) to individual anti-seizure medications (ASMs), and reactions to additional ASMs, is often limited by sample size. This data is vital in helping clinicians identify initial and subsequent ASMs to use in treating persons with epilepsy (PWE). Using a very large dataset, our study attempts to quantify the occurrence of HR across 31 different ASMs. We also attempt to investigate whether certain pairs of ASMs are associated with a higher frequency of HR., Methods: The Slicer-Dicer tool in the Epic electronic medical records system was used to analyze patients seen between 2012 and 2022 at a large healthcare system in Kentucky with recorded exposures to 31 different ASMs. Incidence of HR with these ASMs were identified, both with single drugs or pairs of drugs, as well as incidence of HR stratified by sex and ASM structure., Results: A total of 573,571 patients with 967,168 exposures were analyzed. Phenobarbital had the highest rate of HR at 12.9 %. Usage of aromatic ASMs were most associated with patients having HR to other ASMs. HR to 13/31 studied ASMs was more likely to occur in females, while HR was more likely in males with lacosamide. Aromatic ASMs were more likely (p < 0.0001) to be associated with HR compared to non-aromatic ASMs. Carbamazepine and the related drugs oxcarbazepine and eslicarbazepine were associated with the greatest number of drug pairings in which the patient had HR to both medications at any time point., Discussion: Our data reveals important patterns in HR to ASMs that may be valuable to clinicians treating PWE. Clinicians should monitor closely for HR when beginning a new ASM in a patient who has taken an aromatic ASM, especially carbamazepine, oxcarbazepine, or eslicarbazepine as well as phenobarbital., Competing Interests: Declaration of competing interest The authors report no disclosures or conflicts of interest., (Copyright © 2024 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Developmental and epileptic encephalopathies (DEEs) are a group of childhood-onset epilepsy syndromes characterized by frequent seizures, severe cognitive and behavioral impairments, and poor long-term outcomes. These conditions are typically refractory to currently available medical therapies, prompting recent exploration of neuromodulation treatments such as deep brain stimulation (DBS) and responsive neurostimulation (RNS), which aim to modulate epileptic networks spanning cortical and subcortical regions. These advances have occurred alongside an improved understanding of syndrome-specific and interictal epileptiform discharge/seizure-specific brain networks. By targeting key nodes within these networks, DBS and RNS hold promise for influencing seizures and associated cognitive and behavioral comorbidities. Initial experiences with centromedian (CM) thalamic DBS for Lennox-Gastaut syndrome (LGS) have shown modest efficacy across multiple seizure types. Reports also indicate the application of DBS and RNS across various genetic and structural etiologies commonly associated with DEEs, with mixed success. Although DBS and RNS are increasingly used in LGS and other DEEs, their mixed efficacy highlights a knowledge gap in understanding why some patients with LGS do not respond and which neuromodulation approach is most effective for other DEEs. To address these issues, this review first discusses recent neuroimaging studies showing similarities and differences in the epileptic brain networks underlying various DEEs, revealing the common involvement of the thalamus and the default-mode network (DMN) across multiple DEEs. We then examine thalamic DBS for LGS to illustrate how such network insights may be used to optimize neuromodulation. Although network-based neuromodulation is still in its infancy, the LGS model may serve as a framework for other DEEs, where optimal treatment necessitates consideration of the underlying epileptic networks. Lastly, the review suggests future research directions, including individualized connectivity assessment and biomarker identification through collaborative efforts, which may enhance the therapeutic potential of neuromodulation for individuals living with DEEs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The median cost of anti-seizure medications (ASM) in the United States (U.S.) nearly doubled per person between 2006 and 2021. This increase, combined with shifts in ASM usage and the impact of the COVID-19 pandemic on drug supply chains amid rising inflation, underscored the urgent need to scrutinize ASM pricing dynamics. This study aimed to analyze the complex dynamics of ASM pricing in the U.S. over the past decade (2013-2023); this included how the entry of generic ASMs influenced the pricing of brand-name counterparts and what impacted price variations across different ASM formulations (e.g., significant inflation, the COVID-19 pandemic)., Methods: This study utilized National Average Drug Acquisition Cost (NADAC) data from November 2013 to July 2023. We adjusted ASM prices for inflation using the Consumer Price Index for Medicinal Drugs - Seasonally Adjusted (CPI-MDS). Statistical analyses included fixed effects regressions and multivariable regression analysis to evaluate the impact of inflation, the number of medication labelers, and the COVID-19 pandemic on ASM prices., Results: Our study analyzed 23 ASMs approved by the U.S. Food and Drug Administration (FDA), which encompassed 223 oral formulations:112 brand-name and 111 generics. From 2013-2016 to 2020-2023, accounting for standard deviations (SD), the average price of brand-name ASMs increased from $8.71 (SD 5.9) to $15.43 (SD 10.7), while generic ASMs saw a slight decrease from $1.39 (SD 1.8) to $1.26 (SD 1.6). Consequently, the price gap between brand-name and generic ASMs surged from 1452.39 % to 3399.26 %. The proportion of matched brand-name and generic ASMs with a price difference of 1000 %-9999 % increased from 32.88 % (2013-2016) to 41.43 % (2020-2023), while those exceeding 10,000 % rose from 16.44 % to 20 % in the same period. Generic immediate-release (IR) formulations were significantly less expensive than extended-release (ER) or delayed-release (DR) counterparts, with cost differences reaching up to 7751.20 %. The number of medication labelers was inversely related to generic ASM prices, which decreased by 5.45 % (p = 0.001) with each additional generic labeler, while brand-name ASM prices increased by 2.46 % (p < 0.001) with each additional generic labeler. The COVID-19 pandemic led to a 24.4 % increase in brand-name ASM prices and a 23.1 % decrease in generic ASM prices., Conclusions: The findings reveal an expanding price disparity between brand-name and generic oral ASMs. An inverse relationship was observed between the number of medication labelers and generic ASM prices, with additional labelers driving down generic prices. However, introducing more generic labelers led to a significant increase in brand-name ASM prices. Furthermore, following patent expirations, brand-name ASM prices rose-a trend explained by the "generics paradox," where, contrary to expectations, brand prices do not decrease and may even increase when generics enter the market. These findings underscore the need for targeted interventions in drug pricing policies to manage the rising costs associated with epilepsy treatment. To ensure equitable access to ASMs, stakeholders must understand and address the factors driving these pricing dynamics., Competing Interests: Declaration of competing interest The authors report no disclosures., (Copyright © 2024 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

There are limited treatment options for individuals with drug-resistant idiopathic generalized epilepsy (IGE). Small, limited case series suggest that centromedian thalamus deep brain stimulation (CM-DBS) may be an effective treatment option. The optimal CM-DBS target for IGE is underexamined. Here, we present a retrospective analysis of CM-DBS targeting and efficacy for five patients with drug-resistant IGE. Volume of tissue activated (VTA) overlap with CM nucleus was performed using an open-source toolbox. Median follow-up time was 13 months. Median convulsive seizure frequency reduction was 66%. One patient had only absence seizures, with >99% reduction in absence seizure frequency. Four patients had electrode contacts positioned within the CM nucleus target, all of whom had >50% reduction in primary semiology seizure, with 85% median seizure reduction (p = .004, paired-sample t test). Volumetric "sweet-spot" mapping revealed that best outcomes were correlated with stimulation of the middle ventral CM nucleus. Connectivity strength between the sweet-spot region and central peri-Rolandic cortex was increased significantly relative to other cortical regions (p = 8.6 × 10 -4 , Mann-Whitney U test). Our findings indicate that CM-DBS can be an effective treatment for patients with IGE, highlight the importance of accurate targeting and targeting analysis, and within the context of prior work, suggest that ideal CM-DBS targets may be syndrome specific., (© 2024 International League Against Epilepsy.)

Background: The prognosis for patients with central nervous system (CNS) retinoblastoma (RB) (trilateral or stage 4b metastatic RB) treated with high-dose chemotherapy and autologous stem cell transplant (HDC-ASCT) remains poor. The impact of irradiation when administered as part of upfront therapy post HDC-ASCT on treatment outcomes and survival is unknown., Methods: We performed a retrospective review of all patients with CNS RB (seven stage 4b, eight trilateral, one pineal lesion belonging to methylation group RB) who underwent induction chemotherapy with an intent to proceed to HDC-ASCT at two institutions., Results: Twelve of 16 patients (n = 75%) achieved an objective response to induction chemotherapy, while four patients had progressive/refractory disease; two patients responded to subsequent therapy and proceeded to ASCT, and two patients did not. Seven of 14 patients who underwent HDC-ASCT, received radiotherapy as part of upfront therapy post HDC-ASCT in the form of craniospinal irradiation (CSI) (n = 3), intraventricular radioimmunotherapy (n = 3), or both CSI and intraventricular radioimmunotherapy (n = 1). The Kaplan-Meier estimate of overall survival for these patients was 62.5% at 5 years; no patients developed second malignant neoplasms within the radiation fields. For the seven patients who did not receive radiotherapy, the overall survival was 28.6% at 5 years., Conclusions: CSI (23.4 Gy) alone or in conjunction with intraventricular RIT may have clinical utility in eliminating persistent MRD post HDC-ASCT, contributing to improved disease-free survival in patients with CNS RB. This treatment strategy merits evaluation in a prospective, multicenter clinical trial for patients with CNS metastatic RB., (© 2024 Wiley Periodicals LLC.)

Background: Pediatric stroke is an important cause of morbidity in children. Although research can be challenging, large amounts of data have been captured through collaborative efforts in the International Pediatric Stroke Study (IPSS). This study explores the use of an advanced artificial intelligence program, the Generative Pre-trained Transformer (GPT), to enter pediatric stroke data into the IPSS., Methods: The most recent 50 clinical notes of patients with ischemic stroke or cerebral venous sinus thrombosis at the UTHealth Pediatric Stroke Clinic were deidentified. Domain-specific prompts were engineered for an offline artificial intelligence program (GPT) to answer IPSS questions. Responses from GPT were compared with the human rater. Percent agreement was assessed across 50 patients for each of the 114 queries developed from the IPSS database outcome questionnaire., Results: GPT demonstrated strong performance on several questions but showed variability overall. In its early iterations it was able to match human judgment occasionally with an accuracy score of 1.00 (n = 20, 17.5%), but it scored as low as 0.26 in some patients. Prompts were adjusted in four subsequent iterations to increase accuracy. In its fourth iteration, agreement was 93.6%, with a maximum agreement of 100% and minimum of 62%. Of 2400 individual items assessed, our model entered 2247 (93.6%) correctly and 153 (6.4%) incorrectly., Conclusions: Although our tailored generative model with domain-specific prompt engineering and ontological guidance shows promise for research applications, further refinement is needed to enhance its accuracy. It cannot enter data entirely independently, but it can be employed in tandem with human oversight contributing to a collaborative approach that reduces overall effort., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of competing interest The corresponding author (Mehreen Shahid, DO) confirms on behalf of the other authors (Darina Dinov DO, J. Nicholas Brenton MD) that there are no competing interests with the writing of this manuscript.

The clinical diagnosis of patients with multisystem involvement including a pronounced neurologic damage is challenging. High-throughput sequencing methods remains crucial to provide an accurate diagnosis. In this study, we reported a Tunisian patient manifesting hypotonia and global developmental delay with visual and skin abnormalities. Exome sequencing was conducted followed by segregation analysis and, subsequently additional investigations. In silico analysis of non-synonymous variants (nsSNPs) described in COG5 in conserved positions was made. Results revealed a homozygous missense variant c.298 C > T (p.Leu100Phe) in the COG5 inherited from both parents. This variant altered both protein solubility and stability, in addition to a putative disruption of the COG5-COG7 interaction. This disruption has been confirmed using patient-derived cells in vitro in a COG5 co-immuno-precipitation, where interaction with binding partner COG7 was abrogated. Hence, we established the COG5-CDG diagnosis. Clinically, the patient shared common features with the already described cases with the report of the ichtyosis as a new manifestation. Conversely, the CADD scoring revealed 19 putatively pathogenic nsSNPs (Minor Allele Frequency MAF < 0.001, CADD > 30), 11 of which had a significant impact on the solubility and/or stability of COG5. These properties seem to be disrupted by six of the seven missense COG5-CDG variants. In conclusion, our study expands the genetic and phenotypic spectrum of COG5-CDG disease and highlight the utility of the next generation sequencing as a powerful tool in accurate diagnosis. Our results shed light on a likely molecular mechanism underlying the pathogenic effect of missense COG5 variants, which is the alteration of COG5 stability and solubility., (© 2024. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

To optimize the clinical approach to non-convulsive status epilepticus (NCSE), it is essential to gain insight into its long-term effects on cognition and behaviors. Here, we investigated limbic NCSE-induced hippocampal injury and behavioral deficits in peri-adolescent rats. NCSE was induced in P43 Sprague Dawleyrats with intrahippocampal subconvulsive doses of kainic acid (NCSE group, n = 14) under continuous epidural cortical electroencephalography (EEG). Controls received volume-matched saline (n = 18). Following one month of continuous EEG monitoring, rats were sequentially subjected (P73-91) to the open field, the Morris water maze (MWM), and the modified two-way active avoidance (MAAV). Rats were sacrificed at P91 to histologically assess hippocampal injury with NeuN (neuronal nuclei) staining, levels of GFAP (glial fibrillary acidic protein), and synaptophysin (Syp). Following kainic acid administration, the NCSE group experienced electroclinical seizures characterized by behavioral arrest and oromotor automatisms without tonic-clonic activity (latency: 15.93 ± 4.70 min, duration: 68.35 ± 17.97 min). There were no seizure recurrences in the rest of the long-term recordings. Compared to controls, NCSE rats had impaired place learning in the MWM, and lower rates of context-cued shock avoidance in the MAAV (p < 0.05). The NCSE and control groups had comparable hippocampal neuronal densities and GFAP levels, but NCSE rats had significantly lower hilar Syp levels. One episode of limbic NCSE during peri-adolescence results in later life hippocampal synaptic dysfunction and contextual learning deficits. These data suggest that the diagnosis and treatment of NCSE should be prompt., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Evaluate the relationship between first and second-line medication dosing and progression to refractory status epilepticus (RSE) in children., Methods: This is a retrospective analysis of prospectively collected data from September 2014 to February 2020 of children with status epilepticus (SE) who received at least two antiseizure medications (ASMs). We evaluated the risk of developing RSE after receiving a low total benzodiazepine dose (lower than 100 % of the minimum recommended dose for each benzodiazepine dose administered within 10 min) and a low first non-benzodiazepine ASM dose (lower than 100 % of the minimum recommended dose of non-benzodiazepine ASM given as the first single-dose) using a logistic regression model, adjusting for confounders such as time to ASMs. The proportion of patients receiving low first non-benzodiazepine ASM doses was calculated and a logistic regression model was used to evaluate risk factors for low dosing of the first non-benzodiazepine ASM., Results: Among 320 children, 170 (53.1 %) developed RSE, and 150 (46.9 %) responded to the first non-benzodiazepine ASM dose (non-RSE). One hundred thirty-seven (42.8 %) received a low total benzodiazepine dose, and 128 (40 %) received a low first non-benzodiazepine ASM dose. The odds of developing RSE were not higher after a low total benzodiazepine dose (OR=0.76, 95 %CI 0.47-1.23, p = 0.27) or low first non-benzodiazepine ASM dose (OR=0.85, 95 %CI 0.42-1.71, p = 0.65). Receiving a low first non-benzodiazepine ASM dose was independently associated with having received a low total benzodiazepine dose (OR=1.65, 95 %CI 1.01-2.70, p = 0.04)., Conclusion: For most patients, dosing variability in first and second-line medications for SE was not the sole clinical feature predicting progression to RSE in this cohort of benzodiazepine-resistant patients. Identification of additional modifiable clinical biomarkers that predict progression to RSE is needed. Though lower ASM doses did not predict RSE in this model, the administration of ASMs at doses likely to prevent RSE remains crucial in SE treatment., Competing Interests: Declaration of competig interest TL is part of pending patent applications to detect and predict seizures and to diagnose epilepsy. He receives research support from the NIH, the Epilepsy Research Fund, and Epitel. He received research grants from Sage, Lundbeck, Eisai, Upsher-Smith, Mallinckrodt, Pfizer, and MIKU in the past. He served as a consultant for Engage and Upsher Smith, in the past., (Copyright © 2024. Published by Elsevier Ltd.)

Hypomyelinating leukodystrophy-5 (HLD5) is a rare autosomal recessive hypomyelination disorder characterized by congenital cataract, progressive neurologic impairment, and myelin deficiency in the central and peripheral nervous system, caused by mutations in the HYCC1 gene. Here we report a 23-year-old girl with HLD5 from unrelated families. Molecular analysis was performed using sequence screening of the HYCC1 gene. In addition, in silico prediction tools and molecular investigation were used to predict the structural effect of the mutations. Results showed a novel compound heterozygous mutation in the HYCC1 gene. Moreover, in silico tools and 3D structural modeling revealed that c.521C > A (p.Ala174Glu) and c.652C > G (p.Gln218Glu) mutations could affect the structure, stability, and conformational analyses in the N-ter domain of the Hyccin protein. We also, we compared the phenotype of our patient with those of previously reported cases with HLD5 syndrome and our findings indicate the absence of reliable genotype-phenotype correlations. To the best of our knowledge, this is the first report describing a Tunisian HLD5 patient with compound heterozygous mutations (c.521C > A (p.Ala174Glu) and c.652C > G (p.Gln218Glu)) in HYCC1 gene., (© 2024. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

Background: Accurate classification is essential for addressing childhood movement disorders (MD), but the common coexistence of multiple MDs complicates this process., Objective: The aim was to assess inter-rater agreement on classifying hyperkinetic MDs among pediatric neurologists with expertise in MDs., Methods: Five pediatric neurologists were requested to examine 112 videos of 66 pediatric patients. Based on the Movement Disorder-Childhood Rating Scale, 3 queries were posed: (Q1) Is there more than 1 MD? (Q2) What is the (predominant) MD? (Q3) What is the other MD (if present)?, Results: The final agreement rates were 57.5% for Q1, 66.6% for Q2, and 43.9% for absolute agreement. All videos with absolute agreement at the first evaluation featured 1 MD, whereas only 2 videos with multiple MDs could totally agree in the final review., Conclusions: This study reveals significant discordance in classification even among pediatric neurologists with expertise in MDs and highlights the necessity for a standardized approach., (© 2024 International Parkinson and Movement Disorder Society.)

Objective: To assess for improvement in diagnostic efficiency following implementation of an institutional pediatric stroke alert protocol at a quaternary children's hospital, and to compare characteristics of in-hospital (IH) and out-of-hospital (OH) stroke alert activations., Study Design: We retrospectively reviewed data from pediatric stroke alerts called for children between age 1 month and 21 years of age at our quaternary children's hospital between October 2016 and October 2022 after implementation of an institutional stroke alert protocol. Generalized linear models assessed code-to-image (CTI) time over the study period, with and without interaction terms for alert location. Demographic, clinical, and imaging characteristics between IH and OH alerts were compared using Fisher's exact test or Mann-Whitney U test., Results: Of 206 total stroke activations, 129 (62.6%) occurred IH and 77 (37.4%) occurred OH. Overall mean CTI time decreased by 4.56 minutes per year (P = .007) after adjusting for confounders. The association between year and mean CTI time was significantly stronger for IH alerts (decrease of 8.33 minutes/year) compared with OH alerts (increase of 1.90 minutes/year). Subgroup analyses showed that CTI for computed tomography (CT) ± CT angiography and magnetic resonance imaging (MRI) without sedation improved, although CTI time for MRI with sedation did not change over time. IH/OH divergent trends were consistent for CT ± CTA and nonsedated MRI., Conclusions: After implementation of a pediatric stroke alert protocol, we observed a steady and significant improvement in CTI times for IH, but not OH alerts., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Muscle diseases cover a diverse group of disorders that in most cases are hereditary. The rarity of the individual muscle diseases provides a challenge for researchers when wanting to establish natural history of the conditions and when trying to develop diagnostic tools, therapies, and outcome measures to evaluate disease progression. With emerging molecular therapies in many genetic muscle diseases, as well as biological therapies for the immune-mediated ones, biological biomarkers play an important role in both drug development and evaluation. In this review, we focus on the role of biological biomarkers in muscle diseases and discuss their utility as surrogate endpoints in therapeutic trials. We categorise these as either 1) disease unspecific markers, 2) markers of specific pathways that may be used for more than one disease or 3) disease-specific markers. We also propose that evaluation of specific therapeutic interventions benefits from biological markers that match the intervention., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The diagnosis of Duchenne muscular dystrophy (DMD) is significant at any stage, however an early diagnosis in a presymptomatic or very early phase of DMD, offers unique opportunities and challenges for families and health care providers. Currently, there is limited evidence as to the optimal models of care during this stage of the condition.. To address this, in 2023, Treat-NMD facilitated the Early Diagnosis for DMD project; bringing together 42 experts from across Europe, the US and Australasia, including health care professionals, researchers, and people with lived experience to discuss the complexities of an early or newborn diagnosis of DMD, and provide recommendations regarding approaches to multidisciplinary care. A series of virtual meetings followed by a hybrid workshop resulted in broad recommendations to support clinicians in caring for children and families following an early diagnosis of DMD. The workshop did not define a cut-off for early diagnosis, however much of the discussion focused on diagnoses that occurred prior to 2 years. There is recognition that boys may first present with non-motor symptoms, such as speech delay or neurodevelopmental issues that are secondary to their dystrophinopathy, and therefore this report refers reflects that infants with DMD may be presymptomatic or early symptomatic., Competing Interests: Declaration of competing interest There are no direct conflicts of interest related to this manuscript, however full disclosures are listed below: Michelle Lorentzos has been an investigator on clinical trials sponsored by Pfizer Sarepta, PTC, Antisense and Dyne and engaged in advisory work by way of participation in Medical Advisory Boards for Roche. Laurent Servais has given consultancy/is member of the board for Dyne, Entrada, Wave, Pfizer, Santhera, Italfarmaco, Sysnav, RegenexBio & Solid. Julie Parsons has been an investigator for clinical trials sponsored by Novartis, Biogen, Biohaven, Scholar Rock, PTC Therapeutics and has engaged in advisory work with Novartis, Biogen, Scholar Rock, Pfizer and Genentech. Kristi Jones has been an investigatory on clinical trials sponsored by PTC, Sarepta, Pfizer GSK/Biomarin/Prosensa, Dyne, NS Pharma, Wave Life Sciences, Roche and Antisense Therapeutics and has engaged in work by way of speaking engagements to government on behalf of, and advisory boards for Roche, Precision Biosciences, Pfizer Novartis, Wave Life Sciences, Biomarin/Prosensa Biogen and PTC Therapeutics., (Copyright © 2024.)

The emergence of adeno-associated virus (AAV)-based gene therapy has brought hope to patients with severe monogenic disorders. However, immune responses to AAV vectors and transgene products present challenges that require effective immunosuppressive strategies. This systematic review focuses on the immunosuppressive protocols used in 38 clinical trials and 35 real-world studies, considering a range of monogenic diseases, AAV serotypes, and administration routes. The review underscores the need for a deeper understanding of immunosuppressive regimens to enhance the safety and effectiveness of AAV-based gene therapy. Characterizing the immunological responses associated with various gene therapy treatments is crucial for optimizing treatment protocols and ensuring the safety and efficacy of forthcoming gene therapy interventions. Further research and understanding of the impact of immunosuppression on disease, therapy, and route of administration will contribute to the development of more effective and safer gene therapy approaches in the future., Competing Interests: Declaration of interests M.A. is the academic founder and Chief Scientific Officer of BlackfinBio. M.A. is a co-founder of Crucible Therapeutics. L.S. has given lectures/consultancy for Pfizer/RegenexBio/Sarepta/Novartis and Illumina. J.K. has received research funding from Quell Therapeutics., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The differential diagnosis of suspected multiple sclerosis has been developed using data from North America, northern Europe, and Australasia, with a focus on White populations. People from minority ethnic and racial backgrounds in regions where prevalence of multiple sclerosis is high are more often negatively affected by social determinants of health, compared with White people in these regions. A better understanding of changing demographics, the clinical characteristics of people from minority ethnic or racial backgrounds, and the social challenges they face might facilitate equitable clinical approaches when considering a diagnosis of multiple sclerosis. Neuromyelitis optica, systemic lupus erythematous, neurosarcoidosis, infections, and cerebrovascular conditions (eg, hypertension) should be considered in the differential diagnosis of multiple sclerosis for people from minority ethnic and racial backgrounds in North America, northern Europe, and Australasia. The diagnosis of multiple sclerosis in people from a minority ethnic or racial background in these regions requires a comprehensive approach that considers the complex interplay of immigration, diagnostic inequity, and social determinants of health., Competing Interests: Declaration of interests LA has received research support from the National Multiple Sclerosis Society, National Institutes of Health National Institute of Neurological Disorders and Stroke, Bristol Myers Squibb Foundation, Race to Erase MS Foundation, and Biogen Idec; is a local Principal Investigator for commercial trials funded by Genentech, Sanofi, and Genzyme; and declares consulting fees from Biogen Idec, Novartis, Genentech, and EMD Serono. DR has received research support from MS Canada, the National Multiple Sclerosis Society, Consortium of Multiple Sclerosis Centers, University of Toronto Division of Neurology, and Roche Canada; and has received speaker or consultant fees from Alexion, Biogen, EMD Serono, Horizon Therapeutics, Novartis, Roche, and Sanofi Aventis. OC is a member of the data and safety monitoring board for Novartis, has served on one advisory board for Biogen, and has received a speaker honorarium from Merck. DO has received research support from the National Institutes of Health, National Multiple Sclerosis Society, Patient-Centered Outcomes Research Institute, Race to Erase MS Foundation, Genentech, Genzyme, and Novartis; and has received consulting fees from Biogen Idec, Bristol Myers Squibb, Genentech/Roche, Genzyme, Janssen, Novartis, and Merck. MM has served on scientific advisory boards for Sanofi, Novartis, and Merck; and received honoraria for lecturing from Biogen, Merck, Novartis, Roche, Genzyme, and Bristol Myers Squibb. VR has received honoraria from the Autonomous University of Barcelona, Roche, Corne Neurosciences, and the Multiple Sclerosis Association of America; and is a consultant (Expert Opinion Program) for Teladoc Health International. DK has served as a consultant for CVS Health. RD has received research support from the UK MS Society, National Multiple Sclerosis Society, BMA Foundation, Horne Family Charitable Foundation, Biogen, and Merck; and has received honoraria for advisory boards and educational activities from Biogen, Novartis, Sandoz, Roche, Janssen, and Merck. MW is a co-investigator for a study funded by Genentech; has received honoraria and consulting fees from Alexion, Biogen Idec, Novartis, Genentech, Horizon Therapeutics, EMD Serono, Octave Biosciences, TG Therapeutics, and Sanofi/Genzyme; and has participated in speakers bureau for Biogen Idec, Genentech, EMD Serono, and TG Therapeutics. RAM is a co-investigator on a study funded in part by Biogen and Roche (no funds to her or her institution). JAC has received personal compensation for consulting for Biogen, Convelo, EMD Serono, Gossamer Bio, Mylan, and PSI; and serves as an Editor for Multiple Sclerosis. BB served as a consultant for Novartis, Roche, and UCB; and is funded by the National Multiple Sclerosis Society and National Institutes of Health for work unrelated to this paper. BH served on scientific advisory boards for Novartis; and has served as a data and safety monitoring board member for AllergyCare, Sandoz, Polpharma, Biocon and TG therapeutics; and his institution has received institutional research grants from Roche. BH has received honoraria for counselling for the Gerson Lehrmann Group; and holds part of two patents: (1) the detection of antibodies against KIR4.1 in a subpopulation of patients with multiple sclerosis, and (2) genetic determinants of neutralising antibodies to interferon. SDN reports grants or contracts from Biogen, Roche, Genentech, National Multiple Sclerosis Society, Department of Defense, and Patient Centered Outcomes Research Institute; reports personal compensation for consulting for Biogen, Roche, Genentech, Bristol Myers Squibb, EMD Serono, Greenwich Biosciences, Novartis, Horizon Therapeutics, and TG Therapeutics; and participates on a data safety monitoring board and advisory board for MedDay Pharmaceuticals; and reports support from the Stiff Person Syndrome Research Foundation. AJS reports grant funding from the National Institute of Neurological Disorders and Stroke, National Institutes of Health, and Bristol Myers Squibb; is contracted for research with Sanofi, Biogen, Novartis, Actelion, and Genentec; has received personal compensation for consulting from EMD Serono and Octave Bioscience; has received payment or honoraria for lectures for EMD Serono; has been called for expert testimony by The Jacob D Fuchsberg Law Firm and Koskoff Koskoff & Bieder; participates on a data safety monitoring board for Patient Centered Outcomes Research Institute and Yale University; participates on an advisory board for Genentech, Biogen, Alexion, Celgene, Greenwich Biosciences, TG Therapeutics, and Horizon Therapeutics; and is content Chair for the American Academy of Neurology Institute Multiple Sclerosis Quality Measure Development Work Group and Section Editor for Multiple Sclerosis and Related Disorders. WR3rd has research grant support from the National Institutes of Health and the Veterans Administration; reports honoraria, consulting fees, and support for advisory activities for the Consortium of Multiple Sclerosis Centers, the University of Maryland, the University of Calgary, Temple University, Thomas Jefferson University, the Chan Zuckerberg Initiative, the American Association for Cancer Research, and the Alzheimer's Association of Georgia; and receives compensation for serving as Director of specialty programming for Mediflix. AS and BT declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

The differential diagnosis of multiple sclerosis can present specific challenges in patients from Latin America, Africa, the Middle East, eastern Europe, southeast Asia, and the Western Pacific. In these areas, environmental factors, genetic background, and access to medical care can differ substantially from those in North America and western Europe, where multiple sclerosis is most common. Furthermore, multiple sclerosis diagnostic criteria have been developed primarily using data from North America and western Europe. Although some diagnoses mistaken for multiple sclerosis are common regardless of location, a comprehensive approach to the differential diagnosis of multiple sclerosis in Latin America, Africa, the Middle East, eastern Europe, southeast Asia, and the Western Pacific regions requires special consideration of diseases that are prevalent in those locations. A collaborative effort has therefore assessed global differences in multiple sclerosis differential diagnoses and proposed recommendations for evaluating patients with suspected multiple sclerosis in regions beyond North America and western Europe., Competing Interests: Declaration of interests JC declares receiving grants or research contracts from Biogen and Merck; personal compensation for consulting from Merck; payment or honoraria for lectures from Biogen, Merck, Bristol Myers Squibb, Novartis, and Roche; and support for attending meetings and travel from Merck. JC is a deputy chair International Medical and Scientific Board of Multiple sclerosis International Federation (MSIF), unpaid; and has received equipment, materials, drugs, medical writing, gifts, or other services from Novartis (Investigator initiated award). AJS declares receiving grant funding from National Institute of Neurological Disorders and Stroke, National Institutes of Health and Bristol Myers Squibb (investigator initiated award); has done contracted research with Sanofi, Biogen, Novartis, Actelion, and Genentech; has received personal compensation for consulting from Emmanuel Merck, Darmstadt, Serono and Octave Bioscience; has received payments or honoraria for lectures from Emmanuel Merck, Darmstadt, Serono; has received expert testimony from The Jacob D Fuchsberg Law Firm and Koskoff Koskoff & Bieder; is a participant on a Data Safety Monitoring Board for the Patient Centered Research Institute, and Yale University; declares participation on an advisory board for Genentech, Biogen, Alexion, Celgene, Greenwich Biosciences, TG Therapeutics, and Horizon Therapeutics; and is a content Chair for the American Academy of Neurology (AAN) Institute Multiple Sclerosis Quality Measure Development Work Group and Section Editor for Multiple Sclerosis and Related Disorders. JAC declares personal compensation for consulting from Astoria, Bristol-Myers Squibb, Convelo, EMD Serono, FiND Therapeutics, INMune, and Sandoz; and serving as an editor of Multiple Sclerosis Journal. BLB is funded by the National Multiple Sclerosis Society, and National Institute of Health; is a consultant for Roche, and Sanofi; and is a Board Director AAN (unpaid). TG has served as a consultant and received compensation from Genentech, Horizon, Sanofi, Alexion, and Greenwich Biosciences. BH declares grants from the European Union, Bundesministerium für Bildung und Forschung, and Deutsche Forschungsgemeinschaft; received personal compensation for consulting from Sandoz, Novartis, and GLG consulting; holds patents for antibodies against KIR4·1 in a subpopulation of patients with multiple sclerosis (2012) and genetic determinants of neutralising antibodies to interferon (filed 2010); and participated in a Data Safety and Monitoring Board for Novartis, Allergy Care DSMB, TG Therapeutics, and Polpharma, and Advisory Board for Novartis. HJK declares a research grant from the National Research Foundation of Korea and research support from Aprilbio, UCB, and Eisai; has received consultancy fees from Altos Biologics, AstraZeneca, Biogen, Daewoong, Kaigene, Kolon Life Science, MDimune, Merck Serono, and Roche; declares honoraria for lectures from Alexion, Eisai, GCPharma, Handok, Mitsubishi Tanabe Pharma, and Sanofi Genzyme; has received personal compensation for participation on a Data Safety Monitoring Board from Sanofi-Genzyme; has received compensation as Co-editor for the Multiple Sclerosis Journal and Associate Editor for the Journal of Clinical Neurology; and is a Vice President of Pan-Asian Committee on Treatment and Research in Multiple Sclerosis (unpaid). RAM declares grants or contracts from Biogen, Idec, and Roche. FM has received research funding to her institution from Sumaira Foundation, Genentech, Biogen, Horizon Therapeutics, US National Histitute Institute of Health, US Department of State, Foundation Pierre Fabre, and Novartis; has received consulting fees from Alexion, EMD Serono, Genentech, TG Therapeutics, and Horizon Therapeutics; and declares shares of the startup company Brain Capture (not related to the content of this manuscript). SDN declares grants or contracts (paid directly to institution) from Biogen, Roche, Genentech, National MS Society, Department of Defense, and Patient Centered Outcomes Research Institute; has received personal compensation for consulting from Biogen, Roche, Genentech, Bristol Myers Squibb, EMD Serono, Greenwich Biosciences, Novartis, Horizon Therapeutics, and TG Therapeutics; and is a study lead principal investigator for a Roche clinical trial programme. MAS declares personal honoraria for lectures from Roche, Biogen, Cinnagen, NanoAlvand, Merck, Novartis, and Abidi. DKS declares grants or research contracts from CNPq / Brazil 425331/2016–4 and 308636/2019–8, and Brazilian National Council for Scientific and Technological Development; has received investigator initiated awards from TEVA, Merck, and Biogen; has received personal compensation for consulting from Roche, and Alexion; declares personal honoraria for lectures from Roche, Alexion, Horizon, Merck, Americas Health Foundation; and is a member of International Society of Neuroimmunology, International Advisory Board (unpaid), and Academia Brasileira de Neurologia, Educational Committee (unpaid). DS declares a pilot research grant from the National MS Society paid to the Institution; declares receipt of personal honoraria for lecturing from Roche Pharmaceuticals; declares travel support from Roche Pharmaceutical; and is a Committee member and chair of Multiple Sclerosis International Federation (unpaid). AS has received grants or contracts from the Turkish MS Society, Istanbul University-Cerrahpasa Research Support Funds, and The Scientific and Technological Research Council of Türkiye Health Sciences Research Grants; has received consulting fees from Roche, Merck-Serono, Biogen Idec/Gen Pharma of Turkey , Sanofi-Genzyme, Novartis, and Alexion; has received honoraria for lectures from Sanofi-Genzyme, Novartis, TEVA, and Roche; and has received support for attending meetings from Sanofi-Genzyme, Roche, Merck-Serono, and Alexion. KT declares personal consulting fees from Merck and Eisai; declares payment for lectures from Merck, Eisai, Roche, and Terumo Blood and Cell Technology; and is a member of the Organizing Committee Pan-Asian Committee for Treatment and Research in Multiple Sclerosis (unpaid). MW has received publication royalties from Springer and Elsevier; has received consultancy honoraria from Icometrix, Imcyse, Novartis, Sanofi, Merck, and Biologix; declares personal compensation for lectures or presentations from Alexion, Bayer Healthcare, Biogen, Biologix, Bristol Myers Squibb, Celgene, Genilac, Imcyse, Icometrix, Merck-Serono, Novartis, Roche, and Sanofi-Genzyme; and declares support for attending meetings from Merck-Serono. BGW declares royalties from RSR, Hospices Civils de Lyon, MVZ Labor PD Dr Volkmann und Kollegen GbR , and Oxford University; declares personal consulting fees from Roche, Horizon Therapeutics, Cambridge Pharmaceuticals, and Mitsubishi Tanabe; has received payments for lecture presentations from Roche and Horizon; has a patent planned for NMO-IgG for diagnosis of neuromyelitis optica; and declares participation on a Data Safety Monitoring Board and Advisory borads for Alexion MedImmune/VielaBio/Horizon, and UCB Biosciences. KF declares grants from Ministry of Education, Culture, Sports, Science and Technology of Japan and Ministry of Health, Welfare and Labor of Japan; has received personal compensation for consulting from Merck Biopharma, Japan Tobacco, and Abbvie; has received payment or honoraria forlectures and presentations from Biogen, Eisai, Mitsubishi Tanabe, Novartis, Chugai/Roche, Alexion, VielaBio/Horizon Therapeutics, Teijin, Asahi Kasei Medical, Merck, and Takeda; declares participation in an Advisory Board for Biogen, Mitsubishi Tanabe, Novartis, Chugai/Roche, Alexion, VielaBio/Horizon Therapeutics, and UCB; serves as President of the Pan-Asian Committee for Treatment and Research in Multiple Sclerosis (unpaid), President of the Japanese Society of Neuroimmunology (unpaid), is a Board Member of the Japan Multiple Sclerosis Society (unpaid), is a board member of theEuropean Charcot Foundation (unpaid), and is a Member of the International Medical and Scientific Board, MSIF (unpaid). All other authors declared no competing interest., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Tourette disorder (TD) is a neurodevelopmental disorder characterized by childhood onset of tics lasting more than one year, with multiple motor tics and at least one phonic tic at some point during the course of the symptoms. Treatment of tics may include psychoeducation, non-pharmacologic treatment, or pharmacologic treatment. We review pharmacologic treatment here. Methods: We performed a literature review on pharmacologic treatments for TD. Results: There is no current evidence to suggest that medications impact the prognosis of tic disorders, so current clinical guidelines recommend reassurance of the patient and family and monitoring if there is no change in function or quality of life due to tics. If treatment is indicated, it must be chosen based on the needs of each individual patient. Comprehensive behavioral intervention for tics (CBIT) is considered first-line management for most individuals with bothersome tics, especially if they are mild to moderate in severity. Pharmacotherapy should be considered when tics are impairing daily functioning, causing social problems, accompanied by other neuropsychiatric symptoms, or when the patient is not likely to benefit from CBIT. Current recommended pharmacotherapy options include alpha-2 adrenergic agonists, dopamine modulators, GABAergic medications, dopamine depleters, and botulinum toxin injections. Additionally, there are other novel medications that are being studied in ongoing clinical trials. Conclusions: This review summarizes available pharmacotherapy options for TD in children. It provides an overview of new medications and offers guidance to physicians when selecting appropriate treatments. If medications are indicated for tic management, treatment should be chosen based on the needs of the individual patient.

Spinal muscular atrophy (SMA) is a rare, genetic neurodegenerative disorder caused by insufficient production of survival motor neuron (SMN) protein. Diminished SMN protein levels lead to motor neuron loss, causing muscle atrophy and weakness that impairs daily functioning and reduces quality of life. SMN upregulators offer clinical improvements and increased survival in SMA patients, although significant unmet needs remain. Myostatin, a TGF-β superfamily signaling molecule that binds to the activin II receptor, negatively regulates muscle growth; myostatin inhibition is a promising therapeutic strategy for enhancing muscle. Combining myostatin inhibition with SMN upregulation, a comprehensive therapeutic strategy targeting the whole motor unit, offers promise in SMA. Taldefgrobep alfa is a novel, fully human recombinant protein that selectively binds to myostatin and competitively inhibits other ligands that signal through the activin II receptor. Given a robust scientific and clinical rationale and the favorable safety profile of taldefgrobep in patients with neuromuscular disease, the RESILIENT phase 3, randomized, placebo-controlled trial is investigating taldefgrobep as an adjunct to SMN upregulators in SMA (NCT05337553). This manuscript reviews the role of myostatin in muscle, explores the preclinical and clinical development of taldefgrobep and introduces the phase 3 RESILIENT trial of taldefgrobep in SMA.

Introduction: Executive function (EF) may be impaired in people with human immunodeficiency virus (HIV) infection, and poor EF may affect medication adherence. However, there is little data on EF in children with HIV in sub-Saharan Africa., Methods: 208 children/adolescents with perinatally acquired HIV and 208 HIV-exposed uninfected controls were recruited in Zambia for this prospective cohort study. EF was measured using performance-based, self-report, and parental report measures. Adherence over one year of follow-up was assessed through questionnaires and viral load measurement., Results: Children with HIV performed significantly worse on all three measures of EF. Lower parental rating of EF was associated with poorer antiretroviral therapy adherence (OR: 1.5, 95% CI = 1.02 - 2.2, p = 0.04)., Conclusion: Children with HIV have EF impairments which may lead to consequences like poor medication adherence and treatment failure. Interventions to improve EF or compensate for impaired EF may be necessary in this population., Competing Interests: Competing interests: The authors declare that there is no conflict of interest.

Background: While childhood mortality has been declining in Zambia, it remains high at 58 per 1000 live births. Importantly, many leading causes of mortality in Zambia are preventable. This study was conducted to identify clusters of childhood mortality, causes of death of recently deceased children, barriers to care, and risk factors for mortality in Lusaka, Zambia., Methods: This study was conducted as a prospective cohort study. Family members or lawfully authorized representatives (LARs) were interviewed when they came to pick up death certificates for recently deceased children from Lusaka Children's Hospital. Each interview included a verbal autopsy, determination of the child's location of residence, and collection of demographic information. Demographic data was also collected from a healthy control group. Quantitative Geographic Information Systems was used to visualize mortality and evaluate for clustering., Results: Leading primary causes of death included malnutrition (21%), complications of chronic illnesses (16%), and central nervous system infections (13%), while the leading barriers to care were cost (58%) and difficulties with travel (53%). Compared to controls, recently deceased children came from families with significantly lower incomes (1905 Kwacha vs. 2412 Kwacha, p = 0.03) and were significantly more likely to have a history of malnutrition (16.7% vs. 1.4%, p = 0.005). Mortality was clustered in two high-population density, low-income neighborhoods in Lusaka., Conclusions: Systems to reduce financial barriers to care and improve access to transportation could reduce childhood mortality in Lusaka. The aforementioned neighborhoods are ideal locations for public health interventions or improved healthcare services.

Summary: Cochlear implants to aid sensorineural hearing loss are becoming commonplace. In this study, we describe two cases that showed artifacts related to the cochlear implant device during scalp EEG recording. To our knowledge, cochlear implant artifacts have not been reported previously. Recognizing cochlear implant artifacts will avoid misinterpretation and resultant inappropriate treatment., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 by the American Clinical Neurophysiology Society.)

Advances in genetics led to the identification of hundreds of epilepsy-related genes, some of which are treatable with etiology-specific interventions. However, the diagnostic yield of next-generation sequencing (NGS) in unexplained epilepsy is highly variable (10-50%). We sought to determine the diagnostic yield and clinical utility of NGS in children with unexplained epilepsy that is accompanied by neurodevelopmental delays and/or is medically intractable. A 5-year retrospective review was conducted at the American University of Beirut Medical Center to identify children who underwent whole exome sequencing (WES) or whole genome sequencing (WGS). Data on patient demographics, neurodevelopment, seizures, and treatments were collected. Forty-nine children underwent NGS with an overall diagnostic rate of 68.9% (27/38 for WES, and 4/7 for WGS). Most children (42) had neurodevelopmental delays with (18) or without (24) refractory epilepsy, and only three had refractory epilepsy without delays. The diagnostic yield was 77.8% in consanguineous families (18), and 61.5% in non-consanguineous families (26); consanguinity information was not available for one family. Genetic test results led to anti-seizure medication optimization or dietary therapies in six children, with subsequent improvements in seizure control and neurodevelopmental trajectories. Not only is the diagnostic rate of NGS high in children with unexplained epilepsy and neurodevelopmental delays, but also genetic testing in this population may often lead to potentially life-altering interventions.

While multiple factors impact disease, artificial intelligence (AI) studies in medicine often use small, non-diverse patient cohorts due to data sharing and privacy issues. Federated learning (FL) has emerged as a solution, enabling training across hospitals without direct data sharing. Here, we present FL-PedBrain, an FL platform for pediatric posterior fossa brain tumors, and evaluate its performance on a diverse, realistic, multi-center cohort. Pediatric brain tumors were targeted due to the scarcity of such datasets, even in tertiary care hospitals. Our platform orchestrates federated training for joint tumor classification and segmentation across 19 international sites. FL-PedBrain exhibits less than a 1.5% decrease in classification and a 3% reduction in segmentation performance compared to centralized data training. FL boosts segmentation performance by 20 to 30% on three external, out-of-network sites. Finally, we explore the sources of data heterogeneity and examine FL robustness in real-world scenarios with data imbalances., (© 2024. The Author(s).)

Background: Posterior fossa irradiation with or without whole brain irradiation results in high doses of radiation to the thalamus, hippocampus, and putamen, structures critical to cognitive functioning. As a result, children with brain tumors treated with cranial irradiation (CRT) may experience significant cognitive late effects. We sought to determine the effect of radiation to those structures on neuropsychological outcome., Methods: Forty-seven children with a history of posterior fossa tumor (17 treated with surgery; 11 with surgery and chemotherapy; and 19 with surgery, chemotherapy, and CRT) underwent neuroimaging and neuropsychological assessment at a mean of 4.8 years after treatment, along with 17 healthy sibling controls. The putamen, thalamus, and hippocampus were segmented on each participant's magnetic resonance imaging for diffusion indices and volumes, and in the radiation treatment group, radiation dose to each structure was calculated., Results: Performance on visuoconstruction and spatial learning and memory was lower in patient groups than controls. Volume of the thalamus, when controlling for age, was smaller in the patient group treated with CRT than other groups. Higher radiation doses to the putamen correlated with higher fractional anisotropy in that structure. Higher radiation dose to the hippocampus correlated with lower spatial learning, and higher dose to thalami and putamina to lower verbal and nonverbal reasoning., Conclusions: All children with posterior fossa tumors, regardless of treatment modality, had cognitive deficits compared to their sibling controls. Posterior fossa irradiation may affect thalamic volume and aspects of verbal and nonverbal cognitive functioning., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)