Brain & Development最新文献

Angelman syndrome (AS), a rare neurogenetic disorder affecting approximately 1 in 15,000 live births, results from loss of functional UBE3A gene expression and manifests with severe developmental delay, intellectual disability, absent speech, ataxia, epilepsy, and distinctive behavioral features. Until recently, only symptomatic management was available. This review provides pediatric neurologists with a comprehensive, practice-oriented overview of emerging disease-modifying therapies for AS, focusing on therapeutic approaches advancing through clinical development. The molecular pathophysiology of AS, natural history considerations critical for trial interpretation, and the current evidence for antisense oligonucleotide (ASO) therapies (ION582, GTX-102/apazunersen, rugonersen), gene replacement approaches (MVX-220), and next-generation strategies including CRISPR-based gene editing, artificial transcription factors, small molecules, and novel delivery platforms are reviewed. ASO therapies targeting the UBE3A antisense transcript represent the most clinically advanced approach, with three candidates showing proof-of-concept efficacy in Phase 1/2 studies and two advancing to pivotal Phase 3 trials. Gene replacement therapy offers potential single-administration treatment but faces challenges regarding safety, immune responses, and durability. Next-generation approaches including CRISPR activation, epigenetic editing, and blood-brain barrier-penetrating delivery systems show preclinical promise. Critical challenges include outcome measurement limitations, genotype stratification, long-term safety monitoring, and ensuring equitable access. These advances herald a transformation in AS clinical care and represent a milestone in precision pediatric neurology.

Background: We aim to investigate the quality of life (QoL) in children with idiopathic generalized epilepsy (IGE) compared to children with epilepsy and autism spectrum disorder (ASD) and their respective caregiver's QOL.

Methods: We conducted a case-control study from a single pediatric hospital in Ohio. Inclusion criteria for the epilepsy group included children with a diagnosis of IGE; the ASD group included diagnosis of epilepsy and ASD. Both groups included children aged 2-18 years. To capture patient QoL, adult caregivers completed the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55), and to capture caregiver QoL, adult caregivers completed the Health-Related Social Needs (HRSN) and the CarerQoL-7D instrument.

Results: A total of 43 caregivers completed the surveys. There was a greater distribution of female patients in the IGE group (57.1%) versus the ASD group which had higher distribution of males (86.4%). Cognitive functioning (M = 33.0), emotional functioning (M = 57.4), physical functioning (M = 33.6) and overall QOLCE-55 mean score (M = 45.2) revealed a statistically significant lower QoL in the ASD group (n = 22), compared to the IGE group (n = 21) (M = 76.8, M = 75.4, M = 61.8, M = 75.3 respectively). The overall CarerQol-7D score mirrored these results with a lower score in the ASD group (M = 68.8) compared to the IGE group (M = 80.3). The individual dimensions in the CarerQol and HRSN revealed no differences.

Conclusions: The QoL as assessed by caregivers for the patients and the caregivers themselves was lower in the ASD group compared to the IGE group. QoL assessment should be integrated in clinical care for comprehensive health management.

Objective: To compare treatment preferences and decision-making patterns of pediatricians and pediatric neurologists in Türkiye regarding febrile seizure (FS) management.

Methods: This cross-sectional survey was conducted between June and December 2024 using an online questionnaire distributed nationwide to pediatricians and pediatric neurologists. The 34-item survey assessed demographics, clinical experience, FS encounter frequency, and management strategies for simple febrile seizures (SFS), complex febrile seizures (CFS), and febrile status epilepticus (FSE). Statistical analyses were performed using SPSS, with categorical variables compared using chi-square tests.

Results: A total of 184 physicians participated (97 pediatric neurologists, 87 pediatricians). Pediatric neurologists reported higher monthly FS encounter rates (p < 0.001). In SFS, both groups avoided continuous antiseizure medication (ASM) and preferred rescue therapy. In CFS, pediatric neurologists more often used intermittent prophylaxis, mainly oral diazepam or clobazam, whereas pediatricians more frequently initiated continuous therapy, most commonly levetiracetam (p < 0.05). For FSE, most participants initiated treatment after the first episode, with continuous levetiracetam as the preferred agent. Family history of afebrile seizures and seizure duration most strongly influenced treatment decisions. Over half of respondents reported difficulty explaining intermittent prophylaxis to caregivers and suggested educational materials as helpful.

Conclusion: FS management differs between pediatricians and pediatric neurologists in Türkiye, particularly for complex cases. Pediatric neurologists favor guideline-consistent intermittent benzodiazepine-based strategies, whereas pediatricians more often prescribe continuous ASMs. Clearer guidance and improved caregiver education are needed to support evidence-based practice.

Background: Status epilepticus (SE) is a neurological emergency requiring rapid, stepwise treatment. In Japan, the Guidelines for the Treatment of Pediatric Status Epilepticus 2023 (GL2023) were published; however, real-world practice following their publication remains unclear.

Methods: We conducted a nationwide, cross-sectional web-based survey of pediatric neurologists between January and March 2025. One representative from each institution reported institutional practices for the in-hospital management of pediatric SE. Institutions were stratified by annual SE case volume (≥20 vs. ≤19 cases). General management strategies, antiseizure medication selection, electroencephalography (EEG) utilization, and approaches to refractory and super-refractory SE (RSE and SRSE) were analyzed.

Results: A total of 136 institutions responded. Most institutions reported referring to GL2023 and initiating first-line treatment within 10 min of hospital arrival. Midazolam was the most commonly used first-line drug, with widespread use of non-intravenous routes. Phenytoin or fosphenytoin remained the most commonly selected second-line drug, followed by phenobarbital. For RSE, anesthetic coma therapy with midazolam and barbiturates was used at comparable frequencies. Overall, antiseizure medication selection did not differ by institutional case volume. In contrast, institutions managing ≥20 cases annually more frequently reported having institution-specific protocols, utilizing EEG in the emergency department, administering repeat doses of benzodiazepines, and having experience with advanced therapies for SRSE.

Conclusions: Pediatric SE management in Japan emphasizes rapid treatment and flexible administration routes. Institutional experience is associated with differences in EEG utilization, protocol development, and SRSE management. Further improvement will require continued evidence generation, timely treatment implementation, and reduction of institutional disparities.