Brain & Development最新文献

{"title":"Focus on epilepsy and epilepsy syndromes in children with autism spectrum disorders: a study of 74 patients","authors":"Roberto H. Caraballo ,&nbsp;Sebastian Fortini ,&nbsp;Lucas Beltrán ,&nbsp;Marcos Semprino ,&nbsp;Santiago Galicchio ,&nbsp;Alberto Espeche ,&nbsp;Gabriela Reyes Valenzuela ,&nbsp;Santiago Chacón ,&nbsp;Beatriz Gamboni ,&nbsp;Javier Adi ,&nbsp;Lorena Fasulo ,&nbsp;Agustin Calvo ,&nbsp;Pedro Cachia","doi":"10.1016/j.braindev.2025.104385","DOIUrl":"10.1016/j.braindev.2025.104385","url":null,"abstract":"<div><h3>Background</h3><div>Epilepsy is a common finding in children with autism spectrum disorders (ASD), but few studies describe the characteristics of epilepsy in these children. Our study aimed to characterize the electroclinical features of children with ASD and epilepsy through a retrospective multicenter study.</div></div><div><h3>Material and methods</h3><div>Patients with ASD who subsequently developed epilepsy seen at nine pediatric neurology departments were included. Patients with developmental and epileptic encephalopathies (DEE), chronic neurological diseases with epilepsy who developed autism, and those with non-epileptic paroxysmal disorders were excluded.</div></div><div><h3>Results</h3><div>Overall, 74 patients were included, accounting for 15 % of 494 children with ASD seen between 2015 and 2023; 39 were female (52.7 %) and 35 male (47.3 %). Focal epilepsies were identified in 43 patients (58.1 %), which were non-self-limited in 24 and self-limited in 19. Generalized epilepsies were observed in 19 (25.7 %), including six with generalized tonic-clonic seizures alone (one in childhood, five in adolescence), nine with juvenile myoclonic epilepsy, one with childhood absence epilepsy, and three with juvenile absence epilepsy. Eight patients (10.8 %) had epileptic encephalopathies: EE-SWAS in six and epilepsy with myoclonic atonic seizures in two. Four patients (5.4 %) had combined focal and generalized epilepsy.</div><div>No significant differences were found between epilepsy syndrome or type of epilepsy, seizure type, and comorbidities.</div></div><div><h3>Conclusions</h3><div>No specific epilepsy phenotype was identified in our patients with ASD; the types of epilepsy and syndromes were similar to those seen in the general population. Management should address both epilepsy and the broader complexities of ASD through an integrated approach.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104385"},"PeriodicalIF":1.4,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144306993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hand-arm bimanual intensive therapy versus modified constraint-induced movement therapy in children with hemiparetic cerebral palsy: A randomized controlled trial","authors":"Prateek Kumar Panda ,&nbsp;Indar Kumar Sharawat ,&nbsp;Diksha Gupta ,&nbsp;Achanya Palayullakandi ,&nbsp;S. Senthil Kumaran ,&nbsp;Poonam Sherwani ,&nbsp;Suthiraj Sopanam ,&nbsp;Osama Neyaz","doi":"10.1016/j.braindev.2025.104381","DOIUrl":"10.1016/j.braindev.2025.104381","url":null,"abstract":"<div><h3>Introduction</h3><div>Modified Constraint-Induced Movement Therapy (mCIMT) and Hand-Arm Bimanual Intensive Therapy (HABIT) are widely used for treating hemiparetic cerebral palsy (CP). Prior randomized controlled trials (RCTs) comparing these approaches yielded mixed outcomes.</div></div><div><h3>Methods</h3><div>This RCT evaluated the efficacy of 12 weeks of mCIMT versus HABIT in children aged 5–18 years with hemiparetic CP. Primary objective was to compare improvements in upper limb function (quality of upper extremity skills test [QUEST] total score) in both groups. Secondary objectives were to compare speed of upper limb movements (nine-hole peg board test), muscle strength (thumb strength and hand grip strength), quality of life (CPQoL), compliance to advised therapy in both groups, sustenance of improvement 4 weeks after stopping supervised treatment, and to describe and compare diffusion tensor imaging (DTI) and resting functional magnetic resonance imaging (fMRI) changes. Both groups received 2-h supervised sessions, 8 sessions over 4 weeks, followed by weekly sessions for 8 more weeks. Participants practiced 2 h daily at home, monitored by activity logs and videos when feasible.</div></div><div><h3>Results</h3><div>Each group had 30 participants. Changes in QUEST total scores after 12 weeks were comparable between HABIT and mCIMT (12.00 ± 7.52 vs. 11.35 ± 7.10, <em>p</em> = 0.48). Individual QUEST domain scores, nine-hole peg test times, thumb and grip strength, and CPQoL improvements were also similar between groups (<em>p</em>&gt;0.05 for all). Both groups showed significant improvements across all outcomes at 12 weeks (<em>p</em>&lt;0.05), maintained at 16 weeks. DTI revealed comparable changes in apparent diffusion co-efficient and fractional anisotropy values in the contralateral corticospinal tract (<em>p</em> = 0.63 and 0.71, respectively). fMRI showed increased activation in the contralateral sensorimotor cortex in both groups at 12 weeks.</div></div><div><h3>Conclusion</h3><div>HABIT and mCIMT demonstrate similar efficacy for upper limb function improvement in children with hemiparetic CP.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104381"},"PeriodicalIF":1.4,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144307048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low excretor glutaric acidemia type 1 with transient lesions in the basal ganglia","authors":"Yohane Miyata ,&nbsp;Kei Murayama ,&nbsp;Yasushi Okazaki ,&nbsp;Chunhua Zhang ,&nbsp;Maasa Abe ,&nbsp;Masami Narita","doi":"10.1016/j.braindev.2025.104380","DOIUrl":"10.1016/j.braindev.2025.104380","url":null,"abstract":"<div><h3>Background</h3><div>In some countries, glutaric acidemia type 1 (GA1) is included in newborn screening (NBS) panels using tandem mass spectrometry (MS/MS) analysis of acylcarnitine. However, the low excretor phenotype of glutaric acidemia type 1 (LE-GA1) has been increasingly recognaized and may lead to false-negative NBS results and can be missed by urine organic acid and plasma acylcarnitine profile analyses.</div></div><div><h3>Case</h3><div>We report a case of LE-GA1 with an atypical imaging course. NBS by dried blood spot acylcarnitine profile using MS/MS was normal. At 7 months of age, he developed an acute encephalopathic crisis with bilateral striatal lesions. He underwent intravenous methylprednisolone pulse, intravenous immunoglobulin, vitamin B1, biotin, <span>l</span>-carnitine, and coenzyme Q10 therapy. Abnormal basal ganglia signals disappeared within 4 weeks. Serial brain MRI 6 months later revealed linear lesions in both putamen. The plasma acylcarnitine profile and urine organic acid analyses were normal at onset. Whole exome and Sanger sequencing were performed, and compound heterozygosity for the two known pathogenic variants in the glutaryl-CoA dehydrogenase gene were identified. Metabolomic analyses of the patient's urine showed elevated glutaric acid and 3-hydroxyglutaric acid levels similar to those in another LE-GA1 case. Thus, the patient was diagnosed with LE-GA1.</div></div><div><h3>Conclusions</h3><div>Unlike classical GA1, LE-GA1 may present with variable neuroimaging courses, including transient basal ganglia lesions. If Leigh's encephalopathy-like lesions of the basal ganglia—of unknown cause with acute onset—are present, LE-GA1 should be considered. To ensure timely and accurate diagnosis, genetic analyses should be performed, even if biochemical findings are normal.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104380"},"PeriodicalIF":1.4,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144279500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic analysis of leukodystrophies in children: towards improved diagnostic yield","authors":"Hirotomo Saitsu,&nbsp;Sachiko Miyamoto","doi":"10.1016/j.braindev.2025.104378","DOIUrl":"10.1016/j.braindev.2025.104378","url":null,"abstract":"<div><div>The formation of the myelin sheath in the central nervous system is carried out by oligodendrocytes, and leukodystrophies develop when myelination by oligodendrocytes is impaired. It has been found that the activity of the neurons undergoing myelination is also necessary for complete myelination, meaning that not only abnormalities in oligodendrocytes but also abnormalities in neurons can lead to defective myelination. Many genes involved in leukodystrophy in children have been identified, and comprehensive genetic analysis has been proven useful for genetic diagnosis. However, target panel sequencing, exome sequencing targeting almost all exons, and genome sequencing does not identify the genetic cause in substantial proportion of patients, making it essential to advance research targeting these unresolved cases. Transcriptome analysis has been reported to improve diagnostic rates in individuals with suspected Mendelian conditions, by confirming aberrant splicing caused by candidate DNA variants or by revealing candidate loci through detecting abnormalities in RNA transcription. Because transcription has a tissue specificity, selection of tissues from which RNA extract is of importance. In this mini-review, we first briefly review genetics of leukodystrophies in children along with methodology of genetic analysis, and discuss utility of urine-derived cells for transcriptome analysis of leukodystrophy in children.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104378"},"PeriodicalIF":1.4,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144220920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endocrinological study of low-dose adrenocorticotropic hormone therapy without tapering in infantile epileptic spasms syndrome","authors":"Shumpei Morita ,&nbsp;Taisuke Yamauchi ,&nbsp;Yumie Tamura ,&nbsp;Tomonori Suzuki ,&nbsp;Toshihiro Nomura ,&nbsp;Hiroshi Shiraku ,&nbsp;Koji Takahashi ,&nbsp;Kei Takasawa ,&nbsp;Kenichi Kashimada ,&nbsp;Tomoko Mizuno","doi":"10.1016/j.braindev.2025.104376","DOIUrl":"10.1016/j.braindev.2025.104376","url":null,"abstract":"<div><h3>Background</h3><div>Adrenocorticotropic hormone (ACTH) therapy is effective for infantile epileptic spasms syndrome (IESS) and other types of refractory epilepsy; however, concerns remain regarding the risk of potential adrenal insufficiency, particularly when ACTH therapy is discontinued without dose tapering. Studies on comprehensive endocrinological evaluation of adrenocortical function following low-dose ACTH therapy without tapering are limited.</div></div><div><h3>Methods</h3><div>We collected the data of patients who were diagnosed with IESS and received ACTH therapy using synthetic ACTH at 0.005–0.0125 mg/kg/day (equivalent to natural ACTH at 0.2–0.5 IU/kg/day) for 14 days without tapering, and underwent an ACTH stimulation test following ACTH therapy completion for adrenocortical function evaluation. Moreover, body weight, blood pressure, and electrolytes were measured before and after treatment.</div></div><div><h3>Results</h3><div>A total of 11 patients, aged between 3 months and 1 year and 6 months, were enrolled. ACTH therapy was effective in all 11 patients. During the observation period, 3 patients developed seizure recurrence; however, none of the patients exhibited symptoms of adrenal insufficiency. The ACTH stimulation test confirmed normal adrenocortical function in all cases, with peak cortisol levels exceeding 20 μg/dL. After treatment, a significant increase in body weight and blood pressure were observed.</div></div><div><h3>Conclusion</h3><div>Low-dose ACTH therapy without tapering can be endocrinologically safe. The result provides useful information for reducing hospitalization duration and minimizing side effects. To validate these findings, further studies with larger cohorts are needed.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104376"},"PeriodicalIF":1.4,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144220921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics of febrile seizure after the end of the COVID-19 global health emergency","authors":"Shingo Numoto ,&nbsp;Yoichiro Oro ,&nbsp;Daisuke Nishida ,&nbsp;Masaki Yamamoto ,&nbsp;Yoshinori Omori ,&nbsp;Ayataka Fujimoto ,&nbsp;Akihisa Okumura","doi":"10.1016/j.braindev.2025.104374","DOIUrl":"10.1016/j.braindev.2025.104374","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to clarify the characteristics of febrile seizures (FSs) before and after the coronavirus disease 2019 (COVID-19) global health emergency.</div></div><div><h3>Methods</h3><div>This study was a retrospective study conducted at a single institution in Japan. Clinical data were retrospectively collected from 797 children with FS, aged &lt;16 years, between January 2018 and July 2024. Participants were categorized into four terms: Term I, pre-COVID-19 period; Term II, pre-Omicron period; Term III, Omicron period; and Term IV, post-COVID-19 global health emergency. Late FS was defined as FS in children aged &gt;60 months. Data were compared across these four periods and between COVID-19-related and non-COVID-19-related groups.</div></div><div><h3>Results</h3><div>The monthly average of FSs was 14.4 in Term I, 7.7 in Term II, 11.6 in Term III, and 12.5 in Term IV. The median age in Term IV was 34 months, significantly older than in Terms I, II, and III. Late FS in the COVID-19-related group was 22.6 % in Term III and 25 % in Term IV. In the non-COVID-19-related group, late FS rates were 5.0 % in Term I, 2.7 % in Term II, 4.7 % in Term III, and 26.0 % in Term IV, significantly higher than in Terms I, II, and III.</div></div><div><h3>Conclusions</h3><div>After the end of the COVID-19 global health emergency, the rate of late FS caused by COVID-19 remained high, and the rate of late FS caused by non-COVID-19 infections also increased compared to the pre-COVID-19 period.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104374"},"PeriodicalIF":1.4,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144221064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Motor skills and neurological soft signs: Are they only clinical differences or reflection of distinct etiopathogenesis in tic disorder and primary stereotypic movement disorder?","authors":"Ecem Selin Akbas Aliyev ,&nbsp;Dilek Ünal","doi":"10.1016/j.braindev.2025.104377","DOIUrl":"10.1016/j.braindev.2025.104377","url":null,"abstract":"<div><h3>Background</h3><div>While tic disorders and stereotypic movement disorder are commonly comorbid in pediatric clinics, their clinical and etiological differences remain poorly understood.</div></div><div><h3>Objectives</h3><div>We aimed to investigate the clinical features that differentiate between tic disorders and primary stereotypic movement disorder by evaluating neurological soft signs and motor skills.</div></div><div><h3>Methods</h3><div>The Kiddie-Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version DSM-5 and Sociodemographic and Clinical Data Form were administered to the children. The clinician completed Yale Global Tic Severity Scale, Repetitive Behavior Scale-Revised and Neurological Evaluation Scale. Nine-Hole Peg Test was used for fine motor skills, 1-Minute Sit-to-Stand Test for gross motor skills, Flamingo Balance Test for static balance, Finger-to-Nose Test for bilateral coordination. Parents completed the Conners Parent Rating Scale-Revised Short Form and the Revised Developmental Coordination Disorder Questionnaire.</div></div><div><h3>Results</h3><div>Our sample consisted of 20 tic disorders, 20 primary stereotypic movement disorder, 13 attention deficit hyperactivity disorder patients, and 20 healthy controls. Sequencing of the complex motor acts scores of Neurological Evaluation Scale were significantly higher in the primary stereotypy group than in healthy controls. The primary stereotypy group demonstrated significantly lower dominant hand performance on the Nine-Hole Peg Test than the tic group. Children with stereotypy had significantly lower scores of 1-min sit-to-stand test; higher total and subscale scores of Revised Developmental Coordination Disorder Questionnaire. and higher developmental coordination disorder risk than healthy controls.</div></div><div><h3>Conclusions</h3><div>Our findings offer valuable insights into the distinct etiopathogenesis of tic disorders and primary stereotypic movement disorder, providing a foundation for future neurobiological research.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104377"},"PeriodicalIF":1.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term outcome prediction after pediatric cardiac arrest by continuous electroencephalography","authors":"Eri Ohashi ,&nbsp;Itaru Hayakawa ,&nbsp;Hiroki Kato ,&nbsp;Kentaro Ide ,&nbsp;Shotaro Matsumoto ,&nbsp;Kyongsun Pak ,&nbsp;Yuichi Abe","doi":"10.1016/j.braindev.2025.104375","DOIUrl":"10.1016/j.braindev.2025.104375","url":null,"abstract":"<div><h3>Objective</h3><div>Continuous electroencephalography (cEEG) features after cardiac arrest (CA) are associated with short-term outcome predictions. However, the association between cEEG features and long-term neurobehavioral outcomes in children remains unclear. This study aimed to identify cEEG features that can accurately predict neurobehavioral outcomes in children 6 months after CA.</div></div><div><h3>Methods</h3><div>A single-center, retrospective, observational study was performed at the tertiary care pediatric intensive care unit (PICU) of a national children's hospital. This study included a consecutive cohort of children admitted to the PICU after CA who underwent cEEG monitoring. The initial EEG background, electrographic seizures, and changes in EEG background over time were documented for each time point. The primary outcome was neurobehavioral outcomes at 6 months after resuscitation. To assess the reliability of the predictive model, the area under the receiver operating characteristic curve (AUROC) of models was compared for different combinations of EEG features.</div></div><div><h3>Results</h3><div>The study included 62 infants and children. Unfavorable neurobehavioral outcomes were reported in 39 patients (63 %), including mortality in 20 patients. The combination of initial EEG background category and the EEG change from initial EEG initiation to 24 h, or variability/reactivity alone, were minimal optimal predictive models for unfavorable neurobehavioral outcomes at 6 months (AUROC, 0.99 [95 % confidence interval, 0.98–1.00], and 0.99 [95 % confidence interval 0.97–1.00], respectively).</div></div><div><h3>Conclusions</h3><div>Early cEEG features in the PICU can accurately predict neurobehavioral outcomes in children at 6 months after CA. These results can enhance prognostication and guide clinical decision-making in pediatric CA cases.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104375"},"PeriodicalIF":1.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug-resistant epilepsy in children post-neonatal seizures: Clinical profiles and predictors","authors":"Warisara Saenchai ,&nbsp;Satit Manopunya ,&nbsp;Shanika Kosarat ,&nbsp;Varangthip Khuwuthyakorn ,&nbsp;Watcharee Tantiprabha ,&nbsp;Kamornwan Katanyuwong ,&nbsp;Chinnuwat Sanguansermsri ,&nbsp;Natrujee Wiwattanadittakul","doi":"10.1016/j.braindev.2025.104373","DOIUrl":"10.1016/j.braindev.2025.104373","url":null,"abstract":"<div><h3>Objectives</h3><div>To investigate the clinical profile, etiologies, and outcomes of neonatal seizures and identify predictors of drug-resistant epilepsy (DRE) in children.</div></div><div><h3>Method</h3><div>A retrospective chart review was performed on neonates with seizures admitted to Chiang Mai University Hospital, Thailand, from January 2008 to December 2023. The diagnosis of neonatal seizures was based on clinical findings and/or electroencephalography. Severe impairment refers to limited mobility and minimal speech, while profound impairment indicates being bedridden. DRE is defined as the failure of two antiseizure medications to control seizures.</div></div><div><h3>Results</h3><div>Among 218 patients (58.3 % male), the median seizure onset was 12 h (interquartile range [IQR]: 2.9–87 h). The leading etiology was perinatal asphyxia (58.7 %), followed by hemorrhage (7.8 %). The median follow-up was 27 months (IQR: 31.5 months). Epilepsy developed in 39 (27.3 %) patients, with 19 (48.7 %) meeting DRE criteria. Risk factors for epilepsy included marked abnormal neuroimaging, refractory neonatal seizures and severe to profound developmental impairment (<em>P</em> &lt;0.05). In the multivariate model, profound developmental impairment (odds ratio [OR] = 2.89, <em>p</em> = 0.04, 95 % confidence interval [CI]: 1.79–24.19) and the development of epileptic spasms or multiple seizure types (OR = 114.80, <em>p</em> = 0.01, 95 % CI: 4.79–2746.07) were identified as an independent risk factor for DRE.</div></div><div><h3>Conclusion</h3><div>Perinatal asphyxia is the most common cause of neonatal seizures. One-third of neonates with seizures developed epilepsy, with half of them meeting the criteria for DRE. Neonates who develop epileptic spasms, exhibit multiple seizure types, or have profound developmental impairment are key DRE predictors.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104373"},"PeriodicalIF":1.4,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144134505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MECP2 duplication syndrome: Recent advances in pathophysiology and therapeutic perspectives","authors":"Yuichi Akaba ,&nbsp;Satoru Takahashi","doi":"10.1016/j.braindev.2025.104371","DOIUrl":"10.1016/j.braindev.2025.104371","url":null,"abstract":"<div><div><em>MECP2</em> duplication syndrome (MDS) is an X-linked neurodevelopmental disorder caused by duplication or extra copies of <em>MECP2</em> gene. It primarily affects males and is characterized by intellectual disability, hypotonia, epilepsy, recurrent infections, and autistic features. Methyl-CpG binding protein 2 (MeCP2) encoded by <em>MECP2</em> is a crucial epigenetic regulator of brain function. Expression levels are strictly regulated during brain development and maturation, and altered levels lead to severe neurodevelopmental disorders; excessive levels are associated with MDS, while insufficient levels cause Rett syndrome. This review provides a comprehensive overview of the recent advances in the pathophysiology and therapeutic perspectives of MDS, focusing on its pathophysiology, clinical features, disease models, and therapeutic strategies. Advances in studies using animal and patient-derived induced pluripotent stem cells (iPSCs)-derived neuronal models have provided insights into the molecular and cellular abnormalities associated with MDS and have facilitated therapeutic development. Among the emerging treatments, antisense oligonucleotide (ASO) therapy has gained significant attention as a promising approach for selectively suppressing MeCP2 overexpression. Preclinical studies using MDS mouse models and iPSCs-derived neurons have demonstrated that ASO treatment can partially restore neuronal abnormalities and clinical trials are currently underway.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104371"},"PeriodicalIF":1.4,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144072210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}