Brain & Development最新文献

{"title":"Immune dysregulation in new-onset refractory status epilepticus (NORSE): current insights and therapeutic perspectives","authors":"Aurélie Hanin ,&nbsp;Lawrence J. Hirsch","doi":"10.1016/j.braindev.2025.104406","DOIUrl":"10.1016/j.braindev.2025.104406","url":null,"abstract":"<div><h3>Objective</h3><div>Emerging evidence suggests that cryptogenic new-onset refractory status epilepticus (c-NORSE) arises from innate immunity dysfunction leading to exacerbated inflammation. While immunotherapies have been administered, their efficacy remains variable and unpredictable.</div></div><div><h3>Methods</h3><div>We conducted a comprehensive literature review of studies reporting inflammation biomarkers in patients with NORSE or evaluating targeted immunotherapies. Additionally, we discussed future research directions and therapeutic perspectives.</div></div><div><h3>Results</h3><div>A total of 29 studies reporting inflammation biomarkers in at least five patients were analyzed. Most focused on c-NORSE, frequently describing cerebrospinal fluid pleocytosis, often lymphocytic and usually mild, upon admission. Elevated levels of innate immunity-related pro-inflammatory cytokines were consistently reported in c-NORSE. A large international study further demonstrated significantly higher cytokine levels in c-NORSE compared to other refractory status epilepticus patients, suggesting the importance of innate immunity in c-NORSE pathophysiology. One recent study identified subgroups with distinct inflammatory profiles among c-NORSE, suggesting different treatment approaches.</div><div>More than 30 case series or reports have documented the use of targeted immunotherapies in NORSE. The most commonly used are anakinra (IL1 antagonist) and tocilizumab (IL6 antagonist), both showing seemingly comparable efficacy in seizure control. Recently, intrathecal dexamethasone has gained interest, particularly in pediatric cases, showing promising efficacy with no reported side effects. Other emerging approaches include canakinumab (anti-IL1 antibody), Janus kinase (JAK) inhibitors, and tumor necrosis factor alpha (TNFα) inhibitors.</div></div><div><h3>Conclusions</h3><div>Recent studies have advanced our understanding of innate immunity disturbances in c-NORSE onset and progression. Moreover, they highlight patient heterogeneity, emphasizing the need for personalized strategies targeting specific inflammatory pathways.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 5","pages":"Article 104406"},"PeriodicalIF":1.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144704645","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":"Electroclinical biomarkers predicting EEG normalization and polytherapy needs in self-limited epilepsy with centrotemporal spikes","authors":"Eun Song Song ,&nbsp;Sanghoon Lee ,&nbsp;Young Ok Kim","doi":"10.1016/j.braindev.2025.104449","DOIUrl":"10.1016/j.braindev.2025.104449","url":null,"abstract":"<div><h3>Background</h3><div>Self-limited epilepsy with centrotemporal spikes (SeLECTS) is a well-known self-limited focal epilepsy in children. While centrotemporal discharges remit with age, the timing and biomarkers predicting EEG normalization and polytherapy needs are not well established.</div></div><div><h3>Purpose</h3><div>This study aimed to identify the timing of EEG remission and electroclinical biomarkers influencing remission and polytherapy needs in SeLECTS.</div></div><div><h3>Methods</h3><div>We retrospectively reviewed 153 of 401 patients (&lt;18 years) with SeLECTS whose sleep EEGs normalized (2010–2025, Chonnam National University Hospital).</div></div><div><h3>Results</h3><div>The median age at sleep EEG normalization was 11.4 years (IQR, 10.1–13.2), with a median interval of 45.9 months (IQR, 27.0–66.8). Seizure-onset age correlated positively with EEG normalization age (<em>R</em> = 0.457) and negatively with the interval to normalization (<em>R</em> = −0.508; <em>P</em> &lt; 0.001). EEG normalized younger in patients with unilateral (10.9 vs. 12.0 years, <em>P</em> = 0.002) or right-dominant discharges (11.2 vs. 13.0 years, <em>P</em> = 0.023). The EEG normalization interval increased with a longer gap between the first and second seizures (<em>R</em> = 0.279; <em>P</em> = 0.001). It was shorter in unilateral discharges (28.1 vs. 53.9 months; <em>P</em> &lt; 0.001), and longer in the polytherapy group (57.3 vs. 43.5 months; <em>P</em> = 0.006). Polytherapy was more frequent in early childhood (50.5 % vs. 21.0 %; <em>P</em> = 0.005), and in patients with Todd's paralysis (71.4 % vs. 26.0 %; <em>P</em> = 0.019), daytime seizures (64.7 % vs. 23.5 %; <em>P</em> &lt; 0.001), or attention deficit/hyperactivity disorder (ADHD; 66.7 % vs. 25.7 %; <em>P</em> = 0.015).</div></div><div><h3>Conclusion</h3><div>EEG remission is associated with seizure-onset age and dipole findings, whereas the need for polytherapy is influenced more by atypical clinical than electrical biomarkers.</div><div>Keywords: Child; epilepsy, rolandic; electroencephalography; biomarkers; anticonvulsants.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 5","pages":"Article 104449"},"PeriodicalIF":1.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157450","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":"Understanding Cancer risk in severe motor and intellectual disabilities: The role of external influences","authors":"Christian Messina","doi":"10.1016/j.braindev.2025.104439","DOIUrl":"10.1016/j.braindev.2025.104439","url":null,"abstract":"","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 5","pages":"Article 104439"},"PeriodicalIF":1.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145003694","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":"Response to the letter to the editor “Decoding the pathophysiological role of Fukutin in Fukuyama congenital muscular dystrophy”","authors":"Keiko Ishigaki ,&nbsp;Mariko Taniguchi-Ikeda","doi":"10.1016/j.braindev.2025.104458","DOIUrl":"10.1016/j.braindev.2025.104458","url":null,"abstract":"","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 5","pages":"Article 104458"},"PeriodicalIF":1.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219616","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":"Response to the letter to the editor titled “diagnostic clarification and exclusion of differential diagnoses in pediatric acute encephalopathy” regarding: “National study on pediatric acute encephalopathy in Japan (April 2020 to October 2023): Insights from the third study”","authors":"Taku Omata,&nbsp;Jun-ichi Takanashi","doi":"10.1016/j.braindev.2025.104432","DOIUrl":"10.1016/j.braindev.2025.104432","url":null,"abstract":"","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 5","pages":"Article 104432"},"PeriodicalIF":1.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145060560","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":"Post-COVID-19 trends in pediatric meningitis in the PICU: A multicenter study","authors":"Nihal Akçay ,&nbsp;İlyas Bingöl ,&nbsp;Demet Tosun ,&nbsp;Muhterem Duyu ,&nbsp;Abdulrahman Özel ,&nbsp;Servet Yüce ,&nbsp;Burcu Bursal ,&nbsp;Meningitis Study Group","doi":"10.1016/j.braindev.2025.104408","DOIUrl":"10.1016/j.braindev.2025.104408","url":null,"abstract":"<div><h3>Background</h3><div>Meningitis is a severe and potentially life-threatening infection characterized by inflammation of the leptomeningeal membranes that protect the brain and spinal cord. This study aimed to evaluate the epidemiological and clinical features of pediatric patients with laboratory-confirmed meningitis admitted to pediatric intensive care units (PICUs).</div></div><div><h3>Methods</h3><div>This multicenter retrospective study included patients with laboratory-confirmed meningitis who were admitted to eight tertiary PICUs in Istanbul, Turkey, between January 1, 2023, and December 31, 2024.</div></div><div><h3>Results</h3><div>A total of 66 pediatric patients with laboratory-confirmed meningitis requiring intensive care were included. Of these, 39 (59 %) were diagnosed with bacterial meningitis and 27 (41 %) with viral meningitis. Among the bacterial meningitis cases, the most frequently identified pathogens were <em>Streptococcus pneumoniae</em> (41.0 %), <em>Neisseria meningitidis</em> (15.4 %), and <em>Haemophilus influenzae</em> (10.2 %). In the viral group, the most common pathogens were herpes simplex virus type 1 (25.9 %), enterovirus (22.2 %), and human herpesvirus 6 (22.2 %). The bacterial meningitis group had significantly higher white blood cell counts and C-reactive protein levels, and lower cerebrospinal fluid glucose levels compared with the viral meningitis group (<em>p</em> &lt; 0.05). Signs of meningeal irritation and Pediatric Logistic Organ Dysfunction (PELOD) scores were also significantly higher in the bacterial meningitis group (p &lt; 0.05). Age, sex distribution, PICU length of stay, presenting symptoms, rates of sequelae, and mortality did not differ significantly between the two groups. Intravenous immunoglobulin use was significantly more common in the viral meningitis group (p &lt; 0.05).</div></div><div><h3>Conclusions</h3><div>Bacterial meningitis remains the leading cause of meningitis cases requiring pediatric intensive care. Continued public health efforts are essential to reduce mortality and prevent long-term sequelae associated with this serious condition.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 5","pages":"Article 104408"},"PeriodicalIF":1.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144722531","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 visual search and brain activity in Japanese elementary schoolchildren: A cross-sectional study using functional near-infrared spectroscopy","authors":"Koji Yano ,&nbsp;Akiko Suzuki ,&nbsp;Yachun Qian ,&nbsp;Akiko Megumi ,&nbsp;Jungpil Shin ,&nbsp;Makoto Wada ,&nbsp;Akira Yasumura","doi":"10.1016/j.braindev.2025.104401","DOIUrl":"10.1016/j.braindev.2025.104401","url":null,"abstract":"<div><h3>Introduction</h3><div>Visual search is a crucial behavior that supports learning, work, and other daily activities. However, the specific characteristics of visual search and the associated brain activity in Japanese elementary school children have not been thoroughly investigated. This study aimed to elucidate these characteristics by examining visual search behavior and prefrontal cortex (PFC) activity in this population.</div></div><div><h3>Methods</h3><div>Seventy-one schoolchildren were divided into three age groups (7–8 years, 9–10 years, and 11–12 years). Their PFC activity was measured using functional near-infrared spectroscopy (fNIRS) while they performed a cancellation task under two conditions: a structured array and a random array. Visual search behavior was evaluated using multiple indices, including the number of correct responses and the ratio of intersections, analyzed from multiple perspectives.</div></div><div><h3>Results</h3><div>The number of correct responses reflecting visual search processing ability, was significantly higher in the older age group. The ratio of intersections, an index of the systematicity of visual search, was significantly lower in the structured array condition compared to the random array condition, but only in the 11–12-year-old group. Additionally, this group showed significantly greater PFC activation during the structured array condition than during the random array, whereas the younger groups exhibited the opposite pattern.</div></div><div><h3>Conclusion</h3><div>These findings suggest a developmental relationship between the systematicity of visual search and changes in PFC activity. A multifaceted approach combining physiological and behavioral measures may offer deeper insights into the characteristics of visual search in elementary school children.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 5","pages":"Article 104401"},"PeriodicalIF":1.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144849705","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":"Gene therapy for Duchenne muscular dystrophy","authors":"Yuko Shimizu-Motohashi","doi":"10.1016/j.braindev.2025.104424","DOIUrl":"10.1016/j.braindev.2025.104424","url":null,"abstract":"<div><div>Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disorder caused by variants of the <em>DMD</em> that leads to progressive muscle degeneration. Recent advances in gene therapy have opened new therapeutic avenues, particularly through the use of adeno-associated virus (AAV)-mediated micro-dystrophin delivery. Delandistrogene moxeparvovec, the first FDA-approved gene therapy for DMD, has demonstrated transgene expression and potential functional improvement in early phase trials, although its long-term efficacy, durability, and safety remain unconfirmed. Immune-mediated toxicities including myositis, myocarditis, and liver injury present significant clinical challenges, prompting the need for careful patient selection, immunoprophylaxis, and post-treatment monitoring. In addition to micro-dystrophin replacement, novel gene therapy approaches such as endogenous dystrophin upregulation, exon skipping, and adjunctive muscle-enhancement strategies are being explored. Future studies focus on overcoming vector size limitations by using dual/triple AAV systems or non-viral platforms, improving muscle tropism through capsid and promoter engineering, and expanding eligibility through desensitization protocols. This review provides an integrated overview of the current progress, challenges, and future perspectives in gene therapy for DMD, with the aim of supporting its safe and effective clinical implementation.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 5","pages":"Article 104424"},"PeriodicalIF":1.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144887560","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":"Parent-child interaction therapy as a therapeutic approach for children with autism spectrum disorder in Japan","authors":"Mieko Hirose","doi":"10.1016/j.braindev.2025.104434","DOIUrl":"10.1016/j.braindev.2025.104434","url":null,"abstract":"<div><h3>Background</h3><div>Children with autism spectrum disorder (ASD) often face difficulties in parent-child relationships and exhibit problematic behaviors. This study retrospectively examines the effects of standard Parent-Child Interaction Therapy (PCIT) for children with ASD and their caregivers in Japan, focusing on reducing parental stress and children's problematic behaviors.</div></div><div><h3>Methods</h3><div>Eight parent-child dyads with children aged 2.5–7 years with ASD underwent standard PCIT. Measures included the Eyberg Child Behavior Inventory (ECBI), Beck Depression Inventory-II (BDI-II), Parenting Stress Index-Short Form (PSI-SF), and Child Behavior Checklist for Ages 4–18 (CBCL/4–18), assessed pre- and post-treatments.</div></div><div><h3>Results</h3><div>For parents, ECBI problem score decreased from 16.8 (SD ± 4.4) to 3.0 (SD ± 4.1) pre- and post-treatment (<em>p</em> &lt; 0.05, effect size 1.9). PSI-SF parent section scores dropped from 28.7 (SD ± 7.1) to 22.1 (SD ± 6.2) (<em>p</em> &lt; 0.01, effect size 2.0). The total PSI-SF score from 58.1 (SD ± 10.9) to 45.0 (SD ± 11.1), (<em>p</em> &lt; 0.01, effect size 1.7). For children, ECBI intensity scores decreased from 147.9 (SD ± 20.3) to 85.5 (SD ± 17.7) (<em>p</em> &lt; 0.01, effect size 3.4). PSI-SF child section scores fell from 29.4 (SD ± 4.8) to 22.9 (SD ± 5.8) (<em>p</em> &lt; 0.05, effect size of 1.2), and total CBCL from 70.3 (SD ± 5.9) to 62.0 (SD ± 8.4) (<em>p</em> &lt; 0.05, effect size of 1.5).</div></div><div><h3>Conclusion</h3><div>The standard PCIT for children with ASD and their parents in Japan significantly reduces parental stress and children's problematic behaviors, improving parent-child interactions.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 5","pages":"Article 104434"},"PeriodicalIF":1.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145088441","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":"When neutral isn't negative: missteps in survey data analysis.","authors":"Prateek Kumar Panda, Indar Kumar Sharawat","doi":"10.1016/j.braindev.2025.104417","DOIUrl":"10.1016/j.braindev.2025.104417","url":null,"abstract":"","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 5","pages":"104417"},"PeriodicalIF":1.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144818405","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}