Brain & Development最新文献

{"title":"Structural brain alterations in persistent developmental stuttering: a whole-brain voxel-based morphometry (VBM) analysis of grey and white matter","authors":"Seyedehsamaneh Shojaeilangari ,&nbsp;Mohammad Ehsan Taghizadeh ,&nbsp;Narges Radman","doi":"10.1016/j.braindev.2025.104464","DOIUrl":"10.1016/j.braindev.2025.104464","url":null,"abstract":"<div><h3>Objective</h3><div>Persistent developmental stuttering (PDS), also known as childhood-onset speech fluency disorder, is characterized by involuntary disruptions in normal speech fluency, such as sound repetitions, prolongations, and silent pauses. Although structural neuroimaging techniques, particularly voxel-based morphometry (VBM), have been widely used to explore brain abnormalities in PDS, the precise brain regions predominantly affected remain unclear. This study aimed to investigate grey matter (GM) and white matter (WM) volumetric differences in adults with PDS compared to fluent speakers.</div></div><div><h3>Methods</h3><div>Magnetic resonance imaging (MRI) scans were obtained from 15 adults with PDS and 15 fluent control participants matched for age, sex, education, and hand preference. Whole-brain VBM analysis was conducted to assess GM and WM volume differences between the two groups.</div></div><div><h3>Results</h3><div>Compared to fluent speakers, adults with PDS demonstrated reduced WM volume in the cerebellum. GM alterations included increased volumes in the right postcentral gyrus and the left middle temporal gyrus (MTG), while decreased volumes were observed in the left superior frontal gyrus (SFG), bilateral paracentral lobule, right cuneus, and right cerebellum.</div></div><div><h3>Conclusion</h3><div>These findings provide evidence of both grey and white matter abnormalities in adults with PDS, highlighting the involvement of specific cortical and subcortical regions. The results support the significance of structural brain differences in understanding the neurobiological basis of persistent stuttering.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 6","pages":"Article 104464"},"PeriodicalIF":1.3,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145236099","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 advancements in Duchenne muscular dystrophy: Overlooked challenges","authors":"Daniel Matovu","doi":"10.1016/j.braindev.2025.104460","DOIUrl":"10.1016/j.braindev.2025.104460","url":null,"abstract":"","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 5","pages":"Article 104460"},"PeriodicalIF":1.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202167","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":"Association between total hydrocortisone dose and neurodevelopmental outcome at 3 years old in newborns under 28 weeks of gestation","authors":"Toshimitsu Takayanagi,&nbsp;Mizuko Hashimoto ,&nbsp;Tada-Aki Shiraishi ,&nbsp;Hiroyuki Tomino,&nbsp;Shun Ogiwara,&nbsp;Akinori Shichijo,&nbsp;Masakazu Egashira,&nbsp;Tomoko Mizukami,&nbsp;Tomoko Egashira","doi":"10.1016/j.braindev.2025.104452","DOIUrl":"10.1016/j.braindev.2025.104452","url":null,"abstract":"<div><h3>Background</h3><div>Ventilated very-low-birth-weight infants (VLBWIs) frequently receive hydrocortisone (HDC). The HDC dose increases in more serious cases, but the association between the actual HDC dose and neurodevelopmental outcomes is unclear.</div></div><div><h3>Method</h3><div>A total of 274 VLBWIs were divided into four groups according to the total HDC dose: zero (0 mg/kg), low (1–25 mg/kg), moderate (25–75 mg/kg), high (&gt;75 mg/kg). The developmental quotient (DQ) in each group were compared. Using simple and multiple linear regression analyses, we evaluated the presence of a significant relationship between total DQ and total HDC dose in 274 and 153 VLBWIs receiving HDC therapy. In addition, the association between HDC therapy and the total DQ was investigated in 274 VLBWIs.</div></div><div><h3>Results</h3><div>The total DQ in the zero group was significantly higher than that in the moderate and high groups but equivalent to that in the low group. Despite a significant association between total DQ and total HDC dose in the single linear regression analysis, no significant association was found between total DQ and total HDC dose in 274 VLBWIs (<em>p</em> = 0.07) and 153 VLBWIs receiving HDC (<em>p</em> = 0.18) using a multiple linear regression analysis, after adjusting for the days of artificial ventilation, gestational age, and the onset of late-stage circulatory collapse. No significant association was observed between total DQ and HDC therapy (<em>p</em> = 0.58).</div></div><div><h3>Conclusion</h3><div>HDC therapy during NICU admission may not have a significant effect on total DQ at three years old in VLBWIs.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 5","pages":"Article 104452"},"PeriodicalIF":1.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202227","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":"Development and future prospects of exon-skipping therapy for Duchenne muscular dystrophy","authors":"Yasuhiro Takeshima,&nbsp;Tomoko Lee,&nbsp;Hideki Shimomura","doi":"10.1016/j.braindev.2025.104457","DOIUrl":"10.1016/j.braindev.2025.104457","url":null,"abstract":"<div><div>Duchenne muscular dystrophy (DMD) is an inherited progressive muscle disease that is caused by variants in the <em>DMD</em> gene. The development of therapies for DMD that promote dystrophin protein production or ameliorate dystrophin deficiency-induced pathology is currently underway. Therapies that promote dystrophin production are known as disease-modifying therapies, and include exon-skipping therapy using antisense oligonucleotides (AS-oligo). This therapy suppresses the function of a splicing enhancer sequence within an exon using AS-oligo and removes the exon from the mRNA, thereby converting an out-of-frame deletion (as occurs in DMD) to an in-frame deletion and inducing the expression of functional dystrophin protein. In 2016, eteplirsen, which induces exon 51 skipping, received accelerated approval in the United States. AS-oligo that induce the skipping of exons 45 and 53 are also currently being applied in clinical practice. AS-oligo that induce skipping of other exons are expected to be developed in the future, as well as modified nucleic acids that act more potently. Notably, however, the evaluation of the efficacy of these therapies in clinical practice after accelerated approval remains insufficient. In addition, many issues, such as the effectiveness of early treatment and the combination of these therapies with other novel therapeutic agents, need to be considered. It is therefore important to establish a system to follow-up the long-term efficacy and safety of treatment in the future. The establishment of an early diagnostic system may also need to be considered. The present review outlines the development and future challenges of exon-skipping therapy for DMD and the expansion of splice-switching therapy (a therapy that uses AS-oligo to control splicing), including exon-skipping therapy, to other diseases.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 5","pages":"Article 104457"},"PeriodicalIF":1.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208585","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":"Impact of the coronavirus disease pandemic on emergency transport times for pediatric febrile seizures: A retrospective study","authors":"Taisuke Matsumoto ,&nbsp;Masahiro Nishiyama ,&nbsp;Yusuke Ishida ,&nbsp;Satoshi Matsui ,&nbsp;Azusa Maruyama","doi":"10.1016/j.braindev.2025.104456","DOIUrl":"10.1016/j.braindev.2025.104456","url":null,"abstract":"<div><h3>Background</h3><div>Febrile seizures are a common cause of emergency pediatric transport. Although the coronavirus disease (COVID-19) pandemic disrupted healthcare systems, including emergency services, its impact on transport times for pediatric febrile seizures remains unclear. This study aimed to evaluate how the pandemic affected transport times.</div></div><div><h3>Methods</h3><div>We retrospectively reviewed emergency department visits at our hospital between 2018 and 2022. Patients with febrile seizures in 2019 (before the COVID-19 pandemic) and in 2022 (during the pandemic) were included. Transport times and clinical data were compared between those years. Multivariate regression analysis was used to identify factors associated with longer transport times.</div></div><div><h3>Results</h3><div>There were 329 and 282 patients in 2019 and 2022, respectively. The median transport time increased significantly from 33 min in 2019 to 39 min in 2022 (<em>p</em> &lt; 0.001). The proportion of cases exceeding 46 min increased from 10 % to 28 %, whereas those exceeding 60 min increased from 1.2 % to 7.4 %. A longer transport time was associated with seizure duration, onset year (2022), and transport from distant areas. Onset in 2022 was identified as an independent factor. Stratified analysis showed significantly longer transport times in adjacent and remote areas during the pandemic no significant difference in transport times near the hospital.</div></div><div><h3>Conclusion</h3><div>Transport times for pediatric febrile seizures increased significantly during the COVID-19 pandemic, with more delays of over 60 min, especially in remote areas. These findings highlight the need to strengthen regional emergency transportation systems to reduce time to care, particularly for patients living farther from hospitals.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 5","pages":"Article 104456"},"PeriodicalIF":1.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202186","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":"Serum matrix metallopeptidase-9 levels in patients with infantile epileptic spasms syndrome before and after the initiation of vigabatrin therapy","authors":"Ryuki Matsuura ,&nbsp;Shin-ichiro Hamano ,&nbsp;Atsuro Daida ,&nbsp;Azusa Oba ,&nbsp;Haruhito Horita ,&nbsp;Yuko Hirata ,&nbsp;Reiko Koichihara ,&nbsp;Kenjiro Kikuchi ,&nbsp;Akira Oka","doi":"10.1016/j.braindev.2025.104447","DOIUrl":"10.1016/j.braindev.2025.104447","url":null,"abstract":"<div><h3>Purpose</h3><div>Epileptic spasms are the predominant seizure type in infantile epileptic spasms syndrome (IESS). The pathophysiology of IESS, including blood–brain barrier (BBB) function involvement, remains unclear. To address this issue, we evaluated the serum matrix metallopeptidase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels in patients with IESS before and after initiating vigabatrin therapy.</div></div><div><h3>Methods</h3><div>IESS was defined as epileptic spasms occurring within 2 years after birth. We prospectively assessed serum MMP-9 and TIMP-1 levels before and after initiating vigabatrin therapy in patients with IESS who attended Saitama Children's Medical Center between February 2019 and December 2024 (<em>n</em> = 12; 5 boys) and compared them with those in age-matched controls (<em>n</em> = 14; 8 boys).</div></div><div><h3>Results</h3><div>The median ages at epileptic spasm onset and vigabatrin therapy initiation were 3.5 (1−11) and 8 (3−13) months, respectively. Serum MMP-9 levels were higher in patients with IESS than in the controls (<em>p</em> &lt; 0.001). Serum MMP-9 and MMP-9/TIMP-1 ratios decreased significantly after vigabatrin therapy (MMP-9: 308 [160–664] ng/mL vs. 220 [112–367] ng/mL, <em>p</em> &lt; 0.01; MMP-9/TIMP-1 ratio: 1.48 [0.61–8.14] vs. 1.11 [0.31–1.92], <em>p</em> &lt; 0.05). MMP-9 levels decreased in 9 of 11 patients whose epileptic spasms had disappeared by the time of the last measurement.</div></div><div><h3>Conclusion</h3><div>Decreased MMP-9 levels after the initiation of vigabatrin therapy suggested an improvement in BBB dysfunction. Our findings shed light on the role of the BBB in IESS and the role of vigabatrin in the recovery of this function.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 5","pages":"Article 104447"},"PeriodicalIF":1.3,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157449","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":"Corrigendum to \"Fukuyama congenital muscular dystrophy: Clinical features and therapeutic advances\" [Brain Dev. 47(5) (2025) 104437].","authors":"Keiko Ishigaki, Mariko Taniguchi-Ikeda","doi":"10.1016/j.braindev.2025.104459","DOIUrl":"https://doi.org/10.1016/j.braindev.2025.104459","url":null,"abstract":"","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":" ","pages":"104459"},"PeriodicalIF":1.3,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182378","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":"Efficacy and safety of risperidone and aripiprazole in reducing severity of irritability in children with autism spectrum disorder: A randomized controlled trial","authors":"Prateek Kumar Panda ,&nbsp;Indar Kumar Sharawat ,&nbsp;Diksha Gupta ,&nbsp;Achanya Palayullakandi ,&nbsp;Suthiraj Sopanam ,&nbsp;Sarama Saha","doi":"10.1016/j.braindev.2025.104454","DOIUrl":"10.1016/j.braindev.2025.104454","url":null,"abstract":"<div><h3>Background</h3><div>Both risperidone and aripiprazole are effective in reducing irritability severity in children with autism spectrum disorder (ASD). However, head-to-head comparison trials between these two drugs are scarce in the literature and have shown conflicting results.</div></div><div><h3>Methods</h3><div>This trial compared the efficacy and safety of risperidone and aripiprazole in children and adolescents with ASD, aged 6–18 years. After a two-week placebo trial, placebo responders were excluded. The remaining participants were randomized into two groups. The outcomes were the change in the irritability subscale of the Aberrant Behavior Checklist (ABC-I), Childhood Autism Rating Scale (CARS2), Conners' Parent Rating Scale-Revised (CPRS-R), Children's Sleep Habits Questionnaire (CSHQ), Sensory Profile-2 (SP-2), cognition and the nature and frequency of treatment-emergent adverse events.</div></div><div><h3>Results</h3><div>Seventy-two patients (36 in each group) were recruited. Changes in the ABC-I score (−13.6 ± 4.3 vs. -12.2 ± 3.9, <em>p</em> = 0.15), ABC total score (−27.5 ± 15.9 vs. -26.8 ± 15.7, <em>p</em> = 0.85), CARS score (−2.9 ± 0.7 vs. -2.7 ± 0.8, <em>p</em> = 0.26), CPRS-R Global Index T-score (−10.63 ± 8.54 vs. -9.61 ± 8.92, <em>p</em> = 0.62), number of patients with significant sensory processing abnormalities (18/36 vs. 18/36, <em>p</em> = 1.0), CSHQ score (−4.6 ± 3.8 vs. -3.9 ± 3.1, <em>p</em> = 0.39), and full-scale IQ (1.9 ± 1.6 vs. 1.8 ± 1.5, <em>p</em> = 0.75) were comparable between groups. In multivariate regression analysis, CPRS-R Global Index T-score (<em>p</em> = 0.02) and full-scale intelligence quotient (<em>p</em> = 0.03) were independent predictors of changes in the ABC-I score. The frequency of adverse events was similar in both groups. Serum prolactin levels decreased in the aripiprazole group at 12 weeks but increased in the risperidone group.</div></div><div><h3>Conclusions</h3><div>Risperidone and aripiprazole demonstrate comparable efficacy and safety in managing irritability in children and adolescents with ASD.</div><div><strong>Trial Registry no:</strong> Clinical Trial Registry of India (CTRI/2021/12/038721).</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 5","pages":"Article 104454"},"PeriodicalIF":1.3,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157447","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":"2025-09-25","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}