Brain & Development最新文献

{"title":"A dilemma in pediatric migraine: Headache or school performance? – A comparison of topiramate and flunarizine","authors":"Ünal Akca ,&nbsp;Gülfer Akca ,&nbsp;Şeyma Karatekin","doi":"10.1016/j.braindev.2025.104390","DOIUrl":"10.1016/j.braindev.2025.104390","url":null,"abstract":"<div><h3>Background</h3><div>Migraine prophylaxis reduces pain severity and duration in pediatric patients, improving school and social adaptation. Topiramate (TPM) and flunarizine (FLN) are effective monotherapies for migraine prevention. This study compares their efficacy in pain management and impact on school and social life.</div></div><div><h3>Methods</h3><div>This two-group comparative study (2018–2023) included pediatric patients (aged 9–18 years) diagnosed with episodic or chronic migraine based on International Classification of Headache Disorders, 3rd edition (ICHD-3 beta) criteria. Patients were assessed for demographic characteristics, pain duration, pain frequency, pain intensity using the Visual Analogue Scale (VAS), Pediatric Migraine Disability Assessment Scale (PedMIDAS) scores, side effects, and treatment attitudes at baseline and after three months of TPM or FLN treatment.</div></div><div><h3>Results</h3><div>Among 226 patients, TPM showed a greater reduction in pain frequency than FLN (9.0 vs. 7.5; <em>p</em> = 0.007). The percentage reduction in monthly pain frequency was higher with TPM (83.5 % vs. 70.7 %; <em>p</em> = 0.022). Side effects were significantly lower in the FLN group. TPM caused weight loss, paresthesia, speech/memory impairment, and appetite reduction, while FLN caused weight gain (<em>p</em> &lt; 0.001). TPM was more effective in reducing pain frequency (relative risk [RR] = 0.118; 95 % confidence interval [CI] -0.946 to -0.681; <em>p</em> = 0.011), pain duration (RR = 0.858, 95 % CI -2.640 to -1.350; <em>p</em> &lt; 0.001), and pain intensity (RR = 0.729, 95 % CI -1.849 to -0.539; p &lt; 0.001). However, FLN was superior in PedMIDAS scores, particularly in school attendance and participation (p &lt; 0.001). No patients withdrew, but some were reluctant to use TPM due to concerns about stigmatization. Notably, substantial placebo effects have been observed in pediatric migraine trials, and the current evidence for the efficacy of preventive medications in this population remains limited.</div></div><div><h3>Conclusion</h3><div>TPM and FLN are effective migraine treatments. TPM is superior for pain reduction, while FLN has fewer side effects and benefits school attendance and participation. Weight changes and stigma should be considered when prescribing TPM.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104390"},"PeriodicalIF":1.4,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144549469","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":"Relationship between cerebrospinal fluid cytokines/chemokines and clinical impact of myelin oligodendrocyte glycoprotein antibody-associated disorders in children","authors":"SunMin Lee ,&nbsp;Juhyun Kong ,&nbsp;Sooyoung Lyu ,&nbsp;Sang Ook Nam ,&nbsp;Taek Jin Lim ,&nbsp;Ji-Yeon Song ,&nbsp;Gyu Min Yeon ,&nbsp;Young Mi Kim ,&nbsp;Ara Ko ,&nbsp;Yun-Jin Lee","doi":"10.1016/j.braindev.2025.104389","DOIUrl":"10.1016/j.braindev.2025.104389","url":null,"abstract":"<div><h3>Background</h3><div>Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) has been increasingly reported in children at the first presentation of an acquired central nervous system (CNS) demyelinating disorder and can have a relapsing course. This study aimed to evaluate cerebrospinal fluid (CSF) cytokine/chemokine profiles in children with acute-phase inflammatory demyelinating disorders according to MOG-IgG positivity and/or recurrent relapses.</div></div><div><h3>Methods</h3><div>A total of 24 cytokines/chemokines were measured using multiplex immunoassay in the CSF of 85 children, who were divided into serum MOG-IgG positive (MOG-P, <em>n</em> = 28) [acute disseminated encephalomyelitis (<em>n</em> = 19), optic neuritis (<em>n</em> = 8), neuromyelitis optica spectrum disorder (<em>n</em> = 1)] group, MOG-negative (MOG<img>N, <em>n</em> = 27) demyelinating disorder group, and control (<em>n</em> = 30) group.</div></div><div><h3>Results</h3><div>All four CSF B-cell related (APRIL, BAFF, BLC/CXCL13, and MIP-3β/CCL19), Treg-related (IL-10), and the majority of CSF Th17-related (IL-6, IL-17 A, IL-21, G-CSF/CSF-3, and GM-CSF) cytokines/chemokines were significantly elevated during the acute phase in the MOG-P group compared to the MOG-N group. The mean values of B-cell-related and Treg-related (IL-10) molecules, as well as the seropositivity rate for MOG-IgG, were significantly higher in the relapse group than in the non-relapse group. Furthermore, the levels of all B-cell- and Treg-related IL-10, along with two Th17-related cytokines (IL-6, and IL-17 A), were positively correlated with the MOG-IgG titers in children with MOGAD.</div></div><div><h3>Conclusion</h3><div>Children with MOG-IgG positivity exhibit a pronounced CNS inflammatory response characterized by elevated levels of humoral immunity-associated cytokines/chemokines, and selected Th17-related molecules. CSF cytokine/chemokine profiles may aid in predicting relapse, monitoring inflammation and disease activity, and identifying novel therapeutic targets in pediatric MOGAD.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104389"},"PeriodicalIF":1.4,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144534898","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":"Early hypoglycemia is not an independent risk factor for 2-year neurodevelopmental impairment in appropriate-for-gestational age preterm infants < 32 weeks","authors":"Martina Palazzo ,&nbsp;Margherita Bonanni ,&nbsp;Alessio Correani ,&nbsp;Enrica Ferretti ,&nbsp;Rita D'Ascenzo ,&nbsp;Chiara Biagetti ,&nbsp;Ilaria Burattini ,&nbsp;Paola Cogo ,&nbsp;Virgilio Carnielli","doi":"10.1016/j.braindev.2025.104391","DOIUrl":"10.1016/j.braindev.2025.104391","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate whether hypoglycemia within the first 6 h of life (HOL) is an independent risk factor for 2-year neurodevelopmental impairment in appropriate-for-gestational age (AGA) preterm infants with a gestational age (GA) &lt;32^+0/7 weeks/days.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed data of 598 AGA preterm infants (GA: 24^+0/7–31^+6/7 weeks/days). Infants with at least one episode of hypoglycemia within the first 6 HOL (blood glucose concentration below 40 mg/dL; Glyc&lt;40^[Birth-6HOL]) were compared with infants without any hypoglycemia (Glyc≥40^[Birth-6HOL]). Propensity score matching analysis was conducted for comparisons. Logistic regression analyses were used to evaluate the association of Glyc&lt;40^[Birth-6HOL] with 2-year cognitive (COG) and motor (MOT) impairments defined as a Bayley-III score &lt; 85.</div></div><div><h3>Results</h3><div>Of the 598 AGA preterm infants, 129 (21.6 %) were classified as Glyc&lt;40^[Birth-6HOL], and 469 (78.4 %) as Glyc≥40^[Birth-6HOL]. Time from birth to intravenous glucose infusion did not significantly differ between Glyc&lt;40^[Birth-6HOL] and Glyc≥40^[Birth-6HOL]. After multiple adjustments, Glyc&lt;40^[Birth-6HOL] infants did not have a significantly higher risk of both 2-year COG (ExpB: 1.150, <em>p</em> = 0.656) and MOT (ExpB: 0.982, <em>p</em> = 0.834) impairment compared to Glyc≥40^[Birth-6HOL]. No differences in 2-year neurodevelopmental scores were found between the 79 matched infant pairs.</div></div><div><h3>Conclusion</h3><div>In a clinical setting with strict glycemic monitoring and standardized glucose management, early hypoglycemia (≤6 HOL) was not identified as an independent risk factor for 2-year COG and MOT impairment in AGA preterm infants with a GA between 24^+0/7 and 31^+6/7 weeks/days.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104391"},"PeriodicalIF":1.4,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144523079","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":"L-NAME improves the morphology and necrosis of skeletal muscle by activating PINK1-PARKIN mediated mitophagy in mdx mice","authors":"Junxia Li ,&nbsp;Wenjuan Wu ,&nbsp;Guang Ji ,&nbsp;Hui Dong ,&nbsp;Hongran Wu ,&nbsp;Xueqin Song","doi":"10.1016/j.braindev.2025.104388","DOIUrl":"10.1016/j.braindev.2025.104388","url":null,"abstract":"<div><h3>Background</h3><div>This study investigates mitophagy in Duchenne muscular dystrophy (DMD, OMIM #<span><span>310200</span><svg><path></path></svg></span>), focusing on how nitric oxide synthase (NOS) inhibition improves muscle tissue pathology by affecting mitophagy, which is implicated in muscle weakness due to dystrophin deficiency and may affect DMD-related cardiomyopathy and respiratory problems.</div></div><div><h3>Methods</h3><div>Histopathological analysis, immunofluorescence staining, Western blot were used to study the mitophagy status of the tibialis anterior muscle in mdx mice without treatment or mdx mice administered L-NAME (L-N^G-nitro arginine methylester), an inhibitor of NOS. For in vitro experiment, the effect of S-nitrosylation enzyme, N6022, on mitophagy in C2C12 cells was assessed using TEM (transmission electron microscopy), and Western blot.</div></div><div><h3>Results</h3><div>Mdx mice showed dystrophic muscle pathology and elevated LC3 (microtubule-mssociated protein 1 light chain) and VDAC (voltage-dependent anion channel) expression, indicating increased mitophagy. Reduced PINK1 (PTEN-induced putative kinase 1) and PARKIN (E3 ubiquitin ligase PARK2) levels suggested incomplete mitochondrial clearance. L-NAME treatment improved muscle morphology and reduced necrosis, partially restoring mitophagy by increasing LC3 without matching VDAC upregulation. However, PINK1 and PARKIN were further reduced, suggesting mitophagic inefficiency. In C2C12 cells, GSNOR(S-nitrosoglutathione reductase) inhibition via N6022 elevated nitrosylation, impaired mitophagy, and caused mitochondrial accumulation with increased PINK1 but unchanged PARKIN, highlighting a critical role of nitrosylation balance in mitophagy regulation.</div></div><div><h3>Conclusions</h3><div>NOS inhibition may serve as a key point for further research on the progression of DMD disease and as a potential therapeutic target for this incurable disease.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104388"},"PeriodicalIF":1.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144523078","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":"National study on pediatric acute encephalopathy in Japan (April 2020 to October 2023): Insights from the third study","authors":"Taku Omata ,&nbsp;Hiroshi Sakuma ,&nbsp;Hiroaki Nagase ,&nbsp;Yuichi Abe ,&nbsp;Ichiro Kuki ,&nbsp;Akihisa Okumura ,&nbsp;Yoshihiro Maegaki ,&nbsp;Kei Murayama ,&nbsp;Yasunari Sakai ,&nbsp;Ai Hoshino ,&nbsp;Masashi Mizuguchi ,&nbsp;Jun-ichi Takanashi","doi":"10.1016/j.braindev.2025.104387","DOIUrl":"10.1016/j.braindev.2025.104387","url":null,"abstract":"<div><h3>Background</h3><div>Previous national studies of acute encephalopathy in Japan were conducted in 2007–2010 and 2014–2017. In this third study (April 1, 2020–October 31, 2023), spanning the coronavirus disease 2019 (COVID-19) outbreak, we compared results to assess trends in pediatric viral infections and therapeutic practices.</div></div><div><h3>Methods</h3><div>Questionnaires were sent to 430 hospitals of the Japanese Pediatric Society, yielding 241 responses and 1197 cases. A secondary survey to 151 facilities received 110 responses (72.8 %), identifying 622 eligible patients (604 for treatment, 544 for outcome analysis). Data on patient background, syndrome classification, causative virus, treatment, and prognosis were collected.</div></div><div><h3>Results</h3><div>Among 622 cases (54.6 % boys), the highest incidence was in 1-year-olds, with case numbers peaking during COVID-19 and influenza outbreaks. The frequency of clinical syndromes was: acute encephalopathy with biphasic seizures and late reduced diffusion, 35.1 %; clinically mild encephalitis/encephalopathy with a reversible splenial lesion, 17.8 %; hemorrhagic shock and encephalopathy syndrome (HSES), 6.9 %; acute encephalitis with refractory, repetitive partial seizures, 3.7 %; acute fulminant cerebral edema (AFCE), 2.2 %; acute necrotizing encephalopathy, 1.6 %; and unclassifiable, 31.4 %. Notably, the combined HSES/AFCE rate increased from 1.9 % in the 2014–2017 survey to 9.1 %, likely due to enhanced diagnosis and COVID-19 impact. Pathogens were exanthem subitum (16.1 %), severe acute respiratory syndrome coronavirus 2 (15.9 %), and influenza (7.7 %). Treatments included steroid pulse therapy (68.9 %), mitochondrial cocktails (42.5 %), and targeted temperature management (31.0 %).</div></div><div><h3>Conclusion</h3><div>This study provides a comprehensive overview of pediatric acute encephalopathy during COVID-19 outbreaks, shows increases in the incidence of HSES/AFCE, and presents current treatment.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104387"},"PeriodicalIF":1.4,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144472251","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":"Hematopoietic stem cell gene therapy of neurometabolic lysosomal storage diseases","authors":"Giulia Consiglieri ,&nbsp;Francesca Tucci ,&nbsp;Maria Ester Bernardo","doi":"10.1016/j.braindev.2025.104384","DOIUrl":"10.1016/j.braindev.2025.104384","url":null,"abstract":"<div><div>Neurometabolic disorders are rare, inherited monogenic diseases arising from mutations in genes whose products are essential for brain functions and cause local accumulation of toxic substrates. Central nervous system involvement can be severe, is progressive and frequently appears early in life. Current treatment options for neurometabolic disorders are represented mainly by enzyme replacement therapy (ERT) and allogeneic hematopoietic stem cell transplantation (HSCT) which do not sufficiently address clinical manifestations and leave patients with a substantial residual disease burden. Given this unmet medical need, alternative strategies based on genetic manipulation of patient's cells have been developed. Hematopoietic stem progenitor cells-gene therapy (HSPC-GT) entails the harvest autologous HSPCs which are ex-vivo manipulated by means of viral vectors to express the therapeutic gene and infused back into the patient after chemotherapy-based preparation. Modified HSPCs engraft and differentiate into the various hematopoietic cell lineages, producing the functional enzyme at either normal or supranormal levels. The number of clinical trials with HSPC-GT in neurometabolic disorders is rapidly increasing and some HSPC-GT products have recently received market approval. This review focuses on HSPC-GT strategies summarizing the most recent developments in the field of neurometabolic disorders.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104384"},"PeriodicalIF":1.4,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144471518","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":"Tuberous sclerosis complex: Clinical, genetic and 7T-MRI neuroimaging findings","authors":"Conceição Campanario da Silva Pereira ,&nbsp;Felipe Diego Gomes Dantas ,&nbsp;Wagner Antonio da Rosa Baratela ,&nbsp;Fabiola Antunes da Costa ,&nbsp;Leandro Tavares Lucato ,&nbsp;Fernando Kok","doi":"10.1016/j.braindev.2025.104386","DOIUrl":"10.1016/j.braindev.2025.104386","url":null,"abstract":"<div><h3>Background</h3><div>Tuberous sclerosis complex (TSC) is a multisystemic disorder caused by monoallelic pathogenic variants in <em>TSC1</em> or <em>TSC2</em> genes. Neuropathological hallmark is the presence of cortical and subcortical tubers, among others. Epilepsy affects up to 85 %.</div></div><div><h3>Aims</h3><div>The objective was to correlate the number and location of tubers with neuropsychological and genetic characteristics in three groups of TSC patients: with active epilepsy, controlled epilepsy and without epilepsy.</div></div><div><h3>Methods</h3><div>Brain 7T-MRI study was performed in 30 subjects with TSC who had previously done brain conventional MRI. Molecular analysis of <em>TSC1</em> and <em>TSC2</em> was conducted post-enrollment. Data on epilepsy characteristics, neuropsychological performance and regional and total tuber counts as seen on 7T-MRI, were collected.</div></div><div><h3>Results</h3><div>Tuber counting in the frontal lobe was significantly higher in the group with active epilepsy compared to the groups with controlled or without epilepsy (<em>p</em> = 0.008). Total and frontal tuber count were significantly higher in individuals with <em>TSC2</em> variants. Total, verbal and executive intelligence quotient (IQ) scores were significantly higher in the group without epilepsy compared to the controlled epilepsy group. Attention deficit/hyperactivity disorder (ADHD) was less frequent in the group without epilepsy.</div></div><div><h3>Conclusion</h3><div>Severity of epilepsy in TSC correlates with the number of tubers, especially in the frontal lobe, and with the <em>TSC2</em> deleterious variant. Future studies involving a larger number of patients may provide new insights into advanced imaging epilepsy biomarkers.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104386"},"PeriodicalIF":1.4,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338454","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":"Molecular pathologies and therapies for Pelizaeus-Merzbacher disease","authors":"Ken Inoue","doi":"10.1016/j.braindev.2025.104383","DOIUrl":"10.1016/j.braindev.2025.104383","url":null,"abstract":"<div><div>Pelizaeus-Merzbacher disease (PMD) is the most common and representative disorder among hypomyelinating leukodystrophies, affecting myelin in the central nervous system. PMD is caused by various mutations in the <em>PLP1</em> gene, including the most common duplications, point mutations (which often lead to severe forms), deletions/null mutations (resulting in milder forms), and deep intron mutations associated with hypomyelination of early myelinated structures (HEMS), a mild variant with characteristic MRI findings. Each mutation type is known to trigger distinct cellular and molecular mechanisms. Understanding these mutation-specific pathologies provides crucial insights for developing targeted therapies. For instance, duplication mutations lead to overexpression of the wild-type PLP1 protein, which disrupts myelination by oligodendrocytes, suggesting that gene suppression could be a potential treatment strategy. Therapeutic approaches under investigation include antisense oligonucleotides and artificial miRNA gene therapy. On the other hand, point mutations in mutant PLP1 proteins often confer cytotoxicity, which has been linked to endoplasmic reticulum stress responses, ferroptosis, and intracellular transport dysfunction within the secretory pathway. As a result, therapies targeting these molecular mechanisms are being explored, including antisense oligonucleotides and iron chelators. Given these advancements, it is not overly optimistic to anticipate that PMD could become a treatable disease in the near future.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104383"},"PeriodicalIF":1.4,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329977","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":"Epilepsy phenotypes and responses to antiseizure medications in pediatric patients with EEF1A2-related epilepsy","authors":"Hee-Jeong Yun ,&nbsp;Soo Yeon Kim ,&nbsp;Woojoong Kim ,&nbsp;Seungbok Lee ,&nbsp;Jong-Hee Chae ,&nbsp;Ki Joong Kim ,&nbsp;Byung Chan Lim","doi":"10.1016/j.braindev.2025.104382","DOIUrl":"10.1016/j.braindev.2025.104382","url":null,"abstract":"<div><h3>Objective</h3><div>To delineate the epilepsy spectrum and evaluate the response of pediatric patients with <em>EEF1A2</em>-related epilepsy to antiseizure medications (ASMs).</div></div><div><h3>Methods</h3><div>We conducted a retrospective analysis of seven pediatric patients with <em>EEF1A2</em> mutations identified at our institution, combined with 69 cases from prior literature, resulting in a cohort of 76 patients. Data for age of seizure onset, seizure types, epilepsy syndromes, ASM responses, and neurodevelopmental outcomes were collected and analyzed. Epilepsy syndromes were classified following the International League Against Epilepsy guideline.</div></div><div><h3>Results</h3><div>Among the 76 patients, 61 (80 %) presented with epilepsy, with a median seizure onset age of 4.5 months. Of these, 56 % experienced seizure onset before the age of 12 months. Generalized seizures were predominant (67 %), including epileptic spasms, myoclonic, tonic, and tonic-clonic seizures. Developmental epileptic encephalopathy (DEE) was observed in 59 % of patients, although a range of milder epilepsy phenotypes was also present. Broad-spectrum ASMs, such as valproic acid, lamotrigine, and levetiracetam, demonstrated effectiveness in controlling seizures in 65 % of patients. Recurrent mutations such as p.Gly70Ser and p. Glu122Lys were predominantly associated with severe DEE.</div></div><div><h3>Conclusions</h3><div><em>EEF1A2</em>-related epilepsy encompasses a broad spectrum of phenotypes, from early-onset severe syndromes to milder forms. Specific mutations within <em>EEF1A2</em> seemed to be correlated with severe DEE.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104382"},"PeriodicalIF":1.4,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144321535","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":"Prevalence and management of gastrointestinal complications in Duchenne muscular dystrophy: A retrospective cohort study","authors":"Yu Aihara ,&nbsp;Yusuke Ito ,&nbsp;Eri Takeshita ,&nbsp;Mari Oba ,&nbsp;Kaoru Yamamoto ,&nbsp;Noriko Sumitomo ,&nbsp;Hisako Yamamoto ,&nbsp;Shimpei Baba ,&nbsp;Yuko Shimizu-Motohashi ,&nbsp;Takashi Saito ,&nbsp;Hirofumi Komaki","doi":"10.1016/j.braindev.2025.104379","DOIUrl":"10.1016/j.braindev.2025.104379","url":null,"abstract":"<div><h3>Background</h3><div>Gastrointestinal complications in Duchenne muscular dystrophy (DMD) have been understudied, particularly in Asian populations. This study aimed to determine the frequency and clinical characteristics of gastrointestinal complications.</div></div><div><h3>Methods</h3><div>This single-center, retrospective study reviewed medical records of 459 Asian patients with genetically or biopsy-confirmed DMD, aged 1–48 years, from September 1, 2010, to January 1, 2023.</div></div><div><h3>Results</h3><div>Constipation was the most common complication, affecting 149 patients (32.5 %), followed by dysphagia in 43 patients (9.4 %). Other conditions included irritable bowel syndrome in 8, gastroesophageal reflux disease in 7, hemorrhoids in 6, acute dilatation of stomach in 4, sigmoid colon volvulus in 2, and pneumatosis cystoides intestinalis in 2. Additionally, 1 case each of appendicitis, esophageal diverticulum, paralytic ileus, aerophagia, anal atresia, malabsorption syndrome, fecal incontinence, inflammatory bowel disease, gastrointestinal bleeding, and rectal prolapse was observed. Treatments for constipation included no intervention in 20 patients (13.4 %), sodium picosulfate hydrate in 62 (41.6 %), magnesium oxide in 59 (39.6 %), and polyethylene glycol 4000 in 20 (13.4 %). Logistic regression analysis showed that body mass index (BMI), age and angiotensin converting enzyme inhibitor use was significantly associated with constipation.</div></div><div><h3>Conclusions</h3><div>This study highlighted constipation as the most frequent gastrointestinal complication in DMD and identified several rare but serious complications, offering key insights into real-world clinical practice.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104379"},"PeriodicalIF":1.4,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144321534","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}