Brain & Development最新文献

{"title":"Inherited white matter disorders in Japan: focusing on demyelinating leukodystrophy","authors":"Masayuki Sasaki","doi":"10.1016/j.braindev.2025.104404","DOIUrl":"10.1016/j.braindev.2025.104404","url":null,"abstract":"<div><div>We reviewed published articles on representative inherited cerebral white matter disorders that develop in childhood. In this paper, we described demyelinating disorders (adrenoleukodystrophy, globoid cell leukodystrophy or Krabbe disease, and metachromatic leukodystrophy), astrocytic disorders (Alexander disease and vanishing white matter disease), and disorders of water homeostasis in the myelin sheath (megalencephalic leukoencephalopathy with subcortical cysts and <em>CLCN2</em>-related leukoencephalopathy). The causes, symptoms, diagnostic imaging, and forefront of treatment for these disorders are discussed. Each disease is rare and progressive. Although the number of analyzed cases is very small, establishing a radical treatment is still necessary. We do hope that the patients with these disorders could be treated completely in the near future.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 5","pages":"Article 104404"},"PeriodicalIF":1.3,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144722530","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":"Letter to the editor: A case of spinal muscular atrophy type 0 treated with nusinersen without progression of early-onset scoliosis","authors":"Meghan Moore Burk ,&nbsp;Carolyn Kelley ,&nbsp;Kelli Browning ,&nbsp;Anne Stratton ,&nbsp;Susan Apkon ,&nbsp;Melissa Wright ,&nbsp;Michele L. Yang","doi":"10.1016/j.braindev.2025.104411","DOIUrl":"10.1016/j.braindev.2025.104411","url":null,"abstract":"","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 5","pages":"Article 104411"},"PeriodicalIF":1.3,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144722533","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":"2025-07-29","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":"Diagnostic clarification and exclusion of differential diagnoses in pediatric acute encephalopathy","authors":"Josef Finsterer","doi":"10.1016/j.braindev.2025.104407","DOIUrl":"10.1016/j.braindev.2025.104407","url":null,"abstract":"","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 5","pages":"Article 104407"},"PeriodicalIF":1.3,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144722532","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":"An atypical case of macrocephaly and severe intellectual disability associated with a missense variant in the guanine nucleotide exchange factor-1 domain of TRIO","authors":"Takuya Hiraide ,&nbsp;Taiju Hayashi ,&nbsp;Kaori Yamoto ,&nbsp;Yohei Masunaga ,&nbsp;Miki Asahina ,&nbsp;Tsutomu Ogata ,&nbsp;Hirotomo Saitsu ,&nbsp;Tokiko Fukuda","doi":"10.1016/j.braindev.2025.104405","DOIUrl":"10.1016/j.braindev.2025.104405","url":null,"abstract":"<div><h3>Background</h3><div>Trio rho guanine nucleotide exchange factor (<em>TRIO</em>)<em>,</em> encodes a guanine nucleotide exchange factor (GEF) that is critical for neurodevelopment and regulates Rho guanosine triphosphatase. It has been shown that missense variants in the GEF1 or GEF2 domains or loss-of-function variants in <em>TRIO</em> are associated with microcephaly while gain-of-function variants in the spectrin repeat domain result in macrocephaly. Rare cases of macrocephaly linked to missense variants in the GEF1 domain have been reported; however, clinical details remain limited.</div></div><div><h3>Case presentation</h3><div>We describe the case of a Japanese boy with macrocephaly, severe intellectual disability, distinctive facial features, scoliosis, and growth hormone deficiency. Brain magnetic resonance imaging revealed a thin corpus callosum and pituitary hypoplasia. His occipitofrontal circumference was +2.5 standard deviations above the normal range, while his height and weight were below the average. He displayed many features characteristic of <em>TRIO</em>-related neurodevelopmental disorders caused by gain-of-function variants. However, trio-based exome sequencing identified a <em>de novo</em> missense variant (instead of gain-of-function variant) in the GEF1 domain of <em>TRIO</em> (NM_007118.4:c.4104T&gt;A, p.(Asp1368Glu)).</div></div><div><h3>Conclusions</h3><div>This case expands the phenotypic spectrum of <em>TRIO</em>-related neurodevelopmental disorders, highlighting macrocephaly associated with a missense variant in the GEF1 domain. Further studies are required to clarify the functional effects of <em>TRIO</em> variants and their phenotypic consequences.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 5","pages":"Article 104405"},"PeriodicalIF":1.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144704648","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":"Duchenne muscular dystrophy: Evolving therapeutic strategies and multidimensional evaluation approaches","authors":"Hirofumi Komaki","doi":"10.1016/j.braindev.2025.104397","DOIUrl":"10.1016/j.braindev.2025.104397","url":null,"abstract":"<div><div>Duchenne muscular dystrophy (DMD) is a severe X-linked muscular disorder caused by the absence of dystrophin. Standard therapies prolong survival; however, there is an increasing need for disease-modifying approaches and sensitive evaluation tools. This review presents a summary of the recent advances in DMD therapeutic strategies and multidimensional evaluation approaches, emphasizing their clinical applicability and future perspectives. In this study, a comprehensive review of the current literature was conducted focusing on mutation-specific therapies (exon skipping and gene therapy), non-mutation-specific pharmacological interventions (steroids, vamorolone, and histone deacetylase inhibitors), and emerging modalities such as cell-based therapy. The clinical outcome measures used across the disease stages were also examined, ranging from functional motor tests and imaging biomarkers to digital endpoints and quality of life (QOL) indices. Exon skipping and microdystrophin gene therapies have shown promising results in restoring partial dystrophin expression. Vamorolones and givinostat are alternative drugs with improved safety profiles. Time-based motor tests (such as time to sand, 10 m run) and digital biomarkers (Stride Velocity 95th Centile) enable the earlier detection of disease progression. Natural history data, including large registry-based datasets, enhance the interpretation of clinical trials. Patient-reported outcomes and disease-specific QOL measures, such as the DMD-QoL, are increasingly being incorporated to assess meaningful treatment benefits. The therapeutic landscape of DMD is evolving toward combination and personalized approaches. Multidimensional stage-specific evaluations are essential to capture functional changes and their therapeutic effects. Ongoing research on gene-, pharmacological-, and cell-based therapies, coupled with robust outcome assessments, may further improve patient care and QOL.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 5","pages":"Article 104397"},"PeriodicalIF":1.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144704644","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":"Clinical features and prognostic factors of group B Streptococcus Meningitis in infants","authors":"Wenjie Li ,&nbsp;Xueqian Xia ,&nbsp;Lingyu Zhang ,&nbsp;Xiaoling Peng ,&nbsp;Li Jiang ,&nbsp;Yue Hu","doi":"10.1016/j.braindev.2025.104398","DOIUrl":"10.1016/j.braindev.2025.104398","url":null,"abstract":"<div><h3>Purpose</h3><div>To summarize the clinical features of group B streptococcus (GBS) meningitis in infants and identify the risk factors for poor prognosis.</div></div><div><h3>Methods</h3><div>The clinical data of 52 infants with GBS meningitis treated at Children's Hospital of Chongqing Medical University from January 2012 to December 2021 were retrospectively analyzed.</div></div><div><h3>Results</h3><div>A total of 48 infants (48/52, 92.3 %) presented with symptom onset at ≤90 days of age. Among 52 patients, the most prevalent clinical manifestations were fever (98.1 %), altered mental status (84.6 %) and decreased appetite (63.5 %). Subdural effusion (30/52, 57.7 %) was the most common neurological complication. One patient (1.9 %) died from cerebral herniation. Positive blood culture alone was observed in 41 cases (78.8 %), isolated cerebrospinal fluid (CSF) culture positivity in 5 (9.6 %), and dual blood-CSF culture positivity in 6 (11.5 %). The median hospital stay was 33 days. The most frequently administered antibiotic regimens were vancomycin combined with carbapenems (18/52, 34.6 %) and vancomycin plus third-generation cephalosporins (15/52, 28.8 %). Univariate analysis indicated an association between glucocorticoid use and clinical outcomes; however, multivariate analysis yielded no statistically significant variables (<em>P</em> &lt; 0.05).</div></div><div><h3>Conclusions</h3><div>GBS meningitis is most common in infants below 3 months. Both clinical manifestations and ancillary tests may be nonspecific, and definitive diagnosis relies on etiological confirmation. The risk of neurological complications is high.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 5","pages":"Article 104398"},"PeriodicalIF":1.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144704646","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":"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":"2025-07-24","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":"Letter to the editor: ‘Prevalence and management of gastrointestinal complications of Duchenne muscular dystrophy: A retrospective cohort study’","authors":"Sabri Selcuk Atamanalp","doi":"10.1016/j.braindev.2025.104402","DOIUrl":"10.1016/j.braindev.2025.104402","url":null,"abstract":"","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104402"},"PeriodicalIF":1.4,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144672476","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 epilepsy and attention deficit/hyperactivity disorder – correlation between interictal epileptiform discharges and behavioral disturbances","authors":"Hideaki Kanemura","doi":"10.1016/j.braindev.2025.104403","DOIUrl":"10.1016/j.braindev.2025.104403","url":null,"abstract":"<div><div>A relationship between epileptic activities and neuropsychological dysfunction has been indicated in epileptic children. Epileptic activities including frequent/prolonged seizures and severe EEG abnormalities could be associated with cognitive decline and behavioral disturbances. Frequent, prolonged seizures could induce growth disturbances in the prefrontal cortex, leading to behavioral disturbance. Meanwhile, frequent epileptic seizures or EEG abnormalities, including interictal epileptiform discharges (IEDs), are evident in attention deficit/hyperactivity disorder (ADHD). Subclinical IEDs could lead to neuropsychological dysfunction in epileptic and ADHD children. The concurrence of IED frequency and prolonged periods of high-frequency IEDs may predict the atypical evolution of self-limited epilepsy with centrotemporal spikes. In developmental and epileptic encephalopathy with spike-wave activation during sleep, cognitive/behavioral disturbances correlate with frequent IEDs such as secondary bilateral synchrony (SBS). On the other hand, EEG manifestations, particularly IED locations, could represent important predictors of optimal outcome in epilepsy and ADHD. Abnormal paroxysms in the frontal region could lead to neuropsychological dysfunctions, so frontal IEDs could be associated with cognitive/behavioral disturbances in epilepsy and ADHD. Frontal IEDs could predict atypical clinical features including behavioral disturbance and ultimate neuropsychological outcomes in epileptic/ADHD children. Early remission of clinical seizures and reduction of IEDs might be necessary to accomplish optimal outcomes for children presenting with behavioral disturbances. A therapeutic strategy comprising prompt suppression of IEDs (including frontal IEDs/SBS) could improve quality of life in at least some children with epilepsy and ADHD.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 4","pages":"Article 104403"},"PeriodicalIF":1.4,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144662823","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}