Brain & Development最新文献

{"title":"Clinical profiles of tuberous sclerosis complex: A regionally based survey","authors":"Misae Yamada ,&nbsp;Jun Natsume ,&nbsp;Yuki Maki ,&nbsp;Soichiro Ishimaru ,&nbsp;Shingo Numoto ,&nbsp;Satoru Kobayashi ,&nbsp;Ayako Hattori ,&nbsp;Yoshihisa Matsukawa ,&nbsp;Keiko Wakahara ,&nbsp;Naoko Ishihara ,&nbsp;Hitomi Sasaki ,&nbsp;Yuji Ito ,&nbsp;Hiroyuki Yamamoto ,&nbsp;Tomohiko Nakata ,&nbsp;Hiroyuki Kidokoro ,&nbsp;Tetsushi Yoshikawa ,&nbsp;Shinji Saitoh ,&nbsp;Akihisa Okumura ,&nbsp;Yoshiyuki Takahashi","doi":"10.1016/j.braindev.2025.104479","DOIUrl":"10.1016/j.braindev.2025.104479","url":null,"abstract":"<div><h3>Background</h3><div>This study aimed to clarify the clinical profiles of patients with tuberous sclerosis complex (TSC) in the general population by a regionally based survey of medical facilities in a region with 7.5 million residents, and investigate differences in clinical profiles according to medical facility size and type.</div></div><div><h3>Methods</h3><div>A survey was sent to 146 hospitals and clinics regarding clinical profiles of patients with TSC who lived in Aichi Prefecture, Japan, between 2013 and 2018. Medical facilities were classified as large hospitals (≥750 beds or a children's hospital), small hospitals (&lt;750 beds), institutions for handicapped children, and private clinics.</div></div><div><h3>Results</h3><div>Information was obtained of 232 patients (median age, 25 years; range, 1–81 years). Estimated prevalence of TSC was 3.1 per 100,000. Cortical tubers were present in 88 %, epilepsy in 81 %, autism spectrum disorder in 44 %, and subependymal giant cell astrocytoma in 17 %. Hypomelanotic macules, facial angiofibroma, renal angiomyolipoma, and cardiac rhabdomyoma were present in &gt;50 % of patients. Rates of epilepsy with frequent seizures and autism spectrum disorder were both higher in patients in institutions for handicapped children. In more than half of patients in institutions for handicapped children information on cranial MRI findings was not obtained.</div></div><div><h3>Conclusions</h3><div>Our regionally based study confirmed the clinical profiles previously reported in specialized hospitals for TSC and found that clinical characteristics differed among the types and sizes of medical facilities. Multicenter information sharing and collaboration between general hospitals and institutions for handicapped children are important for the comprehensive care of patients with TSC.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 6","pages":"Article 104479"},"PeriodicalIF":1.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145364704","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":"The effect of robotic assisted gait training on physical activity, motor function, and quality of life in children with spastic cerebral palsy: Exploratory pilot study","authors":"Yeon-Gyu Jeong ,&nbsp;Won-Cheol Kim ,&nbsp;Yeon-Jae Jeong ,&nbsp;Ha-Neul Jang ,&nbsp;Joo-Young Lee ,&nbsp;Jae-Soon Chung ,&nbsp;Kyu-Hoon Lee","doi":"10.1016/j.braindev.2025.104482","DOIUrl":"10.1016/j.braindev.2025.104482","url":null,"abstract":"<div><h3>Background</h3><div>Children with spastic cerebral palsy (CP) experience motor impairments and reduced physical activity, negatively impacting health and quality of life. Objective: The study aimed to assess the effects of wearable exoskeleton robot-assisted gait training on physical activity, motor function, and quality of life in children with CP. Methods: Ten children with spastic CP (mean age 9.20 ± 2.57 years; gross motor function classification system levels I–IV) received twelve 30-min sessions of robot-assisted gait training over six weeks at a university hospital rehabilitation center. Physical activity was measured using a tri-axial accelerometer to assess energy expenditure, metabolic equivalents (METs), intensity levels, vector magnitude counts per minute (VM CPM), and step counts. Motor function was evaluated using the Gross Motor Function Measure (GMFM), Timed Up and Go Test (TUG), and 6-Minute Walk Test (6MWT). Quality of life was assessed with the Cerebral Palsy Quality of Life questionnaire (CP-QOL). Repeated measures MANOVA and Cohen's d were used for statistical analysis. Results: Significant improvements were observed in METs (<em>p</em> = 0.02, d = 0.38), light (<em>p</em> = 0.03, d = 0.51) and moderate physical activity time (<em>p</em> = 0.01, d = 0.42), and VM CPM (<em>p</em> = 0.02, d = 0.55), along with reduced sedentary time (p = 0.02, d = −0.49). Functional outcomes improved in GMFM (<em>p</em>&lt;0.01, d = 0.22), TUG (<em>p</em> = 0.03, d = −0.33), and 6MWT (p = 0.02, d = 0.52). No significant changes were found in CP-QOL scores. Conclusion: Wearable robot-assisted gait training appears to enhance physical activity and mobility in children with spastic CP and may be considered a promising therapeutic intervention.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 6","pages":"Article 104482"},"PeriodicalIF":1.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145467259","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 odyssey of opsoclonus-myoclonus syndrome and barriers to early detection","authors":"Nobuaki Tsuiki ,&nbsp;Itaru Hayakawa ,&nbsp;Yuichi Abe","doi":"10.1016/j.braindev.2025.104484","DOIUrl":"10.1016/j.braindev.2025.104484","url":null,"abstract":"<div><h3>Objectives</h3><div>Opsoclonus-myoclonus syndrome (OMS) is a rare immune-mediated disorder of central nervous systems characterized by chaotic eye movements (opsoclonus), myoclonus, ataxia, and behavioral disturbances. OMS remains diagnostically challenging despite its recognizable clinical features.</div></div><div><h3>Methods</h3><div>We conducted a single-center cohort study of patients with OMS at a tertiary care children's medical center (2002–2024). Using the diagnostic odyssey plot methodology, we mapped individual diagnostic pathways, compared early (≤28 days) versus delayed (&gt;28 days) diagnosis groups, and analyzed symptoms as well as patterns of diagnostic errors.</div></div><div><h3>Results</h3><div>Twenty cases were ascertained. Ten patients were diagnosed early (median 16.5 days), while the remaining experienced a delayed diagnosis (equal to or more than 28 days, median 124 days). Provisional diagnoses of acute cerebellar ataxia, acute disseminated encephalomyelitis, and acute cerebellitis were common. Analysis of symptoms revealed that nystagmus appeared at the same time in both the early- and delayed-diagnosed groups, but opsoclonus was recognized later in the delayed diagnosed group (11.5 days versus 96 days, <em>p</em> &lt; 0.01). The presence or absence of neuroblastoma did not contribute to the diagnostic delay.</div></div><div><h3>Conclusions</h3><div>The unique diagnostic journey of OMS is presented. Reconsidering the diagnosis in cases of prolonged or relapsing ataxia and recognizing opsoclonus early on are vital for the early detection of OMS.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 6","pages":"Article 104484"},"PeriodicalIF":1.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520433","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":"Neurological manifestations and clinical outcomes in pediatric Alexander disease: single-center cohort and identification of novel GFAP variants","authors":"Renu Suthar ,&nbsp;Yashu Sharma ,&nbsp;Arushi Gahlot Saini ,&nbsp;Pawan Kumar ,&nbsp;Sadhna Lal ,&nbsp;Prateek Bhatia ,&nbsp;Vikas Bhatia ,&nbsp;Sameer Vyas ,&nbsp;Priyanka Srivastava ,&nbsp;Balamurugan Nagarajan ,&nbsp;Savita Attri ,&nbsp;Jitendra Sahu ,&nbsp;Naveen Sankhyan","doi":"10.1016/j.braindev.2025.104488","DOIUrl":"10.1016/j.braindev.2025.104488","url":null,"abstract":"<div><h3>Background</h3><div>We aimed to analyze the prevalence, clinico-radiological and genetic features, and outcomes in children with Alexander disease (AD) with special emphasis on atypical presentations.</div></div><div><h3>Methods</h3><div>This cross-sectional study evaluated children with AD seen over the past 10 years. Neuroimaging was evaluated by a trained neuroradiologist. <em>In-silico</em> tools were used to predict the pathogenicity of the novel variants detected by whole-exome sequencing.</div></div><div><h3>Results</h3><div><em>N</em> = 12 children (males 58.3 %) with genetically-confirmed AD were evaluated. Disease subtypes were infantile (<em>n</em> = 7, 58.3 %), juvenile (<em>n</em> = 3, 25 %), and neonatal (<em>n</em> = 2, 16.7 %) AD. The clinic-based prevalence of AD was 0.34 cases per 1000 pediatric neurology patients per year, or an average of 1.2 cases per year. Clinical features were developmental delay (<em>n</em> = 9, 75 %), macrocephaly (n = 9, 75 %), spasticity (<em>n</em> = 6, 50 %), and epilepsy (<em>n</em> = 8, 66.7 %); two children with juvenile-onset disease had atypical visual and bulbar manifestations. Pathogenic variations were most common in exons 1 (<em>n</em> = 5, 42 %), and exon 4 (<em>n</em> = 4, 33.3 %). These were missense type (<em>n</em> = 11, 91.6 %) or deletion (n = 1, 8.3 %). Three novel variants were detected: c.251T&gt;G (p.Ile84Ser) in exon 1, c.810_818 deletion (p.Asn271_Glu273del) in exon 5, and c.292G&gt;C (p.Ala98Pro) in exon 1 in the <em>GFAP</em> gene (NM_002055). Majority of children developed spastic paresis (<em>n</em> = 9, 83 %) and mortality rate was 33.3 % (<em>n</em> = 4/12).</div></div><div><h3>Conclusion</h3><div>AD is a rare leukodystrophy with high mortality and progressive spastic paraparesis. Neonatal and juvenile types may present atypically and delay correct diagnosis. Deletions may account for a minor proportion of pathogenic variants. Our study expands the clinico-radiological spectrum of AD in children.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 6","pages":"Article 104488"},"PeriodicalIF":1.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145617802","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: “AESD and vitamin therapy: The need for biomarkers and follow-up”","authors":"Yuichi Abe ,&nbsp;Tatsuya Takahashi ,&nbsp;Itaru Hayakawa ,&nbsp;Saeko Irie ,&nbsp;Nobuaki Tsuiki ,&nbsp;Atsuhi Nishioka ,&nbsp;Hiroto Ida ,&nbsp;Tsuyoshi Aihara ,&nbsp;Kentaro Ide","doi":"10.1016/j.braindev.2025.104463","DOIUrl":"10.1016/j.braindev.2025.104463","url":null,"abstract":"","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 6","pages":"Article 104463"},"PeriodicalIF":1.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145314362","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 regarding the article “The impact of intraventricular hemorrhage on brainstem auditory function in preterm babies”","authors":"Gül Yücel ,&nbsp;Nur Yücel Ekici","doi":"10.1016/j.braindev.2025.104474","DOIUrl":"10.1016/j.braindev.2025.104474","url":null,"abstract":"","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 6","pages":"Article 104474"},"PeriodicalIF":1.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318938","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":"Associations between cerebrospinal fluid pressure levels, clinical features, and MRI abnormalities in pediatric idiopathic intracranial hypertension: A retrospective study","authors":"Hasan Emral ,&nbsp;Tülay Kamaşak ,&nbsp;İlker Eyüboğlu ,&nbsp;Yusuf Emre Bostan ,&nbsp;Ali Cansu","doi":"10.1016/j.braindev.2025.104477","DOIUrl":"10.1016/j.braindev.2025.104477","url":null,"abstract":"<div><h3>Background</h3><div>Idiopathic intracranial hypertension (IIH) is a condition characterized by increased cerebrospinal fluid (CSF) pressure without an identifiable cause. Although neuroimaging features are often used to support diagnosis, the relationship between CSF pressure and MRI findings remains unclear, particularly in pediatric populations.</div></div><div><h3>Objective</h3><div>To investigate the association between CSF opening pressure and clinical as well as MRI features in children diagnosed with IIH.</div></div><div><h3>Methods</h3><div>We retrospectively reviewed 30 pediatric patients (aged 6–18 years) diagnosed with IIH between 2015 and 2020. Patients were divided into two groups based on CSF opening pressure: Group 1 (200–350 mm H₂O) and Group 2 (≥350 mm H₂O). Clinical symptoms and MRI features—including optic nerve sheath dilation, posterior globe flattening, optic nerve tortuosity, and transverse sinus stenosis—were compared between groups.</div></div><div><h3>Results</h3><div>The mean CSF opening pressure was 363.8 mm H₂O. No statistically significant differences were observed between groups with respect to demographic features, clinical symptoms, or MRI abnormalities (<em>p</em> &gt; 0.05). The most frequent imaging findings were posterior globe flattening (73.3 %) and optic nerve sheath dilation (70 %). Spearman correlation analysis demonstrated a significant positive association between CSF opening pressure and optic nerve sheath dilation (<em>r</em> = 0.417, <em>p</em> = 0.022), with borderline correlations noted for optic nerve tortuosity (<em>r</em> = 0.358, <em>p</em> = 0.052) and transverse sinus stenosis (<em>r</em> = 0.438, <em>p</em> = 0.069).</div></div><div><h3>Discussion</h3><div>CSF opening pressure alone did not distinguish clinical or imaging features between groups. However, higher pressures correlated with optic nerve sheath dilation and showed trends toward tortuosity and venous stenosis, suggesting these may be secondary markers of disease severity.</div></div><div><h3>Conclusion</h3><div>Pediatric IIH appears multifactorial rather than purely pressure-driven. Multimodal evaluation is essential, and larger prospective studies are warranted to clarify the prognostic value of imaging correlates.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 6","pages":"Article 104477"},"PeriodicalIF":1.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145314279","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":"Acute encephalopathy with biphasic seizures: Is cerebrospinal fluid glutamate truly specific?","authors":"Christian Messina","doi":"10.1016/j.braindev.2025.104466","DOIUrl":"10.1016/j.braindev.2025.104466","url":null,"abstract":"","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 6","pages":"Article 104466"},"PeriodicalIF":1.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145304473","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":"Adrenoleukodystrophy: Current understanding of disease mechanisms, diagnosis, and therapeutic advances–a recent review","authors":"Chakresh Kumar Jain,&nbsp;Sarita Maurya,&nbsp;Pankaj Kumar Tripathi","doi":"10.1016/j.braindev.2025.104476","DOIUrl":"10.1016/j.braindev.2025.104476","url":null,"abstract":"<div><div>Adrenoleukodystrophy (ALD) is a complex and devastating X-linked neurodegenerative disorder classified as rare brain disease with profound effects on patients and their families. It can manifest in various clinical forms, ranging from adult-onset adrenomyeloneuropathy (AMN) to rapidly developing childhood cerebral adrenoleukodystrophy (CCALD), each presenting unique diagnostic and treatment challenges. At the molecular level, ALD results from mutations in the ATP-binding cassette subfamily D member 1 (<em>ABCD1</em>) gene, which disrupts peroxisomal β-oxidation, leading to the accumulation of very long-chain fatty acids (VLCFAs) and subsequent neurological damage. Understanding these pathogenic mechanisms has led to significant improvements in diagnosis and treatment strategies. Advances such as newborn screening and molecular profiling have facilitated early detection and intervention, contributing to improved clinical outcomes. Therapeutic innovations, including gene therapy and hematopoietic stem cell transplantation (HSCT), hold promise for modifying disease progression and enhancing quality of life. Despite these developments, major challenges remain, including the identification of disease modifiers, discovery of new therapeutic targets, and establishing the personalized treatment strategies. This review summarizes the current understanding of ALD, including its clinical spectrum, molecular basis, diagnostic approaches, and emerging therapies. Ongoing research and interdisciplinary collaboration are crucial for establishing the effective management of this debilitating disorder.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 6","pages":"Article 104476"},"PeriodicalIF":1.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145364703","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 of the human cerebellum from midgestation to the perinatal period: A morphological study","authors":"Katsuyuki Yamaguchi,&nbsp;Takuya Yazawa","doi":"10.1016/j.braindev.2025.104453","DOIUrl":"10.1016/j.braindev.2025.104453","url":null,"abstract":"<div><h3>Introduction</h3><div>The human cerebellum has large hemispheres (HS) and develops slowly over the pre- and postnatal periods. Several morphological studies have reported regional differences during the fetal period. This study aimed to investigate these differences by evaluating serial brain sections.</div></div><div><h3>Materials and methods</h3><div>Ten cerebellar samples aged 21–43 postmenstrual weeks (PW) were analyzed. Horizontal serial sections were cut and stained using the Klüver–Barrera method. After microscopic observations, a volumetric analysis was performed for the cerebellar cortex and medulla among the HS, vermis (VM), and flocculus (FL).</div></div><div><h3>Results</h3><div>The lamina dissecans (LD) was more prominent and lasted longer in the HS than in the VM and FL. The maturation of Purkinje cells and the accumulation of granule cells in the internal granular layer started earlier in the latter than in the former. Cortical differentiation was most delayed in the inferior semilunar and tonsillar lobules. Volumetric analysis showed that volume increased more in the HS than in the VM and FL after midgestation, and that it increased more intensively in the cortex than in the medulla in each region.</div></div><div><h3>Conclusions</h3><div>The human cerebellar cortex may develop through three stages in fetal period: (1) three-layers stage (before 20 PW); (2) five-layers stage (20–30 PW); (3) four-layers stage (after 30 PW). Particularly, the second stage is characterized by a transient appearance of the LD, which is most evident in the HS. Regional differences should be carefully considered when interpreting morphogenetic data.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 6","pages":"Article 104453"},"PeriodicalIF":1.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145271503","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}