Pub Date : 2025-12-07DOI: 10.1016/j.braindev.2025.104487
Susanna Stjerna , Lina-Maria Hämäläinen , Mari Videman
Background
Antiseizure medications (ASM) are essential for patients with epilepsy. Though prenatal exposure to ASMs is associated with increased risk for malformations and neurocognitive problems, whether prenatal ASM exposure modifies offsprings' natural developmental trajectory has not yet been studied.
Methods
This prospective study explores the effect of prenatal ASM exposure on the trajectory of cognitive development of children by studying the association of Bayley Scales III scores at 2 years with WISC-IV scores at 6 years of age and by comparing the results against those of unexposed children. Neurocognitive performance of 30 children with prenatal ASM exposure and 37 unexposed control children were evaluated. Correlations and separate ANCOVAs across these ages were compared between ASM exposed and unexposed controls. Results were controlled for maternal education, type of maternal epilepsy, child sex and child age at the assessment.
Results
In unexposed participants, cognitive scores at the age of two years associated positively with working memory and processing speed at six years of age and receptive language scores at the age of two years associated with working memory at six years old. Conversely, with exposed children, there were no significant associations between two- and six-year test scores, and coefficients between receptive language and six-year-old working memory or processing speed differed significantly from unexposed children's coefficients. However, small sample size restricts the stability of the results, and the observed group differences in coefficients were not significant after removal of outlier.
Conclusion
ASM exposure in utero may affect the trajectory of neurocognitive development, but the findings were impacted by an outlier and should be confirmed in larger cohort.
{"title":"Does in utero exposure to antiseizure medications affect the trajectory of cognitive development from 2 to 6 years of age?","authors":"Susanna Stjerna , Lina-Maria Hämäläinen , Mari Videman","doi":"10.1016/j.braindev.2025.104487","DOIUrl":"10.1016/j.braindev.2025.104487","url":null,"abstract":"<div><h3>Background</h3><div>Antiseizure medications (ASM) are essential for patients with epilepsy. Though prenatal exposure to ASMs is associated with increased risk for malformations and neurocognitive problems, whether prenatal ASM exposure modifies offsprings' natural developmental trajectory has not yet been studied.</div></div><div><h3>Methods</h3><div>This prospective study explores the effect of prenatal ASM exposure on the trajectory of cognitive development of children by studying the association of Bayley Scales III scores at 2 years with WISC-IV scores at 6 years of age and by comparing the results against those of unexposed children. Neurocognitive performance of 30 children with prenatal ASM exposure and 37 unexposed control children were evaluated. Correlations and separate ANCOVAs across these ages were compared between ASM exposed and unexposed controls. Results were controlled for maternal education, type of maternal epilepsy, child sex and child age at the assessment.</div></div><div><h3>Results</h3><div>In unexposed participants, cognitive scores at the age of two years associated positively with working memory and processing speed at six years of age and receptive language scores at the age of two years associated with working memory at six years old. Conversely, with exposed children, there were no significant associations between two- and six-year test scores, and coefficients between receptive language and six-year-old working memory or processing speed differed significantly from unexposed children's coefficients. However, small sample size restricts the stability of the results, and the observed group differences in coefficients were not significant after removal of outlier.</div></div><div><h3>Conclusion</h3><div>ASM exposure in utero may affect the trajectory of neurocognitive development, but the findings were impacted by an outlier and should be confirmed in larger cohort.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"48 1","pages":"Article 104487"},"PeriodicalIF":1.3,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696507","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}
Pub Date : 2025-12-03DOI: 10.1016/j.braindev.2025.104489
Yuko Shimizu-Motohashi
{"title":"Reply to the letter to the editor “Gene therapy advancements in Duchenne muscular dystrophy: Overlooked challenges”","authors":"Yuko Shimizu-Motohashi","doi":"10.1016/j.braindev.2025.104489","DOIUrl":"10.1016/j.braindev.2025.104489","url":null,"abstract":"","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"48 1","pages":"Article 104489"},"PeriodicalIF":1.3,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145659098","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}
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.
Methods
This cross-sectional study evaluated children with AD seen over the past 10 years. Neuroimaging was evaluated by a trained neuroradiologist. In-silico tools were used to predict the pathogenicity of the novel variants detected by whole-exome sequencing.
Results
N = 12 children (males 58.3 %) with genetically-confirmed AD were evaluated. Disease subtypes were infantile (n = 7, 58.3 %), juvenile (n = 3, 25 %), and neonatal (n = 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 (n = 9, 75 %), macrocephaly (n = 9, 75 %), spasticity (n = 6, 50 %), and epilepsy (n = 8, 66.7 %); two children with juvenile-onset disease had atypical visual and bulbar manifestations. Pathogenic variations were most common in exons 1 (n = 5, 42 %), and exon 4 (n = 4, 33.3 %). These were missense type (n = 11, 91.6 %) or deletion (n = 1, 8.3 %). Three novel variants were detected: c.251T>G (p.Ile84Ser) in exon 1, c.810_818 deletion (p.Asn271_Glu273del) in exon 5, and c.292G>C (p.Ala98Pro) in exon 1 in the GFAP gene (NM_002055). Majority of children developed spastic paresis (n = 9, 83 %) and mortality rate was 33.3 % (n = 4/12).
Conclusion
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.
{"title":"Neurological manifestations and clinical outcomes in pediatric Alexander disease: single-center cohort and identification of novel GFAP variants","authors":"Renu Suthar , Yashu Sharma , Arushi Gahlot Saini , Pawan Kumar , Sadhna Lal , Prateek Bhatia , Vikas Bhatia , Sameer Vyas , Priyanka Srivastava , Balamurugan Nagarajan , Savita Attri , Jitendra Sahu , 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>G (p.Ile84Ser) in exon 1, c.810_818 deletion (p.Asn271_Glu273del) in exon 5, and c.292G>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}
Pub Date : 2025-11-15DOI: 10.1016/j.braindev.2025.104485
Dominique Enyama , Daniel Gams Massi , Diomede Noukeu Njinkui , Zakiatou Benazir Abdourahmani , Joël Aquilas Ngalandeu Kwemo , Abouame Palma Haoua , Daniel Armand Kago Tague , Arielle Annick Sime Tchouamo , Danielle Christiane Kedy Mangamba
Introduction
Epilepsy is a chronic brain disorder characterized by recurrent seizures. Limited data on childhood epilepsy in Cameroon prompted this study.
Methods
We conducted a cross-sectional study with retrospective data collection over six months (December 2023–May 2024). Medical records of children aged 3 months to 15 years, diagnosed with epilepsy and followed at Douala General Hospital between January 2020 and December 2023, were analyzed. Statistical analysis used SPSS 26.0, with Fisher's exact and chi-square tests for associations, and logistic regression for predictive factors (p < 0.05).
Results
142 patients were included (male-to-female ratio = 1.21). Epilepsy prevalence was 2.4 %. Generalized seizures predominated (65.7 %) with focal epileptic abnormalities in 50.7 % of cases. Idiopathic generalized epilepsy represented 57.7 % of cases. Sodium valproate was used in 52.8 % of cases. Main etiological factors included: neonatal convulsions (61; 43 %), febrile seizures (49; 34.5 %) and neonatal asphyxia (35; 24.6 %). Seizures persisted in 35 patients (24.6 %) under treatment. Predictive factors for poor seizure control included unknown seizure type (OR 14.25 [1.10–183.97]; p = 0.04), cryptogenic focal epilepsy (OR 12.55 [1.58–99.71]; p = 0.02), and use of prayers or traditional medicines (OR 7.45 [1.01–55.13]; p = 0.05). Memory disorders significantly impacted school performance (OR 4.95 [1.80–13.59]; p = 0.002), along with lack of concentration (OR 3.04 [1.04–8.84]; p = 0.04).
Conclusion
This study identified specific predictive factors for poor epileptic control and confirms cognitive impact on schooling, providing intervention targets to optimize neurological and educational management in Cameroon.
癫痫是一种以反复发作为特征的慢性脑部疾病。关于喀麦隆儿童癫痫的有限数据促使了这项研究。方法采用横断面研究，回顾性收集数据6个月（2012月- 2024年5月）。分析了2020年1月至2023年12月期间在杜阿拉总医院诊断为癫痫并随访的3个月至15岁儿童的医疗记录。统计学分析采用SPSS 26.0，相关性采用Fisher精确检验和卡方检验，预测因素采用logistic回归（p < 0.05）。结果共纳入142例患者，男女比为1.21。癫痫患病率为2.4%。全身性癫痫发作占多数（65.7%），局灶性癫痫异常占50.7%。特发性全身性癫痫占57.7%。52.8%的病例使用丙戊酸钠。主要病因包括新生儿惊厥（61例；43%）、热性惊厥（49例；34.5%）和新生儿窒息（35例；24.6%）。35例（24.6%）患者在治疗中持续发作。癫痫控制不良的预测因素包括未知癫痫类型（OR 14.25 [1.10-183.97]; p = 0.04）、隐源性局灶性癫痫（OR 12.55 [1.58-99.71]; p = 0.02）和使用祈祷或传统药物（OR 7.45 [1.01-55.13]; p = 0.05）。记忆障碍显著影响学习成绩（OR 4.95 [1.80-13.59]; p = 0.002），以及注意力不集中（OR 3.04 [1.04-8.84]; p = 0.04）。结论本研究确定了癫痫控制不良的具体预测因素，确认了认知对学校教育的影响，为优化喀麦隆的神经和教育管理提供了干预目标。
{"title":"Childhood epilepsy in Cameroon: Clinical patterns, predictive factors, and educational impact at a tertiary hospital","authors":"Dominique Enyama , Daniel Gams Massi , Diomede Noukeu Njinkui , Zakiatou Benazir Abdourahmani , Joël Aquilas Ngalandeu Kwemo , Abouame Palma Haoua , Daniel Armand Kago Tague , Arielle Annick Sime Tchouamo , Danielle Christiane Kedy Mangamba","doi":"10.1016/j.braindev.2025.104485","DOIUrl":"10.1016/j.braindev.2025.104485","url":null,"abstract":"<div><h3>Introduction</h3><div>Epilepsy is a chronic brain disorder characterized by recurrent seizures. Limited data on childhood epilepsy in Cameroon prompted this study.</div></div><div><h3>Methods</h3><div>We conducted a cross-sectional study with retrospective data collection over six months (December 2023–May 2024). Medical records of children aged 3 months to 15 years, diagnosed with epilepsy and followed at Douala General Hospital between January 2020 and December 2023, were analyzed. Statistical analysis used SPSS 26.0, with Fisher's exact and chi-square tests for associations, and logistic regression for predictive factors (<em>p</em> < 0.05).</div></div><div><h3>Results</h3><div>142 patients were included (male-to-female ratio = 1.21). Epilepsy prevalence was 2.4 %. Generalized seizures predominated (65.7 %) with focal epileptic abnormalities in 50.7 % of cases. Idiopathic generalized epilepsy represented 57.7 % of cases. Sodium valproate was used in 52.8 % of cases. Main etiological factors included: neonatal convulsions (61; 43 %), febrile seizures (49; 34.5 %) and neonatal asphyxia (35; 24.6 %). Seizures persisted in 35 patients (24.6 %) under treatment. Predictive factors for poor seizure control included unknown seizure type (OR 14.25 [1.10–183.97]; <em>p</em> = 0.04), cryptogenic focal epilepsy (OR 12.55 [1.58–99.71]; <em>p</em> = 0.02), and use of prayers or traditional medicines (OR 7.45 [1.01–55.13]; <em>p</em> = 0.05). Memory disorders significantly impacted school performance (OR 4.95 [1.80–13.59]; <em>p</em> = 0.002), along with lack of concentration (OR 3.04 [1.04–8.84]; <em>p</em> = 0.04).</div></div><div><h3>Conclusion</h3><div>This study identified specific predictive factors for poor epileptic control and confirms cognitive impact on schooling, providing intervention targets to optimize neurological and educational management in Cameroon.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 6","pages":"Article 104485"},"PeriodicalIF":1.3,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520345","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}
Pub Date : 2025-11-14DOI: 10.1016/j.braindev.2025.104486
Gül Yücel
{"title":"Comment on “Survival motor neuron protein is the optimal biomarker for evaluating the risdiplam treatment”","authors":"Gül Yücel","doi":"10.1016/j.braindev.2025.104486","DOIUrl":"10.1016/j.braindev.2025.104486","url":null,"abstract":"","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 6","pages":"Article 104486"},"PeriodicalIF":1.3,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520346","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}
Pub Date : 2025-11-14DOI: 10.1016/j.braindev.2025.104484
Nobuaki Tsuiki , Itaru Hayakawa , Yuichi Abe
Objectives
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.
Methods
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 (>28 days) diagnosis groups, and analyzed symptoms as well as patterns of diagnostic errors.
Results
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, p < 0.01). The presence or absence of neuroblastoma did not contribute to the diagnostic delay.
Conclusions
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.
目的眼阵挛-肌阵挛综合征（OMS）是一种罕见的免疫介导的中枢神经系统疾病，以眼动混乱（眼阵挛）、肌阵挛、共济失调和行为障碍为特征。尽管OMS具有可识别的临床特征，但其诊断仍然具有挑战性。方法对某三级儿童医疗中心（2002-2024）的OMS患者进行单中心队列研究。使用诊断奥德赛图方法，我们绘制了个体诊断途径，比较早期（≤28天）和延迟（>；28天）诊断组，并分析了症状和诊断错误的模式。结果共确诊20例。10例患者早期诊断（中位16.5天），其余患者延迟诊断（等于或超过28天，中位124天）。临时诊断为急性小脑性共济失调，急性播散性脑脊髓炎和急性小脑炎是常见的。症状分析显示，早期和延迟诊断组眼球震颤同时出现，但延迟诊断组眼冠的发现较晚（11.5 d对96 d， p < 0.01）。神经母细胞瘤的存在或不存在不会导致诊断延迟。结论总结了OMS独特的诊断历程。对长期或复发性共济失调的病例重新考虑诊断，及早发现眼阵挛对OMS的早期发现至关重要。
{"title":"Diagnostic odyssey of opsoclonus-myoclonus syndrome and barriers to early detection","authors":"Nobuaki Tsuiki , Itaru Hayakawa , 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 (>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> < 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":"2025-11-14","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}
Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a rare disorder caused by antibodies against platelet factor 4 (PF4) triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines using non-replicable adenoviral vectors. It emerged during the pandemic, with patients typically presenting with thrombosis at uncommon sites, thrombocytopenia, and elevated D-dimer levels. VITT antibodies and heparin-dependent antibodies bind to distinct PF4 epitopes. Recently, VITT-like clinical, laboratory, and anti-PF4 antibody features have also been observed in patients with adenoviral infections. Only four pediatric cases of cerebral venous sinus thrombosis (CVST) have been reported.
Case report
The patient was a previously healthy 2-year-old girl with no history of heparin exposure or SARS-CoV-2 vaccination. She presented with fever and was diagnosed with adenovirus infection. The fever resolved by day 4, but by day 6 she became increasingly lethargic and experienced vomiting. On day 12, Laboratory data showed severe thrombocytopenia and elevated D-dimer levels. Computed tomography revealed CVST along with a secondary hemorrhage in the right temporal lobe. She underwent hematoma removal with external/internal decompression and was started on continuous intravenous unfractionated heparin, and she was switched to warfarin. The thrombus decreased, platelet count spontaneously increased. Platelet activation assays using acute-phase serum identified a PF4-dependent platelet-activating antibody.
Conclusion
We report a case of CVST in a 2-year-old girl following adenovirus infection. Unlike heparin-induced thrombocytopenia, where heparin exacerbates the condition, it is effective here by competitively inhibiting anti-PF4 antibody binding. In patients with prior adenovirus infection presenting with CVST and thrombocytopenia, anti-PF4 disorders should be considered.
{"title":"A pediatric case of anti-PF4 antibody-induced cerebral venous sinus thrombosis and thrombocytopenia following adenovirus infection: a literature review","authors":"Kohei Nagai , Tadahiro Mitani , Yuta Kawahara , Hirofumi Oguma , Akira Gomi , Atsushi Yasumoto , Toshihiro Tajima , Kazuhiro Muramatsu , Hitoshi Osaka","doi":"10.1016/j.braindev.2025.104483","DOIUrl":"10.1016/j.braindev.2025.104483","url":null,"abstract":"<div><h3>Introduction</h3><div>Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a rare disorder caused by antibodies against platelet factor 4 (PF4) triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines using non-replicable adenoviral vectors. It emerged during the pandemic, with patients typically presenting with thrombosis at uncommon sites, thrombocytopenia, and elevated D-dimer levels. VITT antibodies and heparin-dependent antibodies bind to distinct PF4 epitopes. Recently, VITT-like clinical, laboratory, and anti-PF4 antibody features have also been observed in patients with adenoviral infections. Only four pediatric cases of cerebral venous sinus thrombosis (CVST) have been reported.</div></div><div><h3>Case report</h3><div>The patient was a previously healthy 2-year-old girl with no history of heparin exposure or SARS-CoV-2 vaccination. She presented with fever and was diagnosed with adenovirus infection. The fever resolved by day 4, but by day 6 she became increasingly lethargic and experienced vomiting. On day 12, Laboratory data showed severe thrombocytopenia and elevated D-dimer levels. Computed tomography revealed CVST along with a secondary hemorrhage in the right temporal lobe. She underwent hematoma removal with external/internal decompression and was started on continuous intravenous unfractionated heparin, and she was switched to warfarin. The thrombus decreased, platelet count spontaneously increased. Platelet activation assays using acute-phase serum identified a PF4-dependent platelet-activating antibody.</div></div><div><h3>Conclusion</h3><div>We report a case of CVST in a 2-year-old girl following adenovirus infection. Unlike heparin-induced thrombocytopenia, where heparin exacerbates the condition, it is effective here by competitively inhibiting anti-PF4 antibody binding. In patients with prior adenovirus infection presenting with CVST and thrombocytopenia, anti-PF4 disorders should be considered.</div></div>","PeriodicalId":56137,"journal":{"name":"Brain & Development","volume":"47 6","pages":"Article 104483"},"PeriodicalIF":1.3,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145490967","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}
Pub Date : 2025-11-08DOI: 10.1016/j.braindev.2025.104482
Yeon-Gyu Jeong , Won-Cheol Kim , Yeon-Jae Jeong , Ha-Neul Jang , Joo-Young Lee , Jae-Soon Chung , Kyu-Hoon Lee
Background
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 (p = 0.02, d = 0.38), light (p = 0.03, d = 0.51) and moderate physical activity time (p = 0.01, d = 0.42), and VM CPM (p = 0.02, d = 0.55), along with reduced sedentary time (p = 0.02, d = −0.49). Functional outcomes improved in GMFM (p<0.01, d = 0.22), TUG (p = 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.
背景痉挛性脑瘫（CP）患儿会出现运动障碍和身体活动减少，对健康和生活质量产生负面影响。目的：本研究旨在评估可穿戴外骨骼机器人辅助步态训练对CP患儿身体活动、运动功能和生活质量的影响。方法：10例痉挛性CP患儿（平均年龄9.20±2.57岁，大运动功能分类系统等级I-IV级）在某大学医院康复中心接受了12次30分钟的机器人辅助步态训练，为期6周。使用三轴加速度计测量身体活动，以评估能量消耗、代谢当量（METs）、强度水平、每分钟矢量量级计数（VM CPM）和步数。运动功能通过大运动功能测量（GMFM）、计时起床和行走测试（TUG）和6分钟步行测试（6MWT）进行评估。采用脑瘫生活质量问卷（CP-QOL）评估患者的生活质量。采用重复测量方差分析（MANOVA）和Cohen’s d进行统计分析。结果：在METs （p = 0.02, d = 0.38）、轻度（p = 0.03, d = 0.51）和中度体力活动时间（p = 0.01, d = 0.42）和VM CPM （p = 0.02, d = 0.55）以及减少久坐时间（p = 0.02, d = - 0.49）方面观察到显著改善。功能结果改善GMFM(术中;0.01 d = 0.22),拖船(p = 0.03, d =−0.33),和6 mwt (p = 0.02, d = 0.52)。CP-QOL评分无明显变化。结论：可穿戴机器人辅助的步态训练似乎可以增强痉挛性脑瘫儿童的身体活动和活动能力，可能被认为是一种有前途的治疗干预措施。
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Pub Date : 2025-10-30DOI: 10.1016/j.braindev.2025.104480
Ze Dong Jiang
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