Brain & Development最新文献_第2页

A lipidation inhibitor rescues impaired neurite outgrowth caused by the CDC42 mutation associated with Takenouchi-Kosaki syndrome in Neuro2A cells 在Neuro2A细胞中，一种脂化抑制剂可拯救由与Takenouchi-Kosaki综合征相关的CDC42突变引起的神经突生长受损。

IF 1.3 4区医学 Q4 CLINICAL NEUROLOGY

Brain & Development

Pub Date : 2026-02-01 Epub Date: 2026-01-24 DOI: 10.1016/j.braindev.2026.104503

Etsuko Daimon , Yukinao Shibukawa , Natsuko Yamazaki , Masanobu Kawai , Saori Kinoshita , Nobuhiko Okamoto

Background

Takenouchi-Kosaki syndrome (TKS), caused by the CDC42 c.191A>G (p.Tyr64Cys; Y64C) variant, characterized by a range of clinical manifestations, including developmental delay with intellectual disability (ID). While CDC42 is essential for neurogenesis, the mechanisms by which the Y64C mutation contributes to the neurological impairments observed in TKS patients remain unclear.

Objective

This study aimed to investigate the functional impact of ectopically expressing the Y64C variant on the neurite outgrowth of neuroblastoma cells, Neuro2A.

Methods

Neuro2A cells were transfected with the Y64C variant to assess changes in neurite outgrowth and cellular morphology. The cells were also treated with a lipidation inhibitor, GGTI-298, or CDC42 activity inhibitor, ML141 to evaluate its ability to ameliorate the mutation-induced phenotypes. Whole transcriptome sequencing and differentially expressed gene (DEG) analysis were performed between WT- and Y64C-expressing cells.

Results

The overexpression of the Y64C variant impaired neurite outgrowth and changed the cell morphology of Neuro2A cells. Both the neurite outgrowth defect and the enhanced membrane localization induced by Y64C overexpression were restored by GGTI-298 treatment but not by ML141. To explore the molecular basis of these phenotypes, we performed DEG analysis and identified 32 upregulated and 19 downregulated genes, including Smarca1. Consistent with the transcriptomic findings, Smarca1 protein expression was decreased in Y64C-expressing cells in comparison to WT. Treatment with GGTI-298 effectively preserved Smarca1 levels, whereas ML141 reduced its expression in both WT- and Y64C-expressing cells.

Conclusions

The Y64C variant disrupts neurite outgrowth, attributable to altered CDC42 activity and localization. The restoration of neurite outgrowth by GGTI-298 highlights the importance of CDC42 signaling for neurite outgrowth in Neuro2A cells. Our findings raise the possibility that molecular disruptions caused by the Y64C mutation may contribute to the brain malformations and neurodevelopmental features observed in TKS.

背景：Takenouchi-Kosaki综合征（TKS）由CDC42 c.191A>G （p.Tyr64Cys; Y64C）变异引起，以一系列临床表现为特征，包括发育迟缓伴智力残疾（ID）。虽然CDC42对神经发生至关重要，但在TKS患者中观察到的Y64C突变导致神经损伤的机制尚不清楚。目的：本研究旨在探讨异位表达Y64C变异对神经母细胞瘤细胞Neuro2A神经突生长的功能影响。方法：用Y64C变异体转染神经2a细胞，评估神经突生长和细胞形态的变化。细胞也用脂化抑制剂GGTI-298或CDC42活性抑制剂ML141处理，以评估其改善突变诱导表型的能力。在WT-和y64c表达细胞之间进行全转录组测序和差异表达基因（DEG）分析。结果：Y64C变异体的过表达损害了神经突的生长，改变了神经2a细胞的细胞形态。GGTI-298处理能恢复Y64C过表达引起的神经突生长缺陷和膜定位增强，而ML141处理不能。为了探索这些表型的分子基础，我们进行了DEG分析，鉴定出32个上调基因和19个下调基因，包括Smarca1。与转录组学结果一致，与WT相比，Smarca1蛋白在表达y64c的细胞中表达降低。GGTI-298有效地保持了Smarca1蛋白的水平，而ML141在表达WT和y64c的细胞中均降低了其表达。结论：Y64C变异体破坏神经突生长，可归因于CDC42活性和定位的改变。GGTI-298对神经突生长的恢复突出了CDC42信号在Neuro2A细胞神经突生长中的重要性。我们的研究结果提出了由Y64C突变引起的分子破坏可能导致TKS中观察到的脑畸形和神经发育特征的可能性。

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引用次数: 0

Brain health in youth - what are we measuring? – A comprehensive review 青少年的大脑健康——我们在衡量什么？-全面检讨

IF 1.3 4区医学 Q4 CLINICAL NEUROLOGY

Brain & Development

Pub Date : 2026-02-01 Epub Date: 2025-12-11 DOI: 10.1016/j.braindev.2025.104491

Susanne R. De Rooij , Amber Boots

Background

There is a large body of literature on brain health, usually focusing on brain health in adulthood in relation to neurodegenerative diseases. Over the past ten years, brain health has also emerged as a concept in studies conducted in youth. But what is brain health in youth and how can we measure this?

Methods

We summarized the literature on brain health in youth and inventoried operationalizations of brain health and research themes. We searched Medline for studies reporting on brain health in youth (from neonates to late adolescent stage).

Results

We identified 49 eligible studies: 26 operationalized brain health in youth, 13 measured outcomes which they related to brain health and 10 were reviews about youth brain health. Operationalizations of brain health varied widely and included multimodal measures involving questionnaires, cognitive tests, neuroimaging and blood biomarkers. Identified research themes were obesity/fitness/lifestyle as determinants of youth brain health, neonatal brain health, traumatic brain injury and brain health, technological options for measuring brain health, and childhood determinants of brain health.

Conclusion

This review offers a comprehensive overview of possibilities for measuring brain health in youth, which could serve as a valuable foundation for a commonly accepted definition, framework and operationalization of brain health in youth.

有大量的关于大脑健康的文献，通常集中在成年期大脑健康与神经退行性疾病的关系上。在过去的十年里，大脑健康也作为一个概念出现在青少年研究中。但什么是年轻人的大脑健康，我们如何衡量它？方法对有关青少年脑健康的文献进行综述，并对脑健康的运作方式和研究主题进行梳理。我们在Medline上搜索了关于青少年（从新生儿到青春期晚期）大脑健康的研究报告。结果我们确定了49项符合条件的研究：26项研究是关于青少年大脑健康的，13项研究测量了与大脑健康相关的结果，10项研究是关于青少年大脑健康的综述。脑健康的操作方法差异很大，包括多模式测量，包括问卷调查、认知测试、神经成像和血液生物标志物。确定的研究主题是肥胖/健康/生活方式作为青少年大脑健康的决定因素，新生儿大脑健康，创伤性脑损伤和大脑健康，测量大脑健康的技术选择，以及儿童大脑健康的决定因素。结论本文综述了测量青少年大脑健康的可能性，为建立一个被普遍接受的青少年大脑健康的定义、框架和操作提供了有价值的基础。

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引用次数: 0

Diagnostic advances in the etiology of cytotoxic lesions of the corpus callosum (CLOCC): epilepsy relationship and ADC radiomics perspective 胼胝体细胞毒性病变（CLOCC）病因的诊断进展：癫痫与ADC放射组学的关系

IF 1.3 4区医学 Q4 CLINICAL NEUROLOGY

Brain & Development

Pub Date : 2026-02-01 Epub Date: 2025-12-13 DOI: 10.1016/j.braindev.2025.104494

Gül Yücel , Nur Yücel Ekici

引用次数: 0

Quantitative interpretation using ADC values for subjective MRI classification of neonatal hypoxic-ischemic encephalopathy 利用ADC值定量解释新生儿缺氧缺血性脑病的主观MRI分类

IF 1.3 4区医学 Q4 CLINICAL NEUROLOGY

Brain & Development

Pub Date : 2026-02-01 Epub Date: 2026-01-14 DOI: 10.1016/j.braindev.2025.104499

Katsumi Hayakawa , Koichi Tanda , Masakazu Nishimoto , Akira Nishimura , Daisuke Kinoshita , Yuko Sano

Background

MRI-based classification of hypoxic–ischemic encephalopathy (HIE), particularly using diffusion-weighted imaging (DWI), remains susceptible to subjective bias in determining the presence or absence of diffusion restriction. Quantitative measures such as apparent diffusion coefficient (ADC) values may provide a more objective assessment of injury severity.

Purpose

To evaluate the depth and distribution of brain injury in neonatal HIE by quantitatively assessing regional ADC values across MRI pattern classifications, independent of subjective visual interpretation of DWI signal changes.

Materials and methods

Seventy-three consecutively enrolled full-term infants with HIE underwent brain MRI, and ADC values were measured at five predefined brain regions. Correlations between regional ADC values and MRI pattern groups were analyzed.

Results

Five MRI patterns were identified: normal, white matter injury (WMI), watershed (WS), basal ganglia/thalamus injury (BGT), and near total brain injury (nTBI). ADC distribution analysis demonstrated two principal findings: (1) no significant differences among the normal, WMI, and WS pattern groups; and (2) significantly lower ADC values in the nTBI group compared with the BGT group at all brain regions during the first week of life, and at the centrum semiovale during the second week.

Conclusion

Quantitative analysis revealed distinct ADC distribution differences between the BGT and nTBI patterns during the first and second weeks of life, indicating substantially more severe and widespread brain injury in the nTBI pattern.

背景：基于mri的缺氧缺血性脑病（HIE）分类，特别是使用弥散加权成像（DWI），在确定是否存在弥散限制时仍然容易受到主观偏见的影响。定量测量如表观扩散系数（ADC）值可以提供更客观的损伤严重程度评估。目的通过定量评估不同MRI模式分类的区域ADC值来评估新生儿HIE脑损伤的深度和分布，不依赖于DWI信号变化的主观视觉解释。材料与方法73例连续入组的HIE足月婴儿行脑MRI，并在5个预先确定的脑区测量ADC值。分析区域ADC值与MRI分型组的相关性。结果发现5种MRI模式：正常、白质损伤（WMI）、分水岭（WS）、基底节区/丘脑损伤（BGT）和近全脑损伤（nTBI）。ADC分布分析显示了两个主要发现：(1)正常、WMI和WS模式组之间无显著差异；(2)与BGT组相比，nTBI组在出生后第一周的所有脑区以及第二周的半瓣中心区的ADC值均显著降低。结论定量分析显示，BGT和nTBI模式在出生后第1周和第2周的ADC分布存在明显差异，表明nTBI模式的脑损伤更为严重和广泛。

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引用次数: 0

Ferroptosis susceptibility in primary coenzyme Q10 deficiency: Cellular insights from patient fibroblasts and clinical course of six individuals 原发性辅酶Q10缺乏症的铁中毒易感性：来自患者成纤维细胞的细胞见解和六个人的临床病程。

IF 1.3 4区医学 Q4 CLINICAL NEUROLOGY

Brain & Development

Pub Date : 2026-02-01 Epub Date: 2025-12-29 DOI: 10.1016/j.braindev.2025.104497

Chika Watanabe , Akihiko Miyauchi , Shiho Aoki , Miyuki Watanabe , Eriko F. Jimbo , Yuudai Miyama , Hirotsugu Kitayama , Yuichi Uno , Kenji Watanabe , Yuka Hattori , Yuka Yotsumoto , Takanori Onuki , Yohei Sugiyama , Keiko Ichimoto , Yukiko Yatsuka , Yasushi Okazaki , Toshiyuki Imasawa , Kei Murayama , Akira Ohtake , Takanori Yamagata , Hitoshi Osaka

Background

Primary coenzyme Q₁₀ (CoQ₁₀) deficiency is a group of mitochondrial disorders caused by pathogenic variants of genes involved in CoQ₁₀ biosynthesis. Although some patients respond to oral CoQ₁₀ supplementation, the pathophysiology remains poorly understood. Ferroptosis, a form of iron-dependent cell death driven by lipid peroxidation, is suppressed by reduced CoQ₁₀ via ferroptosis suppressor protein 1 (FSP1). However, its involvement in primary CoQ₁₀ deficiency has not yet been studied using patient-derived cells.

Cases and results

We reported six patients from three families and investigated ferroptosis susceptibility in fibroblasts from three representative patients: one with COQ2 variants and two with COQ4 variants. Fibroblasts with COQ2 variants showed increased vulnerability to ferroptosis inducers, plasma membrane lipid peroxidation. In contrast, fibroblasts with COQ4 variants exhibited only mild changes. Notably, susceptibility to ferroptosis remained unchanged after increasing intracellular CoQ₁₀ levels. Despite this persistent ferroptosis sensitivity in vitro, the COQ2 patient exhibited significant clinical improvement following CoQ₁₀ supplementation. These findings suggest that ferroptosis may contribute to cellular vulnerability in primary CoQ₁₀ deficiency but may not be the primary driver of renal and neurological symptoms.

Conclusions

Our results highlight a complex interplay between CoQ₁₀ biosynthesis, ferroptosis defense, and therapeutic response, warranting further investigation of subcellular CoQ₁₀ distribution and ferroptosis-related mechanisms.

背景：初级辅酶Q10 （CoQ10）缺乏症是一组由参与辅酶Q10生物合成的基因致病性变异引起的线粒体疾病。尽管一些患者对口服辅酶q10补充剂有反应，但其病理生理机制仍知之甚少。铁下垂是一种由脂质过氧化驱动的铁依赖性细胞死亡形式，通过铁下垂抑制蛋白1 （FSP1）减少coq10来抑制铁下垂。然而，其在原发性辅酶q10缺乏症中的作用尚未使用患者来源的细胞进行研究。病例和结果：我们报道了来自三个家庭的6例患者，并研究了来自三个代表性患者的成纤维细胞的铁下垂易感性：一个COQ2变异，两个COQ4变异。COQ2变异的成纤维细胞对铁下垂诱导剂、质膜脂过氧化的易感性增加。相比之下，COQ4变异的成纤维细胞只表现出轻微的变化。值得注意的是，增加细胞内CoQ10水平后，对铁下垂的易感性保持不变。尽管体外存在这种持续的铁下垂敏感性，COQ2患者在补充CoQ10后表现出显着的临床改善。这些发现表明，铁下垂可能有助于原发性辅酶q10缺乏的细胞易感性，但可能不是肾脏和神经系统症状的主要驱动因素。结论：我们的研究结果强调了辅酶q10生物合成、铁下垂防御和治疗反应之间复杂的相互作用，需要进一步研究辅酶q10亚细胞分布和铁下垂相关机制。

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引用次数: 0

Electroencephalogram abnormalities in children presenting with language development delay 以语言发展迟缓为表现的儿童的脑电图异常

IF 1.3 4区医学 Q4 CLINICAL NEUROLOGY

Brain & Development

Pub Date : 2026-02-01 Epub Date: 2026-01-21 DOI: 10.1016/j.braindev.2026.104504

Merve Yavuz , Feyza Gülağız , Aycan Ünalp , Pakize Karaoğlu , Ünsal Yılmaz

Background

EEG abnormalities are frequently reported in children with developmental language disorders, particularly in language-associated regions, though existing data remain inconsistent.

Aim

This study investigated the frequency, density, and localization of epileptiform discharges in children with language delays, and the incidence of epilepsy within a 12-month follow-up.

Method

A total of 132 children with language delay were evaluated. Ten later diagnosed with autism spectrum disorder were excluded, leaving 122 for analysis. Epileptiform discharges were assessed for frequency, localization, and spike-wave index (SWI). Clinical, demographic, neuroimaging, and developmental data were collected. Comparative analyses were performed between children with and without epileptiform discharges, and between those who did and did not develop epilepsy.

Results

The mean age at admission was 39.6 months, with boys comprising 73.8% of the cohort. Epileptiform discharges were present in 14 children (11.5%), predominantly in the temporoparietal region (83.3%), mostly right-sided or bilateral. Notably, no patient exhibited unilateral discharges on the left. Epilepsy developed in six children during follow-up, all of whom had epileptiform discharges on initial EEG. None with a normal baseline EEG developed epilepsy. Age, sex, parental consanguinity, or family history of language delay, epilepsy, or febrile seizures showed no significant differences between groups. Although SWI values increased significantly over one year, neither baseline SWI nor its temporal change was associated with the development of epilepsy.

Conclusion

EEG abnormalities and epilepsy are not rare in children with language delay. Those with epileptiform discharges on initial EEG require careful monitoring, as they carry a higher risk of developing epilepsy.

背景：尽管现有数据不一致，但在发育性语言障碍儿童中经常报道deeg异常，特别是在语言相关区域。目的探讨语言迟缓儿童癫痫样放电的频率、密度和局部性，以及随访12个月后癫痫的发生率。方法对132例语言迟缓儿童进行评估。10名后来被诊断为自闭症谱系障碍的人被排除在外，留下122名进行分析。评估癫痫样放电的频率、定位和峰波指数（SWI）。收集临床、人口统计学、神经影像学和发育数据。在有和没有癫痫样放电的儿童之间以及有和没有癫痫的儿童之间进行了比较分析。结果入院时平均年龄39.6个月，男孩占73.8%。癫痫样放电14例（11.5%），主要发生在颞顶区（83.3%），多发生在右侧或双侧。值得注意的是，没有患者表现出左侧单侧出院。随访期间有6例患儿出现癫痫，所有患儿初始脑电图均显示癫痫样放电。基线脑电图正常的患者均未发生癫痫。年龄、性别、父母亲属关系、语言迟缓、癫痫或热性惊厥家族史在组间无显著差异。虽然SWI值在一年内显著增加，但基线SWI及其时间变化与癫痫的发展无关。结论脑电图异常和癫痫在语言迟缓患儿中并不少见。初次脑电图显示癫痫样放电的患者需要仔细监测，因为他们患癫痫的风险较高。

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引用次数: 0

Construction and clinical validation of a fetal brain magnetic resonance imaging-prediction model based on multimodal AI fusion algorithm 基于多模态AI融合算法的胎儿脑磁共振成像预测模型构建及临床验证

IF 1.3 4区医学 Q4 CLINICAL NEUROLOGY

Brain & Development

Pub Date : 2026-02-01 Epub Date: 2025-12-10 DOI: 10.1016/j.braindev.2025.104492

BingGuang Liu, FangJing Zhang, JiMin Guo, Wei Lu, ZhiJun Zhu, Yang Liu, ChenWang Yin

Objective

To develop a multimodal artificial intelligence (AI) fusion model predicting abnormal fetal brain development from magnetic resonance imaging (MRI).

Methods

Using fetal brain MRI data and clinical indicators from pregnant women (from January 2021 to December 2023), who were split 7:3 into training and validation sets. In the training set, key predictors were identified via univariate analysis and multivariate logistic regression, including both clinical indicators and continuous MRI biometric parameters. Three multimodal AI fusion models，including Convolutional Neural Network-Recurrent Neural Network (CNN-RNN) model, attention mechanism-based model, and feature concatenation model were developed. Performance was assessed by accuracy, precision, recall, F1-score, and the area under the receiver operating characteristic curve (AUC).

Results

Among the total 806 participants, 108 cases (19.15 %) had fetal brain abnormalities in the training set (n = 564), 45 cases (18.59 %) in the validation set (n = 242). Multivariate logistic regression analysis showed that gestational age, gestational diabetes mellitus, alpha-fetoprotein, lateral ventricular width, and sulcation development score were independent risk factors for fetal brain abnormalities. The attention mechanism fusion model achieved the highest AUC in both the training set (0.876) and the validation set (0.869), significantly outperforming the CNN-RNN fusion model (AUC in training set: 0.776; AUC in validation set: 0.718) and the feature concatenation fusion model (AUC in training set: 0.754; AUC in validation set: 0.720).

Conclusion

The multimodal AI fusion model, particularly using attention mechanisms, effectively identifies high-risk fetal brain abnormalities, offering potential for early clinical intervention and improved prenatal counseling to enhance detection and prognosis of neurological disorders.

目的建立多模态人工智能（AI）融合模型，通过磁共振成像（MRI）预测胎儿脑发育异常。方法利用2021年1月至2023年12月孕妇的胎儿脑MRI数据和临床指标，按7:3分成训练组和验证组。在训练集中，通过单变量分析和多变量逻辑回归确定关键预测因子，包括临床指标和连续MRI生物特征参数。建立了卷积神经网络-递归神经网络（CNN-RNN）模型、基于注意机制的模型和特征拼接模型三种多模态人工智能融合模型。通过准确度、精密度、召回率、f1评分和受试者工作特征曲线下面积（AUC）来评估其表现。结果806例受试者中，训练组（n = 564） 108例（19.15%）胎儿脑异常，验证组（n = 242） 45例（18.59%）胎儿脑异常。多因素logistic回归分析显示，胎龄、妊娠期糖尿病、甲胎蛋白、侧脑室宽、乳管发育评分是胎儿脑异常的独立危险因素。注意机制融合模型在训练集和验证集上的AUC均最高（0.876），显著优于CNN-RNN融合模型（训练集AUC为0.776，验证集AUC为0.718）和特征拼接融合模型（训练集AUC为0.754，验证集AUC为0.720）。结论多模态人工智能融合模型可有效识别高危胎儿脑异常，特别是利用注意机制，为早期临床干预和改进产前咨询提供可能，以提高神经系统疾病的发现和预后。

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引用次数: 0

Evaluation of perinatal arterial ischemic stroke patients: Underlying etiologic factors and long-term prognosis 围生期动脉缺血性脑卒中患者的评估：潜在病因和长期预后

IF 1.3 4区医学 Q4 CLINICAL NEUROLOGY

Brain & Development

Pub Date : 2026-02-01 Epub Date: 2026-01-15 DOI: 10.1016/j.braindev.2026.104501

Çisem Duman Kayar , Rıdvan Avcı , Fulya Kürekçi , Ceyda Öney Yılmaz , Ceyda Bayraktar Eltutan , Vugar Abbasaliyev , Serap Karaman , Mehmet Barbüroğlu , Hülya Maraş Genç , Edibe Pembegül Yıldız

Background

Perinatal arterial ischemic stroke (PAIS) is a major cause of long-term neurological impairments. Understanding its etiologic and prognostic factors is essential for improving outcomes.

Methods

A retrospective single-center study was conducted on children diagnosed with PAIS between 2008 and 2024. Clinical, imaging, and EEG data were analyzed to identify predictors of epilepsy and poor outcomes based on modified Rankin Scale (mRS) scores.

Results

A total of 44 patients (9 neonatal arterial ischemic stroke [NAIS], 35 Presumed perinatal arterial ischemic stroke [PPAIS]) with a mean follow-up of 6.49 years were included. Seizure was the first symptom in 45.5%, and focal motor deficit in 54.5%. The most affected artery was the middle cerebral artery (92%), particularly the M1 branch (36.4%). Cortical involvement was noted in 59.1%. Fourteen patients developed epilepsy; 14.2% were drug-resistant. Focal EEG slowing (odds ratio [OR] = 8.484, p = 0.019) and cortical involvement (OR = 6.857, p = 0.023) significantly predicted epilepsy. Poor mRS outcomes (≥3) were seen in 44.2%, and were associated with epilepsy (OR = 5.556, p = 0.016), EEG slowing (OR = 5.353, p = 0.035), and cortical involvement (OR = 7.467, p = 0.008).

Conclusions

Early EEG and MRI findings are crucial in predicting long-term prognosis in PAIS. Further multicenter studies are needed to validate and enhance outcomes.

背景围产期动脉缺血性中风（PAIS）是导致长期神经功能损伤的主要原因。了解其病因和预后因素对改善预后至关重要。方法对2008 ~ 2024年诊断为PAIS的儿童进行回顾性单中心研究。对临床、影像学和脑电图数据进行分析，以确定基于改良兰金量表（mRS）评分的癫痫和不良预后的预测因素。结果共纳入44例患者，其中新生儿动脉缺血性卒中9例，围产期动脉缺血性卒中35例，平均随访6.49年。癫痫是45.5%的第一症状，54.5%为局灶性运动障碍。受影响最大的动脉为大脑中动脉（92%），尤其是M1分支（36.4%）。59.1%的患者有皮层受累。14例发生癫痫；14.2%耐药。局灶性脑电图减慢（优势比[OR] = 8.484, p = 0.019）和皮层受累（OR = 6.857, p = 0.023）与癫痫有显著相关性。44.2%的患者出现不良mRS结果（≥3），并与癫痫（OR = 5.556, p = 0.016）、脑电图减慢（OR = 5.353, p = 0.035）和皮层受累（OR = 7.467, p = 0.008）相关。结论早期脑电图和MRI表现对预测PAIS的远期预后至关重要。需要进一步的多中心研究来验证和增强结果。

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引用次数: 0

Pediatric neuromyelitis optica spectrum disorders in Dakar: Insights from a preliminary multicentric case series in Senegal 达喀尔儿童视神经脊髓炎谱系障碍：来自塞内加尔初步多中心病例系列的见解

IF 1.3 4区医学 Q4 CLINICAL NEUROLOGY

Brain & Development

Pub Date : 2026-02-01 Epub Date: 2026-01-28 DOI: 10.1016/j.braindev.2026.104505

Ndiaga Matar Gaye , Rokhaya Diagne , Khalifa Ababacar Mbaye , Alice Ingabiré Goumba , Marie Emilie Ndong , Seynabou Dieng , Adjaratou Dieynabou Sow , El Hadji Makhtar Ba , Moustapha Ndiaye

Aim

To describe the epidemiological, diagnostic, therapeutic, and outcome aspects of pediatric neuromyelitis optica spectrum disorders (NMOSD) in Dakar, Senegal.

Methods

We conducted a multicenter retrospective and prospective study including patients with pediatric-onset NMOSD (<18 years) diagnosed according to the 2015 Wingerchuk criteria.

Results

Over 7 years and 3 months, 8 children (7 females) were included, with a median age at symptom onset of 13.5 years (range 8–17). The main neurological manifestations during the disease course were myelitis (7/8), optic neuritis (5/8), and area postrema syndrome (4/8). Brain magnetic resonance imaging revealed nonspecific white matter abnormalities in 2 patients. Anti-aquaporin 4 antibodies were positive in 6 patients. Cerebrospinal fluid analysis, performed in 4 patients, showed lymphocytic pleocytosis in 2 of them (72 and 17 cells/mm³). All patients received prednisone; 7 also received azathioprine. After a median follow-up of 26.5 months, the mean Expanded Disability Status Scale was 4.44. Six patients had a relapsing-remitting course, with a median time to second relapse of 3 months (range 2–6).

Conclusion

This preliminary study highlights the clinical heterogeneity, female predominance, and frequent AQP4-IgG positivity of pediatric NMOSD in Senegal, broadly comparable to international cohorts. However, diagnostic delays, limited access to intensive therapies, and significant disability were observed, underscoring regional disparities in treatment and prognosis and the need for earlier diagnosis and improved access to effective therapies to optimize outcomes in sub-Saharan Africa.

目的描述塞内加尔达喀尔儿童视谱神经脊髓炎（NMOSD）的流行病学、诊断、治疗和预后。方法我们开展了一项多中心回顾性和前瞻性研究，纳入了根据2015年Wingerchuk标准诊断的儿科发病NMOSD（18岁）患者。结果7岁零3个月，8名儿童（7名女性）被纳入，症状发作时的中位年龄为13.5岁（范围8 - 17岁）。病程中主要的神经学表现为脊髓炎（7/8）、视神经炎（5/8）和后脑区综合征（4/8）。2例脑磁共振成像显示非特异性白质异常。6例患者抗水通道蛋白4抗体阳性。对4例患者进行脑脊液分析，其中2例显示淋巴细胞增多症（72和17个细胞/mm3）。所有患者均接受强的松治疗；7人同时接受硫唑嘌呤治疗。中位随访26.5个月后，平均扩展残疾状态量表为4.44。6例患者的复发缓解过程，到第二次复发的中位时间为3个月（范围2-6）。结论本初步研究突出了塞内加尔儿童NMOSD的临床异质性、女性优势和AQP4-IgG频繁阳性，与国际队列大致相当。然而，诊断延误、获得强化治疗的机会有限以及严重残疾的情况也被观察到，这突出了撒哈拉以南非洲地区在治疗和预后方面的地区差异，以及需要更早诊断和改善获得有效治疗的机会，以优化结果。

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引用次数: 0

Does in utero exposure to antiseizure medications affect the trajectory of cognitive development from 2 to 6 years of age? 子宫内接触抗癫痫药物会影响2 - 6岁儿童的认知发展轨迹吗？

IF 1.3 4区医学 Q4 CLINICAL NEUROLOGY

Brain & Development

Pub Date : 2026-02-01 Epub Date: 2025-12-07 DOI: 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.

背景：抗癫痫药物（ASM）对癫痫患者至关重要。虽然产前暴露于ASM与畸形和神经认知问题的风险增加有关，但产前暴露于ASM是否会改变后代的自然发育轨迹尚未得到研究。方法：本前瞻性研究通过研究2岁时Bayley量表III评分与6岁时WISC-IV评分的相关性，并与未暴露儿童的结果进行比较，探讨产前ASM暴露对儿童认知发展轨迹的影响。对30例产前ASM暴露儿童和37例未暴露儿童的神经认知能力进行了评价。ASM暴露组和未暴露组在这些年龄段的相关性和单独ANCOVAs进行比较。结果对照了评估时的母亲教育程度、母亲癫痫类型、儿童性别和儿童年龄。结果：在未接触的参与者中，两岁时的认知得分与六岁时的工作记忆和处理速度呈正相关，两岁时的接受性语言得分与六岁时的工作记忆呈正相关。相反，对于接触过的儿童，两岁和六岁的测试成绩之间没有显著的联系，接受性语言和六岁工作记忆或处理速度之间的系数与未接触过的儿童的系数有显著差异。但样本量小限制了结果的稳定性，剔除离群值后所观察到的组间系数差异不显著。结论：子宫内接触ASM可能会影响神经认知发育的轨迹，但这一发现受到了一个异常值的影响，应该在更大的队列中得到证实。

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