Seizure-European Journal of Epilepsy最新文献_第4页

Clinical and genetic analysis of epilepsy in children with SCN8A gene variants SCN8A基因变异儿童癫痫的临床与遗传分析。

IF 2.8 3区医学 Q2 CLINICAL NEUROLOGY

Seizure-European Journal of Epilepsy

Pub Date : 2025-12-02 DOI: 10.1016/j.seizure.2025.12.002

Rui Li , Chu Wang , Runlu Geng , Xiaoqing Xu , Yichen Tao , Yuanyuan Dai

Objective

To analyse the clinical and genetic characteristics of children with epilepsy associated with SCN8A gene variants.

Methods

High-throughput whole-exome sequencing was performed on children suspected of having gene variant-related epilepsy. A total of 14 children with seizures caused by SCN8A gene variants were identified. A retrospective analysis was conducted to collect and summarise the medical records and genetic results of these children.

Results

Eleven cases were identified with de novo variants and three with inherited heterozygous variants. The earliest age of onset was 10 min after birth, and the maximum age of onset was 2 years. Three patients were treated with a single drug, four were treated with two anti-seizure medicines (ASMs), seven were treated with three or more ASMs and two were treated with a ketogenic diet, but the efficacy was not satisfactory. Eight patients responded to sodium channel blockers, with doses ranging from higher than the standard paediatric dosage. Except for one case with a normal electroencephalogram, all others showed abnormalities, mainly characterised by multifocal and widespread discharges.

Conclusion

Typically, SCN8A gene variants cause early-onset childhood epilepsy, often within the first year of life, even in the neonatal period, and most cases are caused by de novo variants. Sodium channel blockers show some efficacy, but often require higher doses, and single-drug therapy is usually insufficient. The clinical phenotype of de novo variants is severe, with frequent seizures. Most patients still experience seizures despite treatment with 3–4 drugs, and focal or focal secondary generalised seizures are common. Seizure types such as spasms and myoclonus are rare.

目的：分析小儿癫痫SCN8A基因变异的临床及遗传特点。方法：对怀疑患有基因变异相关性癫痫的儿童进行高通量全外显子组测序。共鉴定出14例由SCN8A基因变异引起的癫痫患儿。回顾性分析收集和总结了这些儿童的医疗记录和遗传结果。结果：11例为新生变异，3例为遗传杂合变异。最早发病年龄为出生后10分钟，最大发病年龄为2岁。单药治疗3例，双药治疗4例，三药及以上治疗7例，生酮饮食治疗2例，疗效均不理想。8名患者对钠通道阻滞剂有反应，剂量从高于标准儿科剂量不等。除1例脑电图正常外，其余均表现异常，主要表现为多灶性和广泛性放电。结论：SCN8A基因变异通常会引起早发性儿童癫痫，通常发生在生命的第一年，甚至在新生儿时期，大多数病例是由新生变异引起的。钠通道阻滞剂显示出一定的疗效，但通常需要更高的剂量，单药治疗通常不够。新发变异的临床表型是严重的，经常发作。尽管使用3-4种药物治疗，大多数患者仍会出现癫痫发作，局灶性或局灶继发性全身性癫痫发作很常见。发作类型如痉挛和肌阵挛是罕见的。

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引用次数: 0

PIGA variants are associated with focal epilepsy with favorable outcome and the sub-molecular effect PIGA变异与局灶性癫痫有关，具有良好的预后和亚分子效应。

IF 2.8 3区医学 Q2 CLINICAL NEUROLOGY

Seizure-European Journal of Epilepsy

Pub Date : 2025-11-30 DOI: 10.1016/j.seizure.2025.11.021

Meizhuang Zhou , Yu Luo , Ruihan Yang , Liting Zhang , Weili Hao , Dezhi Cao , Zhigang Liu , Qing Zhou , Xiaorong Liu , Bingmei Li , Peng Zhou , Bin Li , Xingwang Song

Background

The PIGA gene plays a critical role in glycosylphosphatidylinositol (GPI) biosynthesis. PIGA variants have been linked to multiple congenital anomalies-hypotonia-seizures syndrome 2. While epilepsy is a common manifestation and patients usually show developmental delay, it is unclear whether PIGA variants are associated with pure epilepsy.

Method

Trio-based whole-exome sequencing was performed on individuals with focal epilepsy from the China Epilepsy Gene 1.0 project. The sub-molecular effect, damaging effect of the variants, and spatial-temporal expression of PIGA were analyzed to explore its role in epilepsy.

Results

Six PIGA variants were identified in seven unrelated cases with focal epilepsy. In one family, the variant co-segregated with two affected males. All the variants were inherited from the asymptomatic mothers, consistent with an X-linked recessive inheritance pattern. Five of the variants were absent in the general population and one variant had extremely low frequencies. These variants were predicted to be damaging by commonly used in silico tools. Four cases presented with developmental delay and three showed normal development. Further analysis revealed that variants associated with a severe phenotype were located within the GPI biosynthesis domain, whereas variants associated with focal epilepsy and a favorable outcome were outside functional domains, suggesting a sub-molecular effect. Patients with more severe phenotype also had variants with higher damaging scores, indicating a potential genotype-phenotype correlation. PIGA was highly expressed at the embryoid stage, decreased after birth, and then increased again during infancy and the juvenile stage, consistent with the onset age of the patients.

Conclusion

PIGA variants are potentially associated with focal epilepsy with favorable outcome. The sub-molecular effect helps explain phenotype variations.

背景：PIGA基因在糖基磷脂酰肌醇（GPI）的生物合成中起关键作用。PIGA变异与多种先天性异常有关，如张力低下-癫痫综合征2。虽然癫痫是一种常见的表现，患者通常表现为发育迟缓，但目前尚不清楚PIGA变异是否与纯粹的癫痫有关。方法：对中国癫痫基因1.0项目局灶性癫痫患者进行三基全外显子组测序。通过分析PIGA的亚分子效应、损伤效应和时空表达，探讨其在癫痫中的作用。结果：在7例不相关的局灶性癫痫中发现6个PIGA变异。在一个家庭中，这种变异与两个受影响的男性共同分离。所有变异均遗传自无症状母亲，符合x连锁隐性遗传模式。其中五种变体在一般人群中不存在，一种变体的频率极低。通常使用的硅工具预测这些变体具有破坏性。4例发育迟缓，3例发育正常。进一步的分析显示，与严重表型相关的变异位于GPI生物合成域内，而与局灶性癫痫和有利结果相关的变异位于功能域外，表明亚分子效应。表型更严重的患者也具有更高的破坏性评分，表明潜在的基因型-表型相关性。PIGA在胚胎期高表达，出生后下降，在婴儿期和少年期再次升高，与患者发病年龄一致。结论：PIGA变异可能与局灶性癫痫有关，预后良好。亚分子效应有助于解释表型变异。

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引用次数: 0

Tocilizumab for super-refractory status epilepticus in children with FIRES: A case series 托珠单抗治疗儿童FIRES的超难治性癫痫持续状态：一个病例系列。

IF 2.8 3区医学 Q2 CLINICAL NEUROLOGY

Seizure-European Journal of Epilepsy

Pub Date : 2025-11-28 DOI: 10.1016/j.seizure.2025.11.019

Sumitha Murugesu, Ahmad Rithauddin Mohamed, Husna Binti Musa, Jun Xiong Lee, Muhamad Azamin Anuar, Teik Beng Khoo

Purpose

Febrile infection-related epilepsy syndrome (FIRES) is a catastrophic epileptic encephalopathy that can occur at any age, with limited treatment options. Conventional immunotherapies often show poor efficacy. We evaluated the effectiveness and safety of the interleukin-6 receptor blocker, tocilizumab, in children with FIRES.

Methods

We retrospectively reviewed medical records, electroencephalography, and neuroimaging of seven children with FIRES treated at our center between 2018 and 2022. Outcomes included cessation of super-refractory status epilepticus (SRSE), seizure burden, and functional outcome using the Pediatric Cerebral Performance Category (PCPC) scale.

Results

Seven previously healthy children (median age 9 years; range 2–13) developed SRSE following febrile illness. Extensive investigations, including cerebrospinal fluid studies, viral panels, and autoimmune testing were negative, consistent with cryptogenic FIRES. Initial MRI was normal in six children; one showed symmetrical T2/FLAIR hyperintensities involving deep grey matter structures. All patients received a multimodal therapeutic strategy including intravenous midazolam, high-dose phenobarbitone, ketogenic diet, therapeutic hypothermia, and/or immunotherapy—prior to tocilizumab. Intravenous tocilizumab was initiated at a median of 17 days from illness onset (range 6–46). SRSE resolved within a median of 5 days (range 2–12) after administration. At 6-month follow-up, six of seven patients developed chronic epilepsy, characterised by weekly to monthly seizures, while one remained seizure free. Functional recovery was noted in four patients, each achieving a Pediatric Cerebral Performance Category (PCPC) score of ≤2. Adverse events included grade 2 leukopenia or diarrhoea (n = 3) and grade 4 sepsis (n = 1); all resolved with treatment. No deaths occurred.

Conclusion

Tocilizumab was associated with rapid resolution of SRSE, seizure reduction, and functional recovery in children with FIRES, with manageable side effects. While causality cannot be confirmed given concurrent therapies and variable timing of administration, these findings support consideration of interleukin-6 blockade as a potential adjunctive treatment in FIRES.

目的：发热性感染相关癫痫综合征（FIRES）是一种灾难性的癫痫性脑病，可发生在任何年龄，治疗方案有限。常规免疫疗法往往疗效不佳。我们评估了白细胞介素-6受体阻滞剂tocilizumab在儿童fire中的有效性和安全性。方法：回顾性分析2018年至2022年期间在本中心治疗的7名儿童的病历、脑电图和神经影像学。结果包括停止超难治性癫痫持续状态（SRSE）、癫痫发作负担和使用儿科脑功能分类（PCPC）量表的功能结果。结果：7名先前健康的儿童（中位年龄9岁，范围2-13岁）在发热性疾病后发展为SRSE。广泛的调查，包括脑脊液研究、病毒检测和自身免疫检测均为阴性，与隐源性FIRES一致。6例患儿初始MRI正常；1例显示对称的T2/FLAIR高信号，涉及深部灰质结构。所有患者在使用托珠单抗之前接受了多模式治疗策略，包括静脉注射咪达唑仑、大剂量苯巴比妥、生酮饮食、治疗性低温和/或免疫治疗。静脉注射tocilizumab开始于发病后中位17天（范围6-46天）。SRSE在给药后5天（范围2-12天）内消失。在6个月的随访中，7名患者中有6名发展为慢性癫痫，其特征是每周到每月发作一次，而1名患者仍然没有发作。4例患者功能恢复，每例均达到儿科脑功能分类（PCPC）评分≤2。不良事件包括2级白细胞减少或腹泻（n = 3）和4级败血症（n = 1）；经过治疗，一切都解决了。没有人员死亡。结论：Tocilizumab可快速缓解儿童的SRSE，减少癫痫发作和功能恢复，副作用可控。虽然由于同时治疗和给药时间的变化，不能确认因果关系，但这些发现支持考虑白细胞介素-6阻断作为FIRES的潜在辅助治疗。

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引用次数: 0

Shared and divergent neuromagnetic network signatures in childhood absence epilepsy and self-limited epilepsy with centrotemporal spikes 儿童期缺失性癫痫和自限性癫痫伴中央颞叶尖峰的共享和发散性神经磁网络特征

IF 2.8 3区医学 Q2 CLINICAL NEUROLOGY

Seizure-European Journal of Epilepsy

Pub Date : 2025-11-28 DOI: 10.1016/j.seizure.2025.11.020

Yingfan Wang , Minghao Li , Xu Huang , Peilin Jiang, Xinyi Zhou, Ke Hu, Xiaoshan Wang

Objectives

Childhood Absence Epilepsy (CAE) and Self-Limited Epilepsy with Centrotemporal Spikes (SeLECTS) are common, clinically associated syndromes, yet their shared and distinct pathophysiological mechanisms remain unclear. This study aimed to systematically compare interictal resting-state neuromagnetic networks among drug-naive children with CAE, SeLECTS, and healthy controls (HC) to identify common and syndrome-specific neurophysiological signatures.

Methods

We recruited 51 drug-naive CAE patients, 50 SeLECTS patients, and 30 age- and sex-matched HC. We analyzed 30-second epochs of interictal epileptiform discharge (IED)-free resting-state magnetoencephalography (MEG) data. Source-level spectral power and functional connectivity (corrected amplitude envelope correlation, AEC-c) were computed across six frequency bands (delta to high-gamma). Group differences were assessed using Network-Based Statistics (NBS) and cluster-based permutation test.

Results

Both epilepsy groups, compared to HCs, exhibited a shared pattern of pathological brain 'slowing': significantly increased low-frequency (delta) power and decreased high-frequency (alpha, beta, gamma) power. At the network level, this was mirrored by alpha-band hyperconnectivity and gamma-band hypoconnectivity. Crucially, syndrome-specific patterns emerged. CAE was characterized by global network dysregulation, with widespread delta/theta hyperconnectivity and a profound reduction in parieto-occipital alpha power. In contrast, SeLECTS displayed features of focal origin with widespread impact, including extreme low-to-mid frequency (delta-to-alpha) hyperconnectivity across distinct subnetworks and a widespread decrease in high-frequency (beta to gamma) power, most prominent in the temporal lobes.

Significance

This study provides the first direct neuromagnetic comparison of drug-naive CAE and SeLECTS. While a shared signature of pathological brain slowing suggests a common substrate of network instability, their distinct patterns of network dysfunction—global dysregulation in CAE versus focal-origin hyperconnectivity and widespread high-frequency power collapse in SeLECTS—elucidate divergent pathophysiological mechanisms. These syndrome-specific neuromagnetic features hold potential as non-invasive biomarkers for differential diagnosis and therapeutic monitoring.

儿童期缺失癫痫（CAE）和自限性癫痫伴中央颞叶尖峰（SeLECTS）是常见的临床相关综合征，但其共同和独特的病理生理机制尚不清楚。本研究旨在系统比较CAE、select和健康对照（HC）患儿间期静息状态神经磁网络，以识别常见和综合征特异性神经生理特征。方法我们招募51例无药CAE患者，50例select患者和30例年龄和性别匹配的HC患者。我们分析了无癫痫样放电（IED）间歇期30秒的静息状态脑磁图（MEG）数据。源级谱功率和功能连通性（校正振幅包络相关，AEC-c）在六个频段（delta到high-gamma）上进行计算。采用基于网络的统计（NBS）和基于聚类的排列检验评估组间差异。结果与hc相比，两组癫痫患者均表现出一种共同的病理性脑“减速”模式：低频（δ）功率显著增加，高频（α、β、γ）功率显著降低。在网络层面，这反映在α波段超连通性和γ波段低连通性上。至关重要的是，综合征特异性模式出现了。CAE的特征是全球网络失调，广泛的δ / θ超连通性和顶枕α功率的严重降低。相比之下，select表现出具有广泛影响的病灶起源特征，包括跨不同子网络的极低到中频（δ到α）超连通性和高频（β到γ）功率的广泛下降，在颞叶中最为突出。意义本研究首次提供了药物初始CAE和select的直接神经磁比较。虽然病理性脑减慢的共同特征表明了网络不稳定的共同基础，但它们不同的网络功能失调模式——CAE的全局失调与选择性的局灶性超连接和广泛的高频功率崩溃——阐明了不同的病理生理机制。这些综合征特异性的神经磁特征具有作为鉴别诊断和治疗监测的非侵入性生物标志物的潜力。

{"title":"Shared and divergent neuromagnetic network signatures in childhood absence epilepsy and self-limited epilepsy with centrotemporal spikes","authors":"Yingfan Wang , Minghao Li , Xu Huang , Peilin Jiang, Xinyi Zhou, Ke Hu, Xiaoshan Wang","doi":"10.1016/j.seizure.2025.11.020","DOIUrl":"10.1016/j.seizure.2025.11.020","url":null,"abstract":"<div><h3>Objectives</h3><div>Childhood Absence Epilepsy (CAE) and Self-Limited Epilepsy with Centrotemporal Spikes (SeLECTS) are common, clinically associated syndromes, yet their shared and distinct pathophysiological mechanisms remain unclear. This study aimed to systematically compare interictal resting-state neuromagnetic networks among drug-naive children with CAE, SeLECTS, and healthy controls (HC) to identify common and syndrome-specific neurophysiological signatures.</div></div><div><h3>Methods</h3><div>We recruited 51 drug-naive CAE patients, 50 SeLECTS patients, and 30 age- and sex-matched HC. We analyzed 30-second epochs of interictal epileptiform discharge (IED)-free resting-state magnetoencephalography (MEG) data. Source-level spectral power and functional connectivity (corrected amplitude envelope correlation, AEC-c) were computed across six frequency bands (delta to high-gamma). Group differences were assessed using Network-Based Statistics (NBS) and cluster-based permutation test.</div></div><div><h3>Results</h3><div>Both epilepsy groups, compared to HCs, exhibited a shared pattern of pathological brain 'slowing': significantly increased low-frequency (delta) power and decreased high-frequency (alpha, beta, gamma) power. At the network level, this was mirrored by alpha-band hyperconnectivity and gamma-band hypoconnectivity. Crucially, syndrome-specific patterns emerged. CAE was characterized by global network dysregulation, with widespread delta/theta hyperconnectivity and a profound reduction in parieto-occipital alpha power. In contrast, SeLECTS displayed features of focal origin with widespread impact, including extreme low-to-mid frequency (delta-to-alpha) hyperconnectivity across distinct subnetworks and a widespread decrease in high-frequency (beta to gamma) power, most prominent in the temporal lobes.</div></div><div><h3>Significance</h3><div>This study provides the first direct neuromagnetic comparison of drug-naive CAE and SeLECTS. While a shared signature of pathological brain slowing suggests a common substrate of network instability, their distinct patterns of network dysfunction—global dysregulation in CAE versus focal-origin hyperconnectivity and widespread high-frequency power collapse in SeLECTS—elucidate divergent pathophysiological mechanisms. These syndrome-specific neuromagnetic features hold potential as non-invasive biomarkers for differential diagnosis and therapeutic monitoring.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"134 ","pages":"Pages 106-116"},"PeriodicalIF":2.8,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145693651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Seizure control, delivery, and neonatal outcomes in pregnant women with focal epilepsies: a prospective cohort study 局灶性癫痫孕妇的癫痫控制、分娩和新生儿结局：一项前瞻性队列研究

IF 2.8 3区医学 Q2 CLINICAL NEUROLOGY

Seizure-European Journal of Epilepsy

Pub Date : 2025-11-24 DOI: 10.1016/j.seizure.2025.11.018

Shahla Melikova , Aytan Mammadbayli

Objective

To prospectively investigate seizure control during pregnancy in women with focal epilepsies, to assess the impact of specific forms of focal epilepsy (FE) on delivery and neonatal outcomes, and to compare these outcomes with those in pregnancies of women without epilepsy.

Methods

Seventy-nine women with FE, recruited from a large cohort of pregnant women, were prospectively evaluated for over a ten-year period. Seizure, obstetric, and neonatal outcomes were analyzed across the different forms of FE.

Results

Seizures occurred in 77.2 % of women with FE, with higher incidence in frontal lobe epilepsy (FLE) (88.2 %) and temporal lobe epilepsy (TLE) (84.1 %) compared with other focal epilepsies (OFEs) (50.0 %) (p = 0.02 and p = 0.0078, respectively). Women with FLE experienced higher rates of seizure worsening and lower odds of remaining seizure-free during pregnancy compared with those with temporal lobe epilepsy TLE and OFEs. Non-adherence to antiseizure medications was significantly associated with increased seizure frequency (p < 0.0001). WWE had higher rates of cesarean section, preterm birth, and premature rupture of membranes compared with women without epilepsy. Neonates of WWE had higher rates of five-minute Apgar scores ≤7 and perinatal hypoxia (pH), with pH significantly associated with any in utero seizure exposure (OR 9.33; p = 0.04), independent of seizure form. Offspring of women with FLE had the highest prevalence of low Apgar scores compared with TLE and OFEs.

Conclusion

Seizure occurrence during pregnancy, rather than the specific form of FE alone, can be considered the primary factor contributing to adverse maternal and neonatal outcomes. These findings emphasize the importance of continuous seizure management, ASM adherence, and individualized perinatal care in WWE.

目的前瞻性研究局灶性癫痫孕妇妊娠期间的癫痫控制情况，评估特定形式局灶性癫痫（FE）对分娩和新生儿结局的影响，并将这些结局与非癫痫孕妇的结局进行比较。方法从大量孕妇队列中招募79名FE妇女，对其进行为期10年的前瞻性评估。分析了不同形式FE的癫痫发作、产科和新生儿结局。结果癫痫发作发生率为77.2%，其中额叶癫痫（FLE）和颞叶癫痫（TLE）发生率分别为88.2%和84.1%，高于其他局灶性癫痫（OFEs）（50.0%）（p = 0.02和p = 0.0078）。与颞叶癫痫（TLE）和颞叶癫痫（OFEs）患者相比，FLE患者在怀孕期间癫痫发作恶化的几率更高，癫痫无发作的几率更低。抗癫痫药物不依从性与癫痫发作频率增加显著相关（p < 0.0001）。与没有癫痫的女性相比，WWE患者有更高的剖宫产、早产和胎膜早破率。WWE新生儿5分钟Apgar评分≤7和围产期缺氧（pH）的发生率较高，pH值与子宫内癫痫发作暴露显著相关（OR 9.33; p = 0.04），与癫痫发作形式无关。与TLE和OFEs相比，FLE女性的后代低Apgar评分的发生率最高。结论妊娠期癫痫发作是导致孕产妇和新生儿不良结局的主要因素，而非单纯的特定形式的FE。这些发现强调了持续癫痫发作管理、ASM依从性和个体化围产期护理在WWE中的重要性。

{"title":"Seizure control, delivery, and neonatal outcomes in pregnant women with focal epilepsies: a prospective cohort study","authors":"Shahla Melikova , Aytan Mammadbayli","doi":"10.1016/j.seizure.2025.11.018","DOIUrl":"10.1016/j.seizure.2025.11.018","url":null,"abstract":"<div><h3>Objective</h3><div>To prospectively investigate seizure control during pregnancy in women with focal epilepsies, to assess the impact of specific forms of focal epilepsy (FE) on delivery and neonatal outcomes, and to compare these outcomes with those in pregnancies of women without epilepsy.</div></div><div><h3>Methods</h3><div>Seventy-nine women with FE, recruited from a large cohort of pregnant women, were prospectively evaluated for over a ten-year period. Seizure, obstetric, and neonatal outcomes were analyzed across the different forms of FE.</div></div><div><h3>Results</h3><div>Seizures occurred in 77.2 % of women with FE, with higher incidence in frontal lobe epilepsy (FLE) (88.2 %) and temporal lobe epilepsy (TLE) (84.1 %) compared with other focal epilepsies (OFEs) (50.0 %) (<em>p</em> = 0.02 and <em>p</em> = 0.0078, respectively). Women with FLE experienced higher rates of seizure worsening and lower odds of remaining seizure-free during pregnancy compared with those with temporal lobe epilepsy TLE and OFEs. Non-adherence to antiseizure medications was significantly associated with increased seizure frequency (<em>p</em> < 0.0001). WWE had higher rates of cesarean section, preterm birth, and premature rupture of membranes compared with women without epilepsy. Neonates of WWE had higher rates of five-minute Apgar scores ≤7 and perinatal hypoxia (pH), with pH significantly associated with any in utero seizure exposure (OR 9.33; <em>p</em> = 0.04), independent of seizure form. Offspring of women with FLE had the highest prevalence of low Apgar scores compared with TLE and OFEs.</div></div><div><h3>Conclusion</h3><div>Seizure occurrence during pregnancy, rather than the specific form of FE alone, can be considered the primary factor contributing to adverse maternal and neonatal outcomes. These findings emphasize the importance of continuous seizure management, ASM adherence, and individualized perinatal care in WWE.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"134 ","pages":"Pages 117-125"},"PeriodicalIF":2.8,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145693581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Efficacy and safety of cenobamate in developmental and epileptic encephalopathies: A systematic review and meta-analysis cenobamate治疗发育性和癫痫性脑病的疗效和安全性：一项系统综述和荟萃分析

IF 2.8 3区医学 Q2 CLINICAL NEUROLOGY

Seizure-European Journal of Epilepsy

Pub Date : 2025-11-23 DOI: 10.1016/j.seizure.2025.11.016

Debopam Samanta , Sunil Naik

Objective

To evaluate the efficacy and safety of cenobamate in developmental and epileptic encephalopathies (DEE) through systematic review and meta-analysis.

Methods

We systematically searched electronic databases for studies reporting cenobamate outcomes in DEE. Primary outcome was the proportion of patients achieving ≥50 % seizure reduction. Secondary outcomes included seizure freedom, treatment retention, and treatment-emergent adverse events (TEAEs). Study quality was assessed using the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool. Generalized linear mixed-model (GLMM) meta-analyses with logit transformation were performed. Between-study heterogeneity was assessed using I² statistics. Leave-one-out sensitivity analysis identified influential studies. Meta-regression explored associations between study characteristics and outcomes. Evidence quality was evaluated using GRADE criteria.

Results

Fourteen studies involving 368 DEE patients were included; individual studies reported mean ages ranging from 8.7 to 42 years and follow-up durations of 3 to 24 months. Patients had extensive treatment histories (8–15 prior antiseizure medications). The pooled ≥50 % responder rate was 56.8 % (95 % CI: 41.9–70.6 %; I² = 74.9 %). Sensitivity analysis excluding four influential studies produced a similar estimate (63.4 %, 95 % CI: 46.5–77.6 %) with no heterogeneity. Seizure freedom was achieved in 10.3 % (95 % CI: 6.6–15.7 %; I² = 21.3 %). Treatment retention was high at 88.6 % (95 % CI: 66.9–96.7 %), though longitudinal data showed decline over time. TEAEs occurred in 60.3 % (95 % CI: 53.5–66.7 %), most often somnolence, dizziness, and ataxia, typically manageable with dose adjustments. No cases of DRESS were reported. Meta-regression found no significant association between age, follow-up duration, or prior/current antiseizure medication burden and treatment response.

Significance

Cenobamate demonstrates promising efficacy in highly refractory DEEs, with over half of patients achieving ≥50 % seizure reduction and ∼10 % attaining seizure freedom despite extensive prior treatment failures. The high retention rate and manageable safety profile support its use as a valuable therapeutic option in this difficult-to-treat population.

目的通过系统评价和荟萃分析，评价欣奥巴肽治疗发育性和癫痫性脑病（DEE）的疗效和安全性。方法系统地检索电子数据库中报道DEE预后良好的研究。主要结局是癫痫发作减少≥50%的患者比例。次要结局包括癫痫发作自由、治疗保留和治疗出现的不良事件（teae）。使用非随机干预研究的偏倚风险（ROBINS-I）工具评估研究质量。采用logit变换进行广义线性混合模型（GLMM）元分析。采用I²统计量评估研究间异质性。留一敏感性分析确定了有影响的研究。荟萃回归探讨了研究特征与结果之间的关系。采用GRADE标准评价证据质量。结果纳入14项研究，共368例DEE患者；个别研究报告的平均年龄为8.7至42岁，随访时间为3至24个月。患者有广泛的治疗史（既往抗癫痫药物8-15次）。总有效率≥50%为56.8% （95% CI: 41.9 - 70.6%; I²= 74.9%）。排除四项有影响的研究的敏感性分析得出了类似的估计（63.4%,95% CI: 46.5 - 77.6%），没有异质性。10.3%的患者癫痫发作自由（95% CI: 6.6 - 15.7%; I²= 21.3%）。治疗保留率高达88.6% (95% CI: 66.9 - 96.7%)，尽管纵向数据显示随着时间的推移而下降。teae发生率为60.3% (95% CI: 53.5 - 66.7%)，最常见的是嗜睡、头晕和共济失调，通常可以通过剂量调整来控制。无DRESS病例报告。meta回归发现年龄、随访时间或既往/当前抗癫痫药物负担与治疗反应之间无显著关联。ecenobamate在高度难治性癫痫患者中显示出良好的疗效，超过一半的患者实现≥50%的癫痫发作减少，约10%的患者实现癫痫发作自由，尽管先前的治疗大量失败。高保留率和可管理的安全性支持其作为这一难以治疗人群的宝贵治疗选择。

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引用次数: 0

Cenobamate in adult patients with epilepsy and intellectual disability 在成人癫痫和智力残疾患者中使用

IF 2.8 3区医学 Q2 CLINICAL NEUROLOGY

Seizure-European Journal of Epilepsy

Pub Date : 2025-11-23 DOI: 10.1016/j.seizure.2025.11.017

David Steinbart , Rebekka Geelhaar , Rebekka Lehmann , Anja Grimmer , Martin Holtkamp

Objective

In people with intellectual disability (ID), prevalence of epilepsy is up to 50-times higher than in the general population and often difficult to treat. Multiple randomized controlled, observational and retrospective studies have demonstrated favorable efficacy of adjunctive cenobamate (CNB). So far, people with epilepsy and ID (PWE+ID) have remained significantly underrepresented. This retrospective study evaluated efficacy and tolerability of CNB specifically in adult PWE+ID compared to those without ID (PWE-ID).

Methods

Between 2021 and 2024, PWE at a tertiary epilepsy center were surveyed by telephone on a quarterly basis as part of clinical quality control after starting CNB. Retention rate, seizure outcome (comparing the preceding 3 months to 3 months baseline), and adverse events were assessed. Chi-square and Mann–Whitney U tests were used to compare groups, and a Bayesian analysis evaluated non-inferiority.

Results

A total of 108 PWE (51 PWE+ID) were monitored over 12 months after CNB initiation. Retention rates significantly differed between patients with and without ID after 3 months (100 % vs. 84 %, p = 0.04), but were not different after 6 (88 % vs. 77 %, p = 0.57) and 12 months (75 % vs. 70 %, p = 0.99). The 50 % responder rates were comparable at 6 months (46 % in PWE+ID vs. 47 % in PWE-ID, p = 0.99) and at 12 months (53 % vs. 53 %, p = 0.99). At 12 months, 21 % of PWE+ID (13 % of PWE-ID, p = 0.69) have remained free of disabling seizures. In Bayesian analysis, the probability of non-inferiority of 12-month outcomes in PWE+ID compared to PWE-ID was 97 % for retention and 94 % for 50 % responder rates. Adverse events (most frequently tiredness and dizziness) were reported by 59 % of PWE+ID (60 % of PWE-ID, p = 0.99) and resulted in CNB discontinuation within 12 months in 24 % of PWE+ID (28 % of PWE-ID, p = 0.70).

Significance

In adult PWE and intellectual disability, cenobamate is similarly efficacious and tolerated as in patients without ID.

目的在智力残疾人群中，癫痫的患病率是一般人群的50倍，且往往难以治疗。多项随机对照、观察性和回顾性研究表明，佐剂cenobamate （CNB）疗效良好。到目前为止，患有癫痫和ID （PWE+ID）的人仍然严重不足。本回顾性研究评估了CNB在成人PWE+ID与无PWE-ID患者（PWE-ID）中的疗效和耐受性。方法于2021 - 2024年间，对某三级癫痫中心的PWE进行季度电话调查，作为启动CNB后临床质量控制的一部分。评估留置率、癫痫发作结果（比较前3个月和3个月基线）和不良事件。组间比较采用卡方检验和Mann-Whitney U检验，贝叶斯分析评价非劣效性。结果CNB启动后12个月内共监测了108例PWE（51例PWE+ID）。3个月后患者与非ID患者的保留率差异显著（100%对84%，p = 0.04），但6个月后（88%对77%，p = 0.57）和12个月后（75%对70%，p = 0.99）没有差异。50%的应答率在6个月时（PWE+ID组46%对PWE-ID组47%，p = 0.99）和12个月时（53%对53%，p = 0.99）具有可比性。在12个月时，21%的PWE+ID患者（13%的PWE-ID患者，p = 0.69）没有出现致残性癫痫发作。在贝叶斯分析中，与PWE-ID相比，PWE+ID的12个月结果的非劣效性概率为保留率为97%，50%应答率为94%。59%的PWE+ID患者（60%的PWE-ID患者，p = 0.99）报告了不良事件（最常见的是疲倦和头晕），24%的PWE+ID患者（28%的PWE-ID患者，p = 0.70）在12个月内停止服用CNB。在成人PWE和智力残疾患者中，cenobamate与没有ID的患者同样有效和耐受性。

{"title":"Cenobamate in adult patients with epilepsy and intellectual disability","authors":"David Steinbart , Rebekka Geelhaar , Rebekka Lehmann , Anja Grimmer , Martin Holtkamp","doi":"10.1016/j.seizure.2025.11.017","DOIUrl":"10.1016/j.seizure.2025.11.017","url":null,"abstract":"<div><h3>Objective</h3><div>In people with intellectual disability (ID), prevalence of epilepsy is up to 50-times higher than in the general population and often difficult to treat. Multiple randomized controlled, observational and retrospective studies have demonstrated favorable efficacy of adjunctive cenobamate (CNB). So far, people with epilepsy and ID (PWE+ID) have remained significantly underrepresented. This retrospective study evaluated efficacy and tolerability of CNB specifically in adult PWE+ID compared to those without ID (PWE-ID).</div></div><div><h3>Methods</h3><div>Between 2021 and 2024, PWE at a tertiary epilepsy center were surveyed by telephone on a quarterly basis as part of clinical quality control after starting CNB. Retention rate, seizure outcome (comparing the preceding 3 months to 3 months baseline), and adverse events were assessed. Chi-square and Mann–Whitney <em>U tests</em> were used to compare groups, and a Bayesian analysis evaluated non-inferiority.</div></div><div><h3>Results</h3><div>A total of 108 PWE (51 PWE+ID) were monitored over 12 months after CNB initiation. Retention rates significantly differed between patients with and without ID after 3 months (100 % vs. 84 %, <em>p</em> = 0.04), but were not different after 6 (88 % vs. 77 %, <em>p</em> = 0.57) and 12 months (75 % vs. 70 %, <em>p</em> = 0.99). The 50 % responder rates were comparable at 6 months (46 % in PWE+ID vs. 47 % in PWE-ID, <em>p</em> = 0.99) and at 12 months (53 % vs. 53 %, <em>p</em> = 0.99). At 12 months, 21 % of PWE+ID (13 % of PWE-ID, <em>p</em> = 0.69) have remained free of disabling seizures. In Bayesian analysis, the probability of non-inferiority of 12-month outcomes in PWE+ID compared to PWE-ID was 97 % for retention and 94 % for 50 % responder rates. Adverse events (most frequently tiredness and dizziness) were reported by 59 % of PWE+ID (60 % of PWE-ID, <em>p</em> = 0.99) and resulted in CNB discontinuation within 12 months in 24 % of PWE+ID (28 % of PWE-ID, <em>p</em> = 0.70).</div></div><div><h3>Significance</h3><div>In adult PWE and intellectual disability, cenobamate is similarly efficacious and tolerated as in patients without ID.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"134 ","pages":"Pages 126-133"},"PeriodicalIF":2.8,"publicationDate":"2025-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145693582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Asymmetry in the diffusion tensor image analysis along the perivascular space index predicts seizure outcome in MRI-negative focal epilepsy 沿血管周围空间指数的扩散张量图像分析的不对称性预测mri阴性局灶性癫痫的发作结果

IF 2.8 3区医学 Q2 CLINICAL NEUROLOGY

Seizure-European Journal of Epilepsy

Pub Date : 2025-11-20 DOI: 10.1016/j.seizure.2025.11.015

Jungyon Yum , Wonwoo Lee , Woo-Seok Ha , JaeWook Jeong , Kyung Min Kim , Min Kyung Chu , Won-Joo Kim , Soomi Cho

Purpose

We evaluated diffusion tensor image analysis along the perivascular space (DTI-ALPS) index asymmetry as an imaging correlate of glymphatic activity and its prognostic value in MRI-negative focal epilepsy.

Methods

We retrospectively studied 134 patients with MRI-negative focal epilepsy who underwent DTI (3T MRI) with >2-year follow-up. DTI-ALPS asymmetry index (AI) was calculated as |left-right|/mean. Multivariable logistic regression identified predictors of seizure freedom (SF; >1 year seizure-free) at last follow-up. Significant AI-correlated variables underwent mediation analysis. Cox proportional hazards models evaluated the association between DTI-ALPS AI and time to (1) first post-MRI SF and (2) final SF.

Results

Of the 134 patients (median age, 31 years; 72 female), 76 (57%) achieved SF at last follow-up. Compared to those without SF, patients with SF had significantly shorter epilepsy duration (median, 8 years vs. 15 years; p = 0.029), lower seizure frequency (median, 1 vs. 5; p < 0.001), and lower DTI-ALPS AI (median, 0.064 vs. 0.119; p < 0.001). In multivariable logistic regression, DTI-ALPS AI (odds ratio [OR] per 0.1 increase, 0.271; 95% confidence interval [CI], 0.135–0.493; p < 0.001) and seizure frequency (OR, 0.967; 95% CI, 0.940–0.992; p = 0.013) predicted SF at last follow-up. The effect of DTI-ALPS AI on long-term seizure outcomes was not significantly mediated by disease duration (average direct effect, –0.670; 95% CI, –0.841 to –0.486; p < 0.001; average causal mediated effect, –0.098; 95% CI, –0.259 to 0.056; p = 0.266). Patients with low DTI-ALPS AI (< 0.074) achieved SF earlier after MRI (p_Log-rank = 0.012, p_{Cox regression} = 0.006) and were more likely to be seizure-free at last follow-up (both p_Log-rank and p_{Cox regression} < 0.001).

Conclusion

Asymmetry in the DTI-ALPS index may reflect interhemispheric differences in glymphatic function that are driven by localized, lateralized seizure activity, and may thereby serve as a prognostic marker in MRI-negative focal epilepsy.

目的探讨沿血管周围间隙弥散张量图像分析（DTI-ALPS）指数不对称性与mri阴性局灶性癫痫中淋巴活性的影像相关性及其预后价值。方法回顾性分析134例MRI阴性局灶性癫痫患者行DTI （3T MRI）检查，随访2年。DTI-ALPS不对称指数（AI）计算为|左右|/平均值。多变量logistic回归确定了最后随访时癫痫发作自由（SF; >；1年无癫痫发作）的预测因素。对显著ai相关变量进行中介分析。Cox比例风险模型评估了DTI-ALPS AI与到达(1)mri后首次SF和(2)最终SF的时间之间的关系。结果134例患者（中位年龄31岁，女性72例）中，76例（57%）在末次随访时实现SF。与没有SF的患者相比，SF患者癫痫持续时间明显缩短（中位数，8年对15年，p = 0.029），发作频率明显降低（中位数，1比5；p < 0.001）， DTI-ALPS AI明显降低（中位数，0.064比0.119;p < 0.001）。在多变量logistic回归中，DTI-ALPS AI（比值比[OR]每增加0.1,0.271；95%可信区间[CI]， 0.135-0.493; p < 0.001）和癫痫发作频率（OR, 0.967; 95% CI, 0.940-0.992; p = 0.013）预测末次随访时SF。DTI-ALPS AI对长期癫痫发作结局的影响不受疾病持续时间的显著介导（平均直接效应，-0.670;95% CI, -0.841 ~ -0.486; p < 0.001；平均因果介导效应，-0.098;95% CI, -0.259 ~ 0.056; p = 0.266）。低DTI-ALPS AI患者（< 0.074）在MRI后更早出现SF (pLog-rank = 0.012， pCox回归= 0.006)，并且在最后随访时更有可能无癫痫发作（pLog-rank和pCox回归<； 0.001）。结论DTI-ALPS指数的不对称可能反映了局部、偏侧癫痫活动驱动的半球间淋巴功能差异，因此可能作为mri阴性局灶性癫痫的预后指标。

{"title":"Asymmetry in the diffusion tensor image analysis along the perivascular space index predicts seizure outcome in MRI-negative focal epilepsy","authors":"Jungyon Yum , Wonwoo Lee , Woo-Seok Ha , JaeWook Jeong , Kyung Min Kim , Min Kyung Chu , Won-Joo Kim , Soomi Cho","doi":"10.1016/j.seizure.2025.11.015","DOIUrl":"10.1016/j.seizure.2025.11.015","url":null,"abstract":"<div><h3>Purpose</h3><div>We evaluated diffusion tensor image analysis along the perivascular space (DTI-ALPS) index asymmetry as an imaging correlate of glymphatic activity and its prognostic value in MRI-negative focal epilepsy.</div></div><div><h3>Methods</h3><div>We retrospectively studied 134 patients with MRI-negative focal epilepsy who underwent DTI (3T MRI) with >2-year follow-up. DTI-ALPS asymmetry index (AI) was calculated as |left-right|/mean. Multivariable logistic regression identified predictors of seizure freedom (SF; >1 year seizure-free) at last follow-up. Significant AI-correlated variables underwent mediation analysis. Cox proportional hazards models evaluated the association between DTI-ALPS AI and time to (1) first post-MRI SF and (2) final SF.</div></div><div><h3>Results</h3><div>Of the 134 patients (median age, 31 years; 72 female), 76 (57%) achieved SF at last follow-up. Compared to those without SF, patients with SF had significantly shorter epilepsy duration (median, 8 years vs. 15 years; <em>p</em> = 0.029), lower seizure frequency (median, 1 vs. 5; <em>p</em> < 0.001), and lower DTI-ALPS AI (median, 0.064 vs. 0.119; <em>p</em> < 0.001). In multivariable logistic regression, DTI-ALPS AI (odds ratio [OR] per 0.1 increase, 0.271; 95% confidence interval [CI], 0.135–0.493; <em>p</em> < 0.001) and seizure frequency (OR, 0.967; 95% CI, 0.940–0.992; <em>p</em> = 0.013) predicted SF at last follow-up. The effect of DTI-ALPS AI on long-term seizure outcomes was not significantly mediated by disease duration (average direct effect, –0.670; 95% CI, –0.841 to –0.486; <em>p</em> < 0.001; average causal mediated effect, –0.098; 95% CI, –0.259 to 0.056; <em>p</em> = 0.266). Patients with low DTI-ALPS AI (< 0.074) achieved SF earlier after MRI (p<sub>Log-rank</sub> = 0.012, p<sub>Cox regression</sub> = 0.006) and were more likely to be seizure-free at last follow-up (both p<sub>Log-rank</sub> and p<sub>Cox regression</sub> < 0.001).</div></div><div><h3>Conclusion</h3><div>Asymmetry in the DTI-ALPS index may reflect interhemispheric differences in glymphatic function that are driven by localized, lateralized seizure activity, and may thereby serve as a prognostic marker in MRI-negative focal epilepsy.</div></div>","PeriodicalId":49552,"journal":{"name":"Seizure-European Journal of Epilepsy","volume":"134 ","pages":"Pages 97-104"},"PeriodicalIF":2.8,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145624252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Response to comments of Ďurčová et al 对Ďurčová等人评论的回应

IF 2.8 3区医学 Q2 CLINICAL NEUROLOGY

Seizure-European Journal of Epilepsy

Pub Date : 2025-11-19 DOI: 10.1016/j.seizure.2025.11.014

Rekha Dwivedi, Yogendra Kumar Gupta, Meenakshi Singh, Rupa Joshi, Prabhakar Tiwari, Thomas Kaleekal, Manjari Tripathi

引用次数: 0

Scoping review: Sexual dysfunction in people with epilepsy 范围回顾：癫痫患者的性功能障碍。

IF 2.8 3区医学 Q2 CLINICAL NEUROLOGY

Seizure-European Journal of Epilepsy

Pub Date : 2025-11-16 DOI: 10.1016/j.seizure.2025.11.013

Sumika Ouchida , Armin Nikpour , Greg Fairbrother

Background

There are many comorbidities related to epilepsy that affect the quality of life of people with epilepsy (PWE); sexual dysfunction (SD) is one of them.

Aim

We conducted a review to identify gaps in the literature to estimate the size of the problem and examined sexual dysfunction types, factors associated with SD, epilepsy care management, and facilitators/barriers reported for treatment success/failure.

Method

We searched for articles on sexual dysfunction, sexual problems, sexual behaviour, and erectile dysfunction in relation to epilepsy. We searched research databases, including Embase, Medline, PsycINFO, and PubMed, for articles written in English and published between 2000 and 2023.

Results

There is a high prevalence of SD in PWE, and multiple factors have been identified as being associated with SD. A range of validated questionnaire-based SD assessments is available. SD affects men and women differently. While several treatments and therapies are available to manage SD, there is limited evidence supporting their use for PWE. Healthcare professionals' lack of education relevant to SD affects their ability to treat PWE effectively.

Conclusion

Sexual problems are common in PWE. Healthcare providers should investigate drug-induced sexual problems as they can significantly affect patients' quality of life. Unfortunately, there are no established guidelines for treating sexual problems in epilepsy patients. More research is needed on treatments, and healthcare providers require additional education on SD-related issues to diagnose and effectively address these problems.

背景：有许多与癫痫相关的合并症影响癫痫患者（PWE）的生活质量；性功能障碍（SD）就是其中之一。目的：我们进行了一项综述，以确定文献中的差距，以估计问题的大小，并检查了性功能障碍的类型、与SD相关的因素、癫痫护理管理以及治疗成功/失败的促进因素/障碍。方法：我们检索与癫痫有关的性功能障碍、性问题、性行为和勃起功能障碍的文章。我们检索了研究数据库，包括Embase、Medline、PsycINFO和PubMed，检索了2000年至2023年间发表的英文文章。结果：PWE患者SD患病率高，且多种因素与SD相关。一系列有效的基于问卷的可持续发展评估是可用的。SD对男性和女性的影响是不同的。虽然有几种治疗方法可用于治疗SD，但支持它们用于PWE的证据有限。医疗保健专业人员缺乏与SD相关的教育影响了他们有效治疗PWE的能力。结论：PWE患者存在性问题。医疗保健提供者应调查药物引起的性问题，因为它们可以显著影响患者的生活质量。不幸的是，目前还没有治疗癫痫患者性问题的既定指南。需要对治疗方法进行更多的研究，医疗保健提供者需要更多关于sd相关问题的教育，以诊断和有效地解决这些问题。

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引用次数: 0