Epilepsy Research最新文献_第2页

Evaluating the impact of cenobamate in the management in patients with drug resistant focal epilepsy – A retrospective real world observational study of patients attending NHS Greater Glasgow and Clyde 评价cenobamate对耐药局灶性癫痫患者管理的影响——一项对大格拉斯哥和克莱德NHS患者的回顾性观察性研究

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research

Pub Date : 2025-12-02 DOI: 10.1016/j.eplepsyres.2025.107717

M. Taha , L. Stephen , S. Nichol , S. Yule , S. MacBride-Stewart , AD Marshall , CA Heath

Introduction

Cenobamate (CNB) is the latest ASM to be licensed in the UK as an adjunctive treatment for adults with focal epilepsy. Early clinical trials have been encouraging with up to 50.4 % of patients showing a 50 % improvement at 12 weeks and 71 % were still receiving Cenobamate at 48 months. Regulatory studies of this nature provide useful information, but real-world data is often more informative.

Since Scottish Medicine Consortium approval in 2022, we have been collecting audit data on outcomes from patients receiving cenobamate.

Methods

Adult patients were included if they received at least one prescription for cenobamate between March 2022 and April 2024 and had at least 12 months of data available before their first prescription.

Patients dispensed cenobamate were identified from the national Prescribing Information System (PIS) to ensure complete patient capture.

A manual review of electronic patient records was undertaken. The primary outcome of interest was change in seizure frequency on a stable dose. Secondary outcomes included epilepsy-related admissions, changes in ASMs and healthcare resource utilisation costs.

Results

145 patients received at least 1 CNB prescription, 144 of whom had reached an endpoint. 94/144 (65.2 %) had a favourable response. The median length of treatment was 655 days (range 180–922 days), with a median dose of 150 mg/d (range 25–400 mg/d). The median number of previous ASM was 5 (1−13).

48/145 (33.1 %) discontinued CNB – 35 due to adverse effects, 6 due to lack of efficacy. 2 patients died.

Early analysis suggest a reduction in Health care resource use although long term follow up is required.

Conclusion

These results offer insights for clinicians regarding the real-world effectiveness, retention rates, and healthcare cost implications of CNB therapy in a cohort consisting largely of patients with severe drug resistant epilepsy. Further studies are ongoing to assess the efficacy of CNB when used earlier and also to provide a comprehensive assessment of health care resource use in this real world settings.

cenobamate （CNB）是最新在英国获得许可的ASM，作为成人局灶性癫痫的辅助治疗。早期临床试验结果令人鼓舞，在12周时，50.4% %的患者表现出50% %的改善，而在48个月时，仍有71% %的患者在服用Cenobamate。这种性质的监管研究提供了有用的信息，但真实世界的数据往往更有用。自苏格兰医学联盟于2022年批准以来，我们一直在收集接受cenobamate的患者的结果审计数据。方法纳入在2022年3月至2024年4月期间至少服用过一次cenobamate处方的成年患者，并且在首次处方前至少有12个月的数据。从国家处方信息系统（PIS）中识别分配了cenobamate的患者，以确保完整的患者捕获。对电子病历进行了人工审查。研究的主要结果是在稳定剂量下癫痫发作频率的变化。次要结局包括癫痫相关入院、asm变化和医疗资源利用成本。结果145例患者接受了至少1个CNB处方，其中144例达到终点。94/144（65.2 %）表示赞成。中位治疗时间为655天（180-922天），中位剂量为150 mg/d（25-400 mg/d）。既往ASM中位数为5（1 ~ 13）。48/145（33.1% %）因不良反应停用CNB - 35, 6因缺乏疗效。2例死亡。早期分析表明，尽管需要长期随访，但卫生保健资源的使用有所减少。这些结果为临床医生提供了关于CNB治疗在现实世界中的有效性、保留率和医疗成本影响的见解，这些队列主要由严重耐药癫痫患者组成。目前正在进行进一步的研究，以评估早期使用CNB的效果，并对现实世界环境中卫生保健资源的使用情况进行全面评估。

{"title":"Evaluating the impact of cenobamate in the management in patients with drug resistant focal epilepsy – A retrospective real world observational study of patients attending NHS Greater Glasgow and Clyde","authors":"M. Taha , L. Stephen , S. Nichol , S. Yule , S. MacBride-Stewart , AD Marshall , CA Heath","doi":"10.1016/j.eplepsyres.2025.107717","DOIUrl":"10.1016/j.eplepsyres.2025.107717","url":null,"abstract":"<div><h3>Introduction</h3><div>Cenobamate (CNB) is the latest ASM to be licensed in the UK as an adjunctive treatment for adults with focal epilepsy. Early clinical trials have been encouraging with up to 50.4 % of patients showing a 50 % improvement at 12 weeks and 71 % were still receiving Cenobamate at 48 months. Regulatory studies of this nature provide useful information, but real-world data is often more informative.</div><div>Since Scottish Medicine Consortium approval in 2022, we have been collecting audit data on outcomes from patients receiving cenobamate.</div></div><div><h3>Methods</h3><div>Adult patients were included if they received at least one prescription for cenobamate between March 2022 and April 2024 and had at least 12 months of data available before their first prescription.</div><div>Patients dispensed cenobamate were identified from the national Prescribing Information System (PIS) to ensure complete patient capture.</div><div>A manual review of electronic patient records was undertaken. The primary outcome of interest was change in seizure frequency on a stable dose. Secondary outcomes included epilepsy-related admissions, changes in ASMs and healthcare resource utilisation costs.</div></div><div><h3>Results</h3><div>145 patients received at least 1 CNB prescription, 144 of whom had reached an endpoint. 94/144 (65.2 %) had a favourable response. The median length of treatment was 655 days (range 180–922 days), with a median dose of 150 mg/d (range 25–400 mg/d). The median number of previous ASM was 5 (1−13).</div><div>48/145 (33.1 %) discontinued CNB – 35 due to adverse effects, 6 due to lack of efficacy. 2 patients died.</div><div>Early analysis suggest a reduction in Health care resource use although long term follow up is required.</div></div><div><h3>Conclusion</h3><div>These results offer insights for clinicians regarding the real-world effectiveness, retention rates, and healthcare cost implications of CNB therapy in a cohort consisting largely of patients with severe drug resistant epilepsy. Further studies are ongoing to assess the efficacy of CNB when used earlier and also to provide a comprehensive assessment of health care resource use in this real world settings.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"220 ","pages":"Article 107717"},"PeriodicalIF":2.0,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145665355","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}

引用次数: 0

Analysis of risk factors for recurrence after the withdrawal of ASMs in 135 children with epilepsy. 135例癫痫患儿停药后复发危险因素分析。

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research

Pub Date : 2025-12-01 Epub Date: 2025-08-06 DOI: 10.1016/j.eplepsyres.2025.107638

Yuchen Gao, Xuan Li, Zenghua Yong, Baoqiang Yuan, Yunlong Dou

Objective: To identify risk factors for seizure recurrence following anti-seizure medication (ASM) withdrawal in children with epilepsy who achieved sustained seizure freedom.

Methods: This retrospective cohort study analyzed 135 children with epilepsy from a single tertiary center (2022--2023) meeting withdrawal criteria (aged <16 years, seizure-free ≥2 years on stable ASMs, followed ≥1 year after withdrawal). Participants were grouped by postwithdrawal seizure relapse status: recurrent (n = 42) and nonrecurrent (n = 93). Thirteen risk factors were compared via chi-square tests. Variables significantly associated (P < 0.05) with recurrence in univariate analysis were entered into multivariate logistic regression to identify independent predictors (reported as ORs with 95 % CIs). The analyses were performed with SPSS 19.0.

Results: The overall recurrence rate was 31.11 % (42/135), with 80.95 % of recurrences occurring during ASM tapering or within the first year after withdrawal. Univariate analysis revealed significant differences between the recurrence and nonrecurrence groups regarding prewithdrawal EEG abnormalities (P = 0.006), ASM polytherapy (P = 0.003), time to seizure freedom > 1 year (P = 0.037), pretreatment epilepsy duration > 1 year (P = 0.011), presence of comorbidities (P < 0.001), and multiple seizure types (P = 0.020). Multivariate logistic regression confirmed three independent risk factors for recurrence: (1) abnormal EEG before withdrawal (OR=9.268, 95 % CI: 2.255-38.092, P = 0.002), (2) ASM polytherapy (OR=3.205, 95 % CI: 1.159-8.866, P = 0.025), and (3) pretreatment epilepsy duration > 1 year (OR=5.363, 95 % CI: 1.781-16.150, P = 0.003).

Conclusion: Abnormal EEG before withdrawal, polytherapy, and pretreatment duration > 1 year predicted recurrence. Enzyme-induction patterns showed exploratory associations requiring further validation.

目的：探讨癫痫患儿抗癫痫药物停药后癫痫复发的危险因素。方法：本回顾性队列研究分析了来自单一三级中心（2022- 2023）的135例符合停药标准的癫痫患儿（年龄）。结果：总复发率为31.11 %(42/135)，其中80.95 %的复发发生在ASM逐渐减少或停药后一年内。单变量分析发现复发之间的显著差异,但组织关于prewithdrawal脑电图异常(P = 0.006),ASM polytherapy (P = 0.003),发作时间自由> 1年(P = 0.037),预处理癫痫持续时间> 1年(P = 0.011),出现并发症(P  1年(或= 5.363,95 % CI: 1.781 - -16.150, P = 0.003)。结论：停药前、多药前、预处理时间> 1年脑电图异常预测复发。酶诱导模式显示探索性关联，需要进一步验证。

{"title":"Analysis of risk factors for recurrence after the withdrawal of ASMs in 135 children with epilepsy.","authors":"Yuchen Gao, Xuan Li, Zenghua Yong, Baoqiang Yuan, Yunlong Dou","doi":"10.1016/j.eplepsyres.2025.107638","DOIUrl":"10.1016/j.eplepsyres.2025.107638","url":null,"abstract":"<p><strong>Objective: </strong>To identify risk factors for seizure recurrence following anti-seizure medication (ASM) withdrawal in children with epilepsy who achieved sustained seizure freedom.</p><p><strong>Methods: </strong>This retrospective cohort study analyzed 135 children with epilepsy from a single tertiary center (2022--2023) meeting withdrawal criteria (aged <16 years, seizure-free ≥2 years on stable ASMs, followed ≥1 year after withdrawal). Participants were grouped by postwithdrawal seizure relapse status: recurrent (n = 42) and nonrecurrent (n = 93). Thirteen risk factors were compared via chi-square tests. Variables significantly associated (P < 0.05) with recurrence in univariate analysis were entered into multivariate logistic regression to identify independent predictors (reported as ORs with 95 % CIs). The analyses were performed with SPSS 19.0.</p><p><strong>Results: </strong>The overall recurrence rate was 31.11 % (42/135), with 80.95 % of recurrences occurring during ASM tapering or within the first year after withdrawal. Univariate analysis revealed significant differences between the recurrence and nonrecurrence groups regarding prewithdrawal EEG abnormalities (P = 0.006), ASM polytherapy (P = 0.003), time to seizure freedom > 1 year (P = 0.037), pretreatment epilepsy duration > 1 year (P = 0.011), presence of comorbidities (P < 0.001), and multiple seizure types (P = 0.020). Multivariate logistic regression confirmed three independent risk factors for recurrence: (1) abnormal EEG before withdrawal (OR=9.268, 95 % CI: 2.255-38.092, P = 0.002), (2) ASM polytherapy (OR=3.205, 95 % CI: 1.159-8.866, P = 0.025), and (3) pretreatment epilepsy duration > 1 year (OR=5.363, 95 % CI: 1.781-16.150, P = 0.003).</p><p><strong>Conclusion: </strong>Abnormal EEG before withdrawal, polytherapy, and pretreatment duration > 1 year predicted recurrence. Enzyme-induction patterns showed exploratory associations requiring further validation.</p>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"218 ","pages":"107638"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811960","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}

引用次数: 0

The SEEG brain network predicts epileptic surgical outcomes of radiofrequency thermocoagulation SEEG脑网络预测射频热凝的癫痫手术结果。

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research

Pub Date : 2025-11-29 DOI: 10.1016/j.eplepsyres.2025.107715

Jingxian Shen , Hongping Tan , Bocheng Wu , Jiabin Luo , Guangrui Yang , Xuchu Weng , Qiang Guo , Jiuxing Liang

Predicting the postoperative outcome of stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) remains challenging despite its increasing use in epilepsy treatment. Although SEEG-guided RF-TC has attracted extensive clinical interest, reliable biomarkers for treatment efficacy are still lacking. This study aims to address this gap by analyzing the altered brain network to predict postoperative outcome. Thirty-one focal cortical dysplasia epileptic patients who underwent RF-TC based on SEEG were enrolled in this study. They were included in the favorable outcome and poor outcome groups according to the follow-up. Partial Directed Coherence and Directed Transfer Function were applied to construct SEEG brain networks, and then brain network features were extracted. Subsequently, the differences in the presurgical and postsurgical brain network features were compared using the Wilcoxon test in the favorable and poor outcome groups, respectively. Finally, four machine learning models were applied to predict the outcome of RF-TC. After RF-TC surgery, the Characteristic Path Length (L) and average Betweenness Centrality (BC) increased while the average Clustering Coefficient (C) and Assortativity Coefficient (R1, R2) decreased in the favorable outcomes group. In contrast, there were no significant changes in the patient group with poor outcomes. The Support Vector Machine (SVM) model achieved the highest performance, with accuracy, sensitivity, specificity, and ROC values of 0.887, 0.821, 0.920, and 0.879, respectively. This study sheds light on the mechanisms of epilepsy from the perspective of brain networks and introduces a novel therapeutic strategy by altering network features. These feature alterations can also support machine learning models in effectively distinguishing favorable from poor outcomes.

尽管立体脑电图引导的射频热凝术（SEEG-guided RF-TC）在癫痫治疗中的应用越来越多，但预测其术后结果仍然具有挑战性。尽管seeg引导的RF-TC已经引起了广泛的临床兴趣，但仍然缺乏可靠的治疗效果生物标志物。本研究旨在通过分析改变的脑网络来预测术后结果来解决这一差距。31例局灶性皮质发育不良癫痫患者接受了基于SEEG的RF-TC治疗。根据随访情况分为预后良好组和预后不良组。利用部分有向相干和有向传递函数构建SEEG脑网络，提取脑网络特征。随后，分别使用Wilcoxon检验比较好结局组和差结局组术前和术后脑网络特征的差异。最后，应用四种机器学习模型来预测RF-TC的结果。结果良好组RF-TC术后特征路径长度(L)和平均中间性中心性（BC）增加，平均聚类系数(C)和分类系数（R1, R2）下降。相比之下，预后较差的患者组没有明显变化。支持向量机（Support Vector Machine， SVM）模型的准确率、灵敏度、特异度和ROC值分别为0.887、0.821、0.920和0.879。本研究从脑网络的角度揭示了癫痫的发病机制，并提出了一种通过改变脑网络特征来治疗癫痫的新策略。这些特征的改变也可以支持机器学习模型有效地区分有利和不利的结果。

{"title":"The SEEG brain network predicts epileptic surgical outcomes of radiofrequency thermocoagulation","authors":"Jingxian Shen , Hongping Tan , Bocheng Wu , Jiabin Luo , Guangrui Yang , Xuchu Weng , Qiang Guo , Jiuxing Liang","doi":"10.1016/j.eplepsyres.2025.107715","DOIUrl":"10.1016/j.eplepsyres.2025.107715","url":null,"abstract":"<div><div>Predicting the postoperative outcome of stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) remains challenging despite its increasing use in epilepsy treatment. Although SEEG-guided RF-TC has attracted extensive clinical interest, reliable biomarkers for treatment efficacy are still lacking. This study aims to address this gap by analyzing the altered brain network to predict postoperative outcome. Thirty-one focal cortical dysplasia epileptic patients who underwent RF-TC based on SEEG were enrolled in this study. They were included in the favorable outcome and poor outcome groups according to the follow-up. Partial Directed Coherence and Directed Transfer Function were applied to construct SEEG brain networks, and then brain network features were extracted. Subsequently, the differences in the presurgical and postsurgical brain network features were compared using the Wilcoxon test in the favorable and poor outcome groups, respectively. Finally, four machine learning models were applied to predict the outcome of RF-TC. After RF-TC surgery, the Characteristic Path Length (L) and average Betweenness Centrality (BC) increased while the average Clustering Coefficient (C) and Assortativity Coefficient (R1, R2) decreased in the favorable outcomes group. In contrast, there were no significant changes in the patient group with poor outcomes. The Support Vector Machine (SVM) model achieved the highest performance, with accuracy, sensitivity, specificity, and ROC values of 0.887, 0.821, 0.920, and 0.879, respectively. This study sheds light on the mechanisms of epilepsy from the perspective of brain networks and introduces a novel therapeutic strategy by altering network features. These feature alterations can also support machine learning models in effectively distinguishing favorable from poor outcomes.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"219 ","pages":"Article 107715"},"PeriodicalIF":2.0,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145660225","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}

引用次数: 0

Real-world evidence on the use of new antiseizure medications in brain tumor–related epilepsy 新的抗癫痫药物用于脑肿瘤相关癫痫的真实证据。

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research

Pub Date : 2025-11-22 DOI: 10.1016/j.eplepsyres.2025.107709

Nasim Tabrizi , Mehran Frouzanian , Sajad Shafiee , Reza Alizadeh-Navaei

Objective

Brain tumor-related epilepsy (BTRE) is a common and disabling complication of primary brain tumors. While older antiseizure medications (ASMs) are limited by adverse effects and drug interactions, newer ASMs such as levetiracetam (LEV), lamotrigine (LTG), and lacosamide (LCS) may offer better tolerability and seizure control. This study aimed to evaluate the efficacy and safety of these newer ASMs in patients with BTRE.

Methods

A retrospective observational study was conducted on BTRE patients treated between 2018 and 2023 at a university hospital and private neurology clinics. Adult patients with primary brain tumors and at least one seizure episode were included if treated with LEV, LTG, or LCS either as monotherapy or in polytherapy. Data on demographics, tumor characteristics, treatment strategies, seizure outcomes, and adverse events were collected. The primary outcomes were 12-month seizure freedom and retention rate.

Results

A total of 106 patients (mean age 55.3 ± 15.3 years; 52.8 % male) were analyzed. Monotherapy with LEV, LTG, or LCS was used in 74 patients, achieving an overall 12-month seizure freedom of 64.9 % and retention rate of 79.7 %. No significant differences in seizure freedom were found among the three monotherapies (p = 0.258).

Conclusion

Newer ASMs demonstrated favorable seizure control and tolerability in BTRE. LEV remains the most used agent, though LTG and LCS showed comparable efficacy. Tumor and treatment-related factors influenced outcomes more than ASM choice.

目的：脑肿瘤相关性癫痫（BTRE）是原发性脑肿瘤常见的致残并发症。虽然较老的抗癫痫药物（asm）受到不良反应和药物相互作用的限制，但较新的asm，如左乙拉西坦（LEV），拉莫三嗪（LTG）和拉科沙胺（LCS）可能具有更好的耐受性和癫痫发作控制。本研究旨在评估这些新asm在BTRE患者中的疗效和安全性。方法：回顾性观察研究2018 - 2023年在某大学医院和私立神经病学诊所治疗的BTRE患者。原发性脑肿瘤且至少有一次癫痫发作的成年患者，无论是单独治疗还是联合治疗，均纳入LEV、LTG或LCS治疗。收集了人口统计学、肿瘤特征、治疗策略、癫痫发作结局和不良事件的数据。主要观察指标为12个月癫痫发作自由率和滞留率。结果：共分析106例患者，平均年龄55.3 ± 15.3岁，男性52.8 %。74例患者采用LEV、LTG或LCS单药治疗，总体12个月癫痫发作自由度为64.9 %，保留率为79.7% %。三种单药治疗的癫痫发作自由度差异无统计学意义（p = 0.258）。结论：较新的asm在BTRE中表现出良好的癫痫控制和耐受性。LEV仍然是最常用的药物，尽管LTG和LCS的疗效相当。肿瘤和治疗相关因素对预后的影响大于ASM选择。

{"title":"Real-world evidence on the use of new antiseizure medications in brain tumor–related epilepsy","authors":"Nasim Tabrizi , Mehran Frouzanian , Sajad Shafiee , Reza Alizadeh-Navaei","doi":"10.1016/j.eplepsyres.2025.107709","DOIUrl":"10.1016/j.eplepsyres.2025.107709","url":null,"abstract":"<div><h3>Objective</h3><div>Brain tumor-related epilepsy (BTRE) is a common and disabling complication of primary brain tumors. While older antiseizure medications (ASMs) are limited by adverse effects and drug interactions, newer ASMs such as levetiracetam (LEV), lamotrigine (LTG), and lacosamide (LCS) may offer better tolerability and seizure control. This study aimed to evaluate the efficacy and safety of these newer ASMs in patients with BTRE.</div></div><div><h3>Methods</h3><div>A retrospective observational study was conducted on BTRE patients treated between 2018 and 2023 at a university hospital and private neurology clinics. Adult patients with primary brain tumors and at least one seizure episode were included if treated with LEV, LTG, or LCS either as monotherapy or in polytherapy. Data on demographics, tumor characteristics, treatment strategies, seizure outcomes, and adverse events were collected. The primary outcomes were 12-month seizure freedom and retention rate.</div></div><div><h3>Results</h3><div>A total of 106 patients (mean age 55.3 ± 15.3 years; 52.8 % male) were analyzed. Monotherapy with LEV, LTG, or LCS was used in 74 patients, achieving an overall 12-month seizure freedom of 64.9 % and retention rate of 79.7 %. No significant differences in seizure freedom were found among the three monotherapies (p = 0.258).</div></div><div><h3>Conclusion</h3><div>Newer ASMs demonstrated favorable seizure control and tolerability in BTRE. LEV remains the most used agent, though LTG and LCS showed comparable efficacy. Tumor and treatment-related factors influenced outcomes more than ASM choice.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"219 ","pages":"Article 107709"},"PeriodicalIF":2.0,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145603172","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}

引用次数: 0

Automated detection of the epileptogenic zone in stereoelectroencephalography for drug-resistant epilepsy using multi-epileptogenic biomarker machine learning 应用多致痫生物标志物机器学习在立体脑电图中自动检测耐药癫痫的致痫区。

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research

Pub Date : 2025-11-22 DOI: 10.1016/j.eplepsyres.2025.107710

Chuan Du , Weipeng Jin , Le Wang , Jingtao Yan , Guangfeng Li , Yuzhang Wu , Guangrui Zhao , Jingheng Wu , Deqiu Cui , Shaoya Yin

Objective

Neurosurgery is a viable treatment option for patients with drug-resistant epilepsy (DRE), where accurate localization of the epileptogenic zone (EZ) is crucial for surgical success. This study aims to develop an interpretable machine learning (ML) framework that integrates electrophysiological features to enhance EZ localization.

Methods

We retrospectively reviewed patients with DRE who underwent stereoelectroencephalography (SEEG) exploration between January 2020 and December 2023. Multiple epileptogenic biomarkers, including the Epileptogenicity Index (EI), spike rate, ripple rate, and fast ripple rate, were computed. For improved EZ localization, model development was conducted using various machine learning algorithms that integrated these interictal and ictal electrophysiological features. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). SHapley Additive exPlanations (SHAP) were employed to interpret the ML models.

Results

A total of 38 patients with 1671 SEEG channels were included in the final analysis. Four ML models were tested, achieving AUCs ranging from 0.767 to 0.798 for predicting the EZ in patients with DRE. Among these, the deep learning model demonstrated the highest performance, with an AUC of 0.798, and was selected as the optimal predictive model. SHAP analysis identified spike rate and the EI as the most influential features, underscoring their dominant role in the model's decision-making.

Conclusion

Machine learning is a reliable tool for predicting the epileptogenic zone in patients with drug-resistant epilepsy. The use of SHAP methods to interpret the deep learning model offers clinically relevant insights and may assist clinicians in optimizing patient-specific management strategies.

目的：神经外科手术是耐药癫痫（DRE）患者的一种可行的治疗选择，其中准确定位癫痫区（EZ）对手术成功至关重要。本研究旨在开发一种可解释的机器学习（ML）框架，该框架集成了电生理特征，以增强EZ定位。方法：我们回顾性分析了2020年1月至2023年12月期间接受立体脑电图（SEEG）探查的DRE患者。计算多种致痫性生物标志物，包括致痫性指数（EI）、峰值率、纹波率和快速纹波率。为了改进EZ定位，使用各种机器学习算法进行模型开发，这些算法集成了这些间歇期和间歇期电生理特征。使用接收器工作特征曲线下面积（AUC）评估模型性能。采用SHapley加性解释（SHAP）解释ML模型。结果：38例患者共1671个SEEG通道纳入最终分析。对四种ML模型进行了测试，预测DRE患者EZ的auc范围为0.767至0.798。其中，深度学习模型表现最好，AUC为0.798，被选为最优预测模型。SHAP分析发现尖峰率和EI是最具影响力的特征，强调了它们在模型决策中的主导作用。结论：机器学习是预测耐药癫痫患者致痫区可靠的工具。使用SHAP方法来解释深度学习模型提供了与临床相关的见解，并可能帮助临床医生优化针对患者的管理策略。

{"title":"Automated detection of the epileptogenic zone in stereoelectroencephalography for drug-resistant epilepsy using multi-epileptogenic biomarker machine learning","authors":"Chuan Du , Weipeng Jin , Le Wang , Jingtao Yan , Guangfeng Li , Yuzhang Wu , Guangrui Zhao , Jingheng Wu , Deqiu Cui , Shaoya Yin","doi":"10.1016/j.eplepsyres.2025.107710","DOIUrl":"10.1016/j.eplepsyres.2025.107710","url":null,"abstract":"<div><h3>Objective</h3><div>Neurosurgery is a viable treatment option for patients with drug-resistant epilepsy (DRE), where accurate localization of the epileptogenic zone (EZ) is crucial for surgical success. This study aims to develop an interpretable machine learning (ML) framework that integrates electrophysiological features to enhance EZ localization.</div></div><div><h3>Methods</h3><div>We retrospectively reviewed patients with DRE who underwent stereoelectroencephalography (SEEG) exploration between January 2020 and December 2023. Multiple epileptogenic biomarkers, including the Epileptogenicity Index (EI), spike rate, ripple rate, and fast ripple rate, were computed. For improved EZ localization, model development was conducted using various machine learning algorithms that integrated these interictal and ictal electrophysiological features. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). SHapley Additive exPlanations (SHAP) were employed to interpret the ML models.</div></div><div><h3>Results</h3><div>A total of 38 patients with 1671 SEEG channels were included in the final analysis. Four ML models were tested, achieving AUCs ranging from 0.767 to 0.798 for predicting the EZ in patients with DRE. Among these, the deep learning model demonstrated the highest performance, with an AUC of 0.798, and was selected as the optimal predictive model. SHAP analysis identified spike rate and the EI as the most influential features, underscoring their dominant role in the model's decision-making.</div></div><div><h3>Conclusion</h3><div>Machine learning is a reliable tool for predicting the epileptogenic zone in patients with drug-resistant epilepsy. The use of SHAP methods to interpret the deep learning model offers clinically relevant insights and may assist clinicians in optimizing patient-specific management strategies.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"219 ","pages":"Article 107710"},"PeriodicalIF":2.0,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145603187","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}

引用次数: 0

Time-dependent risk of stroke following epilepsy: A nationwide cohort study in South Korea 癫痫后中风的时间依赖性风险：韩国一项全国性队列研究

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research

Pub Date : 2025-11-22 DOI: 10.1016/j.eplepsyres.2025.107695

Seung Won Lee , Yejin Lee , Chaeyoon Kang , Haerim Cho , Nakyung Shin , Sunhwa Kim , Hohyun Jung , Youngoh Bae

Background

Epilepsy(ICD-10 G40–G41) and stroke—including hemorrhagic stroke (HS: I60–I62) and ischemic stroke (IS: I63))—are major neurological disorders. Although epilepsy has been proposed as a risk factor for stroke, large-scale evidence from Asian populations and analyses of time-dependent risk remain limited. This study investigated long-term risks of HS and IS after epilepsy using a nationwide cohort in South Korea.

Methods

A population-based retrospective cohort study was conducted using the Korean National Health Insurance Service–National Sample Cohort (2002–2013). Newly diagnosed epilepsy cases were identified after a 2-year washout and matched 1:10 with controls. Incident HS and IS were evaluated using crude incidence rates (IRs), incidence rate ratios (IRRs), Kaplan–Meier analyses, and 2-year interval time-stratified Cox models.

Results

Over 10 years of follow-up, epilepsy was associated with increased risks of HS (IRR 3.50, 95 % CI 2.50–4.91) and IS (IRR 2.52, 95 % CI 2.16–2.95). Risk elevations were more pronounced in males and individuals < 60 years. Time-dependent analyses revealed a biphasic pattern: HS risk peaked during the first 0–2 years (aHR 4.25, 95 % CI 2.68–6.74), while IS risk increased at 0–2 years (aHR 2.99, 95 % CI 2.41–3.71) and again at 6–8 years (aHR 3.00, 95 % CI 1.51–5.99).

Conclusion

Epilepsy was associated with substantial and time-varying risks of HS and IS. Although causal relationships cannot be confirmed, these findings highlight the need for vigilant early monitoring and sustained, individualized stroke prevention strategies in individuals with epilepsy.

癫痫（ICD-10 G40-G41）和中风（包括出血性中风（HS: I60-I62）和缺血性中风（IS: I63））是主要的神经系统疾病。虽然癫痫已被认为是中风的一个危险因素，但来自亚洲人群的大规模证据和对时间依赖性风险的分析仍然有限。本研究通过韩国全国队列调查癫痫后HS和IS的长期风险。方法采用韩国国民健康保险服务-国民样本队列（2002-2013）进行基于人群的回顾性队列研究。新诊断的癫痫病例在2年洗脱期后确定，并与对照组1:10匹配。使用粗发病率（IRs）、发病率比（IRRs）、Kaplan-Meier分析和2年间隔时间分层Cox模型对HS和IS事件进行评估。结果随访10年，癫痫与HS （IRR 3.50, 95 % CI 2.50-4.91）和IS （IRR 2.52, 95 % CI 2.16-2.95）风险增加相关。风险升高在男性和60岁以上的个体中更为明显。时间相关分析显示了双相模式：HS风险在前0-2年达到顶峰（aHR 4.25, 95 % CI 2.68-6.74），而IS风险在0-2年增加（aHR 2.99, 95 % CI 2.41-3.71），在6-8年再次增加（aHR 3.00, 95 % CI 1.51-5.99）。结论癫痫与HS和IS的风险存在显著的时变相关性。虽然因果关系不能得到证实，但这些发现强调了对癫痫患者进行警惕的早期监测和持续的、个性化的中风预防策略的必要性。

{"title":"Time-dependent risk of stroke following epilepsy: A nationwide cohort study in South Korea","authors":"Seung Won Lee , Yejin Lee , Chaeyoon Kang , Haerim Cho , Nakyung Shin , Sunhwa Kim , Hohyun Jung , Youngoh Bae","doi":"10.1016/j.eplepsyres.2025.107695","DOIUrl":"10.1016/j.eplepsyres.2025.107695","url":null,"abstract":"<div><h3>Background</h3><div>Epilepsy(ICD-10 G40–G41) and stroke—including hemorrhagic stroke (HS: I60–I62) and ischemic stroke (IS: I63))—are major neurological disorders. Although epilepsy has been proposed as a risk factor for stroke, large-scale evidence from Asian populations and analyses of time-dependent risk remain limited. This study investigated long-term risks of HS and IS after epilepsy using a nationwide cohort in South Korea.</div></div><div><h3>Methods</h3><div>A population-based retrospective cohort study was conducted using the Korean National Health Insurance Service–National Sample Cohort (2002–2013). Newly diagnosed epilepsy cases were identified after a 2-year washout and matched 1:10 with controls. Incident HS and IS were evaluated using crude incidence rates (IRs), incidence rate ratios (IRRs), Kaplan–Meier analyses, and 2-year interval time-stratified Cox models.</div></div><div><h3>Results</h3><div>Over 10 years of follow-up, epilepsy was associated with increased risks of HS (IRR 3.50, 95 % CI 2.50–4.91) and IS (IRR 2.52, 95 % CI 2.16–2.95). Risk elevations were more pronounced in males and individuals < 60 years. Time-dependent analyses revealed a biphasic pattern: HS risk peaked during the first 0–2 years (aHR 4.25, 95 % CI 2.68–6.74), while IS risk increased at 0–2 years (aHR 2.99, 95 % CI 2.41–3.71) and again at 6–8 years (aHR 3.00, 95 % CI 1.51–5.99).</div></div><div><h3>Conclusion</h3><div>Epilepsy was associated with substantial and time-varying risks of HS and IS. Although causal relationships cannot be confirmed, these findings highlight the need for vigilant early monitoring and sustained, individualized stroke prevention strategies in individuals with epilepsy.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"219 ","pages":"Article 107695"},"PeriodicalIF":2.0,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145621588","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}

引用次数: 0

Surgery for epilepsy secondary to vascular insults: A systematic review and meta-analysis of individual patient data 继发性血管损伤癫痫的手术治疗：对个体患者数据的系统回顾和荟萃分析。

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research

Pub Date : 2025-11-21 DOI: 10.1016/j.eplepsyres.2025.107711

Adrian E. Jimenez, Neil A. Feldstein, Guy M. McKhann, E. Sander Connolly, Brett E. Youngerman

Background

While epilepsy secondary to vascular insults represents a well-documented cause of drug-resistant epilepsy that requires surgical intervention for optimal management, the prognostic factors for postoperative seizure-freedom among this patient population have not been well-established. This individual-patient data (IPD) meta-analysis aimed to 1) determine prognostic factors associated with seizure-freedom postoperatively and 2) factors associated with postoperative complications.

Methods

This study was a PRISMA-compliant systematic review and IPD meta-analysis involving studies relating to the surgical treatment of post-stroke epilepsy. An IPD meta-analysis was conducted using mixed-effects, multivariable logistic regression models to identify predictors of seizure freedom (Engels class I or International League Against Epilepsy [ILAE] class 1 or 2) and postoperative complications.

Results

A total of 11 studies provided patient-level data for our IPD meta-analysis. Our results demonstrated that etiology of cerebrovascular insult, specifically ischemic or hemorrhagic stroke when compared to ulegyria, was significantly and independently associated with higher odds of postoperative seizure-freedom (OR=10.21, p = 0.031). Further, patients with a greater number of years between epilepsy onset and surgical treatment were significantly less likely to experience seizure-freedom postoperatively (OR=0.93, p = 0.023). Patients with ischemic or hemorrhagic strokes were significantly less likely to experience a postoperative complication relative to patients with ulegyria in univariate analysis (OR=0.053, p = 0.015), and this association remained significant in multivariable analysis (OR=0.16, p = 0.035).

Conclusion

Our findings synthesize the existing literature on the surgical treatment of stroke-related epilepsy and establish important prognostic factors for seizure-freedom in this patient population. We hope our results are useful in guiding future research efforts and further optimizing postoperative outcomes.

背景：虽然继发于血管损伤的癫痫是一种有充分文献记载的耐药癫痫的病因，需要手术干预以获得最佳治疗，但在这类患者群体中，术后癫痫发作自由的预后因素尚未确定。这项个体患者数据（IPD）荟萃分析旨在1)确定与术后癫痫发作自由相关的预后因素和2)与术后并发症相关的因素。方法：本研究是一项符合prisma标准的系统评价和IPD荟萃分析，涉及与卒中后癫痫手术治疗相关的研究。采用混合效应、多变量logistic回归模型进行IPD荟萃分析，以确定癫痫发作自由（恩格斯I级或国际抗癫痫联盟[ILAE] 1级或2级）和术后并发症的预测因素。结果：共有11项研究为我们的IPD荟萃分析提供了患者水平的数据。我们的研究结果表明，与尿失禁相比，脑血管损伤的病因学，特别是缺血性或出血性中风，与术后癫痫自由发作的几率较高有显著且独立的相关性（or =10.21, p = 0.031）。此外，癫痫发作和手术治疗之间的时间间隔较长的患者术后癫痫发作自由的可能性显着降低（OR=0.93, p = 0.023）。在单因素分析中，缺血性或出血性卒中患者发生术后并发症的可能性明显低于尿路患者（or =0.053, p = 0.015），在多变量分析中，这种相关性仍然显著（or =0.16, p = 0.035）。结论：我们的研究结果综合了卒中相关癫痫手术治疗的现有文献，并确定了卒中相关癫痫患者癫痫发作自由的重要预后因素。我们希望我们的结果对指导未来的研究工作和进一步优化术后结果有用。

{"title":"Surgery for epilepsy secondary to vascular insults: A systematic review and meta-analysis of individual patient data","authors":"Adrian E. Jimenez, Neil A. Feldstein, Guy M. McKhann, E. Sander Connolly, Brett E. Youngerman","doi":"10.1016/j.eplepsyres.2025.107711","DOIUrl":"10.1016/j.eplepsyres.2025.107711","url":null,"abstract":"<div><h3>Background</h3><div>While epilepsy secondary to vascular insults represents a well-documented cause of drug-resistant epilepsy that requires surgical intervention for optimal management, the prognostic factors for postoperative seizure-freedom among this patient population have not been well-established. This individual-patient data (IPD) meta-analysis aimed to 1) determine prognostic factors associated with seizure-freedom postoperatively and 2) factors associated with postoperative complications.</div></div><div><h3>Methods</h3><div>This study was a PRISMA-compliant systematic review and IPD meta-analysis involving studies relating to the surgical treatment of post-stroke epilepsy. An IPD meta-analysis was conducted using mixed-effects, multivariable logistic regression models to identify predictors of seizure freedom (Engels class I or International League Against Epilepsy [ILAE] class 1 or 2) and postoperative complications.</div></div><div><h3>Results</h3><div>A total of 11 studies provided patient-level data for our IPD meta-analysis. Our results demonstrated that etiology of cerebrovascular insult, specifically ischemic or hemorrhagic stroke when compared to ulegyria, was significantly and independently associated with higher odds of postoperative seizure-freedom (OR=10.21, p = 0.031). Further, patients with a greater number of years between epilepsy onset and surgical treatment were significantly less likely to experience seizure-freedom postoperatively (OR=0.93, p = 0.023). Patients with ischemic or hemorrhagic strokes were significantly less likely to experience a postoperative complication relative to patients with ulegyria in univariate analysis (OR=0.053, p = 0.015), and this association remained significant in multivariable analysis (OR=0.16, p = 0.035).</div></div><div><h3>Conclusion</h3><div>Our findings synthesize the existing literature on the surgical treatment of stroke-related epilepsy and establish important prognostic factors for seizure-freedom in this patient population. We hope our results are useful in guiding future research efforts and further optimizing postoperative outcomes.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"219 ","pages":"Article 107711"},"PeriodicalIF":2.0,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145602196","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}

引用次数: 0

Hippocampal, fornix, and mammillary body atrophy in patients with mesial temporal sclerosis 内侧颞叶硬化患者的海马、穹窿和乳状体萎缩

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research

Pub Date : 2025-11-21 DOI: 10.1016/j.eplepsyres.2025.107713

Mia Mojica , Hannah Fleming , Timo Krings , Mary Pat McAndrews

This study investigates structural changes in the hippocampus, fornix, and mammillary bodies in patients with mesial temporal sclerosis (MTS), examining their relationship to clinical characteristics and association with memory performance. We conducted a retrospective study involving 104 patients with unilateral MTS and 47 age-matched healthy controls. Automatic segmentation of MRI scans was performed to calculate volumes, and atrophy was assessed relative to average values in the control group. Volume differences between patients and controls as well as associations of circuit atrophy with clinical features and memory impairment were examined. In the left MTS group, all three structures showed significantly lower normalized volumes compared to healthy controls whereas atrophy was confined to the hippocampus and fornix in the right MTS group. No significant correlations were found between atrophy and disease duration or age at seizure onset for any structure, though age at MRI was significantly correlated with hippocampal atrophy. Volume reductions in each of the circuit endpoints (hippocampus and mammillary bodies) were correlated with the degree of atrophy in the bridging white matter structure, the fornix. Lastly, comparisons between subgroups with hippocampal atrophy only versus those with greater circuit damage revealed no significant differences in memory scores, age of onset, or duration. Our findings support the view that MTS involves network-level degeneration affecting multiple memory-related structures beyond the hippocampus. Unexpectedly, no significant associations were found between atrophy and clinical or memory measures, suggesting structural damage in this portion of the Papez circuit may be of limited clinical relevance in this population.

本研究探讨了内侧颞叶硬化（MTS）患者海马、穹窿和乳状体的结构变化，研究了它们与临床特征和记忆表现的关系。我们进行了一项回顾性研究，涉及104例单侧MTS患者和47例年龄匹配的健康对照。对MRI扫描进行自动分割以计算体积，并相对于对照组的平均值评估萎缩。检查了患者和对照组之间的体积差异以及电路萎缩与临床特征和记忆障碍的关联。在左侧MTS组中，与健康对照组相比，所有三个结构的标准化体积都显着降低，而在右侧MTS组中，萎缩仅限于海马和穹窿。对于任何结构而言，萎缩与疾病持续时间或癫痫发作年龄之间均未发现显著相关性，尽管MRI年龄与海马萎缩显著相关。每个回路端点（海马和乳状体）的体积减少与桥接白质结构穹窿的萎缩程度相关。最后，比较只有海马萎缩的亚组和有更大回路损伤的亚组，发现在记忆评分、发病年龄或持续时间方面没有显著差异。我们的研究结果支持MTS涉及影响海马以外多个记忆相关结构的网络级退化的观点。出乎意料的是，在萎缩和临床或记忆测量之间没有发现显著的关联，这表明这部分Papez回路的结构损伤在该人群中可能具有有限的临床相关性。

{"title":"Hippocampal, fornix, and mammillary body atrophy in patients with mesial temporal sclerosis","authors":"Mia Mojica , Hannah Fleming , Timo Krings , Mary Pat McAndrews","doi":"10.1016/j.eplepsyres.2025.107713","DOIUrl":"10.1016/j.eplepsyres.2025.107713","url":null,"abstract":"<div><div>This study investigates structural changes in the hippocampus, fornix, and mammillary bodies in patients with mesial temporal sclerosis (MTS), examining their relationship to clinical characteristics and association with memory performance. We conducted a retrospective study involving 104 patients with unilateral MTS and 47 age-matched healthy controls. Automatic segmentation of MRI scans was performed to calculate volumes, and atrophy was assessed relative to average values in the control group. Volume differences between patients and controls as well as associations of circuit atrophy with clinical features and memory impairment were examined. In the left MTS group, all three structures showed significantly lower normalized volumes compared to healthy controls whereas atrophy was confined to the hippocampus and fornix in the right MTS group. No significant correlations were found between atrophy and disease duration or age at seizure onset for any structure, though age at MRI was significantly correlated with hippocampal atrophy. Volume reductions in each of the circuit endpoints (hippocampus and mammillary bodies) were correlated with the degree of atrophy in the bridging white matter structure, the fornix. Lastly, comparisons between subgroups with hippocampal atrophy only versus those with greater circuit damage revealed no significant differences in memory scores, age of onset, or duration. Our findings support the view that MTS involves network-level degeneration affecting multiple memory-related structures beyond the hippocampus. Unexpectedly, no significant associations were found between atrophy and clinical or memory measures, suggesting structural damage in this portion of the Papez circuit may be of limited clinical relevance in this population.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"219 ","pages":"Article 107713"},"PeriodicalIF":2.0,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145621532","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}

引用次数: 0

Long-term administration of EQU-001 (ivermectin) suppresses spasms in a rat model of infantile epileptic spasms syndrome 长期服用伊维菌素（eque -001）可抑制婴儿癫痫痉挛综合征大鼠模型中的痉挛。

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research

Pub Date : 2025-11-21 DOI: 10.1016/j.eplepsyres.2025.107712

Chian-Ru Chern , Antonia Schonwald , Kayla Vieira , Jana Velíšková , Libor Velíšek

We investigated effects of long-term and acute administration of EQU-001 (ivermectin) against NMDA-triggered spasms in immature rats prenatally exposed to betamethasone and in the model of infantile epilepsy spasms syndrome (IESS). Pregnant rats were injected with betamethasone on gestational day 15 (2 ×0.4 mg/kg, i.p.). Offspring were injected with ivermectin once daily (1–4 mg/kg, i.p.) from postnatal day (P) 10 through P15. Spasms were triggered on P15 with NMDA (17 mg/kg, i.p.). Other rats received a single dose of ivermectin (1–8 mg/kg, i.p.) on P15 prior to NMDA to test acute anticonvulsant activity. Also, a randomized model was used: The spasms were triggered on P12 and ivermectin treatment (4 mg/kg) was initiated after this bout of spasms on P12, P13 and P14, with additional spasms elicited on P13 and P15. A nicotinic cholinergic α7 agonist was used to mimic effects of ivermectin, and α7 antagonist was used together with ivermectin to prevent its effects. P10-P15 administration of 4 mg/kg of ivermectin significantly suppressed occurrence of spasms on P15, an effect comparable to that of ACTH (positive control). Conversely, an acute P15 administration of ivermectin had no effects on spasms. Ivermectin in the randomized trial suppressed occurrence of spasms as well P15/P12 ratio of spasms. Ivermectin also decreased body weight gain in those animals. None of the nicotinic cholinergic α7 drugs mimicked or prevented effects of ivermectin. Our data indicate that ivermectin may become a powerful tool in the armamentarium for treatment of IESS, however the mechanisms of this action remain to be determined.

我们在产前暴露于倍他米松的未成熟大鼠和婴儿癫痫痉挛综合征（IESS）模型中研究了长期和急性给药eque -001（伊维菌素）对nmda引发的痉挛的影响。妊娠大鼠在妊娠第15天注射倍他米松（2 ×0.4 mg/kg, i.p.）。子代从出生后第10天至第15天每天注射1次伊维菌素（1-4 mg/kg, i.p）。NMDA（17 mg/kg, i.p.）在P15上触发痉挛。其他大鼠在NMDA之前的P15给予单剂量伊维菌素（1-8 mg/kg, i.p），以测试急性抗惊厥活性。另外，采用随机模型：痉挛在P12部位触发，在P12、P13和P14部位痉挛发作后开始伊维菌素治疗（4 mg/kg）， P13和P15部位痉挛。采用烟碱类胆碱能α7激动剂模拟伊维菌素的作用，α7拮抗剂与伊维菌素联用抑制其作用。给药4 mg/kg伊维菌素可显著抑制P10-P15痉挛的发生，其效果与ACTH（阳性对照）相当。相反，急性P15给药伊维菌素对痉挛没有影响。伊维菌素在随机试验中抑制痉挛的发生以及痉挛的P15/P12比率。伊维菌素还减少了这些动物的体重增加。烟碱能α7类药物均不能模拟或阻止伊维菌素的作用。我们的数据表明，伊维菌素可能成为治疗IESS的有力工具，但这种作用的机制仍有待确定。

{"title":"Long-term administration of EQU-001 (ivermectin) suppresses spasms in a rat model of infantile epileptic spasms syndrome","authors":"Chian-Ru Chern , Antonia Schonwald , Kayla Vieira , Jana Velíšková , Libor Velíšek","doi":"10.1016/j.eplepsyres.2025.107712","DOIUrl":"10.1016/j.eplepsyres.2025.107712","url":null,"abstract":"<div><div>We investigated effects of long-term and acute administration of EQU-001 (ivermectin) against NMDA-triggered spasms in immature rats prenatally exposed to betamethasone and in the model of infantile epilepsy spasms syndrome (IESS). Pregnant rats were injected with betamethasone on gestational day 15 (2 ×0.4 mg/kg, i.p.). Offspring were injected with ivermectin once daily (1–4 mg/kg, i.p.) from postnatal day (P) 10 through P15. Spasms were triggered on P15 with NMDA (17 mg/kg, i.p.). Other rats received a single dose of ivermectin (1–8 mg/kg, i.p.) on P15 prior to NMDA to test acute anticonvulsant activity. Also, a randomized model was used: The spasms were triggered on P12 and ivermectin treatment (4 mg/kg) was initiated after this bout of spasms on P12, P13 and P14, with additional spasms elicited on P13 and P15. A nicotinic cholinergic α7 agonist was used to mimic effects of ivermectin, and α7 antagonist was used together with ivermectin to prevent its effects. P10-P15 administration of 4 mg/kg of ivermectin significantly suppressed occurrence of spasms on P15, an effect comparable to that of ACTH (positive control). Conversely, an acute P15 administration of ivermectin had no effects on spasms. Ivermectin in the randomized trial suppressed occurrence of spasms as well P15/P12 ratio of spasms. Ivermectin also decreased body weight gain in those animals. None of the nicotinic cholinergic α7 drugs mimicked or prevented effects of ivermectin. Our data indicate that ivermectin may become a powerful tool in the armamentarium for treatment of IESS, however the mechanisms of this action remain to be determined.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"219 ","pages":"Article 107712"},"PeriodicalIF":2.0,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145586504","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}

引用次数: 0

Allostatic load of immune cells in the spleen and brain of the Kcna1-null mouse model of temporal lobe epilepsy kcna1缺失小鼠颞叶癫痫模型脾和脑免疫细胞的适应负荷

IF 2 4区医学 Q3 CLINICAL NEUROLOGY

Epilepsy Research

Pub Date : 2025-11-19 DOI: 10.1016/j.eplepsyres.2025.107697

Jillian E. Hinman , Ankita Aggarwal, Amberlee Haggerty, Stephanie A. Matthews, Malavika Deodhar, Shruthi Iyer, Kristina A. Simeone, Timothy A. Simeone

Human temporal lobe epilepsy (TLE), particularly drug-resistant TLE, is associated with chronic peripheral immune activation. Here, we determined whether a similar association was detectable in a genetic mouse model of TLE with spontaneous recurrent seizures (SRS), Kcna1-null mice. Flow cytometry was used with fluorescence-activated cell sorting to determine the presence of lymphocytes, macrophages and granulocytes in isolated brain and spleen of wildtype (WT) and Kcna1-null mice. Splenic analysis revealed uniformly elevated Mac-1⁺MHC-II⁺ macrophages across all epileptic mice, whereas CD8⁺ cytotoxic T-cells increased proportionally with severe seizure frequency and burden, resulting in reduced CD4⁺/CD8⁺ ratios—an immune risk phenotype. Brain tissue showed increased infiltration of both CD4⁺ and CD8⁺ T-cells. Importantly, Kv1.1 was not expressed on T-cells of WT mice. Using an allostatic interpretative framework, our results indicate that the immune system anticipates ongoing challenges (SRS) and maintains elevated readiness with an allostatic shift towards chronic adaptation (macrophages), but in doing so potentially damaging dynamic allostatic loads (CD8⁺ T-cells) are accumulated. The Kcna1-null model provides a valuable tool for investigating epilepsy immunopathogenesis without chemoconvulsant confounds. These findings support the notion that TLE has a significant immunological component which may participate in pathology and be a target for intervention.

人类颞叶癫痫（TLE），特别是耐药TLE，与慢性外周免疫激活有关。在这里，我们确定是否在TLE与自发性复发性癫痫（SRS）的遗传小鼠模型中检测到类似的关联，kcna1缺失小鼠。采用流式细胞术和荧光活化细胞分选法检测野生型（WT）和kcna1缺失小鼠离体脑和脾脏中淋巴细胞、巨噬细胞和粒细胞的存在。脾分析显示，所有癫痫小鼠的Mac-1+MHC-II+巨噬细胞均升高，而CD8+细胞毒性t细胞随着癫痫发作频率和负担的加重而成比例增加，导致CD4+/CD8+比例降低，这是一种免疫风险表型。脑组织CD4+和CD8+ t细胞浸润均增加。重要的是，Kv1.1没有在WT小鼠的t细胞上表达。使用适应解释框架，我们的研究结果表明，免疫系统预测持续的挑战（SRS），并通过适应向慢性适应（巨噬细胞）的转变保持高准备状态，但在这样做时，潜在的破坏性动态适应负荷（CD8+ t细胞）会累积。Kcna1-null模型为研究无化学惊厥药混杂的癫痫免疫发病机制提供了一个有价值的工具。这些发现支持了这样一种观点，即TLE具有重要的免疫学成分，可能参与病理并成为干预的目标。

{"title":"Allostatic load of immune cells in the spleen and brain of the Kcna1-null mouse model of temporal lobe epilepsy","authors":"Jillian E. Hinman , Ankita Aggarwal, Amberlee Haggerty, Stephanie A. Matthews, Malavika Deodhar, Shruthi Iyer, Kristina A. Simeone, Timothy A. Simeone","doi":"10.1016/j.eplepsyres.2025.107697","DOIUrl":"10.1016/j.eplepsyres.2025.107697","url":null,"abstract":"<div><div>Human temporal lobe epilepsy (TLE), particularly drug-resistant TLE, is associated with chronic peripheral immune activation. Here, we determined whether a similar association was detectable in a genetic mouse model of TLE with spontaneous recurrent seizures (SRS), <em>Kcna1</em>-null mice. Flow cytometry was used with fluorescence-activated cell sorting to determine the presence of lymphocytes, macrophages and granulocytes in isolated brain and spleen of wildtype (WT) and <em>Kcna1</em>-null mice. Splenic analysis revealed uniformly elevated Mac-1<sup>+</sup>MHC-II<sup>+</sup> macrophages across all epileptic mice, whereas CD8<sup>+</sup> cytotoxic T-cells increased proportionally with severe seizure frequency and burden, resulting in reduced CD4<sup>+</sup>/CD8<sup>+</sup> ratios—an immune risk phenotype. Brain tissue showed increased infiltration of both CD4<sup>+</sup> and CD8<sup>+</sup> T-cells. Importantly, Kv1.1 was not expressed on T-cells of WT mice. Using an allostatic interpretative framework, our results indicate that the immune system anticipates ongoing challenges (SRS) and maintains elevated readiness with an allostatic shift towards chronic adaptation (macrophages), but in doing so potentially damaging dynamic allostatic loads (CD8<sup>+</sup> T-cells) are accumulated. The <em>Kcna1</em>-null model provides a valuable tool for investigating epilepsy immunopathogenesis without chemoconvulsant confounds. These findings support the notion that TLE has a significant immunological component which may participate in pathology and be a target for intervention.</div></div>","PeriodicalId":11914,"journal":{"name":"Epilepsy Research","volume":"219 ","pages":"Article 107697"},"PeriodicalIF":2.0,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145577658","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}

引用次数: 0