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WONOEP appraisal: Targeted therapy development for early onset epilepsies. WONOEP 评估:针对早发性癫痫的靶向疗法开发。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-01 Epub Date: 2024-11-19 DOI: 10.1111/epi.18187
Pablo M Casillas-Espinosa, Jennifer C Wong, Wanda Grabon, Ana Gonzalez-Ramos, Massimo Mantegazza, Nihan Carcak Yilmaz, Manisha Patel, Kevin Staley, Raman Sankar, Terence J O'Brien, Özlem Akman, Ganna Balagura, Adam L Numis, Jeffrey L Noebels, Stéphanie Baulac, Stéphane Auvin, David C Henshall, Aristea S Galanopoulou

The early onset epilepsies encompass a heterogeneous group of disorders, some of which result in drug-resistant seizures, developmental delay, psychiatric comorbidities, and sudden death. Advancement in the widespread use of targeted gene panels as well as genome and exome sequencing has facilitated the identification of different causative genes in a subset of these patients. The ability to recognize the genetic basis of early onset epilepsies continues to improve, with de novo coding variants accounting for most of the genetic etiologies identified. Although current disease-specific and disease-modifying therapies remain limited, novel precision medicine approaches, such as small molecules, cell therapy, and other forms of genetic therapies for early onset epilepsies, have created excitement among researchers, clinicians, and caregivers. Here, we summarize the main findings of presentations and discussions on novel therapeutic strategies for targeted treatment of early onset epilepsies that occurred during the Workshop on Neurobiology of Epilepsy (WONOEP XVI, Talloires, France, July 2022). The presentations discussed the use of chloride transporter inhibitors for neonatal seizures, targeting orexinergic signaling for childhood absence epilepsy, targeting energy metabolism in Dravet syndrome, and the role of cannabinoid receptor type 2, reversible acetylcholinesterase inhibitors, cell therapies, and RNA-based therapies in early life epilepsies.

早发性癫痫包括一组异质性疾病,其中一些会导致耐药性癫痫发作、发育迟缓、精神并发症和猝死。随着靶向基因组以及基因组和外显子组测序技术的广泛应用,在这些患者中发现不同致病基因的工作取得了进展。识别早发性癫痫遗传基础的能力不断提高,新编码变异占已发现遗传病因的大多数。尽管目前针对特定疾病和改变疾病的疗法仍然有限,但小分子、细胞疗法和其他形式的早发性癫痫基因疗法等新型精准医疗方法在研究人员、临床医生和护理人员中引起了热烈反响。在此,我们总结了癫痫神经生物学研讨会(WONOEP XVI,法国塔卢瓦,2022 年 7 月)期间关于早发性癫痫靶向治疗的新型治疗策略的演讲和讨论的主要结果。发言讨论了氯化物转运体抑制剂在新生儿癫痫发作中的应用、针对儿童失神癫痫的奥曲肽能信号转导、针对Dravet综合征的能量代谢,以及大麻素受体2型、可逆性乙酰胆碱酯酶抑制剂、细胞疗法和基于RNA的疗法在早发性癫痫中的作用。
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引用次数: 0
Development of individualized risk assessment models for predicting post-traumatic epilepsy 1 and 2 years after moderate-to-severe traumatic brain injury: A traumatic brain injury model system study. 发展个体化风险评估模型预测创伤后癫痫后1和2年中度至重度创伤性脑损伤:创伤性脑损伤模型系统研究。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-01 Epub Date: 2024-12-10 DOI: 10.1111/epi.18210
Nabil Awan, Raj G Kumar, Shannon B Juengst, Dominic DiSanto, Cynthia Harrison-Felix, Kristen Dams-O'Connor, Mary Jo Pugh, Ross D Zafonte, William C Walker, Jerzy P Szaflarski, Robert T Krafty, Amy K Wagner

Objective: Although traumatic brain injury (TBI) and post-traumatic epilepsy (PTE) are common, there are no prospective models quantifying individual epilepsy risk after moderate-to-severe TBI (msTBI). We generated parsimonious prediction models to quantify individual epilepsy risk between acute inpatient rehabilitation for individuals 2 years after msTBI.

Methods: We used data from 6089 prospectively enrolled participants (≥16 years) in the TBI Model Systems National Database. Of these, 4126 individuals had complete seizure data collected over a 2-year period post-injury. We performed a case-complete analysis to generate multiple prediction models using least absolute shrinkage and selection operator logistic regression. Baseline predictors were used to assess 2-year seizure risk (Model 1). Then a 2-year seizure risk was assessed excluding the acute care variables (Model 2). In addition, we generated prognostic models predicting new/recurrent seizures during Year 2 post-msTBI (Model 3) and predicting new seizures only during Year 2 (Model 4). We assessed model sensitivity when keeping specificity ≥.60, area under the receiver-operating characteristic curve (AUROC), and AUROC model performance through 5-fold cross-validation (CV).

Results: Model 1 (73.8% men, 44.1 ± 19.7 years, 76.1% moderate TBI) had a model sensitivity = 76.00% and average AUROC = .73 ± .02 in 5-fold CV. Model 2 had a model sensitivity = 72.16% and average AUROC = .70 ± .02 in 5-fold CV. Model 3 had a sensitivity = 86.63% and average AUROC = .84 ± .03 in 5-fold CV. Model 4 had a sensitivity = 73.68% and average AUROC = .67 ± .03 in 5-fold CV. Cranial surgeries, acute care seizures, intracranial fragments, and traumatic hemorrhages were consistent predictors across all models. Demographic and mental health variables contributed to some models. Simulated, clinical examples model individual PTE predictions.

Significance: Using information available, acute-care, and year-1 post-injury data, parsimonious quantitative epilepsy prediction models following msTBI may facilitate timely evidence-based PTE prognostication within a 2-year period. We developed interactive web-based tools for testing prediction model external validity among independent cohorts. Individualized PTE risk may inform clinical trial development/design and clinical decision support tools for this population.

目的:尽管创伤性脑损伤(TBI)和创伤后癫痫(PTE)很常见,但目前还没有量化中重度TBI (msTBI)后个体癫痫风险的前瞻性模型。我们建立了简洁的预测模型来量化msTBI后2年急性住院康复患者之间的个体癫痫风险。方法:我们使用TBI模型系统国家数据库中6089名前瞻性入组参与者(≥16岁)的数据。其中,4126人在受伤后2年内收集了完整的癫痫发作数据。我们使用最小绝对收缩和选择算子逻辑回归进行了案例完整分析,以生成多个预测模型。使用基线预测因子评估2年癫痫发作风险(模型1)。然后评估排除急性护理变量的2年癫痫发作风险(模型2)。此外,我们建立了预测mstbi后第2年新发作/复发发作的预后模型(模型3),并仅预测第2年新发作(模型4)。我们在保持特异性≥时评估模型敏感性。60、受试者工作特征曲线下面积(AUROC),并通过5倍交叉验证(CV)验证AUROC模型的性能。结果:模型1(73.8%男性,44.1±19.7岁,76.1%中度TBI)的模型敏感性= 76.00%,平均AUROC = 0.73±。5倍CV中的02。模型2的模型灵敏度为72.16%,平均AUROC为0.70±。5倍CV中的02。模型3的灵敏度为86.63%,平均AUROC为0.84±。5倍CV中的03。模型4的灵敏度为73.68%,平均AUROC为0.67±。5倍CV中的03。颅内手术、急性发作、颅内碎片和创伤性出血是所有模型一致的预测因子。人口和心理健康变量对某些模型有影响。模拟的,临床的例子模拟个人PTE预测。意义:利用现有信息、急性护理和损伤后1年的数据,简化msTBI后癫痫定量预测模型可以促进2年内及时的基于证据的PTE预测。我们开发了交互式的基于网络的工具,用于在独立队列中测试预测模型的外部有效性。个体化PTE风险可以为该人群的临床试验开发/设计和临床决策支持工具提供信息。
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引用次数: 0
Efficacy and safety of perampanel in patients with seizures associated with Lennox-Gastaut syndrome: A randomized trial. 佩潘奈尔对伴有伦诺克斯-加斯豪特综合征的癫痫发作患者的疗效和安全性:随机试验
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-01 Epub Date: 2024-11-22 DOI: 10.1111/epi.18193
David G Vossler, Brenda E Porter, Ryutaro Kira, Jeehun Lee, Alec Aeby, Anna Patten, Jocelyn Y Cheng, Leock Y Ngo

Objectives: The Phase 3 Study 338 (NCT02834793) assessed long-term clinical outcomes of adjunctive perampanel in patients ≥2 years of age with uncontrolled seizures associated with Lennox-Gastaut syndrome (LGS).

Methods: Eligible patients were diagnosed with LGS and receiving one to four concomitant antiseizure medications with an average of two or more drop seizures/week during baseline. The study comprised an 18-week double-blind, randomized, placebo-controlled Core Study and ≥52-week open-label Extension. The primary endpoint was median percent change in drop seizure frequency per 28 days during the Core Study. Key secondary endpoints included responder rates, seizure-freedom rates, and safety outcomes. Post hoc analyses were performed encompassing a broader range of drop seizures or all countable motor seizures.

Results: Seventy patients were randomized into the Core Study (perampanel, n = 34; placebo, n = 36), and 58 entered the Extension. In the Core Study, numerically greater median percent reductions in drop seizure frequency were observed with perampanel (23.1%) vs placebo (4.5%) using prespecified assessments (p = .107), whereas significantly greater reductions were detected using the broader definition (48.6% vs -.7%, respectively, p = .001) or all countable motor seizures (44.0% vs -.6%, respectively, p = .017). The 50% responder rate for drop seizures was higher with perampanel vs placebo using modern definitions. Reductions in seizure frequency with perampanel were maintained over 52 weeks. Treatment-emergent adverse events occurred in 85.3% of perampanel-treated patients (somnolence [23.5%] was the most frequent) and 72.2% of placebo-treated patients.

Significance: This study had a reduced sample size and was underpowered. Although the difference in reductions in drop seizure frequency between treatments was not statistically significant by prespecified assessments, adjunctive perampanel demonstrated sustained efficacy in reducing drop seizures associated with LGS for ≤71 weeks using modern definitions. No new safety signals emerged. These observations suggest the long-term efficacy and safety of perampanel in the LGS population.

研究目的338期研究(NCT02834793)评估了对年龄≥2岁、与伦诺克斯-加斯豪特综合征(LGS)相关的癫痫发作未得到控制的患者辅助使用perampanel的长期临床效果:符合条件的患者均被确诊为 LGS,同时接受一至四种抗癫痫药物治疗,基线期间平均每周有两次或两次以上的癫痫发作。研究包括为期18周的双盲、随机、安慰剂对照核心研究和≥52周的开放标签扩展研究。主要终点是核心研究期间每 28 天滴注发作频率变化的中位百分数。主要次要终点包括应答率、无癫痫发作率和安全性结果。事后分析包括更广泛的跌伤发作或所有可计数的运动性发作:70名患者被随机选入核心研究(培南帕尼,34人;安慰剂,36人),58人进入扩展研究。在核心研究中,采用预先指定的评估方法,观察到普仑帕尼(23.1%)与安慰剂(4.5%)相比,滴注发作频率减少的中位数百分比更大(p = .107),而采用更广泛的定义(分别为 48.6% 与 -.7%,p = .001)或所有可计数的运动性发作(分别为 44.0% 与 -.6%,p = .017),观察到的减少幅度明显更大。根据现代定义,使用培南帕奈与安慰剂相比,滴注发作的50%应答率更高。使用培南帕尼降低癫痫发作频率的效果可维持52周。在接受培南帕尼治疗的患者中,85.3%出现了治疗突发不良事件(最常见的是嗜睡[23.5%]),而在接受安慰剂治疗的患者中,72.2%出现了治疗突发不良事件:这项研究的样本量较少,研究力量不足。尽管通过预先指定的评估,不同治疗方法在减少跌落性癫痫发作频率方面的差异不具有统计学意义,但根据现代定义,在减少与LGS相关的跌落性癫痫发作方面,辅助用药perampanel显示出持续疗效,且疗程不超过71周。没有出现新的安全性信号。这些观察结果表明,perampanel在LGS人群中具有长期疗效和安全性。
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引用次数: 0
A single-center learning curve for stereotactic laser amygdalohippocampotomy and a surgical framework to manage failures. 立体定向激光杏仁枕切断术的单中心学习曲线和处理失败的手术框架。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-01 Epub Date: 2024-12-20 DOI: 10.1111/epi.18188
Ashley L B Raghu, Jonathan Lau, Matthew A Stern, Razan R Faraj, Faical Isbaine, Dayton Grogan, Katie Bullinger, Rebecca W Roth, Adam S Dickey, Jon T Willie, Daniel L Drane, Robert E Gross

Objective: Stereotactic laser amygdalohippocampotomy (SLAH) is a minimally invasive procedure for mesial temporal lobe epilepsy that preserves more tissue than open procedures. As a result, although patients have better functional outcomes, more patients do not achieve seizure freedom. The rate at which this occurs is evolving with improved surgical practices. However, the risks and benefits of further surgical management for these patients remains a question with limited data to guide decision-making.

Methods: We retrospectively reviewed a continuous series (2011-2019) of SLAH operations at our institution to determine trends in surgical management, identifying cases where further surgery was performed. Pre-operative and follow-up seizure, cognitive, and functional data, and surgical complications were collated.

Results: Of 108 patients undergoing primary SLAH, 21 (19%) underwent further surgery (23 procedures). Stereo-electroencephalography (SEEG) informed seven procedures (30%). There was a trend for quicker SLAH failure in the earlier patients. Similarly, surgical chronology was associated with progression to repeat surgery (p = .007). At 1-year follow-up, 6 of 13 patients (46%) achieved seizure freedom after repeat SLAH and 5 of 8 patients (63%) achieved seizure freedom after anterior temporal lobectomy (ATL), one of whom had failed two SLAHs. Two of three patients undergoing an ablation outside the mesial temporal lobe achieved seizure freedom at 1 year. Neuropsychological sequelae were more prevalent with ATL than SLAH, including decline in visual naming (p = .01) and functional status (p = .007).

Significance: Repeat SLAH and ATL post-SLAH are both practicable and can be effective. Surgical experience, risk to cognition, and marginal benefit relative to existing improvement are principal considerations for further surgery.

目的:立体定向激光扁桃体海马切开术(SLAH)是一种微创治疗内侧颞叶癫痫的手术,比开放手术保留更多的组织。因此,尽管患者有更好的功能结果,但更多的患者不能实现癫痫发作自由。这种情况发生的速度随着外科手术的改进而不断发展。然而,这些患者进一步手术治疗的风险和益处仍然是一个问题,指导决策的数据有限。方法:回顾性分析我院2011-2019年连续进行的SLAH手术,以确定手术管理的趋势,确定进一步手术的病例。对术前和随访的癫痫发作、认知和功能数据以及手术并发症进行整理。结果:在108例原发性SLAH患者中,21例(19%)接受了进一步的手术(23次手术)。立体脑电图(SEEG)为7例手术提供了信息(30%)。早期患者有更快的SLAH衰竭的趋势。同样,手术年表与再次手术的进展相关(p = .007)。在1年的随访中,13例患者中有6例(46%)在重复SLAH后癫痫发作自由,8例患者中有5例(63%)在前颞叶切除术(ATL)后癫痫发作自由,其中1例两次SLAH失败。三名接受内侧颞叶外消融术的患者中有两名在一年内实现了癫痫发作的自由。与SLAH相比,ATL的神经心理后遗症更为普遍,包括视觉识别能力下降(p = 0.01)和功能状态下降(p = 0.007)。意义:重复slh和slh后ATL都是可行且有效的。手术经验、认知风险和相对于现有改善的边际效益是进一步手术的主要考虑因素。
{"title":"A single-center learning curve for stereotactic laser amygdalohippocampotomy and a surgical framework to manage failures.","authors":"Ashley L B Raghu, Jonathan Lau, Matthew A Stern, Razan R Faraj, Faical Isbaine, Dayton Grogan, Katie Bullinger, Rebecca W Roth, Adam S Dickey, Jon T Willie, Daniel L Drane, Robert E Gross","doi":"10.1111/epi.18188","DOIUrl":"10.1111/epi.18188","url":null,"abstract":"<p><strong>Objective: </strong>Stereotactic laser amygdalohippocampotomy (SLAH) is a minimally invasive procedure for mesial temporal lobe epilepsy that preserves more tissue than open procedures. As a result, although patients have better functional outcomes, more patients do not achieve seizure freedom. The rate at which this occurs is evolving with improved surgical practices. However, the risks and benefits of further surgical management for these patients remains a question with limited data to guide decision-making.</p><p><strong>Methods: </strong>We retrospectively reviewed a continuous series (2011-2019) of SLAH operations at our institution to determine trends in surgical management, identifying cases where further surgery was performed. Pre-operative and follow-up seizure, cognitive, and functional data, and surgical complications were collated.</p><p><strong>Results: </strong>Of 108 patients undergoing primary SLAH, 21 (19%) underwent further surgery (23 procedures). Stereo-electroencephalography (SEEG) informed seven procedures (30%). There was a trend for quicker SLAH failure in the earlier patients. Similarly, surgical chronology was associated with progression to repeat surgery (p = .007). At 1-year follow-up, 6 of 13 patients (46%) achieved seizure freedom after repeat SLAH and 5 of 8 patients (63%) achieved seizure freedom after anterior temporal lobectomy (ATL), one of whom had failed two SLAHs. Two of three patients undergoing an ablation outside the mesial temporal lobe achieved seizure freedom at 1 year. Neuropsychological sequelae were more prevalent with ATL than SLAH, including decline in visual naming (p = .01) and functional status (p = .007).</p><p><strong>Significance: </strong>Repeat SLAH and ATL post-SLAH are both practicable and can be effective. Surgical experience, risk to cognition, and marginal benefit relative to existing improvement are principal considerations for further surgery.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":"458-470"},"PeriodicalIF":6.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Discovering EEG biomarkers of Lennox-Gastaut syndrome through unsupervised time-frequency analysis. 通过无监督时频分析发现lenox - gastaut综合征的脑电图生物标志物。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-01 Epub Date: 2024-12-12 DOI: 10.1111/epi.18211
Derek K Hu, Marco A Pinto-Orellana, Mandeep Rana, Linda Do, David J Adams, Shaun A Hussain, Daniel W Shrey, Beth A Lopour

Objective: The discovery and validation of electroencephalography (EEG) biomarkers often rely on visual identification of waveforms. However, bias toward visually striking events restricts the search space for new biomarkers, and low interrater reliability can limit rigorous validation. We present a data-driven approach to biomarker discovery called scalp EEG Pattern Identification and Categorization (s-EPIC), which enables automated, unsupervised identification of EEG waveforms. S-EPIC is validated on Lennox-Gastaut syndrome (LGS), an epilepsy that is difficult to diagnose and assess due to its variable presentation and insidious evolution of symptoms.

Methods: We retrospectively collected 10-min scalp EEG clips during non-rapid eye movement (NREM) sleep from 20 subjects with LGS and 20 approximately age-matched healthy controls. For s-EPIC, EEG events of interest (EOIs) were detected in all subjects using time-frequency analysis. The 11 705 EOIs were characterized based on 11 features and were collectively grouped using both k-means clustering and feature categorization. To provide clinical context, 1350 EOIs were visually reviewed and classified by three epileptologists.

Results: s-EPIC identified four clusters as candidate biomarkers of LGS, each having significantly more LGS EOIs than control EOIs. Two clusters contained EOIs resembling known LGS biomarkers such as interictal epileptiform discharges and generalized paroxysmal fast activity. The other two LGS-associated EEG clusters contained short bursts of power in beta and gamma frequency bands that were primarily unrecognized by epileptologists. This approach also uncovered significant differences in sleep spindles between LGS and control cohorts.

Significance: s-EPIC provides a quantitative approach to waveform identification that could be broadly applied to EEG from both healthy subjects and those with suspected pathology. s-EPIC can objectively identify and characterize relevant EEG waveforms without visual review or assumptions about the waveform's morphology and could therefore be a powerful tool for the discovery and refinement of EEG biomarkers.

目的:脑电图(EEG)生物标志物的发现和验证往往依赖于对波形的视觉识别。然而,对视觉上引人注目的事件的偏见限制了对新生物标志物的搜索空间,并且低互解释器可靠性会限制严格的验证。我们提出了一种数据驱动的生物标志物发现方法,称为头皮EEG模式识别和分类(s-EPIC),它可以自动、无监督地识别EEG波形。S-EPIC在lenox - gastaut综合征(LGS)上得到了验证,LGS是一种由于其多变的表现和潜伏的症状演变而难以诊断和评估的癫痫。方法:我们回顾性地收集了20名LGS患者和20名年龄相近的健康对照者在非快速眼动(NREM)睡眠期间10分钟的头皮脑电图片段。对于s-EPIC,采用时频分析检测所有受试者的感兴趣EEG事件(EOIs)。基于11个特征对11 705个eoi进行了特征表征,并采用k-means聚类和特征分类对其进行了分组。为了提供临床资料,三位癫痫学家对1350例eoi进行了视觉评估和分类。结果:s-EPIC鉴定出4个LGS候选生物标志物簇,每个簇的LGS eoi明显多于对照eoi。两个集群包含类似于已知LGS生物标志物的eoi,如癫痫样间期放电和全局性发作性快速活动。另外两个与lgs相关的脑电图簇包含在β和γ频段的短脉冲,这主要是癫痫学家无法识别的。这种方法还揭示了LGS组和对照组之间睡眠纺锤波的显著差异。意义:s-EPIC提供了一种定量的波形识别方法,可广泛应用于健康受试者和疑似病理受试者的脑电图。s-EPIC可以客观地识别和表征相关的脑电图波形,而无需视觉回顾或对波形形态的假设,因此可以成为发现和改进脑电图生物标志物的有力工具。
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引用次数: 0
Effectiveness of sodium channel blockers in treating neonatal seizures due to arterial ischemic stroke. 钠通道阻滞剂治疗动脉缺血性中风引起的新生儿惊厥的疗效。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-01 Epub Date: 2024-11-23 DOI: 10.1111/epi.18194
Veronica Pegoraro, Renaud Viellevoye, Geneviève Malfilatre, Robertino Dilena, Jacopo Proietti, Isabella Mauro, Cecilia Zardini, Mark Dzietko, Laure Lacan, Beatrice Desnous, Duccio Maria Cordelli, Francesca Campi, Monica Reis Da Silva, Monica Fumagalli, Sylvie Nguyen The Tich, Ursula Felderhoff-Müser, Giulia Ventura, Stefano Sartori, Manon Benders, Carla Pittini, Maria Elena Cavicchiolo, Mathieu Milh, Gaetano Cantalupo, Aline van Maanen, Maria Luisa Tataranno, Maria Roberta Cilio

Objective: Few studies have evaluated the efficacy of antiseizure medications (ASMs) according to the etiology of neonatal acute provoked seizures. We aimed to investigate the response to ASMs in term/near term neonates with acute arterial ischemic stroke (AIS), as well as the type of seizure at presentation and the monitoring approach.

Methods: We retrospectively evaluated neonates from 15 European level IV neonatal intensive care units who presented with seizures due to AIS and were monitored by continuous electroencephalography (cEEG) and/or amplitude-integrated EEG (aEEG) in whom actual recordings, timing, doses, and response to ASMs were available for review.

Results: One hundred seven neonates were referred, and 88 were included. Of those, 56 met the criteria for evaluating the treatment response. The mean time to treatment was 7.9 h (SD = 16.4), and the most frequently administered first-line ASM was phenobarbital (PB; 74/88, 84.1%). Seizures were controlled within 24 h from onset of symptoms in 64.3% (36/56) of neonates. Phenytoin (PHT) was effective in almost all neonates in whom it was trialed (24/25, 96.0%), whereas PB was effective in only 22.0% of patients (11/50). Infants treated with PB or PHT as first-line treatment (53/56, 94.6%) showed a higher response rate with PHT (6/6, 100.0%) than with PB (11/47, 23.4%). Monitoring approach and seizure types were evaluated in 88 infants. Forty-six of 88 (52.3%) were monitored with cEEG and 47.7% (42/88) with aEEG, with or without intermittent cEEG. The mean monitoring duration was 65.8 h (SD = 39.21). In 83 of 88 (94.3%) infants, the type of seizure suspected clinically prior to monitoring was confirmed afterward. Unilateral focal clonic seizures were seen in 71 of 88 infants (80.7%), whereas 11 of 88 (12.5%) presented with ictal apneas.

Significance: Our findings provide evidence in a large, homogenous cohort that PHT is more effective than PB in treating neonatal acute symptomatic seizures due to AIS.

目的:很少有研究根据新生儿急性诱发癫痫发作的病因评估抗癫痫药物(ASM)的疗效。我们旨在研究急性动脉缺血性卒中(AIS)的足月/近足月新生儿对抗癫痫药物的反应,以及发作类型和监测方法:我们回顾性评估了来自 15 个欧洲 IV 级新生儿重症监护病房的新生儿,这些新生儿因 AIS 而出现癫痫发作,并接受连续脑电图(cEEG)和/或振幅积分脑电图(aEEG)监测,其实际记录、时间、剂量和对 ASMs 的反应可供回顾:结果:共转诊了 107 名新生儿,纳入了 88 名。结果:共转诊了 107 名新生儿,纳入了 88 名,其中 56 名符合治疗反应评估标准。平均治疗时间为 7.9 小时(SD = 16.4),最常用的一线 ASM 是苯巴比妥(PB;74/88,84.1%)。64.3%的新生儿(36/56)在发病后24小时内控制住了癫痫发作。苯妥英(PHT)几乎对所有试用过的新生儿都有效(24/25,96.0%),而 PB 仅对 22.0% 的患者有效(11/50)。将 PB 或 PHT 作为一线治疗的婴儿(53/56,94.6%)显示,PHT 的反应率(6/6,100.0%)高于 PB(11/47,23.4%)。对 88 名婴儿的监测方法和癫痫发作类型进行了评估。88 名婴儿中有 46 名(52.3%)接受了 cEEG 监测,47.7%(42/88)接受了 aEEG 监测,包括或不包括间歇性 cEEG 监测。平均监测时间为 65.8 小时(SD = 39.21)。88 名婴儿中有 83 名(94.3%)在监测前临床上怀疑的癫痫发作类型在监测后得到了证实。88 名婴儿中有 71 名(80.7%)出现单侧局灶性阵挛发作,88 名婴儿中有 11 名(12.5%)出现发作性呼吸暂停:我们的研究结果在一个大型同质群组中提供了证据,证明 PHT 在治疗 AIS 引起的新生儿急性症状性癫痫发作方面比 PB 更有效。
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引用次数: 0
Epilepsy surgery education and practice around the globe: An ILAE taskforce report. 全球癫痫外科教育和实践:ILAE特别工作组报告。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-01 Epub Date: 2024-12-05 DOI: 10.1111/epi.18199
Johannes M Nico Enslin, Carrie R Muh, Xiongfei Wang, Tatiana von Hertwig Fernandes de Olivera, Guy M McKhann, Eyiyemisi Damisah, Faisal Al-Otaibi, Bertil Rydenhag, Rushna P Ali, Christian Dorfer, Dario J Englot, Arthur Cukiert

Up to 80% of the world's population with epilepsy lives in low and middle-income countries. Around one-third of these patients will have drug-resistant epilepsy, for which epilepsy surgery is an option. Unfortunately, many of these regions, as well as some more developed nations, lack sufficient epilepsy surgery units and trained neurosurgeons. With this in mind, the International League Against Epilepsy (ILAE) formed the Epilepsy Surgery Education Taskforce to address the shortage of further educational opportunities for surgeons and neurologists and to promote the creation of more epilepsy surgery units around the world. In this article, we publish our findings from a web-based international survey, in which we investigated the global distribution and experience of neurosurgeons who perform epilepsy surgery, their educational paths, and opinions on the further need for epilepsy surgery education, as well as the resources available to them. We report a detailed analysis of the 202 survey replies received from 35 different countries across six continents. The lack of adequate numbers of epilepsy surgery units in the Southern Hemisphere is notable, and the aim of this task force with other ILAE committees, is to improve access to epilepsy surgery for patients and to enhance training for their health care providers.

高达80%的世界癫痫患者生活在低收入和中等收入国家。这些患者中约有三分之一将患有耐药性癫痫,癫痫手术是一种选择。不幸的是,许多这些地区以及一些较发达的国家缺乏足够的癫痫手术单位和训练有素的神经外科医生。考虑到这一点,国际抗癫痫联盟(ILAE)成立了癫痫外科教育工作组,以解决外科医生和神经科医生进一步教育机会的短缺问题,并促进在世界各地建立更多的癫痫外科单位。在这篇文章中,我们发表了一项基于网络的国际调查的结果,在该调查中,我们调查了从事癫痫手术的神经外科医生的全球分布和经验,他们的教育途径,对进一步需要癫痫外科教育的意见,以及他们可用的资源。我们报告了对来自六大洲35个不同国家的202份调查回复的详细分析。值得注意的是,南半球缺乏足够数量的癫痫手术单位,该工作队与国际癫痫学会其他委员会的目的是改善患者接受癫痫手术的机会,并加强对其保健提供者的培训。
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引用次数: 0
Vigabatrin-associated brain magnetic resonance imaging abnormalities and clinical symptoms in infants with tuberous sclerosis complex. 结节性硬化症患儿维加巴林相关脑磁共振成像异常及临床症状
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-01 Epub Date: 2024-12-06 DOI: 10.1111/epi.18190
Carmen Stevering, Maarten Lequin, Kinga Szczepaniak, Krzysztof Sadowski, Saba Ishrat, Alberto De Luca, Alexander Leemans, Willem Otte, David J Kwiatkowski, Paolo Curatolo, Bernhard Weschke, Kate Riney, Martha Feucht, Pavel Krsek, Rima Nabbout, Anna Jansen, Konrad Wojdan, Kamil Sijko, Jagoda Glowacka-Walas, Julita Borkowska, Dorota Domanska-Pakiela, Romina Moavero, Christoph Hertzberg, Hanna Hulshof, Theresa Scholl, Bořivoj Petrák, Miroslav Maminak, Eleonora Aronica, Jessie De Ridder, Lieven Lagae, Sergiusz Jozwiak, Katarzyna Kotulska, Kees Braun, Floor Jansen

Objective: Previous retrospective studies have reported vigabatrin-associated brain abnormalities on magnetic resonance imaging (VABAM), although clinical impact is unknown. We evaluated the association between vigabatrin and predefined brain magnetic resonance imaging (MRI) changes in a large homogenous tuberous sclerosis complex (TSC) cohort and assessed to what extent VABAM-related symptoms were reported in TSC infants.

Methods: The Dutch TSC Registry and the EPISTOP cohort provided retrospective and prospective data from 80 TSC patients treated with vigabatrin (VGB) before the age of 2 years and 23 TSC patients without VGB. Twenty-nine age-matched non-TSC epilepsy patients not receiving VGB were included as controls. VABAM, specified as T2/fluid-attenuated inversion recovery hyperintensity or diffusion restriction in predefined brain areas, were examined on brain MRI before, during, and after VGB, and once in the controls (at approximately age 2 years). Additionally, the presence of VABAM accompanying symptoms was evaluated.

Results: Prevalence of VABAM in VGB-treated TSC patients was 35.5%. VABAM-like abnormalities were observed in 13.5% of all patients without VGB. VGB was significantly associated with VABAM (risk ratio [RR] = 3.57, 95% confidence interval [CI] = 1.43-6.39), whereas TSC and refractory epilepsy were not. In all 13 VGB-treated patients with VABAM for whom posttreatment MRIs were available, VABAM entirely resolved after VGB discontinuation. The prevalence of symptoms was 11.7% in patients with VABAM or VABAM-like MRI abnormalities and 4.3% in those without, implicating no significant association (RR = 2.76, 95% CI = .68-8.77).

Significance: VABAM are common in VGB-treated TSC infants; however, VABAM-like abnormalities also occurred in children without either VGB or TSC. The cause of these MRI changes is unknown. Possible contributing factors are abnormal myelination, underlying etiology, recurrent seizures, and other antiseizure medication. Furthermore, the presence of VABAM (or VABAM-like abnormalities) did not appear to be associated with clinical symptoms. This study confirms that the well-known antiseizure effects of VGB outweigh the risk of VABAM and related symptoms.

目的:以前的回顾性研究已经报道了维加巴林相关的脑磁共振成像(VABAM)异常,尽管临床影响尚不清楚。在一个大型同质性结节性硬化症(TSC)队列中,我们评估了vigabatrin与预先确定的脑磁共振成像(MRI)变化之间的关系,并评估了TSC婴儿中vabam相关症状的报告程度。方法:荷兰TSC登记处和EPISTOP队列提供了80例2岁前接受维加巴林(VGB)治疗的TSC患者和23例未接受VGB治疗的TSC患者的回顾性和前瞻性数据。29例未接受VGB治疗的年龄匹配的非tsc癫痫患者作为对照。VABAM,指定为T2/流体衰减反转恢复高强度或预定义脑区域的扩散限制,在VGB之前,期间和之后进行脑MRI检查,并在对照组(大约2岁)进行一次检查。此外,还评估了伴有症状的VABAM的存在。结果:vgb治疗的TSC患者中VABAM的患病率为35.5%。在所有无VGB的患者中,13.5%观察到vabam样异常。VGB与VABAM有显著相关性(风险比[RR] = 3.57, 95%可信区间[CI] = 1.43-6.39),而TSC和难治性癫痫无显著相关性。在所有13例VGB治疗的VABAM患者中,治疗后mri可用,VABAM在VGB停药后完全消退。有VABAM或VABAM样MRI异常的患者出现症状的比例为11.7%,无VABAM样MRI异常的患者为4.3%,无显著相关性(RR = 2.76, 95% CI = 0.68 -8.77)。意义:VABAM在vgb治疗的TSC婴儿中很常见;然而,vabam样异常也发生在没有VGB或TSC的儿童中。这些MRI变化的原因尚不清楚。可能的影响因素有异常髓鞘形成、潜在病因、复发性癫痫发作和其他抗癫痫药物。此外,VABAM(或VABAM样异常)的存在似乎与临床症状无关。本研究证实,众所周知的VGB抗癫痫作用大于VABAM和相关症状的风险。
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引用次数: 0
TSPO-PET in pre-surgical evaluations: Correlation of neuroinflammation and SEEG epileptogenicity mapping in drug-resistant focal epilepsy. 术前评价TSPO-PET:耐药局灶性癫痫的神经炎症和SEEG致痫性定位的相关性。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-01 Epub Date: 2024-12-16 DOI: 10.1111/epi.18182
Jennifer Kilmer, Sebatian Rodrigo, Ana-Maria Petrescu, Nozar Aghakhani, Anne Herbrecht, Claire Leroy, Nicolas Tournier, Michel Bottlaender, Delphine Taussig, Viviane Bouilleret

Objectives: Resective surgery in drug-resistant focal epilepsy (DRFE) requires extensive evaluation to localize the epileptogenic zone (EZ). When non-invasive phase 1 assessments (electroencephalography, EEG; magnetic resonance imaging, MRI; and 18F-Fluorodeoxyglucose-positron emission tomography, [18F]FDG-PET) are inconclusive for EZ localization, invasive investigations such as stereo-EEG (SEEG) are necessary. Epileptogenicity maps (Ems) visualize the EZ using SEEG-identified ictal high-frequency oscillations (iHFOs). PET imaging with radioligands targeting the18-kDa translocator protein (TSPO), a marker of glial activation, may aid EZ localization. This study investigates the correlation between TSPO-PET imaging and SEEG iHFOs in DRFE to determine the utility of TSPO-PET in pre-surgical assessments, especially in complex or non-lesional cases.

Methods: Patients with DRFE and inconclusive phase 1 assessments were recruited from Bicêtre Hospital (AP-HP) for a prospective study (Eudract 2017-003381-27). They underwent SEEG and [18F]DPA-714 (N,N-diethyl-2-(2-(4-(2-(fluoro-18F)ethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide) (TSPO radioligand) PET imaging. Statistical parametric mapping (SPM) techniques analyzed significant [18F]DPA-714-PET uptake (TSPO-map) and generated epileptogenicity maps (EM-map). Correlation analyses at regional and voxel-of-interest (VOI) levels assessed the relationship between TSPO-map and EM-map.

Results: We were able to obtain and analyze both maps in 12 of 17 patients recruited. A significant positive correlation between EM-map and TSPO-map in focal epilepsies was found regionally (r = .81, p < .00004) and at the VOI level (r = .79, p < .00003). Temporal, insular, parietal, and occipital regions showed particularly strong correspondence. In frontal epilepsies, TSPO-map was more focal than EM-map, suggesting increased specificity for SEEG planning. This study also demonstrated the benefit of the TSPO-map in identifying multiple foci in multifocal epilepsies, with or without lesions.

Significance: These findings suggest that neuroinflammation may be a molecular substrate of the EZ in non-lesional focal epilepsy. Identifying the EZ inpatients with complex DRFE and inconclusive MRI/[18F]FDG-PET imaging is essential to improve resective surgery outcomes. Combining TSPO-PET imaging with SEEG recordings may help bridge this gap.

目的:耐药局灶性癫痫(DRFE)的切除手术需要广泛的评估以定位癫痫区(EZ)。当无创1期评估(脑电图,EEG;磁共振成像;和18F-氟脱氧葡萄糖-正电子发射断层扫描(FDG-PET) [18F]对EZ的定位尚无结论,有创性检查如立体脑电图(SEEG)是必要的。癫痫致痫性图(Ems)使用seeg识别的脑电图高频振荡(ihfo)可视化EZ。PET成像中的放射性配体靶向18 kda转运蛋白(TSPO),这是胶质细胞激活的标志,可能有助于EZ定位。本研究探讨了TSPO-PET成像与DRFE中SEEG - hfos之间的相关性,以确定TSPO-PET在术前评估中的应用,特别是在复杂或非病变病例中。方法:从Bicêtre医院(AP-HP)招募DRFE和不确定i期评估的患者进行前瞻性研究(eudrdraft 2017-003381-27)。他们接受SEEG和[18F]DPA-714 (N,N-二乙基-2-(2-(4-(2-(氟-18F)乙氧基)苯基)-5,7-二甲基吡唑[1,5-a]嘧啶-3-基)乙酰胺)(TSPO放射配体)PET成像。统计参数作图(SPM)技术分析了显著[18F]DPA-714-PET摄取(TSPO-map)和生成的致痫性图(EM-map)。区域和感兴趣体素(VOI)水平的相关分析评估了TSPO-map和EM-map之间的关系。结果:我们能够获得并分析17例患者中12例的两种图谱。局灶性癫痫的EM-map和TSPO-map有显著的区域性正相关(r =。意义:这些发现提示神经炎症可能是非病变局灶性癫痫EZ的分子底物。识别复杂DRFE和MRI/[18F]FDG-PET成像不确定的EZ住院患者对于改善相应的手术结果至关重要。将TSPO-PET成像与SEEG记录相结合可能有助于弥合这一差距。
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引用次数: 0
Piriform cortex is an ictogenic trigger zone in the primate brain. 梨状皮质是灵长类动物大脑中的一个致ictogenic触发区。
IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-01 Epub Date: 2024-12-05 DOI: 10.1111/epi.18201
Karen Gale, David Dybdal, Evan Wicker, Carolina Campos-Rodriguez, Rafael S Maior, Catherine Elorette, Ludise Malkova, Patrick A Forcelli

Objective: Area tempestas, a functionally defined region in the anterior piriform cortex, was identified as a crucial ictogenic trigger zone in the rat brain in the 1980s. However, whether the primate piriform cortex can trigger seizures remains unknown. Here, in a nonhuman primate model, we aimed to localize a similar trigger zone in the piriform cortex and, subsequently, evaluated the ability of focal inhibition of the substantia nigra pars reticulata (SNpr) to suppress the evoked seizures.

Methods: Focal microinjection of the γ-aminobutyric acid type A (GABAA) antagonist bicuculline methiodide into the piriform cortex was performed, in macaque monkeys, on a within-subject basis to map the ictogenic regions within this area. Glutamate antagonists were used to characterize the local circuit pharmacology. Focal inhibition of the substantia nigra by infusion of the GABAA agonist muscimol suppressed seizures evoked from piriform cortex.

Results: We documented a well-defined region highly susceptible to bicuculline-induced seizures in the piriform cortex, just posterior to the junction of the frontal and temporal lobes, indicating that a functional homolog to the rodent area tempestas is present in the primate brain. Focal infusion of glutamate receptor antagonists into the area tempestas revealed that α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated, but not N-methyl-D-aspartate-mediated, neurotransmission was necessary for the expression of seizures. Pharmacological inhibition of the SNpr robustly suppressed area tempestas-evoked seizures.

Significance: Together, these data point to the area tempestas as a potent ictogenic zone in the primate brain and underscore the antiseizure effects of inhibition of the SNpr. Building on decades of studies in rodents, our present findings emphasize the relevance of these targets to the primate brain and provide further rationale for exploring these targets for clinical use.

目的:风暴区是20世纪80年代大鼠脑内梨状皮质前部的一个功能明确的区域,被认为是一个重要的致孕触发区。然而,灵长类动物的梨状皮质是否会引发癫痫仍然未知。在非人类灵长类动物模型中,我们旨在定位梨状皮质中类似的触发区,并随后评估黑质网状部(SNpr)的局灶抑制抑制诱发癫痫发作的能力。方法:将γ-氨基丁酸A型(GABAA)拮抗剂甲氧二库林在猕猴梨状皮质内局部显微注射,在受试者基础上绘制该区域内的致孕区。谷氨酸拮抗剂被用来表征局部回路药理学。输注GABAA激动剂muscimol对黑质的局灶性抑制抑制梨状皮质诱发的癫痫发作。结果:我们在额叶和颞叶交界处后方的梨状皮质中记录了一个明确定义的区域,该区域对双核碱诱发的癫痫非常敏感,这表明灵长类动物的大脑中存在与啮齿动物区域风暴的功能同源。谷氨酸受体拮抗剂局部输注到痉挛区显示α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体介导的神经传递是癫痫发作表达所必需的,而不是n -甲基- d -天冬氨酸介导的神经传递。SNpr的药理抑制有力地抑制了风暴诱发的区域癫痫发作。意义:综上所述,这些数据表明,在灵长类动物大脑中,风暴区是一个强有力的致痫区,并强调了抑制SNpr的抗癫痫作用。基于数十年来对啮齿动物的研究,我们目前的发现强调了这些靶点与灵长类动物大脑的相关性,并为探索这些靶点的临床应用提供了进一步的理论依据。
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引用次数: 0
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Epilepsia
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