胚系遗传变异与癫痫手术反应：272例患者的个体参与者汇总分析。
完整摘要 · 中文译文
背景与目的：基因检测越来越多地应用于术前评估，但生殖系遗传性癫痫中切除和消融的获益率仍不确定。 方法：我们对MEDLINE（PubMed）和Scopus进行了系统综述，并补充了来自3个机构队列和儿童癫痫研究联盟（PERC）数据库的病例，包括除结节性硬化症外携带致病/可能致病生殖系变异且接受了切除或激光消融的个体。病因被分为基于生物学信息的类别（GATORopathy、血管性、过度生长、拷贝数变异（CNV）、通道病、突触病及其他）。主要结局为末次随访时的无发作（Engel I级）。组间比较使用Fisher精确检验和Kruskal-Wallis检验（α = 0.05；适用时采用Bonferroni校正）。预设的敏感性分析按病变状态分层、排除GATORopathy，并仅限于文献病例。 结果：我们纳入了224例文献病例（65项研究）、36例机构病例和12例PERC病例（n = 272）。中位随访时间为24个月（四分位距12-48.0）。无发作率分别为：血管性疾病14/19（73.6%）、GATORopathy 79/120（65.8%）、CNV 18/31（58.0%）、过度生长9/16（56.6%）、通道病13/43（30.0%）、突触病4/18（22.2%）及其他11/25（44.0%）（总体p < 0.001）。在具有可用影像结果的病例中，208/253（82.2%）存在致痫性MRI病变，包括64%的通道病和80%的突触病。在单变量对比中（每个类别 与其他所有类型相比），血管性疾病（2.64倍，95% CI 0.87-9.65）和GATORopathy（2.41倍，95% CI 1.44-4.09）的无癫痫发作几率更高，而突触病（约低4.2倍，OR 0.23，95% CI 0.05-0.77）和通道病（约低4.5倍，OR 0.22，95% CI 0.09-0.48）的几率更低。在预设的敏感性分析中（仅病灶性病例、仅文献病例、排除GATORopathy），方向和幅度保持一致。 讨论：切除性手术对生殖系遗传性癫痫可能有效，但结局因通路而异。具有离散病灶性基质的疾病（GATORopathy、血管性）显示最高的无癫痫发作可能性，而通道病和突触病尽管存在MRI病灶，即使在病灶性病例中成功率也显著较低。需要前瞻性、基因型感知的手术登记系统，采用标准化报告（脑电图、影像学和病理学）以及时间-事件结局，以完善手术候选者的选择并量化癫痫相关和非癫痫相关结局。
完整摘要 · 英文原文
BACKGROUND AND OBJECTIVES: Genetic testing is increasingly used in presurgical evaluation, but the yield of resection and ablation across germline genetic epilepsies remains uncertain. METHODS: We conducted a systematic review of MEDLINE (PubMed) and Scopus and added cases from 3 institutional cohorts and the Pediatric Epilepsy Research Consortium (PERC) databases, including individuals with pathogenic/likely pathogenic germline variants besides tuberous sclerosis who underwent resection or laser ablation. Etiologies were grouped into biologically informed categories (GATORopathies, vascular, overgrowth, copy number variants (CNVs), channelopathies, synaptopathies, and other). Primary outcome was seizure freedom (Engel I) at the last follow-up. Group comparisons used Fisher exact and Kruskal-Wallis tests (α = 0.05; Bonferroni when applicable). Prespecified sensitivity analyses stratified by lesional status, excluded GATORopathies, and restricted to literature-only cases. RESULTS: We included 224 literature cases (65 studies), 36 institutional cases, and 12 PERC cases (n = 272). The median follow-up was 24 months (interquartile range 12-48.0). Seizure freedom was achieved in vascular disorders 14/19 (73.6%), GATORopathies 79/120 (65.8%), CNVs 18/31 (58.0%), overgrowth 9/16 (56.6%), channelopathies 13/43 (30.0%), synaptopathies 4/18 (22.2%), and other 11/25 (44.0%) (overall p < 0.001). Among cases with available imaging results, 208/253 (82.2%) had epileptogenic MRI lesions, including 64% of channelopathies and 80% of the synaptopathies. In univariate contrasts (each category vs all others), odds of seizure freedom were higher for vascular disorders (2.64-fold, 95% CI 0.87-9.65) and GATORopathies (2.41-fold, 95% CI 1.44-4.09), and lower for synaptopathies (∼4.2-fold lower, OR 0.23, 95% CI 0.05-0.77) and channelopathies (∼4.5-fold lower, OR 0.22, 95% CI 0.09-0.48). Direction and magnitude were consistent across prespecified sensitivity analyses (lesional only, literature only, exclusion of GATORopathies). DISCUSSION: Resective surgeries can be effective in germline genetic epilepsies, but outcomes vary by pathway. Disorders with discrete, lesional substrates (GATORopathies, vascular) show the highest likelihood of seizure freedom, whereas channelopathies and synaptopathies, despite the presence of MRI lesions, have substantially lower yields even in lesional cases. Prospective, genotype-aware surgical registries with standardized reporting (EEG, imaging, and pathology) and time-to-event outcomes are needed to refine the selection of surgical candidates and quantify seizure and non-seizure-related outcomes.