脑响应神经刺激治疗耐药局灶性癫痫上市后研究：三年疗效与安全性中期结果
这项开放标签上市后研究纳入324例符合RNS系统适应症的成人耐药局灶性癫痫患者，评估真实世界疗效与安全性。治疗3年时癫痫发作频率中位降低82%，41%患者降低≥90%，未报告严重刺激相关不良事件，SUDEP率为2.3/1000患者年。
要点
- RNS系统治疗3年癫痫发作频率中位降低82%，6个月时降低62%。
- 41%患者3年时发作频率降低≥90%，42.5%至少经历一次≥6个月无发作期。
- 未报告严重刺激相关不良事件，合并所有RNS试验SUDEP率2.3/1000患者年。
核心结论
- 辅助直接脑响应神经刺激可显著且持续减少局灶性癫痫发作频率，真实世界中安全性和疗效与随机对照试验相似或更优。
研究设计与样本
- 开放标签前瞻性上市后研究，纳入32家美国癫痫中心的324例成人耐药局灶性癫痫患者，271例完成3年随访。
主要发现
- 3年时癫痫发作频率中位降低82%（p<0.0001），6个月时降低62%。
- 41%患者3年时发作频率降低≥90%，42.5%至少有一次≥6个月无发作期，22.0%无发作≥12个月。
- 疗效在1或2个发作起源及不同起源部位（内侧颞叶、新皮质或两者）间相似。
- 未报告严重刺激相关不良事件；合并所有RNS试验（n=645）SUDEP率为2.3/1000患者年，显著低于预设比较组（p<0.05）。
关键数值与推荐
- 主要疗效终点为3年治疗时癫痫发作频率中位百分比变化。
- 41%患者3年时发作频率降低≥90%，42.5%至少一次≥6个月无发作，22.0%无发作≥12个月。
- SUDEP率2.3/1000患者年显著低于预设比较组（p<0.05，单侧χ2检验）。
临床怎么用
- 对于符合适应症的成人耐药局灶性癫痫，RNS系统可作为辅助治疗选择，真实世界中可显著减少发作频率且耐受性良好。
局限性
- 为开放标签研究，主要安全性终点分析将在5年时进行，当前报告为中期安全性结果。
以上解读依据论文摘要（全文未开放获取或许可不允许翻译转载）。
原文
BACKGROUND AND OBJECTIVES: Neuromodulation therapies are approved for the treatment of focal epilepsy based on data from randomized controlled trials (RCTs). After approval of a responsive direct brain stimulation device (The RNS System for focal epilepsy), the Food and Drug Administration required a prospective study to evaluate whether real-world safety and effectiveness differed from outcomes in the RCT. METHODS: This open-labeled study enrolled adult participants who met the RNS System-approved indication for use. The primary effectiveness end point was median percent change in seizure frequency at 3 years of treatment. Interim safety is presented; the primary safety endpoint analysis will be conducted at 5 years. RESULTS: Across 32 US epilepsy centers, 324 patients (mean age 37.1, 59.6% female individuals) were implanted and 271 completed 3 years of follow-up. The median percent reduction in seizure frequency at 6 months was 62% and 82% at 3 years (p < 0.0001; Wilcoxon signed-rank test); 41% had a ≥90% reduction in seizure frequency at 3 years, 42.5% of participants had at least 1 seizure-free period of 6 months or more, and 22.0% experienced seizure freedom for 12 months or more. Observed effectiveness was similar across patients with 1 or 2 seizure onsets and across onset locations (mesial temporal, neocortical, or both mesial temporal and neocortical). No serious stimulation-related adverse events were reported. Combining data from all RNS System trials (n = 645), the sudden unexplained death in epilepsy (SUDEP) rate was 2.3/1,000 patient years, which was significantly lower than predefined comparators (p < 0.05; 1-tailed χ2). DISCUSSION: This prospective real-world study contributes to the body of evidence that adjunctive direct brain-responsive neurostimulation provides significant and sustained reductions in the frequency of focal seizures. Seizure reductions were greater and were achieved faster than in the RCT and long-term treatment trials but were similar to a more recent retrospective multicenter real-world study. As in the preapproval studies, treatment was well-tolerated and safe, and the SUDEP rate was low. The RNS System showed similar safety and improved seizure outcomes in real-world use compared with the RCT. Improvements in efficacy may reflect changes in programming practices. Future research efforts will focus on using the brain data obtained by the device to optimize detection and stimulation paradigms for each patient. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov, NCT02403843, submitted March 26, 2015. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in adults with refractory focal-onset seizures, direct brain-responsive neurostimulation reduces seizure frequency without serious adverse events up to 3 years.
引用
- Eliashiv D, Rao VR, Jobst BC, et al. Postapproval Study for Brain-Responsive Neurostimulation for Drug-Resistant Focal Epilepsy: Three-Year Efficacy and Interim Safety Results. Neurology. 2026. PMID: 42030518. doi:10.1212/WNL.0000000000214875
供执业医师工作参考，不替代临床判断；数值与分级以指南原文为准。