Samanta Debopam, Jain Puneet, Cunningham Jessie, Arya Ravindra
Division of Child Neurology, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Epilepsy Program, Division of Neurology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Epilepsia. 2025 Jul 14. doi: 10.1111/epi.18544.
Lennox-Gastaut syndrome (LGS) is a childhood onset developmental and epileptic encephalopathy characterized by multiple seizure types that are often refractory to traditional antiseizure medications. Neuromodulation therapies including vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS) have emerged as potential treatment options, but their comparative efficacy remains unclear.
We conducted a systematic review and meta-analysis of studies reporting outcomes of neuromodulation therapies in patients with LGS. A comprehensive search of electronic databases was performed through July 26, 2024. The primary outcome was the proportion of patients achieving ≥50% seizure reduction. Random-effects models were used to calculate pooled estimates, and meta-regression analyses were performed to identify potential effect modifiers.
Fifty-four studies comprising 1350 patients were included in the analysis (VNS: 37 studies, 1242 patients; DBS: 11 studies, 81 patients; RNS: six studies, 27 patients). The overall pooled responder rate was 55.4% (95% confidence interval [CI] = 48.0%-62.8%). DBS showed the highest responder rate (69.7%, 95% CI = 51.3-88.1%), followed by RNS (63.0%, 95% CI = 30.9-95.1%) and VNS (50.6%, 95% CI = 43.0-58.2%). Meta-regression analysis revealed that intervention type was a significant moderator of treatment effect, with VNS showing significantly lower efficacy compared to DBS (p = .0305). In the DBS subgroup, a later onset of epilepsy was a significant positive predictor of response (p = .0051). Twenty studies qualitatively described quality-of-life outcomes, most commonly noting improved alertness and attention, although heterogeneous assessments precluded meta-analysis. Twenty-seven studies reported complications; VNS was linked to stimulation-related side effects, whereas DBS and RNS had higher rates of serious device-related issues.
This meta-analysis suggests that all three neuromodulation therapies are effective for seizure reduction in LGS, with DBS and RNS demonstrating potentially superior efficacy compared to VNS. These findings may help guide treatment selection for patients with LGS, although prospective comparative studies are needed.
伦诺克斯 - 加斯托综合征（LGS）是一种儿童期起病的发育性和癫痫性脑病，其特征为多种癫痫发作类型，且通常对传统抗癫痫药物难治。包括迷走神经刺激（VNS）、深部脑刺激（DBS）和反应性神经刺激（RNS）在内的神经调节疗法已成为潜在的治疗选择，但其相对疗效仍不明确。
我们对报告LGS患者神经调节疗法结果的研究进行了系统评价和荟萃分析。通过2024年7月26日对电子数据库进行了全面检索。主要结局是癫痫发作减少≥50%的患者比例。采用随机效应模型计算合并估计值，并进行荟萃回归分析以确定潜在的效应修饰因素。
分析纳入了54项研究，共1350例患者（VNS：37项研究，1242例患者；DBS：11项研究，81例患者；RNS：6项研究，27例患者）。总体合并缓解率为55.4%（95%置信区间[CI]=48.0%-62.8%）。DBS显示出最高的缓解率（69.7%，95%CI=51.3-88.1%），其次是RNS（63.0%，95%CI=30.9-95.1%）和VNS（50.6%，95%CI=43.0-58.2%）。荟萃回归分析显示，干预类型是治疗效果的显著调节因素，与DBS相比，VNS的疗效显著较低（p=0.0305）。在DBS亚组中，癫痫发病较晚是缓解的显著正向预测因素（p=0.0051）。20项研究定性描述了生活质量结局，最常见的是注意到警觉性和注意力有所改善，尽管评估的异质性排除了荟萃分析。27项研究报告了并发症；VNS与刺激相关副作用有关，而DBS和RNS的严重器械相关问题发生率较高。
这项荟萃分析表明，所有三种神经调节疗法对LGS患者的癫痫发作减少均有效，与VNS相比，DBS和RNS显示出潜在的更高疗效。这些发现可能有助于指导LGS患者的治疗选择，尽管仍需要前瞻性比较研究。
