Jain Puneet, Arya Ravindra
From the Epilepsy Program (P.J.), Division of Neurology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada; Division of Pediatric Neurology (P.J.), Department of Pediatrics, Danat Al Emarat Hospital for Women and Children, Abu Dhabi, United Arab Emirates; Comprehensive Epilepsy Center (R.A.), Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; and Department of Pediatrics (R.A.), University of Cincinnati College of Medicine, Cincinnati, OH.
Neurology. 2021 May 31;96(22):1041-1051. doi: 10.1212/WNL.0000000000012030.
We synthesized evidence for effectiveness of vagus nerve stimulation (VNS) as adjuvant therapy in pediatric drug-resistant epilepsy (DRE) by obtaining pooled estimates for seizure outcomes and analyzing their determinants.
MEDLINE, EMBASE, and Cochrane databases were searched up to July 2019 for original research on VNS in pediatric (≤18 years of age) epilepsy. The primary outcome was 50% responder rate (50% RR), the proportion of patients with ≥50% seizure reduction, at the last reported follow-up. Other outcomes included a 50% RR and proportion of seizure-free patients at additional reported time points. A random-effects meta-analysis with restricted maximum likelihood estimation was performed to obtain pooled effect estimates. Meta-regression using multiple linear models was performed to obtain determinants of seizure outcomes and sources of heterogeneity.
A total of 101 studies were included. The pooled prevalence estimates for a 50% RR and seizure freedom at last follow-up (mean 2.54 years) were 56.4% (95% confidence intervals [CIs] 52.4, 60.4) and 11.6% (95% CI 9.6, 13.9), respectively. Fewer antiseizure medications (ASMs) tried before VNS and later age at onset of seizures were associated with better seizure outcomes following VNS implantation. An effect of sex distribution of studies on long-term outcomes and a potential publication bias for short-term outcomes were also observed.
Pooled evidence supports possible effectiveness of VNS in pediatric DRE, although complete seizure freedom is less common. Early referral (fewer trials of ASMs) may be a modifiable factor for desirable seizure outcomes with VNS from a clinical perspective.
我们通过获取癫痫发作结局的汇总估计值并分析其决定因素，综合了迷走神经刺激（VNS）作为小儿耐药性癫痫（DRE）辅助治疗有效性的证据。
检索截至2019年7月的MEDLINE、EMBASE和Cochrane数据库，以查找关于小儿（≤18岁）癫痫中VNS的原始研究。主要结局是在最后一次报告的随访时50%缓解率（50%RR），即癫痫发作减少≥50%的患者比例。其他结局包括在其他报告时间点的50%RR和无癫痫发作患者的比例。采用限制最大似然估计的随机效应荟萃分析来获得汇总效应估计值。使用多元线性模型进行荟萃回归以获得癫痫发作结局的决定因素和异质性来源。
共纳入101项研究。最后随访（平均2.54年）时50%RR和无癫痫发作的汇总患病率估计值分别为56.4%（95%置信区间[CI]52.4,60.4）和11.6%（95%CI9.6,13.9）。VNS植入前尝试的抗癫痫药物（ASM）较少以及癫痫发作起始年龄较大与VNS植入后更好的癫痫发作结局相关。还观察到研究的性别分布对长期结局的影响以及短期结局可能存在的发表偏倚。
汇总证据支持VNS在小儿DRE中可能有效，尽管完全无癫痫发作并不常见。从临床角度来看，早期转诊（较少的ASM试验）可能是VNS获得理想癫痫发作结局的一个可改变因素。
