Vagus nerve stimulation and seizure outcomes in pediatric refractory epilepsy

Jain P, Arya R. Vagus Nerve Stimulation and Seizure Outcomes in Pediatric Refractory Epilepsy: Systematic Review and Meta-Analysis. Neurology. 2021 Apr 13:10.1212/WNL.0000000000012030. doi: 10.1212/WNL.0000000000012030. Epub ahead of print. PMID: 33849993.

Abstract

Objective: 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. 

Methods: 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 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. 

Results: A total of 101 studies were included. The pooled prevalence estimates for 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 anti-seizure 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. 

Conclusion: 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.

Russo A, Hyslop A, Gentile V, Boni A, Miller I, Chiarello D, Pellino G, Zenesini C, Martinoni M, Lima M, Ragheb J, Cordelli DM, Pini A, Jayakar P, Duchowny M. Early vagus nerve stimulator implantation as a main predictor of positive outcome in pediatric patients with epileptic encephalopathy. Epileptic Disord. 2021 Jun 29. doi: 10.1684/epd.2021.1299. Epub ahead of print. PMID: 34184987.

Abstract

We describe a multicenter experience with VNS implantation in pediatric patients with epileptic encephalopathy. Our goal was to assess VNS efficacy and identify potential predictors of favorable outcome. This was a retrospective study. Inclusion criteria were: ≤18 years at the time of VNS implantation and at least one year of follow-up. All patients were non-candidates for excisional procedures. Favorable clinical outcome and effective VNS therapy were defined as seizure reduction >50%. Outcome data were reviewed at one, two, three and five years after VNS implantation. Fisher's exact test, Kaplan-Meier and multiple logistic regression analysis were employed. Twenty-seven patients met inclusion criteria. Responder rate (seizure frequency reduction ≥ 50%) at one-year follow-up was 25.9%, and 15.3% at last follow-up visit. The only variable significantly predicting favorable outcome was time to VNS implantation, with the best outcome achieved when VNS implantation was performed within five years of seizure onset (overall response rate of 83.3% at one year of follow-up and 100% at five years). In total, 63% of patients evidenced improved QOL at last follow-up visit. Only one patient exited the study due to an adverse event at two years from implantation. Early VNS implantation within five years of seizure onset was the only predictor of favorable clinical outcome in pediatric patients with epileptic encephalopathy. Improved QOL and a very low incidence of adverse events were observed.