Early Implantation as a Main Predictor of Response to Vagus Nerve Stimulation in Childhood-Onset Refractory Epilepsy

Abstract

Objective: We describe a multicenter experience with vagus nerve stimulator implantation in pediatric patients with drug-resistant epilepsy. Our goal was to assess vagus nerve stimulation efficacy and identify potential predictors of favorable outcome. Methods: This is a retrospective study. Inclusion criteria: ≤18 years at time of vagus nerve stimulator implantation, at least 1 year of follow-up. All patients were previously found to be unsuitable for an excisional procedure. Favorable clinical outcome and effective vagus nerve stimulation therapy were defined as seizure reduction >50%. Outcome data were reviewed at 1, 2, 3, and 5 years after vagus nerve stimulator implantation. Fisher exact test and multiple logistic regression analysis were employed. Results: Eighty-nine patients met inclusion criteria. Responder rate (seizure frequency reduction >50%) at 1-year follow-up was 25.8% (4.5% seizure-free). At last follow-up, 31.5% had a favorable outcome and 5.2% were seizure free. The only factor significantly predicting favorable outcome was time to vagus nerve stimulator implantation, with the best outcome achieved when vagus nerve stimulator implantation was performed within 3 years of seizure onset. Implantation between 3 and 5 years after epilepsy onset correlated with better long-term seizure freedom (13.3% at T5). Overall, 65.2% of patients evidenced improved quality of life at last follow-up. However, 12.4% had adverse events, but most were mild and disappeared after 3-4 months. Conclusions: Early vagus nerve stimulator implantation within 5 years of seizure onset was the only predictor of favorable clinical outcome in pediatric patients. Improved quality of life and a low incidence of significant adverse events were observed.

Patient Characteristics Associated with Seizure Freedom after Vagus Nerve Stimulation in Pediatric Intractable Epilepsy: An Analysis of “Super-Responders”

“…We did not find any significant difference in age at implantation between the two groups (p ¼ 0.64), but epilepsy duration was significantly shorter in the SR group (p ¼ 0.032). Similar results were published recently by Russo et al 17,18 They studied nearly 90 pediatric patients and reported that the only variable significantly predicting favorable outcomes in children was a shorter time from epilepsy onset to VNS device implantation. 17 Jain and Arya performed a metaanalysis of 101 previous studies and concluded that a shorter duration of epilepsy before VNS implantation was associated with a significantly higher response rate at 1 year.…”

“…Similar results were published recently by Russo et al 17,18 They studied nearly 90 pediatric patients and reported that the only variable significantly predicting favorable outcomes in children was a shorter time from epilepsy onset to VNS device implantation. 17 Jain and Arya performed a metaanalysis of 101 previous studies and concluded that a shorter duration of epilepsy before VNS implantation was associated with a significantly higher response rate at 1 year. 19 We agree with their proposal that early referral may be a modifiable factor for desirable seizure outcomes with VNS 19 and early implantation (e.g., within 5 years after seizure onset 17,18 ) may be preferable.…”

“…Russo et al recently proposed that early implantation within 5 years of epilepsy onset was a good predictor of favorable outcomes. 17 18 For pediatric patients, it is reasonable to consider that the effect of the same duration of epilepsy (e.g., 5 years) may differ among patients of different ages at the time of implantation (e.g., between a 5 year old and a 15 year old). The ratio of epilepsy duration to age was significantly smaller ( p = 0.023) in SRs (mean ± SD: 0.52 ± 0.33) compared with NSRs (0.71 ± 0.26) in our study.…”

Effects of Stable Vagus Nerve Stimulation Efficacy on Autistic Behaviors in Ten Pediatric Patients With Drug Resistant Epilepsy: An Observational Study

“…Some case reports supported positive improvements with VNS on autistic behavior in children with DRE and comorbid ASD (20,21), while other studies have reported the opposite effects (22,23). Although several studies have observed that the effect of VNS on autistic behavior are independent of seizure control (21-23), within 2 years of VNS implantation, the proportion of pediatric DRE responders (≥50% reduction in seizure frequency) gradually increases from 20 to 60% (24)(25)(26)(27). Subsequently, the efficacy of VNS tends to stabilize (27)(28)(29).…”

Neuromodulation for Refractory Epilepsy

“…Non-lesional epilepsy and generalized seizure type were found associated with greater VNS efficacy but with a very modest odds ratio, 13 while the role of age remains debated. 12 , 70 - 72 Several neurophysiological and neuroimaging predictors are being investigated but are not yet validated in clinical practice. 73 - 76 Similarly, we lack biomarkers to predict response to ANT-DBS, with some reports suggesting the potential value of temporal theta-band desynchronization, 77 hippocampal-evoked potentials, 78 and increased functional connectivity between ANT and the default mode network.…”