Early vagus nerve stimulator implantation as a main predictor of positive outcome in pediatric patients with epileptic encephalopathy

Abstract

Objective: 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. Methods: 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. Results: 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. Significance: 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.

VNS parameters for clinical response in Epilepsy

“…Thus, it is interesting that shorter duration of epilepsy is associated with improved response probability, despite younger patients being less likely responders. This independent effect of duration of epilepsy is also supported by other recent evidence [35,36], but our model is unique in that it looks at the problem as a linear effect rather than through post-hoc subgroup analysis. This growing body of evidence supports earlier intervention with VNS to achieve the best outcomes with the therapy.…”

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.…”

“…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.…”

Definition of drug‐resistant epilepsy: A reappraisal based on epilepsy types

“…Second, by appropriately identifying drug‐resistance in a patient with epilepsy, the HCP could contemplate and propose other therapeutic options (e.g., epilepsy surgery or ketogenic diet) based on the syndromic diagnosis of the patient in a timely manner. Through the works of many scholars, we know that “early” surgical therapy for drug‐resistant epilepsy is a desired clinical approach and strategy 9,10 . However, we should clarify the meaning of “early” to be pragmatic in practice.…”