Combined use of the ketogenic diet and vagus nerve stimulation in pediatric drug-resistant epilepsy.

Objective: Patients with drug-resistant epilepsy (DRE) pose considerable management challenges for patients, their families, and providers. Both the vagus nerve stimulator (VNS) and the ketogenic diet (KD) have been shown to be safe and effective in treating DRE. Nevertheless, information is lacking regarding treatment with combination of both modalities. This study reports the efficacy and tolerability of combining VNS and KD in a pediatric cohort with intractable epilepsy. Methods: This is a retrospective review of 33 patients (0-17 years) with DRE treated with VNS and KD at a single pediatric level IV epilepsy center. We compared seizure reduction rates for each patient at baseline and at every clinic visit for 24 months after adding the second nonpharmacological therapy. The frequency of adverse events on the combined therapy was collected to assess safety and tolerability. Results: There were a total of 170 visits for all patients while on the combined therapy. At 88% (95% CI: 83%-93%) of the visits, patients reported some reduction in seizure frequency. The proportion of patients reporting a greater than 50% seizure reduction over all visits was 62% (95% CI: 55%-69%). The proportion of a patient's visits with at least a greater than 50% reduction in seizure frequency had a median of 71% (IQR 33%-100%). Continued improvement was seen over time of combined treatment; for every one-unit time unit change (one month), there was a 6% increase in the odds of having a reduction in seizure frequency of >50% (OR = 1.06, 95% CI: 1.01-1.11). Significance: This study shows that combining the VNS and KD in patients with drug-resistant epilepsy is well tolerated and reduces seizure frequency more than either one modality used alone and that the benefits in terms of seizure reduction continue to increase with the length of treatment.

The efficacy and tolerability of auto-stimulation-VNS in children with Lennox-Gastaut syndrome.

OBJECTIVE: Lennox-Gastaut syndrome (LGS) is a severe drug-resistant epilepsy (DRE) of childhood. The Vagus Nerve Stimulator (VNS) is established as a safe and effective treatment for DRE. This study assesses efficacy and tolerability of the auto-stimulation VNS models in pediatric patients with LGS. METHODS: This is a retrospective chart review of a cohort of pediatric patients (Age 1-18 years old) with LGS implanted with an auto-stimulation VNS model at a single level four pediatric epilepsy center. Patient responder's rate was measured as seizure reduction over baseline and improvements in five quality-of-life measures as reported by the patients and families. Efficacy and tolerability were assessed at 1, 3, 6, 12, 18 and 24 months compared to baseline. RESULTS: This cohort includes 71 consecutive children with Lennox-Gastaut syndrome who underwent implantation with one of two models of the auto-stimulation VNS. The average age of the children at implantation was 20.82 months. Of those patients, 55 % of patients achieved greater than 50 % seizure reduction at six months, 67.7 % at 12 months, and 65 % at 24 months. At 12 months 11 % of the patients were completely seizure free and at 24 months 17 % were seizure free. By 24 months post implantation most of the patient families reported at least a 50 % improvement rate in one or more of the quality-of-life measures. The most commonly reported adverse events were dysphonia, paresthesia, and shortness of breath, all of which were tolerated and subsided by 24 months. SIGNIFICANCE: This study provides evidence that VNS models with the auto-stimulation paradigm based on detection of tachycardia are well tolerated and effective in a pediatric population with LGS. Furthermore, this study shows that for this population, the auto-stimulation models of the VNS may provide additional benefits over the earlier VNS versions.