Combined Neuromodulation (Vagus Nerve Stimulation and Deep Brain Stimulation) in Patients With Refractory Generalized Epilepsy: An Observational Study

Abstract

Introduction: This article describes our findings while treating patients with refractory generalized epilepsy with combined vagus nerve stimulation (VNS) and centro-median deep brain stimulation (CMDBS).

Materials and methods: A total of 11 consecutive patients with refractory generalized epilepsy (ten with Lennox-Gastaut syndrome) previously submitted to VNS and who subsequently underwent CMDBS were retrospectively studied. The VNS final parameters were 2 to 2.5 mA, 30 Hz, and 500 μs, cycling mode, 30 seconds "on" and 5 minutes "off" for all patients. The CMDBS final parameters were 4 to 5 V, 130 Hz, and 300 μs, bipolar, continuous stimulation in all patients.

Results: There were eight male participants, ranging in age from eight to 49 years (mean 19 years). Follow-up time after VNS ranged from 18 to 132 months (mean 52 months) and from an additional 18 to 164 months (mean 42 months) during combined VNS-CMDBS. All patients had daily seizures. Atypical absences were noted in eight patients, tonic seizures in seven, bilateral tonic-clonic seizures in four, atonic seizures in three, and myoclonic seizures in two patients. Four patients were initially considered responders to VNS. All these patients also had an additional >50% seizure frequency reduction during combined VNS-CMDBS. Seven patients were not responders to VNS, and of those, four had an additional >50% seizure frequency reduction during combined VNS-CMDBS. Eight patients had an additional >50% reduction in seizure frequency when moved from VNS alone to VNS-CMDBS therapy. There were two nonresponders during combined VNS-CMDBS therapy, and both were nonresponders to VNS alone. Nine patients were considered responders during VNS-CMDBS combined therapy compared with baseline.

Discussion: This study showed that combined VNS-CMDBS therapy was able to double the number of responders compared with VNS alone in a cohort of patients with refractory generalized epilepsy. We believe these data represent the first evidence that combined neuromodulation may be useful in this quite homogeneous patient population.

Keywords: DBS; VNS; generalized epilepsy; observational study; outcome.