Vagus Nerve Stimulation for Treatment of Partial Seizures: 1. A Controlled Study of Effect on Seizures

Abstract

Vagus nerve stimulation (VNS) was shown to reduce seizure frequency in refractory epilepsy patients in two pilot studies. Based on these results, a multicenter, prospectively randomized, parallel, double-blind study of patients with refractory partial seizures was initiated. After a 12-week baseline period, identical vagus nerve stimulators were implanted and patients randomized to either a high or low 14-week VNS treatment paradigm. The primary objective was to demonstrate that high VNS (therapeutic parameters) was more effective in reducing partial seizure frequency than was low VNS (less or noneffective parameters). Patients continued receiving antiepileptic drugs (AEDs) with plasma concentrations held constant throughout the study. We report results of the first 67 patients to exit the 14-week acute phase. After 14 weeks of VNS, 31 patients receiving high VNS experienced a mean seizure frequency percentage reduction of 30.9%, which was statistically significant as compared with the mean seizure frequency percentage reduction of 11.3% in 36 patients receiving low VNS (p = 0.029, t test; p = 0.036, Wilcoxon rank-sum test). In addition to the significant intragroup p-values, mean seizure frequency percentage change reached statistical significance for high VNS (p < 0.001) but not low VNS (p = 0.072) as compared with baseline. Twelve of 31 (38.7%) patients receiving high VNS achieved at least 50% reduction in seizure frequency whereas 7 of 36 (19.4%) patients receiving low VNS experienced at least 50% reduction after 14 weeks. The implant procedure and VNS therapy were well tolerated. Our study confirmed the effectiveness of VNS as treatment for epilepsy patients with refractory partial seizures.

Not all that glitters is gold: A guide to surgical trials in epilepsy

“…Most (9/12) were multicenter studies 3, 9, 11, 12, 14, 18, 31, 32, 33. One was specifically a pediatric RCT 17.…”

“…All were carried out in patients with drug‐resistant epilepsy, although the extent of epilepsy characterization was variable across studies: two studies evaluated patients with drug‐resistant mesial TLE,12, 34 five specified “partial” or “focal” epilepsy in their study criteria,11, 14, 18, 32, 33 one targeted adults with malformations of cortical development,13 and the rest required only “medically refractory seizures,” including two that explicitly included patients with generalized epilepsy 6, 17. Several RCTs (5/12) evaluated VNS (whether implanted9, 14, 17, 31, 32 or transcutaneous6). Two evaluated HS (implanted34 or transcranial12), and the rest individually evaluated CS,35 TNS,11 rTMS,13 thalamic stimulation,33 and RNS 10, 16, 18.…”

“…The lack of comparative effectiveness data, particularly among studies that used heterogeneous populations (including some generalized epilepsy6, 17 or no description of epilepsy phenotype9), limits the ability to define the ideal device for a given patient.…”

“…Resective epilepsy surgery, in appropriately selected patients, is the accepted treatment of choice for DRE as supported by two randomized clinical trials,3, 4 multiple retrospective cohort series, and a practice parameter issued by the American Academy of Neurology recommending a surgical evaluation for any patient with uncontrolled disabling complex partial seizures 5. Similarly, a plethora of nonresective yet surgical DRE treatments have flourished recently, including various neuromodulation procedures6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 and thermal‐based19 and radiation‐based neurosurgeries 20. A position statement by the Practice Management Committee Health Care Reform Workgroup of the American Epilepsy Society called for access and insurance coverage for all patients with epilepsy for more aggressive therapeutic strategies, including neurosurgery and implanted electronic devices, when medications fail to yield optimal seizure control 21.…”

Vagus Nerve Stimulation: Rapid versus Slow Cycling in a Laboratory Model

“…If this rule extended to the clinical trials, then the suppression induced by 30 s of VNS would be expected to last for 2 min. The initial clinical trial employed a schedule of 30 s stimulation on, followed by 5 min off, on a regular clock cycle [6].When the therapeutic response to VNS is suboptimal after 3 months of therapy, increasing the duty cycle (ratio of time on to time off) has been recommended [7]. Benefits of such a change are individual and anecdotal.…”