Anterior Nucleus of the Thalamus Deep Brain Stimulation with Concomitant Vagus Nerve Stimulation for Drug-Resistant Epilepsy

Abstract

BACKGROUND The Food and Drug Administration approved the deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) as an adjunctive therapy for drug-resistant epilepsy (DRE) in the United States in 2018. The DBS Therapy for Epilepsy Post-Approval Study is further evaluating the safety and effectiveness of ANT-DBS among different patients’ groups. For this study, devices for vagus nerve stimulation (VNS) must be removed prior to enrolment. OBJECTIVE To investigate the outcomes of concomitant ANT-DBS and VNS treatment for DRE. METHODS A retrospective analysis was performed for 33 patients who underwent ANT-DBS using previous VNS to define distinct subgroups: standard ANT-DBS (9 subjects), ANT-DBS with functional VNS (12 subjects), and ANT-DBS with the VNS implantable pulse generator explanted or turned off at the time of the DBS (12 subjects). Effectiveness and safety data were analyzed across the whole population and among subgroups. RESULTS A mean decrease in seizure frequency of 55% was observed after a mean follow-up of 25.5 mo. Approximately 67% of patients experienced ≥50% reduction in seizure frequency. Seizure reduction percentage was not significantly different among groups. Approximately 50% of subjects with no appreciable improvement and 75% of those who showed benefit after VNS (including improvement in seizure frequency, seizure severity, and seizure duration or quality of life) achieved a seizure reduction ≥50% after ANT-DBS surgery. There were no complications related to concomitant VNS and ANT-DBS. CONCLUSION ANT-DBS for DRE provides excellent results despite previous and ongoing VNS therapy. Removal of VNS does not appear to be necessary before ANT-DBS.

Anterior thalamic deep brain stimulation in epilepsy patients refractory to vagus nerve stimulation: A single center observational study

“…Eight of 11 patients were DBS treatment responders. In light of the conflicting reports regarding DBS efficacy in VNS non-responders [9] , [11] , [12] , [16] , [10] , our findings provide additional support for the use of DBS treatment in VNS refractory patients.…”

“…A 60 % seizure rate reduction after five years of treatment was found regardless of whether patients had been previously treated with VNS, suggesting that DBS was effective in VNS refractory patients [9] . This conclusion has also been supported by smaller reports [10] , [11] , most recently in a study that compared 12 patients with concomitant DBS and VNS, 12 patients with DBS and prior VNS use, and 9 patients treated by DBS with no history of VNS use, reporting similar efficacy of DBS treatment in all patient groups. This study, also reported, for the first time, that VNS and DBS may effectively function simultaneously [11] .…”

“…This conclusion has also been supported by smaller reports [10] , [11] , most recently in a study that compared 12 patients with concomitant DBS and VNS, 12 patients with DBS and prior VNS use, and 9 patients treated by DBS with no history of VNS use, reporting similar efficacy of DBS treatment in all patient groups. This study, also reported, for the first time, that VNS and DBS may effectively function simultaneously [11] . On the other hand, a smaller study including 11 DRE patients with previous VNS treatment concluded that poor response to VNS is correlated with poor response to DBS treatment [12] .…”

“…It is yet unknown if simultaneous application of two neuromodulatory treatments with differing mechanisms of action can translate to better therapeutic results for patients. A very recent study that explored this question, reported equivalent seizure reduction rates in 12 patients with simultaneous VNS and DBS stimulation, compared to 21 patients treated by DBS only, either with or without a history of prior VNS treatment [11] . An additional recent study demonstrated feasibility of other dual stimulation approaches, namely VNS combined with either RNS or centromedian thalamic nucleus stimulation [25] .…”

Practical considerations in epilepsy neurostimulation

“…19 In both the DBS-ANT and RNS trials, seizure reductions did not depend on prior VNS placement, or on previous epilepsy surgery. 8,40,41 Rates of probable or definite sudden unexpected death in epilepsy (SUDEP) appear to be lower than might otherwise by expected in patients treated with neurostimulation. In the RNS trial, the rate was 2.8 per 1000 patient years (95% confidence interval [CI] 1.2-6.7), 14 whereas for DBS-ANT it was 2.0 (95% CI 0.24-7.12).…”