Lundstrom, Brian Nils

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.

Neurostimulation for epilepsy refers to the application of electricity to affect the central nervous system, with the goal of reducing seizure frequency and severity. We review the available evidence for the use of neurostimulation to treat pediatric epilepsy, including vagus nerve stimulation (VNS), responsive neurostimulation (RNS), deep brain stimulation (DBS), chronic subthreshold cortical stimulation (CSCS), transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). We consider possible mechanisms of action and safety concerns, and we propose a methodology for selecting between available options. In general, we find neurostimulation is safe and effective, although any high quality evidence applying neurostimulation to pediatrics is lacking. Further research is needed to understand neuromodulatory systems, and to identify biomarkers of response in order to establish optimal stimulation paradigms.

Abstract Brain stimulation offers an alternative to focal resection for the treatment of focal drug-resistant epilepsy. Chronic subthreshold cortical stimulation is an individualized biomarker-informed open-loop continuous electrical stimulation approach targeting the seizure onset zone and surrounding areas. Before permanent implantation, trial stimulation is performed during invasive monitoring to assess stimulation efficacy as well as to optimize stimulation location and parameters by modifying interictal EEG biomarkers. We present clinical and neurophysiological results from a retrospective analysis of 21 patients, showing a median percent reduction in seizure frequency of 100% and responder rate of 89% with a median follow-up of 27 months. About 40% of patients were free of disabling seizures for a 12-month period or longer. We find that stimulation-induced decreases in delta (1–4 Hz) power and increases in alpha and beta (8–20 Hz) power during trial stimulation correlate with improved long-term clinical outcomes. These results suggest chronic subthreshold cortical stimulation may be an effective alternative approach to treating focal drug-resistant epilepsy and that short-term stimulation-related changes in spectral power may be a useful interictal biomarker and relate to long-term clinical outcome.

OBJECTIVEEpilepsy surgery is effective for lesional epilepsy, but it can be associated with significant morbidity when seizures originate from eloquent cortex that is resected. Here, the objective was to describe chronic subthreshold cortical stimulation and evaluate its early surgical safety profile in adult patients with epilepsy originating from seizure foci in cortex that is not amenable to resection.METHODSAdult patients with focal drug-resistant epilepsy underwent intracranial electroencephalography monitoring for evaluation of resection. Those with seizure foci in eloquent cortex were not candidates for resection and were offered a short therapeutic trial of continuous subthreshold cortical stimulation via intracranial monitoring electrodes. After a successful trial, electrodes were explanted and permanent stimulation hardware was implanted.RESULTSTen patients (6 males) who underwent chronic subthreshold cortical stimulation between 2014 and 2016 were included. Based on radiographic imaging, intracranial pathologies included cortical dysplasia (n = 3), encephalomalacia (n = 3), cortical tubers (n = 1), Rasmussen encephalitis (n = 1), and linear migrational anomaly (n = 1). The duration of intracranial monitoring ranged from 3 to 20 days. All patients experienced an uneventful postoperative course and were discharged home with a median length of stay of 10 days. No postoperative surgical complications developed (median follow-up length 7.7 months). Seizure severity and seizure frequency improved in all patients.CONCLUSIONSThe authors’ institutional experience with this small group shows that chronic subthreshold cortical stimulation can be safely and effectively performed in appropriately selected patients without postoperative complications. Future investigation will provide further insight to recently published results regarding mechanism and efficacy of this novel and promising intervention.