Chronic subthreshold cortical stimulation for adult drug-resistant focal epilepsy: safety, feasibility, and technique

Abstract

OBJECTIVE Epilepsy 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. METHODS Adult 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. RESULTS Ten 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. CONCLUSIONS The 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.

Modulation of electrocorticographic seizure features predicts response to closed-loop brain stimulation

“…As the RNS detector settings do not systematically improve over time (Sisterson et al, 2018) -a fact that does not favor the direct stimulation effect hypothesis -the documented time-to-response implies an underlying patient-dependent variation in the duration and amount of stimulation required for the establishment of indirect modulation effects. Despite previous reports of effects of acute and subacute chronic stimulation on both ECoG content and seizure control (Velasco et al, 2009;Child et al, 2014;Ludstrom et al, 2016Ludstrom et al, , 2017Valentin et al, 2017), with background normalization over time, and improved seizure control (Velasco et al, 2000;Elisevich et al, 2006;Kerezoudis et al, 2017), our results show that both direct inhibition by stimulation and direct frequency modulation changes observed during the direct stimulation phase have little effect on outcome.…”

“…Penfield was the first to observe and report stimulation-induced inhibitory effects of electrical stimulation on active epileptogenic neural tissue (Penfield and Jasper, 1954), later also verified by stimulation of hippocampal slices in-vitro (Jefferys, 1981;Durand, 1986). Electrical stimulation has also been reported to have a significant inhibitory effect on interictal and ictal cortical activity in epilepsy patients (Velasco et al, 2000;Yamamoto et al, 2002;Kinoshita et al, 2004;Kossoff et al, 2005;Kinoshita et al, 2005;Yamamoto et al, 2006;Elisevich et al, 2006;Velasco et al, 2009;Child et al, 2014;Ludstrom et al, 2016Ludstrom et al, , 2017Valentin et al, 2017;Kerezoudis et al, 2017). The RNS system is a valuable surgical option for patients refractory to both AEDs and traditional epilepsy surgery (Stacey and Litt, 2008), with data supporting its superiority to medical management (Heck et al, 2014;Geller et al, 2017;Jobst et al, 2017).…”

“…Cortical electrical stimulation, in an open-loop acute and/or subacute mode of operation, has been shown to suppress electrographic epileptiform discharges (Velasco et al, 2000;Yamamoto et al, 2002;Kossoff et al, 2004;Kinoshita et al, 2004Kinoshita et al, , 2005, as well as to reduce seizure frequency (Velasco et al, 2000;Yamamoto et al, 2006;Elisevich et al, 2006;Velasco et al, 2009;Child et al, 2014;Ludstrom et al, 2016Ludstrom et al, , 2017Valentin et al, 2017;Kerezoudis et al, 2017). There is Class 1 evidence for the efficacy of RNS in seizure reduction, with a 44% seizure reduction at 1 year post-implantation, 53% at 2 years (Heck et al, 2014), and a range of 48-66% between the 3rd and 6th post-implantation years in open-label continuation studies (Bergey et al, 2015).…”

Commentary on: Corpus callosum low‐frequency stimulation suppresses seizures in an acute rat model of focal cortical seizures

“…The most effective frequency for rodent corpus callosum stimulation (20 Hz) was within the optimal range for vagal nerve stimulation but differed from the 5‐Hz frequency used in the human fornix study, and the high frequencies (100 Hz or more) that are utilized by devices targeting gray matter structures . A study utilizing subthreshold cortical stimulation demonstrated good response when frequencies as low as 2 Hz were chronically applied . Complex, long‐cycle stimuli may also be of benefit.…”

“…[1][2][3] A study utilizing subthreshold cortical stimulation demonstrated good response when frequencies as low as 2 Hz were chronically applied. 9 Complex, long-cycle stimuli may also be of benefit. Intriguing reports of an antiepileptic response to Mozart's Sonata for Two Pianos in D Major (K 448) may relate to the high degree of long-term (10-60 seconds) periodicity in Mozart's music.…”