Authors :
Presenting Author: Tereza Pridalova, MS – Mayo Clinic
Vaclav Kremen, PhD – Mayo Clinic
Filip Mivalt, PhD – Mayo Clinic Rochester
Gamal Eldin Osman, MD – Mayo Clinic
Keith Starnes, MD – Mayo Clinic, Rochester MN, USA.
Brian Lundstrom, MD PhD – Mayo clinic, Rochester, Minnesota
Benjamin Brinkmann, PhD – Mayo Clinic
Kai Miller, MD, PhD – Mayo Clinic
Jamie J Van Gompel, MD – Mayo Clinic, Rochester MN, USA.
Dora Hermes Miller, Ph.D. – Mayo Clinic
Gregory Worrel, MD,PhD – Mayo Clinics
Nicholas Gregg, MD – Mayo clinic, Rochester, Minnesota
Rationale:
Anterior nucleus of the thalamus (ANT-DBS) is an approved therapy for drug-resistant epilepsy, however, seizure freedom is rare, benefit is slow, and it does not work for everyone. Current DBS approaches do not account for epilepsy chronobiology, and changing brain dynamics across wake/sleep states, and for different epilepsy circadian chronotypes. Here, we aimed to characterize the wake/sleep state dependent impact of ANT stimulation on interictal epileptiform discharge (IED) rates, across brain regions, in patients undergoing thalamic sEEG.
Methods:
Twenty-nine subjects with refractory epilepsy underwent trial ANT-DBS during sEEG monitoring that included an ANT lead. High-frequency ( >100 Hz) duty-cycle (1-minute on, 3-5 minutes off) stimulation was delivered to the thalamus and acute changes in IED rate between duty-cycle on- and off-phases were quantified by Cohen’s d effect size (CES). Negative CES indicates a reduction in IED rate during on- compared to off-phases. IEDs were calculated from seizure onset zone contacts and classified into limbic (cingulate and mesial temporal), frontal (extra-limbic), neocortical temporal, and insular regions. Wake/sleep vigilance states were classified by sEEG delta/beta power and expert review. IED rate was assessed per region and wake/sleep state.
Results:
Patients received active stimulation for a median of 3.1 ± 2.2 hours. In wakefulness ANT-DBS induced IED rate suppression was numerically greater in limbic, then frontal, then insula and neocortical temporal regions. In wakefulness 26/29 patients had IED rate suppression, while in sleep 18/22 patients had IED rate suppression in on- versus off-phases. IED rate suppression effect size was greater in wakefulness than sleep for all seizure onset zone regions except the frontal lobe (limbic: awake -0.48 ± 0.07, sleep -0.26 ± 0.06, p < 0.001; insula: awake -0.26 ± 0.08, sleep 0.06 ± 0.11, p < 0.001 and neocortical temporal: awake -0.25 ± 0.06, sleep -0.12 ± 0.08, p = 0.001). In contrast, the frontal lobe showed greatest IED rate suppression in the sleep state (awake: -0.31 ± 0.07, sleep: -0.39 ± 0.07, p = 0.011).
Conclusions:
High-frequency ANT-DBS acutely suppresses interictal activity in most patients with limbic, frontal, temporal neocortical, and insula seizure onset zones, with lobar- and wake/sleep state-dependent effects. This motivates future investigations of personalized, biomarker-targeted, chronotherapy for epilepsy.
Funding:
NIH K23-NS136792 and the Tianqiao & Chrissy Chen Institute (NG)