Authors :
Presenting Author: Juan Luis Alcala-Zermeno, MD – Columbia University
Nicholas Gregg, MD – Mayo Clinic
Gamaleldin Osman, MBBCh – Mayo Clinic
Keith Starnes, MD – Mayo Clinic
Jamie Van Gompel, MD – Mayo Clinic
Kai Miller, MD, PhD – Mayo Clinic
Gregory Worrell, MD, PhD – Mayo Clinic
Brian Lundstrom, MD, PhD – Mayo Clinic
Rationale:
Deep brain stimulation (DBS) in an invasive neuromodulation strategy available to treat drug resistant epilepsy (DRE) that is not amenable to resective epilepsy surgery. Current implantable pulse generators (IPGs) can provide DBS therapy in virtually infinite combinations of amplitude, frequency, pulse width, cycling, and electrode configuration. Yet, the stimulation parameters used for anterior thalamic nuclei (ANT) DBS in focal DRE are often restricted to the SANTE landmark trial settings, which consist of single cathodal referential stimulation using 145 Hz, pulse width of 90 msec, and cycling stimulation 1 min on and 5 min off (Epilepsia, 2010, 51(5), 899-908). Unfortunately, not all patients respond to the SANTE parameters and there is little evidence regarding effective alternatives. Low frequency stimulation (LFS), can reduce seizure frequency when targeting cortex using RNS (Epilepsia, 2023, 64(2), e16-e22) or neocortical chronic subthreshold stimulation (CSS) (JAMA Neurol, 2016, 73(11), 1370-72). In this study, our primary objective is to compare ANT-LFS to ANT high frequency stimulation (HFS) with regard to seizure frequency reduction (SFR).
Methods:
Prospective, randomized, modified cross-over, open trial of two different sets of parameters in patients implanted with bilateral ANT-DBS. After implant, patients are randomized to either: HFS (145 Hz, 90 msec, cycling 1 min on/5 min off) or LFS (7 Hz, 200 msec, cycling off), both using referential stimulation with two cathodes. At 3 months patients are switched to the opposite set, unless they become seizure free. The next assessment occurs after 3 more months when patients either remain on the same settings or switch back, Figure 1a. ASM management is per primary neurologist/epileptologist’s preference. Primary outcome is SFR. Secondary outcomes are changes in seizure severity, life satisfaction and quality of sleep using 1–10-point analog scales, as well as stimulation related side effects. Continuous variables are reported as median with interquartile range (IQR). Wilcoxon signed rank test was used for comparisons with p < 0.05 considered significant.