Optimizing stimulation parameters for anterior thalamic nuclei deep brain stimulation in epilepsy: A randomized cross-over trial

ObjectiveThe effects of brain stimulation for diseases like epilepsy are delayed, making stimulation optimization difficult. The parameters for anterior thalamic nuclei (ANT) deep brain stimulation (DBS) for focal drug-resistant epilepsy (DRE) management are often restricted to those used in the SANTE landmark trial. There is little evidence regarding effective alternatives, and low frequency stimulation is typically neglected. We prospectively compare a widely differing stimulation parameter set to typical settings. MethodsThis randomized, modified cross-over, open trial compares the efficacy and safety of an alternative set of parameters using continuous low frequency stimulation with longer pulse-width (cLFS), (7 Hz, 200 msec, continuous) compared to SANTEs intermittent high frequency stimulation with a short pulse width (iHFS), (145 Hz, 90 msec, cycling 1 min on/5 min off). After 3 months on a randomly assigned first set, patients are switched to the other settings, unless seizure free. Patients are re-evaluated after 3 more months at which point they can either remain on the same settings or switch back. ResultsSixteen patients with a median baseline seizure frequency of 13.8 sz/month (IQR 2.7-22.8) were included in the analysis. At last-follow up, ANT-DBS significantly reduced median seizure frequency (45%, IQR 3 - 80%; p = .04). Both iHFS (33%, IQR 0 - 65; p = .02) and cLFS (72%, IQR 30 - 79; p = .001) significantly reduced median seizure frequency. cLFS showed improved median seizure frequency reduction compared to iHFS (p = .03) and was not associated with any moderate or severe adverse effects. SignificanceResults support cLFS for ANT-DBS as a safe and effective alternative to typical iHFS parameters. Broadly, stimulation with widely differing parameters sets may be as effective or even more effective than typical stimulation parameters.