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

Objective The 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.

This 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 SANTE’s 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.

Sixteen 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. Significance Results 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. Competing Interest Statement G.W. and B.N.L. are named inventors for intellectual property licensed to Cadence Neuroscience, which is co-owned by Mayo Clinic. B.N.L. waived contractual rights to royalties. G.W., N.M.G., and B.N.L. are investigators for the Medtronic EPAS trial and Medtronic-supported NIH grants (UH3-NS95495 and UH3-NS112826). B.N.L. is an investigator for the Neuropace RNS System Responsive Stimulation for Adolescents with Epilepsy (RESPONSE) study and Neuroelectrics tDCS for Patients with Epilepsy study. Mayo Clinic has received consulting fees on behalf of B.N.L. from Epiminder, Medtronic, Neuropace, and Philips Neuro. Mayo Clinic has received research support and consulting fees on behalf of G.W. from UNEEG, NeuroOne, and Medtronic. G.W. has licensed intellectual property developed at Mayo Clinic to NeuroOne. Neither of the other authors has any conflict of interest to disclose. Clinical Trial NCT06617845 Funding Statement No specific funding was received for this study. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This prospective, single center, randomized, cross-over trial (NCT06617845) was approved by the Mayo Clinic Institutional Review Board I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes