Low‐frequency centromedian stimulation in patients with generalized or multifocal drug‐resistant epilepsy previously submitted to high‐frequency stimulation: A prospective study

OBJECTIVE: Drug-resistant epilepsy (DRE) remains a significant clinical challenge, affecting approximately 30% of patients. Deep brain stimulation (DBS) of the centromedian thalamic nucleus (CM) has emerged as a viable therapy for generalized and multifocal seizures. Although high-frequency stimulation (HFS) is the clinical standard, emerging evidence suggests that low-frequency stimulation (LFS) may offer comparable efficacy with improved safety and battery longevity. METHODS: We conducted a prospective, open-label, within-subject study involving 10 patients with generalized or multifocal DRE already treated with CM-DBS. Patients were transitioned from HFS (130-180 Hz) to LFS (6-10 Hz). Primary outcomes included seizure frequency reduction and safety. Secondary outcomes assessed behavioral and cognitive changes using the Vineland Adaptive Behavior Scales, Third Edition (VABS-III). RESULTS: Four patients with absence seizures (44%) had an improvement in seizure frequency noted immediately in the 1st month. One patient (11%) had a transient deterioration in absence seizure frequency in the 1st month but from the 3rd month onward had a 50% improvement compared to the baseline. The other four patients did not have any significant change in any seizure frequency. A substantial reduction in implantable pulse generator energy consumption was observed. Caregivers reported qualitative improvements in social behavior and cognitive engagement, although VABS-III scores did not reach statistical significance. One patient was excluded due to behavioral deterioration during the LFS transition phase. SIGNIFICANCE: This is the first prospective study addressing the efficacy and safety of low-frequency (LF) versus high-frequency CM-DBS in patients with generalized or multifocal epilepsy. LF CM-DBS is a potentially safer and more energy-efficient alternative to HFS, maintaining clinical efficacy in selected patients with generalized or multifocal DRE. These findings warrant further investigation through larger, randomized, double-blind trials.