Low-frequency centromedian stimulation in patients with generalized or multifocal drug-resistant epilepsy previously...

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.

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).

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.

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.