Systematic Review and Meta-Analysis of Bilateral Centromedian Nucleus Neuromodulation for Multifocal and Generalized...

Generalized and multifocal forms of drug-resistant epilepsy are highly prevalent but have limited treatment options. Centromedian nucleus (CMN) thalamic neuromodulation has emerged as an effective treatment for these epilepsies, but head-to-head neuromodulation modality trials do not exist, and optimal stimulation parameters are not established.

Using Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, we conducted a systematic review by searching PubMed and Embase for peer-reviewed studies of bilateral CMN deep brain stimulation (DBS) or responsive neurostimulation (RNS) for generalized and/or multifocal epilepsy. From studies that met the inclusion criteria, we extracted individual patient data and used a mixed-effects model to compare seizure frequency reduction (SR) of modalities and for DBS, across different stimulation frequencies.

A total of 25 studies with 192 total patients were included. DBS and RNS yielded comparable SR (76.8% vs 66.7%, respectively, p = 0.1). Within the DBS cohort, high-frequency (>100 Hz) stimulation was more effective for SR by 20.16% (CI: 6.49-33.83) than low-frequency stimulation. Patients with Lennox-Gastaut Syndrome (LGS) had 13.37% lower SR (CI: -26.17 to -0.56) than did those without this diagnosis. Longer follow-up duration (≥18 months) was associated with 12.60% greater SR (CI: 2.53-22.68).

For CMN thalamic neuromodulation in patients with multifocal or generalized epilepsy, modality type (RNS vs DBS) may matter less for SR than may underlying diagnosis (LGS vs not LGS), stimulation parameters (high- vs low-frequency), and treatment duration. These findings have implications for the therapeutic mechanism(s) of thalamic neuromodulation and motivate further study of optimal stimulation approaches.