Chronic Subthreshold Cortical Stimulation for Paracentral Epilepsy-A Systematic Review

Drug-resistant epilepsy (DRE) affecting the paracentral region poses significant therapeutic challenges, given resective surgery is often infeasible owing to the proximity to eloquent cortex. Neurostimulation modalities such as vagus nerve stimulation, anterior nucleus thalamic deep brain stimulation, and responsive neurostimulation offer alternatives, but their efficacy in achieving seizure freedom remains limited. Chronic subthreshold cortical stimulation (CSCS) represents a novel approach, directly targeting the epileptogenic zone through continuous or cyclic, open-loop subthreshold stimulation, potentially offering superior outcomes in paracentral epilepsy. This systematic review evaluates the efficacy, safety, stimulation parameters, and neurologic outcomes of CSCS in patients with paracentral DRE.

A literature search of PubMed/MEDLINE and EMBASE up to October 2025 identified reports involving chronic electrical stimulation of the primary motor cortex or paracentral region for seizure reduction in human subjects. The inclusion criteria encompassed case reports, case series, and observational studies. Data extracted included seizure outcomes, stimulation parameters, imaging findings, adverse events, quality of life (QOL), and neurologic effects. The primary end points were ≥90% seizure reduction and complete seizure freedom. Risk of bias and quality of evidence were assessed using Oxford, Grading Recommendation Assessment Development and Education, and the criteria of Murad et al. RESULTS: Six studies involving 17 patients were included. The mean follow-up duration was 31.3 ± 22.3 months. Complete seizure freedom was achieved in 47% of patients (8/17), whereas an additional 35% (6/17) experienced ≥90% seizure reduction. Patients with lesional epilepsy indicated significantly higher rates of seizure freedom than did nonlesional cases (p = 0.007). No major surgical or stimulation-related adverse events were reported. Stimulation parameters varied widely (frequency 2-130 Hz; pulse width 90-450 μs; amplitudes up to 7V or 4 mA), and both continuous and cyclic modes were effective. Several patients showed neurologic improvements beyond seizure control, including enhanced motor function, mood, and cognitive performance. QOL improvements also were reported.

CSCS appears to be a promising treatment modality for paracentral DRE, showing high rates of seizure freedom, favorable safety profiles, and potential neuromodulatory benefits beyond seizure suppression. Although preliminary evidence suggests superior efficacy in paracentral cases to other neurostimulation modalities, the present data are limited by publication bias and lack of randomized trials. Future prospective, controlled studies are essential to validate these findings, optimize stimulation protocols, and refine patient selection criteria.