EASEE ^® and Direct: Direct Cortical Stimulation for Focal Epilepsy

Two-Year Outcomes of Epicranial Focal Cortex Stimulation in Pharmacoresistant Focal Epilepsy Schulze-Bonhage A, Hirsch M, Knake S, Mertens A, Rademacher M, Kaufmann E, Kegele J, Jenkner C, Coenen V, Glaser M, Groppa S, Winter Y; EASEE Study Group. Epilepsia . 2025; doi: 10.1111/epi.18448 . Epub ahead of print. PMID: 40377414. Objective: This study was undertaken to report on the long-term safety and efficacy of epicranial focal cortex stimulation (FCS) using the EASEE device as adjunctive neuromodulatory therapy in improving seizure control in adults with pharmacoresistant epilepsy originating from one predominant epileptogenic zone. Methods: Prospective open-label follow-up of patients from the EASEE II and PIMIDES I clinical trials was done for a period of 2 years after the epicranial implantation of the EASEE electrode and stimulator device. Results: Thirty-three patients underwent device implantation, and stimulation was activated in 32 patients. Of these, 26 patients continued stimulation up to 2-year follow-up and provided seizure diary data for efficacy analysis. The 50% responder rate at 2-year follow-up was 65.4% (95% confidence interval = 44.3-82.8), corresponding to a median seizure frequency reduction of 68%. Patients reported improved health-related quality of life. Tolerability was excellent, and there were no severe adverse events considered to be related to implantation or stimulation, nor were adverse effects on mood or cognition reported. Significance: Results of the 2-year follow-up show that epicranial FCS is well tolerated by patients while providing improved seizure control in the long term. It thus offers a minimally invasive treatment option for patients with a predominant epileptic focus. Epileptogenic Zone Characteristics Determine Effectiveness of Electrical Transcranial Stimulation in Epilepsy Treatment Daoud M, Medina-Villalon S, Garnier E, Bratu IF, Damiani G, Salvador R, Wendling F, Ruffini G, Bénar C, Pizzo F, Bartolomei F. Brain Commun . 2025;7(1):fcaf012. doi: 10.1093/braincomms/fcaf012 Transcranial direct current stimulation shows promise as a non-invasive therapeutic method for patients with focal drug-resistant epilepsy. However, there is considerable variability in individual responses to transcranial direct current stimulation, and the factors influencing treatment effectiveness in targeted regions are not well understood. We aimed to assess how the extent and depth of the epileptogenic zone and associated networks impact patient responses to transcranial direct current stimulation therapy. We conducted a retrospective analysis of stereoelectroencephalography data from 23 patients participating in a personalized multichannel transcranial direct current stimulation protocol. We evaluated the extent and depth of the epileptogenic zone network, propagation zone network, and the combined network of the entire epileptogenic and propagation zones, correlating these factors with clinical response measured by the reduction in seizure frequency following repeated transcranial direct current stimulation sessions. Among the patients, 10 (43.5%) were classified as responders (R), experiencing a significant (>50%) decrease in seizure frequency, while 13 were non-responders, showing minimal improvement or increased seizure frequency. Importantly, we found a significant positive correlation between the extent of the epileptogenic zone network and changes in seizure frequency. A smaller epileptogenic zone network extent was associated with better transcranial direct current stimulation efficacy, with responders demonstrating a significantly smaller epileptogenic and propagation zones compared with non-responders. Additionally, non-responders tended to have a significantly deeper epileptogenic zone network compared with responders. Our results highlight the significant impact of the extent and depth of the epileptogenic zone network on transcranial direct current stimulation efficacy in patients with refractory focal epilepsy. Responders typically exhibited a smaller and shallower epileptogenic zone network compared with non-responders. These findings suggest that utilizing individualized epileptogenic zone network characteristics could help refine patient selection for personalized transcranial direct current stimulation protocols, potentially improving therapeutic outcomes.