Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Sep;66(9):3242-3253.
doi: 10.1111/epi.18448. Epub 2025 May 16.

Two-year outcomes of epicranial focal cortex stimulation in pharmacoresistant focal epilepsy

Andreas Schulze-Bonhage  1   2   3   4 , Martin Hirsch  1 , Susanne Knake  5 , Ann Mertens  6 , Michael Rademacher  7 , Elisabeth Kaufmann  8 , Josua Kegele  9 , Carolin Jenkner  10 , Volker Coenen  11 , Martin Glaser  12 , Sergiu Groppa  13 , Yaroslav Winter  5   13 ; EASEE Study Group
Affiliations

Two-year outcomes of epicranial focal cortex stimulation in pharmacoresistant focal epilepsy

Andreas Schulze-Bonhage et al. Epilepsia. 2025 Sep.

Abstract

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.

Keywords: epileptic focus; focal epilepsy; long‐term outcome; neuromodulation; neurostimulation.

PubMed Disclaimer

Conflict of interest statement

A.S.‐B. has received research support from Bial, Precisis, and UNEEG, and personal honoraria for lectures or advice from Angelini Pharma, Eisai, Jazz Pharmaceuticals, Precisis, UCB, and UNEEG. M.H. has received lecture fees or grants from UCB, Angelini Pharma, and UNEEG. A.M. has received consultancy fees from LivaNova and speaker fees from Angelini Pharma. E.K. has received personal honoraria for lectures or advice from UCB, UNEEG, Medtronic, Desitin, and Precisis and has participated in trials sponsored by Medtronic, UCB, Ergomed, and Precisis. V.C. receives a collaborative grant from Brainlab. He serves as an advisor for CereGate and CorTec. He has an ongoing investigator‐initiated trial with Boston Scientific. M.G. has received honoraria and educational grants from Precisis, LivaNova, Abbott, Medtronic, Boston Scientific, and Nevro. S.G. reports research funding from patient groups, Bundesministerium für Bildung und Forschung, DFG (SPP2177 Radiomics), UM Mainz, Abbott, Boston Scientific, Böhringer Foundation, Magventure, National MS Society, Precisis, and Innovationsfond GBA (01NVF22107, INSPIRE—PNRM+), and lecture fees from Abbott, AbbVie, Bial, BVDN, Ipsen, Stada, and UCB. YW reports honoraria for educational presentations and consultations from Angelini Pharma, Arvelle Therapeutics, Bayer, BIAL, Bioprojet, Eisai, Idorsia Pharmaceuticals, Jazz Pharmaceuticals, LivaNova, Novartis, and UCB Pharma. None of the other authors has any conflict of interest to disclose.

Figures

FIGURE 1
FIGURE 1
Study flow diagram. IPG, implantable pulse generator.
FIGURE 2
FIGURE 2
(A) Box plots with mean (diamond) and median (horizontal line in plot) seizure frequency reduction and spread for 2 years following device implantation given per stimulation month (stimulation was generally turned on 1 month after implantation). Note that months without reliable seizure counts in patients´ diaries are considered missing, as reflected by the number given for each month. (B) Patient‐individual outcomes at 2‐year follow‐up for the 26 patients with seizure diary data available (cf. panel A). Responders with at least 50% seizure reduction are depicted in blue, the one patient with >50% seizure increase in orange. (C) Development of treatment response over time (percentage of patients with 50%, 75%, and 90% seizure reduction) over time. RR, responder rate.
FIGURE 3
FIGURE 3
Reduction in seizure frequency per seizure type from baseline to month 23 after stimulation start. One patient with unclear seizure classification and possible nonepileptic events was excluded, as reported severe seizures could not be verified during inpatient monitoring. CPS, complex partial seizure; GTC, generalized tonic–clonic; SPS, simple partial seizure.
FIGURE 4
FIGURE 4
Evolution of patient‐reported outcomes between baseline and 24‐month follow‐up (FU) for the 27 patients with available data. Quality of life (QoL) as assessed with the Quality of Life in Epilepsy–Problems questionnaire (QOLIE‐31‐P) showed a significant improvement. Improvements were also found in cognitive scores as assessed by EpiTrack; however, scores were uncorrected for repeated administration. Mean Neurological Disorders Depression Inventory for Epilepsy (NDDI‐E) scores showed a minor improvement over time.
See this image and copyright information in PMC

References

    1. Simpson HD, Schulze‐Bonhage A, Cascino GD, Fisher RS, Jobst BC, Sperling MR, et al. Practical considerations in epilepsy neurostimulation. Epilepsia. 2022;63:2445–2460. - PMC - PubMed
    1. Schulze‐Bonhage A, Nitsche MA, Rotter S, Focke NK, Rao VR. Neurostimulation targeting the epileptic focus: current understanding and perspectives for treatment. Seizure. 2024;117:183–192. - PubMed
    1. Schulze‐Bonhage A, Hirsch M, Knake S, Kaufmann E, Kegele J, Rademacher M, et al. Focal cortex stimulation with a novel implantable device and antiseizure outcomes in 2 prospective multicenter single‐arm trials. JAMA Neurol. 2023;80:588–596. - PMC - PubMed
    1. Schulze‐Bonhage A. Intracranial and epicranial focus stimulation–concepts and approval status–English Version. Clin Epileptol. 2023;36:125–129.
    1. Hirsch M, Coenen VA, Schulze‐Bonhage A. Termination of seizures by ictal transcranial focal cortex stimulation. Epilepsia Open. 2023;8:673–677. - PMC - PubMed

LinkOut - more resources