Combined MRI Morphometry and Source Imaging Guides Placement of Stereo-EEG Electrodes in Focal Epilepsy with Subtle or Absent Lesions

Peter C. Reinacher¹Dirk-Matthias Altenmüller²Julia M. Nakagawa³Yiwen Li Hegner⁴Cristian Dorign Antal⁵Matthias Duempelmann²Theo Demerath⁶Anke Maren Staack⁷Hans-Jürgen Huppertz⁸Soroush Doostkam⁹Horst Urbach¹⁰Andreas Schulze-Bonhage²Marcel Heers^2*

• ¹Department of Stereotactic and Functional Neurosurgery, University of Freiburg Medical Center, Freiburg, Germany
• ²Epilepsy Center, University of Freiburg Medical Center, Freiburg, Germany
• ³Department of Neurosurgery, University of Freiburg Medical Center, Freiburg, Germany
• ⁴Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Universitatsklinikum Tubingen, Tübingen, Germany
• ⁵The Alfred, Melbourne, Australia
• ⁶Department of Neuroradiology, University of Freiburg Medical Center, Freiburg, Germany
• ⁷Diakonie Kork, Kork, Germany
• ⁸Klinik Lengg, Zürich, Switzerland
• ⁹Department of Neuropathology, University of Freiburg Medical Center, Freiburg, Germany
• ¹⁰Department of Neurradiology, University of Freiburg Medical Center, Freiburg, Germany

Introduction: Planning Stereo-EEG (sEEG) in focal drug-resistant epilepsy with subtle or absent lesions requires accurate non-invasive spatial information about the hypothetical organization of the epileptic focus. The targeting of individual trajectories for a limited number of invasive depth electrodes is particularly challenging in patients who have undergone prior epilepsy surgery. This study investigated how information from multimodal imaging can guide sEEG planning and enable successful epilepsy surgery in patients with non-lesional focal epilepsy. Methods: We studied 15 patients who appeared non-lesional on conventional MRI and were suspected to have mono-focal epilepsy, who underwent sEEG implantation between 10/2019 and 10/2022 based on non-invasive video-EEG monitoring and multimodal imaging. Four patients had undergone prior epilepsy surgery, including two with previous sEEG. All patients had high-resolution 3T MRI and MRI morphometry (MAP) as part of their non-invasive presurgical diagnostics. Electric and electromagnetic source imaging were performed in patient subgroups. sEEG planning incorporated findings from the available imaging methods registered within the stereotactic planning system. Results: A median of nine sEEG electrodes (range 7-11) were implanted per patient, targeting both primary and secondary hypotheses of the epileptic focus location. sEEG recordings identified a monofocal seizure onset in 12/15 patients, who subsequently underwent epilepsy surgery. No bleeding complications occurred. Nine of these patients achieved Engel 1 postsurgical outcomes, while three had Engel ≥2 outcomes. Surgery was not performed in three patients due to multifocal epilepsy (n=2) or unidentified seizure onset zone (n=1). Concordance across multiple imaging modalities was associated with favorable surgical outcomes. Conclusion: In patients with focal epilepsy and subtle or absent lesions, sophisticated sEEG diagnostics guided by advanced multimodal imaging can successfully identify the seizure onset zone. When focal onset is confirmed and multifocal epilepsy excluded through sEEG, subsequent epilepsy surgery frequently results in seizure-free outcomes.