Abstract
BACKGROUND: Cerebral cavernous malformations (CCMs) contribute to focal drug-resistant epilepsy (fDRE), with surgical outcomes varying due to an incomplete understanding of the interplay between CCM-impacted regions and areas exhibiting ictal or interictal epileptogenicity. This study quantified the epileptogenicity of brain structures sampled by stereo-electroencephalography (SEEG) electrodes in patients with fDRE and supratentorial CCMs, focusing on the irritative zone (IZN) and epileptogenic-zone network (EZN). It also established a framework for describing EZN organization relative to CCM-affected regions. METHODS: Retrospective multicentric cohort study involving fDRE patients with supratentorial CCMs, explored using SEEG, recruited from five French tertiary epilepsy centers. SEEG-sampled brain regions were classified as lesional, perilesional, or non-lesion-associated according to their anatomic relationship with the CCMs and using the Virtual Epileptic Patient brain atlas parcellation. IZN quantification was performed using spike rates per minute. EZN was evaluated using the Epileptogenicity Index or Permutation Entropy Index according to the seizure-onset pattern. Data were analyzed using both descriptive and inferential statistics. RESULTS: The study included 22 patients, 10 of whom underwent post-SEEG epilepsy surgery. IZN biomarkers differed significantly between lesional, perilesional, and non-lesion-associated areas, whereas EZN biomarkers did not. EZN included lesional areas in 50% of cases, with complex multi-lobar networks identified in most patients. Postsurgical seizure freedom was achieved in 70% of SEEG-explored patients. CONCLUSIONS: Our findings highlight the complex relationship between CCMs and the EZN, supporting SEEG in the presurgical work-up of selected patients with CCMs and fDRE. A network-based surgical approach may improve outcomes by tailoring resections to the EZN.