Mini-Seizures: Novel Interictal iEEG Biomarker Capturing Synchronization Network Dynamics at the Epileptogenic Zone
Epilepsy affects 1% of the population, with up to one-third of patients being medication-resistant. Surgery is the only curative treatment, yet over one-third of surgical patients fail to achieve seizure freedom due to the lack of a reliable epileptogenic zone (EZ) biomarker. We introduced and validated mini-seizures, frequent hypersynchronization events at EZ hubs that mirror seizure network dynamics, as a novel interictal EEG biomarker. Using a dynamical networks-based model, we analyzed short interictal intracranial EEG from 159 patients across two institutions. Our model, integrating hypersynchronous network properties and clinical data, successfully identified EZ hubs and accurately predicted one-year postoperative seizure outcomes. Our model (mean F1 score: 87%) outperformed the high-frequency oscillations-based model (mean F1 score: 79%) and seizure onset zone resection-status-based model (current clinical standard) (mean F1 score: 78%), supporting its potential as a robust interictal biomarker for EZ localization. Our findings suggest mini-seizures and seizures exist on a continuum of epileptic events, sharing common network properties. Unlike seizure-based analyses that require 1-2 weeks of monitoring to capture spontaneous seizures, mini-seizures provide a rapid alternative using only brief interictal recordings.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis study was funded by the National Institute of Neurological Disorders and Stroke (NINDS) K23NS128318.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The institutional review board at the University of California, Los Angeles (UCLA) and Wayne State University have approved the protocol. We obtained written informed consent from patients or the guardians of pediatric patients.I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.Yes