Spike ripples localize the epileptogenic zone better than other leading biomarkers: a multicenter intracranial study

ObjectiveWe evaluated whether the combination of epileptiform spikes and ripples (spike ripples) outperformed other leading biomarkers in identifying the epileptogenic zone across subjects in a multicenter international study. MethodsWe validated and applied an automated spike ripple detector on intracranial EEG recordings in subjects from 4 centers who subsequently underwent surgical resection with known 1-year seizure outcomes. We evaluated the spike ripple rate in subjects cured after resection (ILAE 1 outcome) and those with persistent seizures (ILAE 2-5) across sites and recording types. We also evaluated spike, wideband HFO (80-500 Hz), fast ripple (250-500 Hz), and ripple (80-250 Hz) rates using validated automated detectors. The proportion of resected events was computed and compared across subject outcomes and biomarkers. Results109 subjects were included. The majority of spike ripples were removed in subjects with ILAE 1 outcome (p = 1e-6), and this was qualitatively observed across the four sites (p = 0.032, p = 0.092, p = 0.0005, p = 0.003) and the two electrode types (p = 0.01, p = 7e-6). A higher proportion of spike ripples were removed in subjects with ILAE 1 outcomes compared to ILAE 2-5 outcomes (p = 0.02). Among ILAE 1 subjects, the proportion of spike ripples removed was higher than the proportion of spikes (p = 0.0004), wideband HFOs (p = 0.0004), fast ripples (p = 0.008), and ripples (p = 0.008) removed. At the individual level, more subjects with ILAE 1 outcome had the majority of spike ripples removed (40/48, 83%) than spikes (69%, p = 0.04), wideband HFOs (63%, p = 0.009), fast ripples (36%, p = 2e-5), or ripples (45%, p = 0.0007) removed. InterpretationWhen surgical resection was successful, the majority of spike ripples were removed. Automatically detected spike ripples have improved specificity for epileptogenic tissue compared to spikes, wideband HFOs, fast ripples, and ripples.