Scalp ripples as prognostic biomarkers of epileptogenicity in pediatric surgery

OBJECTIVE: To assess the ability of high‐density Electroencephalography (HD‐EEG) and magnetoencephalography (MEG) to localize interictal ripples, distinguish between ripples co‐occurring with spikes (ripples‐on‐spike) and independent from spikes (ripples‐alone), and evaluate their localizing value as biomarkers of epileptogenicity in children with medically refractory epilepsy. METHODS: We retrospectively studied 20 children who underwent epilepsy surgery. We identified ripples on HD‐EEG and MEG data, localized their generators, and compared them with intracranial EEG (icEEG) ripples. When ripples and spikes co‐occurred, we performed source imaging distinctly on the data above 80 Hz (to localize ripples) and below 70 Hz (to localize spikes). We assessed whether missed resection of ripple sources predicted poor outcome, separately for ripples‐on‐spikes and ripples‐alone. Similarly, predictive value of spikes was calculated. RESULTS: We observed scalp ripples in 16 patients (10 good outcome). Ripple sources were highly concordant to the icEEG ripples (HD‐EEG concordance: 79%; MEG: 83%). When ripples and spikes co‐occurred, their sources were spatially distinct in 83‐84% of the cases. Removing the sources of ripples‐on‐spikes predicted good outcome with 90% accuracy for HD‐EEG (P = 0.008) and 86% for MEG (P = 0.044). Conversely, removing ripples‐alone did not predict outcome. Resection of spike sources (generated at the same time as ripples) predicted good outcome for HD‐EEG (P = 0.036; accuracy = 87%), while did not reach significance for MEG (P = 0.1; accuracy = 80%). INTERPRETATION: HD‐EEG and MEG localize interictal ripples with high precision in children with refractory epilepsy. Scalp ripples‐on‐spikes are prognostic, noninvasive biomarkers of epileptogenicity, since removing their cortical generators predicts good outcome. Conversely, scalp ripples‐alone are most likely generated by non‐epileptogenic areas.