High-frequency oscillations are not better biomarkers of epileptogenic tissues than spikes

Nicolas Roehri (1) , Francesca Pizzo (1, 2) , Stanislas Lagarde (1, 2) , Isabelle Lambert (1, 2) , Anca Nica (3) , Aileen Mcgonigal (1, 2) , Bernard Giusiano (1) , Fabrice Bartolomei (1, 2) , Christian-George Bénar (1, 2)

1 INS - Institut de Neurosciences des Systèmes
2 APHM - Assistance Publique - Hôpitaux de Marseille
3 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]

Objective: High-frequency oscillations (HFOs) in intracerebral EEG (stereoencephalography, SEEG) are considered as better biomarkers of epileptogenic tissues than spikes. How this can be applied at the patient level remains poorly understood. We investigated how well the HFOs and the spikes can predict epileptogenic regions with a large spatial sampling at the patient level. Methods: We analyzed non-REM sleep SEEG recordings sampled at 2048 Hz of thirty patients. Ripples (R, 80-250 Hz), fast ripples (FR, 250-500 Hz) and spikes were automatically detected. Rates of these markers and several combinations – spikes co-occurring with HFOs or FRs and cross rate (Spk ⊗ HFO) – were compared to a quantified measure of the seizure onset zone (SOZ) by performing a receiver operating characteristic analysis for each patient individually. We used a Wilcoxon sign rank test corrected for false-discovery rate to assess whether a marker was better than the others for predicting the SOZ. Results: A total of 2930 channels was analyzed (median of 100 channels per patient). The HFOs or any of its variants were not statistically better than spikes. Only one feature, the cross-rate was better than all the other markers. Moreover, fast ripples, even though very specific, did not delineate all epileptogenic tissues. Interpretation: At the patient level, the performance of the HFOs is weakened by the presence of strong physiological HFO generators. Fast ripples are not sensitive enough to be the unique biomarker of epileptogenicity. Nevertheless, combining HFOs and spikes using our proposed measure –the cross rate– is a better strategy than using only one marker.

Domaines: Neurosciences

Nicolas Roehri, Francesca Pizzo, Stanislas Lagarde, Isabelle Lambert, Anca Nica, et al.. High-frequency oscillations are not better biomarkers of epileptogenic tissues than spikes. Annals of Neurology, In press, ⟨10.1002/ana.25124⟩. ⟨hal-01672105v2⟩