Abstracts

Rationale: To study the incidence, distribution, and signal characteristics of high frequency oscillations (HFOs) outside the epileptogenic network in the pre-ictal phase during intracranial video EEG evaluation.Methods: Patients with medically intractable epilepsy who underwent invasive intracranial EEG evaluation with a combination of subdural and depth electrodes at Yale Comprehensive Epilepsy Center between 2010-2012 were screened. Cases were included if 1) EEG was sampled at 2000 Hz or higher 2) All major lobes in at least one hemisphere were sampled 3) EEG seizure onset was localizable. Two 10-minute segments of NREM sleep prior to recording the first seizure were selected for analysis. We used an in-house RMS-based and semi-automated MATLAB program to detect and analyze oscillations with peak frequencies higher than 80 Hz. Channels with low signal-to-noise ratio were excluded. For the purposes of this study, a contact location was classified as epileptogenic if it exhibited epileptiform discharges at any time during the intracranial evaluation or was involved ictally within 5 seconds of EEG seizure onset. A contact location was otherwise classified as non-epileptogenic.Results: We analyzed recordings from 699 electrode contacts in 4 patients. The frontal, temporal, parietal, occipital, and insular regions contained 48%, 26%, 13%, 12%, and 1% of the electrodes respectively. The seizure onset was temporal in 3 and frontotemporal in 1. The non-epileptogenic contacts constituted 82.5 % of the total number of channels. Seventy six percent of 10,007 HFO events recorded occurred in non-epileptogenic sites, and were seen in 41 % of the non-epileptogenic contacts (76%, 54%, 34%, and 28% of the occipital, parietal, frontal, and temporal channels respectively). The HFOs from non-epileptogenic sites were seen in all major lobes in all patients. The following sublobes were involved in all the patients: Lateral frontal, lateral parietal, lateral occipital, basal occipital, and mesial occipital. The HFOs from non-epileptogenic sites had longer duration (median 206 vs 137 ms), higher amplitude (median 67 vs 48 mV), and lower peak frequency (median 99 vs 104 Hz) (p<0.0001). High firing rate (> 1/min) was seen in 48 non-epileptogenic electrode contacts, of which 74%, 16%, and 10% were in the occipital, frontal, parietal regions respectively. The peak frequency was less than 126 Hz in 90 % of the HFOs from non-epileptogenic sites. The sensitivity, specificity, positive predictive, and negative predictive values of a contact with HFOs for the seizure onset zone was 61.5 %, 65 %, 3.2 %, and 98.9 % respectively. No fast ripples [>250 Hz] were found in any of the 4 patients from any location.Conclusions: Pre-ictal HFOs are not specific to the seizure onset zone. They are seen in a considerable number of electrode contacts not involved in the epileptic network. In this study, it was 3 times more likely for an HFO event to arise from non-epileptogenic sites than epileptogenic. The consistent occurrence in certain regions in all patients suggests an underlying physiological substrate.