Fast Ripples Measured From Overnight SEEG Recordings as Markers of the Epileptogenic Zone: A Multicenter Validation Study

BACKGROUND AND OBJECTIVES: Epilepsy surgery outcomes after intracranial EEG remain suboptimal necessitating the discovery of additional biomarkers to define the epileptogenic zone. Fast ripples (FRs) are a promising, new interictal epilepsy biomarker. By analyzing a multicenter data set consisting of overnight stereo-EEG (SEEG) recordings, we aimed at validating FRs as an accurate marker of the epileptogenic zone. We hypothesized that removing ≥60% of total FR events would significantly increase the odds of good postsurgical outcome (Engel class I). In addition, we compared FRs with spikes, and spikes co-occurring with FRs (spike-FRs) as surgery outcome predictors. METHODS: This retrospective cohort study included consecutive patients from 4 epilepsy surgery centers in Canada, Finland, and Denmark, who underwent SEEG followed by resective surgery or a preplanned ablation procedure separate from the SEEG and had at least 1 year of follow-up. We detected FRs and spikes automatically from overnight SEEG recordings edited for artifacts. To calculate resection ratios of the detected events, we determined resected SEEG contacts by superimposing the peri-implantation and postresection images. We evaluated postsurgical seizure outcomes from medical records. RESULTS: Of the 73 included patients (mean age 23 ± 12 years, 41% female), 46 had good and 27 had poor (Engel classes II-IV) outcome at the latest follow-up. Patients with FR resection ratio ≥0.6 were more likely to achieve good postsurgical outcome (p < 0.001, diagnostic odds ratio [DOR] 10, 95% CI 2.7-39). Of those with ≥0.6 FR resection ratio, 26 of 29 (90%, 95% CI 74%-96%) achieved good outcome, whereas of those with <0.6 FR resection ratio, 24 of 44 (55%, 95% CI 46%-63%) had poor outcome, with overall accuracy of 68% (95% CI 57%-79%). In addition, the spike-FR resection ratio ≥0.6 was associated with good postsurgical outcome (p = 0.007, DOR 4.1, 95% CI 1.4-12, accuracy 64%, 95% CI 52%-75%), whereas the spike resection ratio ≥0.6 was not. DISCUSSION: In accordance with our hypothesis, the FR resection ratio ≥0.6 significantly increased the odds of attaining good postsurgical seizure outcome. Although the FR resection ratio ≥0.6 accurately predicted good postsurgical outcome, resecting <0.6 of FRs did not necessarily mean poor outcome. As predictors of postsurgical outcome, spikes fared poorly, whereas spike-FRs were comparable with FRs.