Sevoflurane-based enhancement of phase-amplitude coupling and localization of the epileptogenic zone

ObjectivePhase-amplitude coupling between high-frequency ([≥]150 Hz) and delta (3-4 Hz) oscillations - modulation index (MI) - is a promising, objective biomarker of epileptogenicity. We determined whether sevoflurane anesthesia preferentially enhances this metric within the epileptogenic zone. MethodsThis is an observational study of intraoperative electrocorticography data from 621 electrodes chronically implanted into eight patients with drug-resistant, focal epilepsy. All patients were anesthetized with sevoflurane during resective surgery, which subsequently resulted in seizure control. We classified removed and retained brain sites as epileptogenic and non-epileptogenic, respectively. Mixed model analysis determined which anesthetic stage optimized MI-based classification of epileptogenic sites. ResultsMI increased as a function of anesthetic stage, ranging from baseline (i.e., oxygen alone) to 2 minimum alveolar concentration (MAC) of sevoflurane, preferentially at sites showing higher initial MI values. This phenomenon was accentuated just prior to sevoflurane reaching 2 MAC, at which time, the odds of a site being classified as epileptogenic were enhanced by 86.6 times for every increase of 1 MI. ConclusionsIntraoperative MI best localized the epileptogenic zone immediately before sevoflurane reaching 2 MAC in this small cohort of patients. SignificanceProspective, large cohort studies are warranted to determine whether sevoflurane anesthesia can reduce the need for extraoperative, invasive evaluation. Highlights- We measured the modulation index on intraoperative electrocorticography recording. - Sevoflurane enhanced the modulation index differentially across the epileptogenic and non- epileptogenic sites. - The modulation index best discriminated these two groups of sites before sevoflurane reached 2 minimum alveolar concentration.