Abstracts

Rationale: Surgical treatment for drug-resistant epilepsy is often a two-stage process involving extraoperative, intracranial EEG (iEEG) recording, and the dual surgeries are physically, emotionally, and financially taxing on participants. To reduce this burden and optimize postoperative seizure control, there is great need to develop intraoperative techniques capable of localizing the epileptogenic zone. Given that evidence suggests sevoflurane enhances interictal spikes and high-frequency oscillation (HFO) on intraoperative recording, we sought to further investigate defining features of these electrophysiologic signatures to help pave the way for an anesthetic-based iEEG protocol that reduces the need for two-stage surgery. We specifically aimed to better understand how sevoflurane modulates the subdurally-recorded phase-amplitude coupling between HFO and slow waves, as well as their spectrum amplitudes and inter-regional effective connectivity.

Methods: This is an observational study of eight patients with drug-resistant epilepsy, aged 4-22 years old (5 males), who achieved seizure freedom following a two-stage resective surgery at the National Center of Neurology and Psychiatry, Tokyo, Japan. During surgery, each patient was anesthetized with a propofol-based induction followed by sevoflurane-based maintenance, and intraoperative iEEG was recorded throughout. To characterize the effects of sevoflurane on iEEG at the resected and preserved sites, we retrospectively analyzed the amplitude of low-delta (0.5-2 Hz), high-delta (3-4 Hz), and high frequency oscillations (80-300 Hz), as well as phase-amplitude coupling (PAC) between 3-4 Hz and 80-300 Hz. Finally, transfer entropy (TE)—a measure of effective connectivity—was calculated for the three frequency bands mentioned above. All measures were compared between the baseline, three time points during the sevoflurane maintenance, and another when it reached 2 minimum alveolar concentration (MAC).

Results: As sevoflurane was increased from 0 to 2 MAC, HFO amplitude and PAC were increased preferentially in the resected sites; the classification ability of these measures was highest during the period immediately prior to when the sevoflurane reached 2 MAC. In contrast, low- and high-delta amplitude were increased preferentially in the preserved sites. For effective connectivity, resected sites were correlated with elevated HFO-based TE at all time points, although most strongly at 2 MAC. Alternatively, high-delta-based TE was higher in the preserved sites during the period just before achieving 2 MAC.

Conclusions: Increasing sevoflurane may enhance HFO spectral output, PAC with 3-4 Hz delta oscillations, and TE-defined effective connectivity within resected sites. It appears that this enhancement may be permitted via hypersynchronization with slow wave activity, which provides a critical window of disinhibition when high-delta amplitude and TE are reduced immediately prior to achieving 2 MAC of sevoflurane.

Funding: Please list any funding that was received in support of this abstract.: KAKENHI Grant JP19K09494 (to M.I.) and NIH grant NS064033 (to E.A.).