Authors :
Presenting Author: Ethan Firestone, MS – Wayne State University
Hiroshi Uda, MD, PhD – Wayne State University
Naoto Kuroda, MD, PhD – Wayne State University
Kazuki Sakakura, MD, PhD – Rush University
Riyo Ueda, MD, PhD – Wayne State University
Masaki Sonoda, MD, PhD – Yokohama City University
Yu Kitazawa, MD, PhD – Yokohama City University
Min-Hee Lee, PhD – Wayne State University
Jeong-Won Jeong, PhD – Wayne State University
Aimee Luat, MD – Children’s Hospital of Michigan
Michael Cools, MD – Children's Hospital of Michigan
Sandeep Sood, MD – Wayne State University
Eishi Asano, MD, PhD – Wayne State University
Rationale:
Sevoflurane anesthesia may improve intraoperative localization of seizure-causing brain regions because it rapidly and reversibly augments epileptiform signaling on electrocorticography (ECoG). However, our previous study demonstrated that sevoflurane activated two objective ECoG epilepsy biomarkers – high-frequency oscillation (HFO) phase-amplitude coupling with delta waves and effective connectivity – even in non-epileptogenic sites. Before applying this system to prospectively identify seizure networks, it is thus critical to determine the expected response of the ECoG epilepsy biomarkers under sevoflurane, in normative brain.
Methods:
The study analyzed electrodes from 19 pediatric patients who underwent resective surgery for drug-resistant, focal epilepsy. All patients experienced intraoperative ECoG recording under isoflurane and stepwise increasing sevoflurane. A subset of patients also underwent extraoperative intracranial EEG during slow wave sleep. Isoflurane (n = 963 normative electrodes) and slow wave sleep (n = 816 normative electrodes) were redundant controls. To determine the normative anatomical distribution of ECoG biomarkers at various anesthetic stages, pooled electrodes were interpolated onto a standardized cortical surface. Dynamic tractography then delineated white matter pathways linking cortical hotspots with significantly elevated ECoG-based biomarkers. A second analysis utilized all electrodes, regardless of normality (n = 1,608 electrodes isoflurane | n = 1,344 electrodes slow wave sleep), to retrospectively determine if the intraoperative sevoflurane-activated ECoG biomarkers could identify epileptogenic sites.
Results:
Linear mixed model analysis suggested that ECoG biomarkers generally increased as a function of sevoflurane concentration, in normative brain regions. Dynamic tractography demonstrated that normative delta-HFO phase-amplitude coupling hot spots in homotopic Rolandic regions were connected via interhemispheric callosal fibers. Whereas the normative HFO effective connectivity hotspots in frontal and parietal areas were connected via the superior longitudinal fasciculus. Binary logistic mixed model analysis suggested that relatively higher ECoG biomarker values were associated with epileptogenic zone status, especially at a sevoflurane concentration of three to four volume-percent.
Conclusions:
These results lay the groundwork for proper interpretation of delta-HFO phase-amplitude coupling and HFO effective connectivity under sevoflurane. That our binary logistic mixed models were significant prompt prospective studies to assess the efficacy of using sevoflurane-activated ECoG to optimize intracranial EEG electrode sampling and intraoperative localization of the epileptogenic zone.
Funding:
This work was supported by NIH grants F30NS129239 (to E.F.), NS064033 (to E.A.), and NS089659 (to J.W.J.), as well as JSPS KAKENHI grants JP22J23281 and JP22KJ0323 (to N.K.).