Authors :
First Author: Alexander Yearley, BA – Harvard Medical School
Presenting Author: Niels Pacheco, MD, MSc – Brigham and Women Hospital
Elliot Smith, PhD – University of Utah; Tyler Davis, MD, PhD – University of Utah; Daria Anderson, PhD – University of Sydney; Amir Arain, MD, MPH – University of Utah; John Rolston, MD, PhD – Brigham and Women's Hospital
Rationale:
Interictal epileptiform discharges (IEDs) are intermittent high-amplitude electrical signals that occur between seizures, many of which propagate through brain tissue as traveling waves.
1 If properly understood, IEDs have the potential to improve our ability to localize the seizure onset zone (SOZ) quickly and reliably. Current standard of care involves intracranial monitoring for seizure activity by stereo-electroencephalography (SEEG). In this study, we aimed to identify IED travelling waves from SEEG electrode recordings of epilepsy patients and correlate IED characteristics with clinical outcomes, seizure activity, and the location of the SOZ.
Methods:
Continuous 24-hour SEEG recordings from 15 epilepsy patients were collected. After signal filtering and normalization, IEDs were detected using an algorithm that identified overlapping peaks of a minimum prominence that varied by patient. The timings of local voltage minima were regressed against the Euclidean distance, probability of a connection by tractography, and axonal path length between electrodes to identify IED traveling waves. The SOZ in each patient was defined by a neurologist based on SEEG recordings of seizure activity. Traveling wave pathways were compared to the SOZ location and linear regression models were employed to associate IED characteristics with clinical outcomes.
Results:
A median of 22.6 (range 4.4-183.9) IEDs were detected per hour from 15 patients over a mean of 23.2 hours of recording. Across all patients, a median of 61.8% (range 51.4-90.3) of IEDs were traveling waves. A median of 20.8% (range 0.0-54.5) and 53.1% (range 11.5-97.8) of IEDs per patient passed through the SOZ and the immediately surrounding region. Patients with a greater number of IEDs (r2 = 0.44, p = 0.007) and a higher proportion of IED traveling waves (r2 = 0.57, p = 0.001) had a greater proportion of IEDs that localized to the SOZ. The proportion of IED travelling waves inversely correlated with the number of baseline (r2 = 0.26, p = 0.05) and post-treatment seizures (r2 = 0.25, p = 0.06); however, there was no significant association between the proportion of IED traveling waves and the post-treatment change in seizure frequency (r2 = 0.02, p = 0.63).
Conclusions:
IEDs detected on SEEG correlate with seizure activity. IEDs heterogeneously localized to the SOZ, but patients with a greater number of IED detections and a higher proportion of IED traveling waves had a significantly greater degree of IED colocalization to the SOZ, making these attributes potentially useful biomarkers for SOZ localization. Incorporation of IED analyses into the clinical workflow has the potential to improve localization of the SOZ and provide potentially valuable information about a patient’s epilepsy.
References:
1. Smith EH, Liou J-y, Merricks EM, Davis T, Thomson K, Greger B, et al. Human interictal epileptiform discharges are bidirectional traveling waves echoing ictal discharges eLife. 2022 2022/01/20;11:e73541.
Funding:
JDR was supported by an NIH/NINDS K23 Career Development Award (NS114178).