Circadian Distribution of Ictal Activity in the Thalamocortical Lennox-gastaut Network
Abstract number :
1.182
Submission category :
2. Translational Research / 2A. Human Studies
Year :
2024
Submission ID :
1198
Source :
www.aesnet.org
Presentation date :
12/7/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Lise Johnson, PhD – NeuroPace, Inc.
Thomas Tcheng, PhD – NeuroPace
Muhammad Furqan Afzal, PhD – NeuroPace, Inc.
John Rolston, MD, PhD – Brigham and Women's Hospital, Harvard Medical School
Christopher Butson, PhD – University of Florida
Aaron Warren, PhD – Brigham and Women's Hospital, Harvard Medical School
Jiyeoun (Jenna) Yoo, MD – Icahn School of Medicine at Mount Sinai
Robert Gross, MD, PhD – Rutgers New Jersey Medical School
Vikram Rao, MD, PhD – University of California San Francisco
Jerzy Szaflarski, MD, PhD – University of Alabama
Nicole Bentely, MD – University of Alabama, Birmingham
Zeenat Jaisani, MD – University of Alabama, Birmingham
Andrew J. Cole, MD – Massachusetts General Hospital, Harvard Medical School
Saadi Ghatan, MD – Mount Sinai Health System
Edward Chang, MD – University of California, San Francisco
Daniel Friedman, MD – New York University Grossman School of Medicine, NYU Langone Health
Katie Bullinger, MD, PhD – Emory University School of Medicine
Mark Richardson, MD, PhD – Massachusetts General Hospital
Sharanya Arcot Desai, PhD – NeuroPace, Inc.
David Greene, BS – NeuroPace, Inc.
Martha Morrell, MD – NeuroPace
Rationale: Lennox-Gastaut Syndrome (LGS) is a severe generalized epilepsy that is the focus of an ongoing feasibility trial with the RNS® System (NCT05339126). Trial participants have leads implanted in two putative nodes of the LGS network: the frontal cortex and the centromedian nucleus of the thalamus (CM). Although LGS is characterized by frequent and severe seizures, recurrent periods with very few ictal detections are observed in trial patients. Furthermore, because some of the distinctive EEG-features of LGS are associated with sleep, it is expected that detection of ictal activity may be modulated by the time of day. Circadian and multidien patterns are common in epilepsy and have been documented (Baud et al., Nat Comm, 2018, v9:p88) in the time-series of detection counts collected by the RNS System in focal epilepsy. A similar analysis was applied to the thalamocortical trial data to reveal underlying circadian dynamics in the LGS network.
Methods: Trial participants (N=12) received two bilateral neurostimulator implants, each with a cortical strip lead targeted at the LGS cortical “hot spot” and a depth lead targeted at the CM (Warren et al., Brain Comm, 2024, v6:3). Four detectors were enabled on each device: a low frequency and a high frequency detector on each lead. Detection parameters were individually fine-tuned for early and accurate detection of ictal activity. Detections were binned at hour-long resolution and collapsed across detectors on each lead. Circular statistics were used to estimate the mean and standard deviation circadian phase.
Results: Detection rates in all participants were modulated by the time of day (Hodges-Ajne Omnibus test, p< 0.05). The number of cortical detections was much greater than the number of thalamic detections in all patients, and the circadian phase of the cortical detection histograms was more consistent than thalamic across the different treatment periods of the trial. Although the time-of-day distribution of detections was variable across patients, cortical detections tended to peak overnight or in the morning hours. The circadian phase of thalamic detections was not generally in phase with the peak of cortical detections. Within patients, the distributions of cortical detections were similar between the left and right hemispheres (median % overlap=82, range= 66-98, N=11). Thalamic detection patterns were more variable (median % overlap= 62, range=10-89, N=11) and detections were often much more frequent on one side as compared to the other.
Translational Research