Abstracts

Rationale: Sudden unexpected death in epilepsy (SUDEP) is the leading cause of mortality in epilepsy. Although several mechanisms have been proposed, the role of SUDEP-related pulmonary physiologic triggers, albeit with strong biologic plausibility, remains understudied. We leverage integrated stereo-electroencephalography (SEEG) and respiratory recordings to characterize seizure-respiratory physiologic inter-relationships to enhance understanding of SUDEP mechanistic underpinnings. Methods: Recordings of adults undergoing SEEG for surgical localization were analyzed including airflow (temperature and pressure based), respiratory effort (respiratory inductance plethysmography), EKG, pulse oximetry, end tidal CO2 (EtCO2; Nihon Kohden Nomad) and transcutaneous CO2 (TcpCO2; Sentec). Custom data visualization and analysis software allowed for alignment of segments from different systems. Identification of ictal EEG landmarks and determination of baseline, ictal and postictal variables of interest (SpO2 nadir, EEG onset-nadir, peak TcpCO2/ EtCO2 and EEG onset/end-peak CO2) were performed. Results: Sixty-three patients consented and 34 seizures (8 GTC, 23 partial, 3 auras) from 15 patients (age 34 +10, 68% male) were recorded. Most implantations explored posterior perisylvian and limbic networks (6 BL, 7 left, 2 right). Median [IQR] seizure duration was 73 sec [26.0,143.0]. Body positions were supine (55%), side (24%) and sitting (21%). Median nadir SpO2 was 92%[83.0,94.0], minimum 65%, nadir 149.6sec [88.9,471.8] post EEG onset. Median TcpCO2 was 44.8mmHg [42.9,51.4], maximum 69.9mmHg, peak 154.2sec [36.2,356.5] post EEG onset, persisting 39.8sec [-16.8,156.5] post EEG termination. EtCO2 results were similar in short seizures, but not analyzable in others due to artifact (Figure 1: TcpCO2 increases post EEG onset [pink], further post contralateral spread [brown] and EEG termination [green] peaking at 70mmHg 120sec post EEG termination  shown on right and a trend toward increasing EtCO2, but appearing unreliable on left). Seizures with postictal generalized EEG suppression (PGES; N=6, 17.6%) vs. others had similar findings of median SpO2 nadir (72 vs. 92%; p=0.21), peak EtCO2 (50 vs. 44mmHg; p=0.17) and peak TcCO2 (70 vs. 45mmHg; p=0.99). Figure 2 demonstrates signal integration in a 500 sec epoch of SEEG, EtCO2 (green), TcpCO2 (red), respiratory effort, EKG (top to bottom) in a partial seizure lasting 491 sec of left hippocampal/entorhinal/anterior fusiform origin (top EEG) evolving to insula/posterior cingulate (bottom EEG). SpO2 nadir of 70% (not shown) was 118sec and peak TcpCO2 of 54mmHg (red horizontal line, blue arrow) was 9 min post EEG onset. EtCO2 (green line) shows increasing values but appears unreliable with peak of 20mmHg. Irregular, chaotic breathing (black arrow) normalizes at EEG end. Tachycardia coinciding with insular activation (1st red arrows) slows once the seizure ends in that region (2nd arrows). Conclusions: Signal integration allowed for comprehensive visual and analytical assessment of respiratory changes in SEEG-recorded seizures, although capture of optimal signal quality was challenging. TcpCO2 recordings were more reliable than EtCO2. Important but not significantly different SpO2 and CO2 changes were observed despite lack of prone position in seizures with and without PGES. Funding: Clinical Translational Science Collaborative of Cleveland, UL1TR000439.