Abstracts

Rationale: Mechanistic research into sudden unexplained death in epilepsy (SUDEP) has been hampered by the variety of potential pathologic mechanisms that include cardiac, respiratory, and autonomic dysregulation, and electroencephalogram (EEG) suppression. In the seminal MORtality in Epilepsy Monitoring Units Study (MORTEMUS), a generalized tonic-clonic seizure with terminal apnea preceding asystole was consistently associated with SUDEP. A recent study suggested that ictal central apneas are much more common than previously anticipated[1], raising the possibility that ictal apneas may contribute to SUDEP. The precise pathway that produces apneas during seizures remains unclear. Our group has shown that stimulation of the amygdala can produce transient apnea in epilepsy patients[2]. In this study we aimed to determine if seizure propagation to certain mesial structures such as the amygdala will predict onset of apnea in seizures. Methods: We reviewed all invasive EEGs at our institution since 2010 to determine those investigations where (i) multiple mesial electrodes (amygdala and hippocampal) were placed, (ii) we captured seizures, and (iii) patients’ respiration was monitored. We found 89 seizures in 13 patients that met these criteria; an initial review of the respiratory channels during these events determined potential apneas during 39 seizures. These respiratory signals were graded by an expert both by visual and algorithmic inspection to extract 15 seizures from 5 patients in which there was a confirmed apnea with no significant artifacts. An additional 3 patients with high fidelity respiratory signals were found to have seizures where there were no clear apneas. Seizures were evaluated by three experienced reviewers to mark ictal onset and propagation to the amygdala and hippocampal electrodes. Both patient and seizure characteristics were acquired. Results: We found that onset of ictal apnea associated with each seizure was highly correlated with seizure spread to the amygdala compared to the hippocampus (p<0.01). Apnea occurred on average 3.4 ± 0.9 seconds from ictal spread to the amygdala, with 14 of the 15 seizures having apnea onset under 5 seconds from spread to the amygdala. In each of these cases apnea occured prior to seizure generalization. Apnea onset occurred 10.4 ± 1.1 seconds from spread to the hippocampus with only one seizure where apnea onset occurred in under 5 seconds from hippocampal spread and only when there was diffuse activation of the mesial electrodes at onset. Conclusions: Our findings show that seizure spread to the amygdala occurs shortly before onset of ictal central apnea, in agreement with a prior case report in the literature[3]. These data suggest that activation of amygdalar networks is correlated with central apneas during seizures. This study builds on our prior work that demonstrates a role for the amygdala in voluntary respiratory control and suggests a further role in dysfunctional breathing states seen during seizures with implications for SUDEP pathophysiology.References:1. Lacuey N, et al. Epilepsia. 20182. Nobis WP, et al. Ann Neurol. 20183. Dlouhy BJ, et al. J Neurosci. 2015 Funding: CURE Taking Flight AwardNINDS Center for SUDEP Research Pilot and Feasibility Award 2018