Abstracts

Rationale: Sudden unexpected death in epilepsy (SUDEP) is a leading cause of epilepsy-related mortality, yet the physiological mechanisms remain unknown. Epilepsy is a complex syndrome involving seizures and associated comorbidities, including neuroendocrine and sleep dysfunction. These may in turn influence cardiac, respiratory and autonomic physiology. To date, no studies have directly explored these interactions in relation to SUDEP. This study sought to characterize the relationship between epilepsy, neuroendocrine function, sleep disordered breathing, peri-ictal physiology and perceived SUDEP risk.Methods: This was a prospective longitudinal observational study. Participation was offered to eligible subjects admitted to the adult epilepsy monitoring unit at Columbia University Medical Center. Subjects were stratified into high, medium or low SUDEP risk groups based on calculation of the SUDEP-7 inventory score described by DeGiorgio, et al., 2010 and an “ILAE score” based on the total number of independent SUDEP risk factors identified in the combined analysis of Hesdorffer, et al., 2011. Subjects with a SUDEP-7 score 1-4, 4-8, 9-12/ILAE score 0-1, 2-3, 4-5, 5-6 were considered low risk, medium risk, and high risk respectively. Serum levels of testosterone, estradiol, progesterone, LH, FSH, SHBG, cortisol and prolactin were examined. Video-EEG recordings were analyzed for characterization of seizures, peri-ictal cardiorespiratory function and post-ictal generalized EEG suppression (PGES). A measure of heart rate variability, the RMSSD, was calculated. Polysomnography was performed to evaluate for sleep disordered breathing.Results: 33 subjects, 16 female and 17 male, met criteria for inclusion. Mean age was 37 years. Mean duration of epilepsy was 16 years. 16 were classified as having low risk of SUDEP, 13 were medium risk, and 4 were high risk. 25 subjects had seizures recorded which included simple partial seizures, complex partial seizures, myoclonic seizures and generalized tonic clonic seizures (GTCS). None of the four subjects who experienced GTCS were in the high risk group. Ictal arrhythmias were seen in all groups, most commonly ictal tachycardia, but also bradycardia, premature beats and ST-T changes. Peri-ictal respiratory changes included hyperventilation, apnea, gasping and oxygen desaturations. PGES was seen in two medium-risk subjects with GTCS and was not seen in any other seizure type. Evidence of neuroendocrine dysfunction was present in half the subjects. Mild sleep disordered breathing was seen in all groups but was only of sufficient severity to meet criteria for a diagnosis of OSA in the high SUDEP risk group.Conclusions: Peri-ictal cardiorespiratory dysfunction and neuroendocrine disturbances were common in this study, consistent with previous reports. Individuals perceived to be at highest risk for SUDEP were more likely to have sleep disordered breathing. This study suggests the presence of new and potentially modifiable risk factors for SUDEP, which could guide future interventions to reduce SUDEP risk.