Abstracts

Rationale: Sudden unexpected death in epilepsy (SUDEP) is an important cause of mortality in epilepsy, but little is known about its pathophysiology. A recent case-control study (Lhatoo, et al. 2010) prompted by several case reports found SUDEP was associated with post-ictal generalized EEG suppression (PGES). Evidence from animal models and human subjects prescribed SSRIs indicate that serotonin may play a critical role in respiratory function during the post-ictal period. We aimed to explore the relationship between serotonin and PGES, to evaluate occurrence of PGES in our patient population, and to document any associated findings. Methods: PET was performed with 18F-FCWAY for 5HT1A receptor binding estimation and 18F-FDG for glucose metabolism (CMRglc). After partial volume correction, 5HT1A receptor binding and CMRglc were measured in regions drawn on co-registered MRI. 18F-FCWAY PET binding was determined in various regions of interest (ROI) for each patient and asymmetry indices (AI) were calculated for ROIs in the cerebral hemispheres. Patients with medically refractory localization-related epilepsy who had at least one secondarily generalized convulsive seizure recorded on video EEG from 2002-2010 were identified from the 18F-FCWAY PET database. The first such seizure of each patient was reviewed by an author blinded to PET results (JMS) and analyzed for seizure duration (focal/ generalized), PGES duration, return of spontaneous movement, EKG abnormality, and apnea. PGES was defined as generalized absence of electroencephalographic activity > 10 µV in amplitude, allowing for muscle, movement, breathing, and electrode artifacts. We analyzed 18F-FCWAY PET binding in the median raphe nucleus and the ROI corresponding to a patient's seizure focus, then compared values in groups with and without PGES using Student's t-test. Results: Twelve patients who fulfilled the above criteria were identified. 42% were female with mean age 34 years at time of video EEG. Five had right temporal lobe epilepsy, six had left temporal lobe epilepsy, and one had left frontal lobe epilepsy. Seven (58%) had PGES with mean duration 58 seconds. Patient demographics were similar between groups with and without PGES. PGES was not associated with seizure duration (total [p=0.46] and generalized [p=0.44]) or latency to return of spontaneous movement (p=0.85). No patients had apnea or EKG abnormalities other than sinus tachycardia in the post-ictal period. There were no group differences in 18F-FCWAY binding in the median raphe nucleus (p=0.5) and the AI in ROI(s) corresponding to a patient's seizure focus (p=0.77). Conclusions: PGES is common in individuals with medically refractory localization-related epilepsy. It is not known whether a link between PGES and dysfunctional serotonergic neurotransmission exists, or if they represent two separate mechanisms that may contribute to SUDEP. Our study was not sufficiently powered to detect differences in 18F-FCWAY binding. Further study into SUDEP pathophysiology is crucial to guide prevention strategies.