Abstracts

Rationale: Poorly controlled epilepsy is associated with higher mortality rates than the general population. A significant number of these deaths are due to Sudden Unexplained Death in Epilepsy (SUDEP). The mechanisms of SUDEP are not completely understood, but may be linked to defective autonomic control of the heart and impaired Heart Rate Variability (HRV). There is growing evidence that vagus-mediated (parasympathetic) components of HRV may be biomarkers of SUDEP. We report a patient who died of autopsy-confirmed SUDEP who underwent serial monitoring of HRV prior to death. To our knowledge, this is the first documented case of SUDEP in whom long-term serial HRV measures were performed prior to death. Methods: A 33-year-old male with a 15 year history of intractable bi-temporal epilepsy was monitored as part of a longitudinal clinical trial. Three HRV measures were taken at four-month intervals, with the final measure taken five weeks prior to his expiration. The HRV values were determined using 1-hour Holter electrocardiography (Phillips Zymed). Artifacts were removed and automated software (Kubios HRV, Kuopio, Finland) was used to compute time-dependent, frequency-dependent, and non-linear measures of HRV. Results: Key measures of HRV progressively declined during the seven months before death. Measures of HRV taken at the final visit, including SDNN (42.4 ms, decreased 43.5% from baseline), and SDANN (18.2 ms, decreased 42.4%) were substantially lower than his baseline and published norms. (Evreng l 2005) HRV measures specifically associated with vagus-mediated parasympathetic control were particularly depressed, including RMSSD (20.4 ms, decreased 35.9%), pNN50 (2.9%, decreased 72.9%), and HF power (102 ms², decreased 71.1%). Conclusions: A progressive deterioration of HRV occurred prior to the patient's death, especially measures associated with vagus control of the heart (RMSSD, pNN50, and HF power). This supports growing evidence that HRV may be a premorbid biomarker of SUDEP. Serial measures of HRV may help to identify subjects at risk for SUDEP.