Cardiac Autonomic Dysfunction and Risk of Sudden Unexpected Death in Epilepsy

We aimed to test whether patients who died of sudden unexpected death in epilepsy (SUDEP) had an abnormal cardiac autonomic response to sympathetic stimulation by hyperventilation.

We conducted a retrospective, observational, case-control study of a group of patients who died of SUDEP and controls who were matched to the patients for epilepsy type, drug resistance, sex, age at EEG recording, age at onset of epilepsy, and duration of epilepsy. We analyzed the heart rate (HR) and HR variability (HRV) at rest and during and after hyperventilation performed during the patient's last EEG recording before SUDEP. In each group, changes over time in HRV indexes were analyzed with linear mixed models.

Twenty patients were included in each group. In the control group, the HR increased and the root mean square of successive RR-interval differences (RMSSD) decreased during the hyperventilation and then returned to the baseline values. In the SUDEP group, however, the HR and RMSSD did not change significantly during or after hyperventilation. A difference in HR between the end of the hyperventilation and 4 minutes after its end discriminated well between patients with SUDEP and control patients (area under the receiver operating characteristic curve 0.870, sensitivity 85%, specificity 75%).

Most of patients with subsequent SUDEP have an abnormal cardiac autonomic response to sympathetic stimulation through hyperventilation. An index reflecting the change in HR on hyperventilation might be predictive of the risk of SUDEP and could be used to select patients at risk of SUDEP for inclusion in trials assessing protective measures.