Cardiac Autonomic Dysfunction and Risk of Sudden Unexpected Death in Epilepsy

Abstract

Objective:We aimed to test whether patients who died from sudden unexpected death in epilepsy (SUDEP) had an abnormal cardiac autonomic response to sympathetic stimulation by hyperventilation.Methods:We conducted a retrospective, observational, case-control study of a group of patients who died from SUDEP and controls who were matched with the patients for epilepsy type, drug resistance, sex, age at electroencephalogram recording, age at onset of epilepsy, and duration of epilepsy. We analyzed the heart rate (HR) and heart rate variability (HRV) at rest, during and after hyperventilation performed during the patient’s last electroencephalogram recording before SUDEP. In each group, changes over time in HRV indexes were analyzed using linear mixed models.Results:Twenty patients were included in each group. In the control group, the HR increased and the 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 min after its end discriminated well between SUDEP patients and control patients (AUC: 0.870; sensitivity: 85%; specificity: 75%).Conclusion:Most of patients with subsequent SUDEP have an abnormal cardiac autonomic response to sympathetic stimulation through hyperventilation. An index reflecting the change in heart rate upon hyperventilation (dHRh) 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.

Heart rate variability modification as a predictive factor of sudden unexpected death in epilepsy: How far are we? A systematic review and meta‐analysis

“…Of these, 24 articles were excluded (see Table S3 for exclusion reasons). Only seven retrospective studies (five case-control studies and two case reports) fulfilled the selection criteria and accessed the following steps (Figure 1) [29,[33][34][35][36][37][38].…”

“…Generally, if multiple EEG + ECG recordings were available, the one with the best ECG data quality was chosen. In all but one study [34], HRV analysis was performed in a resting-state condition (i.e., patients lying on the bed with a normal breathing rate).…”

Advances in sudden unexpected death in epilepsy

“…In a recent study, the researchers analyzed HR and HRV of the patients at rest and during and after hyperventilation performed during the last EEG recording before SUDEP. They found that they had aberrant cardiac autonomic responses to sympathetic stimulation due to hyperventilation, thus suggesting that an index based on HR change on hyperventilation could be used to select patients at risk of SUDEP 48 …”

“…They found that they had aberrant cardiac autonomic responses to sympathetic stimulation due to hyperventilation, thus suggesting that an index based on HR change on hyperventilation could be used to select patients at risk of SUDEP. 48 Therefore, ictal autonomic changes may serve as clues to diagnosis and provide targets for seizure detection, thus helping us to understand the mechanism of SUDEP. Furthermore, monitoring autonomic changes through wearable devices can be conducive to SUDEP prevention.…”

It is premature for a unified hypothesis of sudden unexpected death in epilepsy: A great amount of research is still needed to understand the multisystem cascade

“…There is a higher susceptibility to autonomic disturbances in refractory epilepsy, in close temporal relation to seizures, and in SUDEP cases. [20][21][22][23][24][25] Interictal sympathetic overactivity is seen in most epilepsy, 26 and decreased vagal function is associated with a higher risk of SUDEP. 27 Autonomic measures have been shown to be lower in people with Dravet syndrome compared to healthy controls.…”