Risk of Sudden Unexpected Death in Patients with Epilepsy and Cardiac Autonomic Dysfunction

An abnormal cardiac autonomic response to sympathetic stimulation from hyperventilation is associated with an increased risk of Sudden Unexpected Death in Epilepsy (SUDEP), according to study results published in Neurology.

While functional changes in the autonomic nervous system can play a key role in the pathophysiology of SUDEP, previous studies have provided mixed data on the association between heart rate variability and risk for SUDEP. The aim of the current study was to determine the effect of hyperventilation on heart rate variability (HRV) in patients with SUDEP and appropriate controls.

This retrospective, observational case-control study included all cases of SUDEP from 5 French university hospitals between January 1, 2010 and March 31, 2019. Heart rate and HRV parameters were measured at rest, during and after hyperventilation during the last Electroencephalogram recording assessed prior to SUDEP. The study researchers compared controls with patients for epilepsy type, drug resistance, gender, age at which the electroencephalogram was recorded, age at onset of epilepsy, and duration of epilepsy.

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They calculated several HRV indices for a time window of 64 seconds: the standard deviation of normal to normal RR intervals, the root mean square of consecutive RR interval differences (RMSSD), and low and high frequency performance. The study researchers then averaged each HRV parameter for 56 consecutive time windows.

The sample included 20 of 35 recorded SUDEP cases (men, 10; mean age at onset of epilepsy, 12.5 years), including 3 definitive SUDEP and 17 probable SUDEP cases.

At rest, there were no differences in HRV parameters between the SUDEP group and controls, with the exception of high frequency performance, which was significantly higher in the SUDEP group (P = 0.033).

During hyperventilation, the heart rate increased and the RMSSD decreased before returning to baseline about 2 and +4 minutes after the end of hyperventilation in patients in the control group. In the SUDEP group, however, there were no significant changes in heart rate and RMSSD during or after hyperventilation.

Differences in heart rate between the consecutive times before and after hyperventilation made it possible to distinguish between SUDEP patients and controls; The greatest differentiating factor between the groups was recorded for the change in heart rate between the end of hyperventilation and 4 minutes later with a sensitivity of 85% and a specificity of 75%.

The study had several limitations, including the small sample size, the exclusion of patients who could not perform hyperventilation, and the retrospective design.

“Most patients with subsequent SUDEP have an abnormal cardiac autonomic response to sympathetic stimulation from hyperventilation. An index reflecting the change in heart rate with hyperventilation (dHRh) could predict SUDEP risk and be used to select SUDEP at risk patients for inclusion in studies to evaluate protective measures, ”the study researchers said.


Szurhaj W., Leclancher A., ​​Nica A. et al. Autonomic cardiac dysfunction and risk of sudden unexpected death in epilepsy. Neurology. Published online April 9, 2021. doi: 10.1212 / WNL.0000000000011998

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