Finding the missing link between ictal bradyarrhythmia, ictal asystole, and sudden unexpected death in epilepsy

Basic science studies of the human brain have supported the cortical representation of cardiovascular responses, including heart rate variability. Clinical observations of ictal bradyarrhythmia may be mechanistically explained by the influence of the central autonomic network, although the localization and lateralization issues need to be considered in the light of patterns of seizure spread, hand dominance, and presence of lesions. Ictal bradyarrhythmia also offers a mechanistic explanation of sudden unexpected death in epilepsy (SUDEP), though it may explain only some but not all cases of SUDEP. The missing links are (1) clinical evidence of common factors shared by patients with ictal bradyarrhythmia and patients who die from SUDEP, (2) evidence of arrhythmia as a risk factor for SUDEP from epidemiological studies, and, (3) determination of the importance of ictal bradyarrhythmia in SUDEP with respect to other proposed mechanisms including apnea and intrinsic cardiac abnormalities. There remains a need to review the seizure mechanisms in cases of SUDEP and to step up the amount of concurrent ECG/intracranial EEG analysis in both ictal bradyarrhythmia and SUDEP cases.