Sudden unexpected death in epilepsy: is death by seizures a cardiac disease?

Sudden unexpected death in epilepsy (SUDEP) gains more and more acknowledgment across the various interdisciplinary fields. Accordingly, we performed in a prospective setting a case-control study of all SUDEP cases in a well-defined part of Denmark (Northern Jutland), between January 1998 and September 2000. We attempted to look into the cardiopathologic mechanism behind this phenomenon by assessing the degree of myocardial fibrosis in SUDEP patients versus controls. The histologic evaluation was possible in 65% of the cases (15/23) whose death was attributed to SUDEP and in 71% (15/21) of controls. Forty percent of the SUDEP cases (6/15) presented several foci of fibrotic changes in the deep and subendocardial myocardium in contrast to 1 control (6.6%, P = 0.03). None of the subjects from the SUDEP group showed fibrotic changes in their conduction system as compared with 1 control (6.6%). The quantitative evaluation of fibrosis demonstrated a trend toward more fibrosis in the deep and subendocardial myocardium of the SUDEP cases. Forty percent of cases in the SUDEP group were men (6/15), characteristically young at time of death (mean age 38 years) and with a late epilepsy onset (mean age 21 years). Antemortem, 73% of the SUDEP patients (11/15) had experienced infrequent seizures (self-reported). We conclude that the SUDEP cases displayed significant fibrosis of the myocardium when this was assessed by qualitative means. This fibrosis may be the consequence of myocardial ischemia as a direct result of repetitive epileptic seizures, which, associated with the ictal sympathetic storm, may lead to lethal arrhythmias.