Abstract
Sudden unexpected death in epilepsy (SUDEP) is defined as a sudden, unexpected, non-traumatic, non-drowning death in a person with epilepsy. SUDEP is generally considered to result from seizure-related cardiac dysfunction, respiratory depression, autonomic nervous dysfunction, or brain dysfunction. Frequency of generalized tonic clonic seizures (GTCS), prone posture, and refractory epilepsy are considered risk factors. SUDEP has also been associated with inherited cardiac ion channel disease and severe obstructive sleep apnea. Most previous studies of SUDEP mechanisms have focused on cardiac and respiratory dysfunction and imbalance of the neural regulatory system. Cardiac-related mechanisms include reduction in heart rate variability and prolongation of QT interval, which can lead to arrhythmias. Laryngospasm and amygdala activation may cause obstructive and central apnea, respectively. Neural mechanisms include impairment of 5-HT and adenosine neuromodulation. The research to date regarding molecular mechanisms of SUDEP is relatively limited. Most studies have focused on p-glycoprotein, catecholamines, potassium channels, and the renin-angiotensin system, all of which affect cardiac and respiratory function.