Sudden unexpected death in epilepsy: Risk factors and potential pathomechanisms
Surges R, Thijs RD, Tan HL, Sander JW, and Medscape (2009) Sudden unexpected death in epilepsy: Risk factors and potential pathomechanisms. Nat Rev Neurol 5:9 492–504.
Abstract: Sudden unexpected death in epilepsy (SUDEP) is the most common cause of death directly related to epilepsy, and most frequently occurs in people with chronic epilepsy. The main risk factors for SUDEP are associated with poorly controlled seizures, suggesting that most cases of SUDEP are seizure-related events. Dysregulation in cardiac and respiratory physiology, dysfunction in systemic and cerebral circulation physiology, and seizure-induced hormonal and metabolic changes might all contribute to SUDEP. Cardiac factors include bradyarrhythmias and asystole, as well as tachyarrhythmias and alterations to cardiac repolarization. Altered electrolytes and blood pH, as well as the release of catecholamines, modulate cardiac excitability and might facilitate arrhythmias. Respiratory symptoms are not uncommon during seizures and comprise central apnea or bradypnea, and, less frequently, obstruction of the airways and neurogenic pulmonary edema. Alterations to autonomic function, such as a reduction in heart rate variability or disturbed baroreflex sensitivity, can impair the body's capacity to cope with challenging situations of elevated stress, such as seizures. Here, we summarize data on the incidence of and risk factors for SUDEP, and consider the pathophysiological aspects of chronic epilepsy that might lead to sudden death. We suggest that SUDEP is caused by the fatal coexistence of several predisposing and triggering factors.
- Thorough overview of potential pathophysiology. Respiratory, cardiac, circulatory, electrolyte, and hormonal changes are discussed. The review highlights the potential for interaction of multiple pathomechanisms, for example, impaired cardiac repolarization due to altered autonomic tone at the same time as decreased blood pH due to adrenergic stimulation, with the potential for newly extracellular protons to further destabilize cardiac function and increase the likelihood of arrhythmia.