The insula lobe and sudden unexpected death in epilepsy: a hypothesis

Sudden unexpected death in epilepsy (SUDEP) is a major cause of death in patients with refractory epilepsy, particularly those with chronic epilepsy. The physiopathological mechanisms underlying SUDEP have not been elucidated. Autonomic dysregulation of cardiac or respiratory function is thought to underlie SUDEP. Here, we present a summary of available evidence on the involvement of the insular lobe in the regulation of cardiorespiratory function. Ictal discharge that originates in the cortex can, primarily or secondarily, involve the insula lobe through epileptogenic signal networks, leading to cardiorespiratory dysfunction, central apnoea, arrhythmias, and sudden death in patients with epilepsy. Thus, the insula lobe appears to be instrumental in the causation of SUDEP.