Left-insular damage, autonomic instability, and sudden unexpected death in epilepsy

•The insula is a cortical structure involved in autonomic function.•Insular damage is associated with mortality through autonomic dysfunction.•In patients with refractory epilepsy and SUDEP, insular damage and autonomic dysfunction may play a role.

We analyzed the only two sudden unexpected death in epilepsy (SUDEP) cases from 320 prospectively recruited patients in the three-year Prevention and Risk Identification of SUDEP Mortality (PRISM) project. Both patients had surgically refractory epilepsy, evidence of left insular damage following previous temporal/temporo-insular resections, and progressive changes in heart rate variability (HRV) in monitored evaluations prior to death. Insular damage is known to cause autonomic dysfunction and increased mortality in acute stroke. This report suggests a possible role for the insula in the pathogenesis of SUDEP. The presence of intrinsic insular lesions or acquired insular damage in patients with refractory epilepsy may be an additional risk factor for SUDEP.