Accumulation of rest deficiency precedes sudden death of epileptic Kv1.1 knockout mice, a model of sudden unexpected death in epilepsy

Abstract

Objective: Chronic sleep deficiency is associated with early mortality. In the epileptic population, there is a higher prevalence of sleep disorders, and individuals with severe refractory epilepsy are at greater risk of premature mortality than the general population. Sudden unexpected death in epilepsy affects 1:1000 cases of epilepsy each year. Ketogenic diet (KD) treatment is one of the few effective options for refractory seizures. Despite KD reducing seizures and increasing longevity in Kv1.1 knockout (KO) mice, they still succumb to sudden death. This study aims to determine whether (1) the rest profiles of KO and KD-treated KO (KOKD) mice resemble each other as a function of either age or proximity to death and (2) the timing of death correlates with acute or chronic changes in rest. Methods: Noninvasive actimetry was used to monitor rest throughout the lives of KO and wild-type (WT) littermates administered standard diet or KD. Results: As KO mice age, rest is reduced (P