Progressive central cardiorespiratory rate downregulation and intensifying epilepsy lead to sudden unexpected death in epilepsy in mouse model of the most common human ATP1A3 mutation

Atp1a3Mashl/+, an alternating hemiplegia of childhood (AHC) model, is also a revealing SUDEP model of Na⁺/K⁺-ATPase mutation resulting in abnormal central respiratory drive and in progressive cardiorespiratory dysregulation concurrent with worsening epilepsy. SUDEP results from seizure-triggered bradypnea/bradycardia followed by terminal apnea, then terminal cardiac arrhythmias. Because many epilepsy/SUDEP models of other etiologies manifest secondary ATPase deficiency, future studies in those models may benefit from considering possible contributions of ATPase dysfunction to SUDEP in those models too.