SUDEP in inherited metabolic epilepsies

Abstract

Inherited metabolic epilepsies (IMEs) have an increased susceptibility for early mortality, including sudden unexpected death in epilepsy (SUDEP), as they often manifest with frequent drug-resistant seizures, including bilateral tonic-clonic and nocturnal seizures. The metabolic defects inherent to their etiology predispose affected individuals to an additional risk of mortality as they can lead to brain injury, which can induce and be exacerbated by seizures, and to systemic conditions that decrease seizure-cessation and auto-resuscitation processes. The increased risk for SUDEP in IMEs mandates that special emphasis should be given to identifying them early and attempting to achieve seizure control by managing acute metabolic decompensations, anti-seizure medications, and targeted therapies when available. Providing education and support to individuals with IMEs and their families about SUDEP risk factors and prevention strategies is imperative. Despite the increased risk for SUDEP in IMEs, this topic remains understudied. As a proceeding of the 2024 Partners Against Mortality in Epilepsy (PAME) meeting and aiming to increase awareness, this Review describes the pathophysiological and clinical elements related to the heightened risk of SUDEP in IMEs and provides the perspective of a parent of a child with an IME who died from SUDEP. Calling for action, future research on epilepsy-related mortality in IMEs is required. Investigating this field may also yield insights into the general pathomechanisms of SUDEP.