Developmental and epileptic encephalopathies (DEEs) represent the most severe group of epilepsies, characterized by drug-resistant seizures, frequent occurrence of epileptiform activity, developmental delay or cognitive impairment. Recent insights have reframed DEEs from static, genetically determined conditions to dynamic disorders with complex and evolving pathophysiology. Several recent studies suggest a link between epilepsy and neurodegeneration, with increased neuronal excitability preceding seizures in conditions characterized by abnormal protein aggregation. Neurodegeneration, defined as the selective and progressive loss of neuronal cells leading to cognitive and functional decline, underlies many progressive neuronal diseases. Although neurodegeneration biomarkers are widely recognized as markers of disease progression in adults, their role in children is still poorly defined and at times controversial. This narrative review aims to summarize current knowledge on the relationship between epilepsy and neurodegeneration, with a focus on potential biomarkers and their implications for disease mechanisms and progression.
Butera et al. (2026) studied this question.