To what extent does status epilepticus contribute to brain damage in the developmental and epileptic Encephalopathies.

Abstract

This paper is based on a presentation made at the 9th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures in April 2024. Status Epilepticus (SE) is a neurological emergency involving prolonged seizures that disrupt brain function and may cause severe, long-term neurological damage. Developmental and Epileptic Encephalopathies (DEEs), a group of severe genetic disorders with early-onset epilepsy, often exhibit SE episodes that compound their inherent cognitive and developmental challenges. In patients with DEEs, SE may intensify excitotoxicity, metabolic strain, and neuroinflammatory processes, exacerbating developmental delays and cognitive deficits. SE episodes in DEEs frequently resist conventional anti-seizure medications, posing heightened risks of progressive neurological decline and mortality. This paper explores how SE contributes to worsening neurodevelopmental outcomes in DEEs, particularly through sustained structural and functional brain alterations observed in human neuroimaging and animal models. Findings from clinical studies and neuroimaging highlight SE's role in structural damage, including cortical atrophy, hippocampal sclerosis, and gray matter loss. Rodent models replicate SE through chemical or electrical induction, providing insights into SE-induced neurodegeneration, network reorganization, especially in critical areas like the hippocampus, which is more known, however few of scientists look that much outside it. The models reveal a progressive cycle where recurrent SE episodes increase brain excitability, predisposing to further seizures and cumulative developmental impairment. Moreover, genetic animal models of DEEs suggest that early-life seizures exacerbate the severity of the epilepsy phenotype and neurocognitive deficits. This paper underscores the need for advanced, individualized therapies to manage SE in DEE patients and prevent recurrence, aiming to minimize long-term neurological and developmental sequelae.