Ricerc@Sapienza

Objective: Dravet syndrome is a rare neurodevelopmental disease, characterized by general cognitive impairment and severe refractory seizures. The majority of patients carry the gene mutation SCN1A, leading to a defective sodium channel that contributes to pathogenic brain excitability. A γ-aminobutyric acid (GABAergic) impairment, as in other neurodevelopmental diseases, has been proposed as an additional mechanism, suggesting that seizures could be alleviated by GABAergic therapies.

Absence seizures (ASs), the most common form of generalized epilepsy, have significant consequences for patients in the form of impaired attention, mood, and social deficits, and the potential for development into generalized tonic-clonic seizures. Althoughmechanistic hypotheses of these paroxysmal oscillations are incomplete, evidence suggests that an increase in extrasynaptic GABAAreceptor (eGABAAR) mediated tonic inhibition in thalamocortical (TC) neurons is sufficient to generate an AS phenotype in multiple rodent models.