Long-term, prospective study evaluating clinical and molecular biomarkers of epileptogenesis in a genetic model of epilepsy – tuberous sclerosis complex

Despite a great progress in the management of epilepsy, still one third of patients is refractory to available medications. The incidence of epilepsy is highest in infancy and 50% of children experience epilepsy-related comorbidities, such as developmental delay and autism. The development of epilepsy (epileptogenesis), extensively studied in animals, is barely studied in humans, as patients usually present AFTER the seizure onset. EPISTOP is the first prospective study of epileptogenesis in humans, beginning BEFORE seizures and continuing through age 2+ years, permitting detailed analysis of the onset, drug-resistance, and comorbidities of epilepsy. To maximize information derived from the study we have chosen homogenous group of patients with prenatal or early infantile diagnosis of Tuberous Sclerosis Complex (TSC). A clinical randomized study of pre-seizure treatment in TSC infants is a part of the project. The aim of EPISTOP is to examine the risk factors and biomarkers of epilepsy and to identify possible new therapeutic targets to block or otherwise modify epileptogenesis in humans. Biomarker analysis will be performed by a multidisciplinary, systematic approach in three clinical settings: 1/ prospective study of epilepsy development in infants with TSC, including analysis of clinical, neuroimaging, and molecular, blood-derived biomarkers at predefined time points: before the onset of seizures, at the onset of epileptiform discharges on EEG, at seizure onset and at the age of 24 months 2/ prospective study of blood-based biomarkers in infants with TSC treated with antiepileptic drugs prior to seizure onset in comparison to children treated only after clinical seizures appearance. 3/ analysis of biomarkers of epileptogenesis and drug-resistant epilepsy in brain specimens obtained from TSC patients who have had epilepsy surgery and TSC autopsy cases.