Biomarkers of response to SEEG Thermocoagulation in patients with refractory focal epilepsy – THALPO

Drug-resistant focal epilepsies are among the most burdensome neurological disorders, affecting 21.5 million people worldwide. Surgery is the only potentially curative treatment for these patients. Intracerebral stereotactic EEG (SEEG) is the reference method in presurgical exploration aiming at the precise mapping of the epileptogenic network comprising the brain region(s) involved in seizure generation. At the end of SEEG procedure, SEEG-guided radiofrequency thermocoagulation (SEEG RFTC) represents a therapeutic option that may be efficient as a palliative treatment in non-operable patients or may lead in some cases to a definitive effect. SEEG RFTC safety and efficacy have been established. However, the rates of seizure-freedom one year after thermocoagulation vary significantly (from 4% to 71%). Such disparity in therapeutic responses could be due to the lack of objective criteria for targets selection but also to the existence of multiple mechanisms of action beyond the direct lesion effect. Decrease of SEEG epileptogenicity markers after thermocoagulation may predict the effectiveness of the procedure. However, no data are available on changes in connectivity, blood-brain barrier alteration, neuro-glio-vascular damage and inflammation or molecular adaptations following RFTC and their link to prognosis. The objective of the THALPO project is to elucidate the mechanisms underlying the clinical effect of SEEG RFTC by studying the changes in electrophysiological (SEEG), structural (ultra-high field MRI) and biological (blood biomarkers of neuro-glio-vascular damage and inflammation, tissue-traces molecular (transcript) adaptations) markers. They will be correlated with clinical outcome in a prospective cohort of patients with drug-resistant focal epilepsy. As advantages for clinical care, this study will allow selection of RFTC targets based on scientifically validated criteria and elaboration of predictive scores for therapeutic response in each patient.