National networking for the study of predictive factors and prevention of sudden unexpected death in pharmacoresistant partial epilepsies (REPO2MSE project)

Abstract

Introduction: The sudden unexpected death in epilepsy (SUDEP) reaches 0.9% per year among patients are candidates for surgical treatment of epilepsy and it has been one of the research priorities of the French League Against Epilepsy, European Commission of the International League Against Epilepsy and associations of patients with epilepsy. So far, we have not effective or validated means to prevent SUDEP. The realization of clinical trials for this purpose is hampered because the SUDEP pathophysiology is not yet fully understood. Evidence supports the occurrence of apneas, central or obstructive, during seizures. It is estimated that about 20% of patients admitted to video-electroencephalography (VEEG) will present an ictal or post-ictal severely enough apnea to cause decreasing in oxygen saturation (SpO2) below 80%. However, studies have not adequately controlled the probable relationship between the occurrence of desaturation and subsequent risk for SUDEP in patients with pharmacoresistant partial epilepsies, submitted or not to epilepsy surgery. Objectives: The main objective is to analyze the relationship between the occurrence of decrease in SpO2 below 80% during seizures recorded in VEEG and the subsequent risk for SUDEP. Secondary objectives are to test other potential risk factors for SUDEP, mainly the precise localization of the epileptogenic zone and heart rhythm abnormalities. Methodology: The recruitment will take place in 14 French centers of epileptology performing pre-surgical VEEG, namely: Centre Hospitalier Sainte-Anne and Salpêtrière in Paris, Rennes, Grenoble, Lyon, Marseille, Montpellier, Strasbourg, Lille, Bordeaux, Toulouse, Tours, Nice and Nancy. The study has a financial support by Hospital Clinical Research Program of the French Ministry of Health. The inclusion criteria are patients aged 18 years and older, admitted to VEEG as part of pre-surgical evaluation of their epilepsy whose accept participating in the study. The VEEG, heart rate and SpO2 recordings will be acquired simultaneously. Clinical data will be collected and each patient will be asked to fill out questionnaires about adverse events, sleep disorders, mood disorders and quality of life in epilepsy. The design is a case-control study in a prospective cohort of patients. It is estimated to include 1,500 patients and the occurrence of 15 cases of SUDEP in three years of study. The cases are patients of the cohort affected by SUDEP before any surgical treatment. The controls are patients of the cohort, without death, whose follow-up period after VEEG and before any surgical treatment is equivalent to the follow-up of the cases they will be paired. It is expected pairing 28 controls and seven cases (4:1) to achieve significant statistical power. Statistical analysis will be performed by the unit of methodology in clinical research of the Centre Hospitalier of Lyon. Our expected results: the main hypothesis is an important relationship, and causality, between the occurrence of SUDEP and ictal or post-ictal decrease in SpO2 below 80%. If the study will confirm this hypothesis, further studies will be proposed among the participating centers to test, for the first time, types of treatments may reduce the SUDEP risk using the ictal or post-ictal SpO2 as the parameter of efficacy. (AU)