📋 Tender Overview
Arousal And Respiratory Co-Dysfunction In Drug-Resistant Epilepsy: From Mechanisms To Therapy
Funded Under
European Research Council (Erc)
Total Cost
€ 1 994 315,00
Eu Contribution
€ 1 994 315,00
Coordinated By
Universite Lyon 1 Claude Bernard
France
Objective
Both seizures and their complications are modulated by patients’ vigilance states. Several epilepsy complications are associated with sleep, including Sudden and Unexpected Death in Epilepsy (SUDEP). SUDEP primarily results from a fatal postictal central apnea after a nocturnal generalized convulsive seizures. While transient seizure-related respiratory dysfunction is frequent in patients, current hypotheses suggest that in some of them, repetition of seizures may induce a chronic alteration of respiratory regulation, increasing the risk of fatal apnea. Reducing the severity of postictal respiratory dysfunction has thus appeared as one of the most promising way to prevent SUDEP. However, no encouraging result has been reported yet, suggesting that epilepsy-related respiratory dysfunction may only be the tip of the iceberg. Given the numerous interconnections between the network that regulates arousal and sleep and the respiratory network, I make the hypothesis that some patients with drug-resistant epilepsy might combine this well-known seizure-related respiratory dysfunction with a chronic alteration of arousal regulation, resulting in abnormal asphyxia-induced arousal. Adenosine system is deeply implicated in the regulation of sleep and central respiratory control and is modulated by seizures. Epilepsy-related alteration of the brainstem adenosine pathway may play a key role in the development of arousal and respiratory co-dysfunction. Using both experimental and clinical studies, EPIAROUSAL will investigate the exact interplay between epilepsy-related respiratory dysfunction and arousal regulation on the one hand, and the relation between long-term repetition of seizures, brainstem adenosine pathway and the respiratory and arousal co-dysfunction on the other hand. The final objective is to validate that adenosine-targeted therapy can restore normal asphyxia-induced arousal in drug-resistant epilepsy, paving the way for a first a clinical trial of SUDEP prevention
