Key information / Informations

•    Funding programme / Programme de financement: Horizon Europe - ERC Consolidator Grant - 2023
•    Coordinator / Coordinateur: Université Claude Bernard Lyon 1 (UCBL), Pr Sylvain RHEIMS (CRNL)
•    Partners’ list / Liste des partenaires :

o    Hospices Civils de Lyon (HCL)

•    Budget : 1 994 315 €
•    Grant / Subvention : 1 994 315 €
•    Début – Fin : 2024-2029

Context / Contexte

Both seizures and their complications are modulated by patients’ vigilance states. The Sudden and Unexpected Death in Epilepsy (SUDEP) primarily results from a fatal postictal central apnea after a nocturnal generalized convulsive seizures. Reducing the severity of postictal respiratory dysfunction has 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, Prof. Rheims makes 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.

Objectives / Objectifs

EPIAROUSAL will study 1) the exact interplay between epilepsy-related respiratory dysfunction and arousal regulation 2) the relation between long-term repetition of seizures, brainstem adenosine pathway and the respiratory and arousal co-dysfunction. Objectives are i) assessing the arousal reactivity in drug-resistant epilepsy, with a specific emphasis on asphyxia-induced arousal ii) investigating the impact of epilepsy on the brainstem adenosine pathway and its relation with arousal and respiratory reactivity iii) validating that adenosine-targeted therapy can restore normal asphyxia-induced arousal in drug-resistant epilepsy.

Expected impact and results / Impact et résultats attendus

The EPIAROUSAL project will provide new and strong evidence on the role of interactions between arousal dysfunction and respiratory control in the cascade of events that lead to seizure-induced severe respiratory dysfunction. This project will thus demonstrate the first specific target for preventive therapy of SUDEP, paving the way for a multicenter controlled phase 3 study coordinated by an ad-hoc international consortium. Negative results will also be important in the field of SUDEP research, pushing to reconsider the largely accepted hypothesis that reducing the severity of postictal respiratory dysfunction is the most promising treatment strategy to prevent SUDEP.
The outcomes of the EPIAROUSAL project will also be useful beyond the field of epilepsy, providing new insights on other pathologies combining alterations in regulation of arousal and respiration control, such as obstructive sleep apnea syndrome, sudden infant death syndrome or rare neurodevelopmental diseases (e.g Prader-Willi Syndrome or Rett Syndrome).

LIP’s contribution / Rôle de LIP

LIP a accompagné le porteur de projet et son partenaire, les Hospices Civils de Lyon, dans toute la phase de montage, coordination du montage administratif et financier du projet, conseil à la rédaction. LIP accompagne l’Université Lyon 1 pour le suivi administratif et financier du projet.