Pathophysiology of SUDEP

The Pathophysiology of SUDEP group was founded in 2019 when Prof. Jefferys was appointed at the Second Faculty of Medicine. Prof. John Jefferys was subsequently awarded a research grant by The Ministry of Health of the Czech Republic.

Our team’s central interest is in the impact of epilepsy, a brain disorder, on the functioning of the organism as a whole, notable the control of breathing and of the heart and circulation. The main focus of the group is sudden unexpected death in epilepsy (SUDEP). These deaths are defined partly by exclusion – unassociated with any injury, drowning or similar causes. The overall risk is about 1 per year per thousand people with epilepsy – quite a low incidence, however, devastating when it happens.

Recent findings have implicated both respiratory and cardiac pathologies in SUDEP pathophysiology; the underlying mechanism however remains unknown. Our goal is to use both animal models and data acquired from epilepsy patients to provide more insight into the impact of epilepsy on the respiratory and cardiac functions and thus help elucidate the mechanism of SUDEP. We have been using the tetanus toxin (TeNT) model of temporal lobe epilepsy in rats and our experimental techniques include telemetry monitoring of EEG, ECG, diaphragm EMG and respiration of freely-moving rats.

Our clinical team at the Department of Neurology, Motol Hospital, specializes in analyzing both acute and long-term seizure-related ECG changes. These changes could serve as biomarkers for assessing SUDEP risk in epilepsy patients. We also aim to introduce chronic respiratory monitoring in the video-EEG unit, enabling the detection of peri-ictal respiratory pathologies and potentially identifying patients with an elevated SUDEP risk.

Research areas

Experimental part

Mechanism of ictal apnea in a model of temporal lobe epilepsy
Investigators: Jefferys, Liška, Pant

SUDEP mechanism
Investigators: Jefferys, Liška, Krajčovič, Pant, Bečvářová, Pšenáková

Clinical part

ECG changes in patients with epilepsy as a potential factor determining the risk of SUDEP
Investigators: Komárek, Krýsl, Kalina, Jefferys, Liška

Ictal and inter-ictal changes in respiratory functions within video-EEG monitoring as a potential factor determining the risk of SUDEP
Investigators: Komárek, Krýsl, Kalina, Jefferys, Liška

Selected publications

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Current grant projects

The mechanisms of respiratory and cardiac dysfunction responsible for the increased risk of sudden unexpected death in epilepsy
Czech Health Research Agency (AZV NU21-04-00601)
Principal Investigator: John Jefferys
Co-proposer: Vladimír Komárek
2021-2025

Do epileptic foci in the insula increase the risk of Sudden Unexpected Death in Epilepsy?
Charles University Grant Agency (GAUK No. 171424)
Principal investigator: Aakash Pant
Supervisor: Karolína Liška
2024-2027

 

International cooperation

 

Keywords

epilepsy, seizure, SUDEP, hippocampus, spreading depolarization, apnoea