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Research Portfolio

GRANT TITLE:

Improved understanding of the mechanisms and intervention strategies for a known risk factor for SUDEP

GRANT TYPE:

ENDEAVOUR PROJECT GRANT

grant amount:

£139,716 over 24 months, awarded in 2022

lead investigator:

Dr Rob Wykes

Co-Investigators:

- Dr Beate Diehl (UCL)

institution:

University College London

Background

Sudden Unexpected Death in Epilepsy (SUDEP) can occur in patients with frequent convulsive seizures, with the underlying mechanism thought to be linked to breathing and cardiovascular failure. EEG recordings after seizures have demonstrated a “flattening”, called “postictal generalized EEG suppression”, or PGES. It is not known what the flattening means for the brain and seizure recovery, but this is likely a risk marker for SUDEP. It has been proposed that one contributing factor to SUDEP is spreading depolarization (SD), a slow spreading wave that suppresses brain cell activity and can temporarily ‘switch off’ areas of the brain. This activity is difficult to detect using traditional EEG and clinical recording systems, and so they have been poorly studied in epilepsy.

"Our aim is to gain a better understanding of the mechanisms that result in respiration depression during and immediately after a seizure, as well as the brain arousal systems that should consequently kick in to regularise breathing and vigilance state post seizure cause.

The Study

Through this research, Dr Wykes will investigate SD in the lab during and after seizures to determine how they are related to PGES using state of the art graphene transistors. These transistors are more sensitive than conventional methods and so the team will be able to better detect SD, helping to shed light on SUDEP risk. Dr Wykes’ co-investigator Dr Beate Diehl will review the records of over 300 patients using previously collected video EEG recordings of seizures with breathing and heart rate data. They will then be able to examine whether brain rhythms we see in clinical EEGs relate to PGES, and cardiorespiratory abnormalities.

Significance

Through this research, Dr Wykes will better understand which brain areas are particularly affected and whether electrical stimulation of those regions can improve recovery from seizures and normalise EEG and breathing – potentially preventing SUDEP. Using these findings, Dr Wykes could improve detection of brain activity that may increase the risk of SUDEP in patients undergoing presurgical telemetry monitoring. This project will not only offer new clinical techniques but inform future research on SUDEP.