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Title: Neuroimaging of sudden unexpected death in epilepsy (SUDEP)
Author: Allen, Luke
ISNI:       0000 0004 8500 6056
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2019
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Background: Sudden unexpected death in epilepsy (SUDEP) is the leading cause of premature death among people with epilepsy. The precise mechanisms underlying SUDEP remain elusive, though work so far demonstrates a potential centrally mediated event in which autonomic, respiratory and/or arousal processes fail to recover following a significant seizure. Neuroimaging enables non-invasive assessment of the structural and functional architecture among sites and networks involved in regulating such processes; damage or alterations may indicate a central predisposition in those at high-risk and who suffer SUDEP, and provide non-invasive biomarkers. Methods: In this thesis, structural and functional imaging techniques were employed to address this possibility. Both retrospective investigations of those who succumbed to SUDEP, and prospective studies of those at high-risk, were performed. Voxel-based morphometry, volumetry and resting-state functional magnetic resonance imaging (RS-fMRI) network analysis techniques were utilised to identify and characterise brain structural and functional alterations relative to low-risk subjects and controls. Results: Brain morphometric and volumetric alterations among sites involved in cardiorespiratory regulation and recovery were found in those who later suffered SUDEP and in matched, living individuals at high risk. Prospective work revealed similar, and additional, structural alterations in those at high-risk which were associated with the extent of seizure-related hypoxemia; notably among the thalamus, periaqueductal grey (PAG), medulla, vermis and hippocampus. Network analysis of functional imaging data revealed disturbed patterns of connectivity in high-risk temporal lobe epilepsy (TLE) patients, and altered functional organisation in confirmed cases of SUDEP, among regulatory brain sites as well as the whole brain. Conclusions: Structural and resting state functional connectivity disturbances were found in patients who suffered SUDEP, and those at elevated risk. Injury and connectivity disturbances may indicate damage or dysfunction within sites and networks involved central regulatory processes, which could facilitate SUDEP. However, further work is required to elucidate the precise mechanisms of volume and functional connectivity alterations, and to provide firm links between centrally mediated autonomic and respiratory dysfunction, SUDEP and related imaging findings. A more immediate use for the imaging outcomes revealed here may rest with the development of non-invasive biomarkers, which may one day assist in identifying those at risk and evaluating individual risk for SUDEP based on injury to brain sites or altered functional networks.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available