eprintid: 10084614
rev_number: 17
eprint_status: archive
userid: 608
dir: disk0/10/08/46/14
datestamp: 2019-11-16 12:47:16
lastmod: 2019-11-16 12:47:16
status_changed: 2019-11-16 12:47:16
type: thesis
metadata_visibility: show
creators_name: Allen, Luke
title: Neuroimaging of Sudden Unexpected Death in Epilepsy (SUDEP)
ispublished: unpub
divisions: A01
divisions: B02
divisions: C07
divisions: D07
note: Copyright © The Author 2019. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms.
abstract: 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.
date: 2019-10-28
date_type: published
oa_status: green
full_text_type: other
thesis_class: doctoral_open
thesis_award: Ph.D
language: eng
thesis_view: UCL_Thesis
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1712675
lyricists_name: Allen, Luke
lyricists_id: LAALL00
actors_name: Allen, Luke
actors_id: LAALL00
actors_role: owner
full_text_status: public
pages: 242
event_title: University College London
institution: UCL (University College London)
department: UCL Queen Square Institute of Neurology
thesis_type: Doctoral
citation:        Allen, Luke;      (2019)    Neuroimaging of Sudden Unexpected Death in Epilepsy (SUDEP).                   Doctoral thesis  (Ph.D), UCL (University College London).     Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10084614/1/Luke_Allen_PhD_Thesis_Neuroimaging_of_SUDEP_final.pdf