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Investigation of pathophysiological mechanisms in clinically isolated syndrome using advanced imaging techniques

Collorone, Sara; (2020) Investigation of pathophysiological mechanisms in clinically isolated syndrome using advanced imaging techniques. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

This thesis concerns an observational study of patients recruited after their first episode of neurological symptoms suggestive of demyelination in the central nervous system and diagnosed either with clinically isolated syndrome or relapsing-remitting multiple sclerosis. In multiple sclerosis, brain tissues can exhibit extensive neuroaxonal microstructural and metabolic abnormalities, but little is known about their presence and significance at the time of the first demyelinating episode. I used a novel multi-parametric quantitative MRI approach, combining neurite orientation dispersion and density imaging (NODDI), which gives information about tissue microstructure, and 23Na MRI, which estimates total sodium concentration, a marker of metabolic dysfunction, in the brains of clinically isolated syndrome patients. I found microstructural and sodium homeostasis alterations in cortical areas of patients that showed clinical relevance. Within the diffuse axonal dispersion found in the normal-appearing white matter, the corpus callosum shared with lesions, signs of axonal damage and metabolic dysfunction, thus emerging as a possible target for early neuroprotective interventions. Structural cortical networks (SCNs) represent patterns of coordinated morphological modifications in cortical areas and they have shown pathophysiological changes in many brain disorders, including multiple sclerosis. I investigated alterations of SCNs at the individual level in this early cohort. Patients showed altered small-world topology, an efficient network organization combining dense local clustering with relatively few long-distance connections. These disruptions were worse for patients with higher lesion load and worse cognitive processing speed indicating that pathophysiological changes in the cortical morphology can influence clinical outcomes. Finally, I hypothesised that the patients in the cohort presenting with optic neuritis may have disturbances in neuropsychological functions related to visual processes. I found that cognitive visuospatial processing is affected after unilateral optic neuritis and improves over time with visual recovery, independently of the structural damage in the visual and central nervous system.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Investigation of pathophysiological mechanisms in clinically isolated syndrome using advanced imaging techniques
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2020. 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. Access may initially be restricted at the author’s request.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neuroinflammation
URI: https://discovery.ucl.ac.uk/id/eprint/10114106
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