Radiology - Theses
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ItemAn investigation of motor disabilities in people with multiple sclerosis using advanced magnetic resonance imaging( 2020)Multiple sclerosis (MS) is an autoimmune disorder of the brain and spinal cord, and the most common cause of neurological disability in young adults. The presentation of MS is highly heterogeneous with an unknown aetiology and no known cure, presenting as inflammation, demyelination and axonal injury/loss. MS pathology is disseminated throughout the central nervous system leading to a broad range of symptoms including cognitive dysfunctions, bowel and bladder problems, fatigue, sensory disturbances and difficulties with walking and balance. Up to 90% of people with MS experience motor impairments that significantly worsen with increasing disease severity, and which can affect both the upper and lower limbs. Motor impairments are often highly debilitating, ranging from muscle weakness, coordination loss, tremors to spasticity. However, while the pathophysiological mechanisms underpinning motor impairments in MS have been widely studied, they are not currently well understood. This is particularly true for early disease, a time when personalised treatment strategies can be formulated and will have maximal effect, preventing future deterioration and accumulation of disability. Consequently, there is an urgent need to understand the pathophysiology underlying motor impairments in MS and elucidate the microstructural and functional changes that occur at their earliest manifestation. To this end, we investigated the pathophysiology of motor impairments associated with dexterity and mobility in people with MS using advanced magnetic resonance imaging (MRI). Our investigations included functional resting-state (Chapters 2.1 and 2.2) and task (Chapter 3.1) MRI, diffusion weighted imaging (Chapter 3.2) and ultra-high field MRI (Chapters 3.1 and 3.2). Our findings consistently demonstrated a clear link between the development of motor impairments and alterations in the structure/function of the sensorimotor system, a system responsible for the integration of sensory information with motor processing in order to facilitate and maintain movement. Specifically, studying the sensorimotor system in its entirety using network analyses in a large cohort of people with MS, we identified functional disturbances within the sensorimotor system of patients with serious disabilities (Chapter 2.1), with disturbances particularly predictive of future progression of upper and lower limb impairments (Chapter 2.2). Further, using high resolution ultra-high field MRI and measures of motor behaviour in a cohort of patients with minimal motor impairments (Chapters 3.1 and 3.2), we similarly found a link between changes in the function and microstructure of the sensorimotor system and the presence of subtle impairments in hand function and walking. These findings provide evidence for the role of the sensorimotor network in the development of motor impairments. Potentially, the sensorimotor network might be central to the development of motor impairments in MS and represent a useful target for the development of imaging biomarkers for use in treatment development as well as understanding and monitoring the evolution of motor impairments. From this and subsequent work, it is hoped that this knowledge will lead to more effective treatments and management of patients, alleviating the burden of these impairments.