An investigation of motor disabilities in people with multiple sclerosis using advanced magnetic resonance imaging

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 informatio