Neurophysiological corelates of fatigue and the feasibility of progressive resistance exercise for ameliorating symptoms of fatigue in people with multiple sclerosis

Ellison, Paula (2020) Neurophysiological corelates of fatigue and the feasibility of progressive resistance exercise for ameliorating symptoms of fatigue in people with multiple sclerosis. Doctoral thesis, Northumbria University.

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Abstract

Clinicians are continually looking for effective treatments for multiple sclerosis (MS)- fatigue, but this has been hampered by unclear definitions of fatigue and studies of heterogeneous people with MS, including those who are highly-fatigued (MS-HF) and those who are less-fatigued (MS-LF). By directly comparing neuromuscular and transcranial magnetic stimulation measures between MS-HF and MS-LF, more light could be shed on the underpinning mechanisms of MS fatigue, and this could serve as a stronger foundation for therapeutic interventions. In addition, progressive resistance exercise has shown potential as an accessible exercise intervention for alleviating MS fatigue, but most studies have not recruited MS-HF or did not include MS fatigue as a primary outcome measure. In addition to positively impacting a range of other functional and mental health outcomes in PwMS, an individually tailored progressive resistance exercise (PRE) intervention has the potential to improve symptoms of fatigue and fatigability by helping to promote the development of new neural pathways (neuroplasticity). Thus, the overarching aim of this thesis was to establish whether neurophysiological differences between MS-HF and MS-LF could be reliably distinguished, and to investigate the feasibility and potential of PRE as a therapeutic exercise intervention for ameliorating perceived MS-fatigue in MS-HF. The series of investigations that set out to address this aim have led to many novel and interesting findings. Firstly, study 1 was the first systematic review and meta-analysis to synthesis the current evidence base comprising studies which used a dichotomised model (MS-HF versus MS-LF) to provide insights into structural and neurophysiological correlates of MS-fatigue. Secondly, Study 2 reports on the good to excellent test-retest reliability for a range of neuromuscular and transcranial magnetic stimulation measures assessed in the upper- and lower-limb muscles in MS-HF and MS-LF. Thirdly, based on the test-retest reliability findings of study 2, study 3 presents data for the differences between MS-HF compared to MS-LF and HC on a range of neuromuscular measures, including an isometric fatiguing exercise task in the upper- and lower-limb (performance fatigability measure). Finally, Study 4 presents important feasibility data regarding the utility of PRE as a therapeutic exercise option for MS-HF. In addition, this study provides preliminary evidence of the efficacy of PRE for ameliorating perceived MS-fatigue, a range of other patient-reported health outcomes and indices of neuromuscular function.

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