Gait rehabilitation and monitoring in multiple sclerosis; optimal rehabilitation interventions, longitudinal changes, sex differences and the protective role of cardiorespiratory fitness

Abstract

Multiple sclerosis (MS) is a chronic demyelinating and autoimmune disease of the central nervous system, characterized by episodes of new or worsening neurologic symptoms, followed by partial or complete recovery. Despite an expanding body of literature on the effectiveness of exercise in MS, the optimal approaches to improve gait are lacking. Notably, people with MS often have low levels of cardiorespiratory fitness, limiting their exercise capacity. Furthermore, covert gait changes precede clinical signs, often not detectable on observation, and measurement of subtle changes in gait, such as variability, could be a potential biomarker of covert neurodegeneration. Both cognition and fitness could influence changes in gait variability over time. The purpose of my doctoral work was to systematically review the optimal interventions to improve gait speed, the intricate relationship between cardiorespiratory fitness, and gait variability—a potential longitudinal biomarker of covert gait changes. The first study critically synthesized randomized controlled trials, consolidating knowledge on optimal rehabilitation interventions to improve gait speed in individuals with MS. Lower limb resistance and treadmill training emerged as the most effective interventions. Overall, there was a positive albeit small effect of interventions on gait speed in individuals with MS. The second study focused on the early detection of covert gait changes in clinically stable people with MS and highlighted gait variability as a sensitive longitudinal biomarker. Notably, it proposed the protective role of cardiorespiratory fitness against covert worsening of gait variability over two years in individuals with MS. The third study assessed cardiorespiratory fitness and examined its association with self-reported moderate to vigorous physical activity, with an emphasis on sex-related differences. The findings showed that males and females had low levels of cardiorespiratory fitness. Furthermore, there was an agreement between self-reported physical activity and aerobic fitness only in females, indicating potential over-reporting by males. This comprehensive thesis contributes valuable insights into treatments and monitoring of gait in MS, specifically identifying optimal rehabilitation interventions, identifying gait variability as a potential longitudinal biomarker for covert neurodegeneration, the protective role of cardiorespiratory fitness and sex differences in fitness and reporting of physical activity.