Peripheral blood flow regulation in persons with multiple sclerosis

2021 Fall.Includes bibliographical references.Multiple sclerosis (MS) is an inflammatory, degenerative disease of the central nervous system that is believed to be autoimmune in nature. The disease affects approximately one million people in the United States and results in a wide variety of symptoms including impaired physical function, reduced exercise capacity, and increased fatigability. Although considerable effort has been invested in improving our understanding of the neuromuscular contributions to these symptoms, no studies have investigated whether cardiovascular autonomic dysfunction compromises skeletal muscle blood flow in persons with MS (PwMS). Indeed, approximately 50% of PwMS have an abnormal response to tests of cardiovascular autonomic function, and skeletal muscle blood flow is positively associated with exercise capacity. Thus, the overall goal of this dissertation was to determine whether PwMS have impaired skeletal muscle blood flow responses to exercise relative to age- and sex-matched healthy controls. The primary findings are that 1) the local control of skeletal muscle blood flow during exercise is intact in PwMS, 2) skeletal muscle blood flow is likely reduced during exercise that engages the autonomic nervous system in MS, which may be due to increased α-adrenergic mediated vascular tone, and 3) that PwMS may experience hypersensitivity to α-adrenergic signaling as evidenced by levels of systemic vascular resistance relative to plasma concentrations of norepinephrine. Together, these studies indicate that compromised skeletal muscle blood flow during exercise may contribute to reduced exercise capacity and increased fatigability in PwMS

Rehabilitative targets to increase physical activity in patients with multiple sclerosis

2016 Spring.Includes bibliographical references.Background: Physical activity has been shown to have positive effects on the disease symptoms of multiple sclerosis. However, patients with multiple sclerosis are less active than their healthy counterparts. Previous studies of the predictors of physical activity in this patient population have been limited in their translation to the rehabilitative setting. Objective: To identify behavioral and functional predictors of physical activity in patients with multiple sclerosis to provide targets for rehabilitative specialists. Methods: A total of 16 behavioral and functional tests were conducted and physical activity was objectively measured for one week. A stepwise multiple regression analysis was performed to identify the strongest predictors of moderate-to-vigorous physical activity and total activity/day. Results: The stepwise procedure converged on a model for moderate-to-vigorous physical activity (R2=0.35, P=0.001) that included total leg strength of the less-affected side (partial r=0.42, P=0.016) and Falls Efficacy Scale-International score (partial r=-0.37, P=0.033). The model for total activity (R2=0.41, P<0.001) included five-times sit-to-stand performance (partial r=-0.42, P=0.014) and total leg strength of the less-affected side (partial r=0.35, P=0.049). Conclusion: Rehabilitative specialists aiming to improve physical activity in patients with multiple sclerosis should implement exercise programs that combine balance and strength training of the legs

Fatigue in Multiple Sclerosis: Misconceptions and Future Research Directions

Fatigue is one of the most disabling side effects in people with multiple sclerosis (PwMS). While this fact is well known, there has been a remarkable lack of progress in determining the pathophysiological mechanisms behind fatigue and the establishment of effective treatments. The main barrier has been the lack of a unified definition of fatigue that can be objectively tested with validated experimental models. In this ‘perspective article’ we propose the use of the following model and definition of fatigue: the decrease in physical and/or mental performance that results from changes in central, psychological, and/or peripheral factors. These changes depend on the task being performed, the environmental conditions it is performed in, and the physical and mental capacity of the individual. Our definition and model of fatigue outlines specific causes of fatigue and how it affects task performance. We also outline the strengths and weaknesses of commonly used measures of fatigue and suggest, based on our model and definition, new research strategies which should include multiple measures. These studies should be mechanistic with validated experimental models to determine changes in central, psychological, and/or peripheral factors that explain fatigue. The proposed new research strategies may lead to the identification of the origins of MS related fatigue and the development of new, more effective treatments