Mechanisms of Low Physical Work Capacity, Fatigue, and Reduced Mobility in Multiple Sclerosis
Abstract
Objectives and Rationale: Individuals with Multiple Sclerosis (MS) experience a range of symptoms, including fatigue, mobility difficulties, cognitive issues, decreased physical function, and very low levels of physical work capacity (PWC). PWC is usually determined by a treadmill or a cycle ergometer stress test and is also a measure of cardiovascular fitness. PWC is especially important, because low PWC is a very important health indicator. Poor PWC is related to increased risk of mortality, cardiovascular disease and cancer, decreased independence, decreased mobility, and increased fatigue. It is often assumed that decreased neural function in the brain caused by MS is the primary reason for most of the symptoms and the low PWC. However, there is little data and research supporting this notion. Instead, based on a few preliminary findings, it is possible that autonomic dysfunction is the culprit. Autonomic dysfunction refers to a dysfunction of the body s ability to control heart rate, blood pressure, and blood flow. As a result, blood may not be delivered to where it is needed, leading to reductions in oxygen delivery to organs and working muscle. This then causes low PWC, fatigue, and reduced mobility. Since PWC is determined by the ability to deliver blood to working muscles, and the ability of those muscles to use the oxygen delivered, it is critical to understand exactly which factors produce the low PWC in persons with MS. Once these factors are identified, appropriate interventions can then be developed to increase PWC, decrease fatigue, and increase mobility. Therefore, our proposed work addresses Focus Area #3 of the FY17 MSRP Exploration - Hypothesis Development Award and will focus on developing an alternative hypothesis to explain low PWC, fatigue, and reduced mobility, as a consequence of altered autonomic function in persons with MS. What Type of Patients Could Benefit and How? This study will include patients with relapsing-remitting MS with Expanded Disability Status Scale (EDSS) scores between 0-4 who are currently independently ambulatory, between the ages of 18-45, and who have been relapse-free for at least 30 days. Patients will be on stable disease-modifying medications but cannot be taking any medications that influence heart rate or blood pressure. All patients must also have physician approval to undertake an exercise stress test. The information gained from this study will allow us to determine what physiologic factors influence PWV, fatigue, and mobility in patients with MS. Understanding what factors are involved will provide the basis for future interventions to increase PWC, decrease fatigue, and increase mobility, which could include both life style interventions and/or medications. Thus, this study will provide a basis for what is needed to improve quality of life and decrease the risk of early mortality due to diseases associated with life style (e.g., cardiovascular disease). What Are The Potential Clinical Applications, Benefits, and Risks? Understanding what physiologic factors contribute to low PWC, fatigue, and decreased mobility has the potential to create more of an "individualized medicine" approach in individual patient treatment plans, designed to optimize treatment for each patient. Hopefully, this will allow us to maximize treatment effects designed to improve quality of life and reduce fatigue while improving mobility and social participation for patients with MS. Thus, the clinical application of study is the identification of factors that could be a focus for future treatments. It will also enhance our understanding of factors not directly related to neuropathology that contribute to low PWC, fatigue, and reduced mobility. Furthermore, individual patients participating in our study will receive information on their own PWC and what factors contribute to it. There are only minimal risks involved in the study. All of the procedures are non-invasive and do not confer
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810466
Entities
People
- Bo Fernhall
Organizations
- United States Army
- University of Illinois at Chicago