The Therapeutic Effects of Forced Aerobic Exercise in Multiple Sclerosis

This project will investigate the feasibility and initial efficacy of two aerobic exercise training approaches, forced and voluntary, to improve motor function in persons with multiple sclerosis (MS). We hypothesize that intensive aerobic exercise training elicits a neurorepairative and neurorestorative response on the central nervous system, which may improve motor function as it relates to gait and mobility. Should aerobic cycling, forced or voluntary, improve gait and functional mobility in persons with MS, it would serve as a new model to restoring function, rather than current models that focus on compensation.

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system characterized by progressive loss of motor function, cognitive function, in addition to symptoms of fatigue and depression. These motor and non-motor symptoms negatively affect the individuals' walking ability, functional mobility, quality of life, ability to maintain gainful employment, and social engagement. Identifying rehabilitation approaches that may delay disease progression or restore lost neurologic function would have considerable impact in the field. The goal of this project is to investigate the feasibility and initial efficacy of forced or voluntary aerobic exercise training to improve gait, functional mobility, fatigue and quality of life in persons with multiple sclerosis (PwMS). Current rehabilitative approaches for PwMS focus on training compensatory strategies rather than restoring neurological function. Substantial evidence indicates that aerobic exercise (AE) training has the potential to enhance neurological function by restoring and repairing damaged cells, leading to improvements in gait, balance, and cognitive function in PwMS. Despite evidence of the potential disease-modifying properties of AE, numerous physical, behavioral, and logistical barriers prevent PwMS from achieving and maintaining AE of sufficient intensity and duration to capitalize on the neurophysiologic benefits of training. Forced exercise (FE) is a novel approach to AE training that has been successfully applied to individuals with Parkinson's disease and stroke, in which the voluntary efforts of the individual are augmented, allowing for disease-altering effects of intensive exercise training. During FE, pedaling cadence on a stationary cycle is augmented by a motor to assist, but not replace, the voluntary efforts of the individual. It is hypothesized that PwMS cannot sustain high rates of voluntary exercise necessary to elicit neural repair; therefore, FE is necessary to overcome physical, behavioral and logistical barriers to enhance neuroplasticity to improve gait, QOL, and the ability to participate in life activities. Positive results from our FE trials in Parkinson's disease and stroke have guided us in designing the scientific methodology for the proposed trial in PwMS. Twenty adults with relapsing-remitting MS and mild to moderate gait impairment will be randomized to undergo 1) FE or 2) voluntary aerobic exercise (VE). Both groups will attend 2X/week for 12 weeks. Exercise variables will be collected for each session as a measure of feasibility to determine how PwMS respond to each exercise approach. Clinical, biomechanical, and self-reported outcomes will be gathered prior to, after, and 4-weeks after the intervention to determine the effects of both modes of exercise on spatiotemporal and kinematic characteristics of gait, functional mobility, balance, fatigue, physical activity levels, and quality of life. Should our findings confirm our hypothesis that intensive exercise training can have disease-altering effects, a new direction for MS rehabilitation approaches would ensue, empowering PwMS to take control of their disease to improve function and reduce disability.

The FE group (N=10) will complete 45 minutes of FE on the custom-engineered cycle designed to augment pedaling rate to greater than 70 revolutions per minute (RPM's). The VE group (N=10) will exercise on an identical semi-recumbent cycle ergometer at their self-selected cadence without assistance.

The VE group (N=10) will exercise on an identical semi-recumbent cycle ergometer for 45 minutes at their self-selected cadence without assistance.

Spatio-temporal and kinematic parameters of gait will be obtained using 3-D motion capture and an instrumented walkway. The following biomechanical outcomes will be calculated: 1) spatio-temporal: velocity; cadence, step length, percentage of gait cycle spent in swing and stance phase, single and double limb support time and percentage; 2) Kinematic: hip and knee flexion and extension; ankle dorsi- and plantar-flexion; pelvic obliquity, rotation and tilt.

The TUG will be administered while participants wear an iPad to collect biomechanical data during the clinical test

Laboratory Assessment: Blood draws will be conducted at 4 different points in time to determine the acute and long-term change in serum Klotho; at week one session one, pre- and post-exercise, and at the last session12-week exercise intervention, pre- and post-exercise.

Inclusion Criteria: Confirmed diagnosis of RRMS with Expanded Disability Status Scale (EDSS) score between 1.5 and 6.5, 18-75 years of age, Deemed minimal risk for cardiovascular event using American College of Sports Medicine Exercise Pre-participation Criteria Exclusion Criteria: hospitalization for myocardial infarction, heart failure or heart surgery within 3 months, serious cardiac arrhythmia, hypertrophic cardiomyopathy, severe aortic stenosis, pulmonary embolus, significant contractures, dysphagia resulting in inability to sufficiently hydrate, and other contraindication to exercise.