Active Voice: Aerobic Exercise Helps Multiple Sclerosis—But How and How Fast?
By Rebecca Spain, M.D., MSPH

Rebecca Spain, M.D., MSPH
It is generally accepted that aerobic exercise is good for cardiovascular health, improving mitochondrial adenosine triphosphate (ATP) production in skeletal muscles, and reducing risks of other chronic diseases. We also know that aerobic exercise improves cognitive function and reduces fatigue—this holds true for people with multiple sclerosis (MS) who often are affected by these consequences of their disease. Less known is how quickly improvements may develop in these functions as a result of participating in aerobic physical activity, nor have the cerebral mechanisms underlying such clinical improvements been identified.

MS is an autoimmune neuro-inflammatory disease of the central nervous system (CNS) that results in demyelination of axons and neurodegeneration. The underlying pathophysiology of MS is complex with inflammatory, oxidative and neurodegenerative pathologies found. MS typically starts as relapsing-remitting cycles with bouts of neurological dysfunction corresponding to CNS inflammation followed by complete or partial recovery of function. A minority of affected individuals have a progressive course from onset. MS symptoms can include weakness, sensory loss, imbalance, incoordination, vision loss, brainstem dysfunction manifesting in double vision and difficulty swallowing, muscle spasticity and neurogenic bladder. “Silent” symptoms of cognitive dysfunction and fatigue can be some of the most disabling.

While the underlying cause of MS is unknown, genetic and environmental risk factors have been identified. Comorbid conditions include obesity, hypertension, diabetes, cardiovascular disease and hyperlipidemia; these risk factors are associated with an accelerated pace of disability accumulation. The “vascular” comorbid conditions can all be prevented or improved by aerobic exercise, suggesting a contribution to disease management that is independent of the immune-mediated therapies most people with MS take. This led us to hypothesize that aerobic exercise may have a unique role in treating MS, and the mechanism may be mediated through improved ATP production.

In our study, as reported in the July 2019 issue of Medicine & Science in Sports & Exercise®, my colleagues and I demonstrated that a high-intensity aerobic exercise program in a mild-to-moderately disabled MS population typically results in rapid cardiovascular improvement and also produced expected benefits of improved V?O2max, peak work, etc. These benefits were achieved despite the subjects’ physical limitations and underlying fatigue. Further, the MS cohort (n=10) also demonstrated significant improvements in cognitive processing speed and reductions in cognitive fatigue compared to a control MS stretching group (n=7). While the exercise training was safe and well-tolerated by the subjects, a re-emergence of exercise-induced syncope served as a reminder that prudence of supervision is essential when initiating a high-intensity exercise program in patients with MS.

We used phosphorous magnetic resonance spectroscopy (31PMRS) to evaluate individual ATP peaks and the rate-constant of phosphocreatine recovery in tibialis anterior muscles. These measures were taken prior to and following the eight-week protocol. As expected, only the aerobic exercisers demonstrated improvements. When using 31PMRS for investigating ATP changes in the brain, only ATP peaks can be detected; we found no pre- to post-intervention changes for this measure in either cohort. However, a cross-sectional comparison of MS and healthy controls did show a significantly higher level of in-the-brain measures for phosphocreatine to inorganic phosphate peak in the MS group. A larger or longer exercise study will help determine if aerobic exercise increases brain ATP levels.

In sum, aerobic exercise benefits people with MS, even if only a brief high-intensity program. Such an intervention can improve cognition, reduce cognitive fatigue and promote cardiovascular benefits. 31PMRS may prove a useful technique to quantitate the benefits of aerobic effects on ATP levels, and this technology may help us design the optimal combination therapies for this complex disease.

About the author:
Rebecca Spain, M.D., MSPH, is an associate professor of neurology at Oregon Health & Science University in Portland and a staff neurologist at the Veteran Affairs Portland Health Care System. She specializes in establishing evidence-based recommendations for wellness approaches to treating multiple sclerosis. Dr. Spain’s research presented here focuses on understanding how quickly aerobic exercise improves clinical outcomes and if it changes brain ATP production as a mechanism of its benefit.

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