Walking impairment is one of the most prevalent and life-altering consequences of multiple sclerosis (MS),
even in the early stages of the disease, and often co-occurs with an increase in the oxygen (O2) cost of
walking. The O2 cost of walking is the amount of O2 consumed per kilogram of body weight per unit distance
traveled and reflects the physiologic strain or burden of ambulation. This physiological measure of walking
dysfunction is 2-3 times higher in persons with MS than adults from the general population and compromises
free-living, community participation. The higher O2 cost of walking further causes early onset of fatigue, hinders
the performance of tasks necessary for daily living, and has been linearly associated with worse disability
status in MS. This is noteworthy, as a primary determinant of disability status and progression in MS includes
cardiovascular comorbidity. Of note, aerobic capacity, a primary indicator of cardiovascular function, has been
identified as a strong correlate of O2 cost of walking in persons with MS who have moderate disability.
Consequently, the logical next step in this line of research involves identifying potential physiological
mechanisms that underlie elevated O2 cost of walking, and vascular function and peripheral blood flow
represent the logical starting points based on associations with aerobic capacity and muscle function.
Vasodilatory capacity of arteries is necessary for appropriate peripheral blood flow delivery and O2 extraction
within the active muscle. Vascular function is typically assessed in the upper limbs (i.e., brachial artery), but
vascular dysfunction of the upper limbs may not be indicative of vascular dysfunction of the lower limbs. This
cross-sectional, comparative study will use non-invasive methods to compare vascular function (i.e., muscle
blood flow and oxygenation) of the lower limbs (i.e., popliteal artery) between persons with MS and controls
matched by age and sex, and then examine markers of vascular function as possible modifiable correlates of
O2 cost of walking in MS. The first aim is to compare the O2 cost of walking and lower-limb muscle blood flow
and oxygenation between persons with MS and controls. We hypothesize persons with MS will demonstrate
higher O2 cost of walking and lower muscle blood flow and oxygenation in the gastrocnemius muscle
compared with controls. The second aim is to examine the associations among the O2 cost of walking, lower-
limb muscle blood flow and oxygenation, and aerobic capacity in persons with MS and controls, controlling for
physical activity. We hypothesize that vascular outcomes, and secondarily aerobic capacity and physical
activity, will account for the difference in the O2 cost of walking between groups. This research may identify
specific underlying vascular mechanisms that explain the poor walking efficiency in MS and guide the design of
targeted approaches for improving walking efficiency and its consequences to promote health and better
overall quality of life. This research aligns with the PI’s research agenda of helping persons with neurological
conditions reintegrate into the community post-diagnosis through improvements in walking efficiency.