Spatiotemporal gait changes in people with multiple sclerosis with different disease progression subtypes.

BACKGROUND: Gait impairment is common in people with multiple sclerosis (MS), but less is known about gait differences between MS disease progression subtypes. The objective here was to examine differences in spatiotemporal gait in MS and between relapsing-remitting and progressive subtypes during the timed-25-ft-walk test. Our specific aims were to investigate (1) spatiotemporal, (2) spatiotemporal variability, and (3) gait modulation differences between healthy controls and MS subtypes at preferred and fast walking speed. METHODS: This study included 27 controls, 18 relapsing-remitting MS, and 13 progressive MS participants. Participants wore six inertial sensors and walked overground without walking aids at preferred and fast-as-possible speeds. FINDINGS: Both MS groups had significantly lower walking speed than controls, with a trend towards lower preferred gait speed in progressive compared to relapsing-remitting MS (ES = 0.502). Although most spatiotemporal gait parameters differed between controls and MS groups, differences were not significant between MS subtypes in these parameters and their variability, with low to moderate effect sizes during preferred and fast walking. Both MS groups showed reduced modulation in gait compared to controls and no significant differences between MS subtypes. INTERPRETATION: Gait in MS is altered compared to controls. Although gait may change with progressive MS, the overall small differences in the gait parameters between the MS subtypes observed in this sample suggests that those with the progressive form of MS who are independently ambulatory and without further clinically meaningful changes in gait speed may not show gait decrements greater than the relapsing-remitting form of the disease.

Oxidative ATP synthesis in human quadriceps declines during 4 minutes of maximal contractions.

KEY POINTS: During maximal exercise, skeletal muscle metabolism and oxygen consumption remain elevated despite precipitous declines in power. Presently, it is unclear whether these responses are caused by an increased ATP cost of force generation (ATPCOST ) or mitochondrial uncoupling; a process that reduces the efficiency of oxidative ATP synthesis (ATPOX ). To address this gap, we used 31-phosphorus magnetic resonance spectroscopy to measure changes in ATPCOST and ATPOX in human quadriceps during repeated trials of maximal intensity knee extensions lasting up to 4 min. ATPCOST remained unchanged. In contrast, ATPOX plateaued by ∼2 min and then declined (∼15%) over the final 2 min. The maximal capacity for ATPOX (Vmax ), as well as ADP-specific rates of ATPOX , were also significantly diminished. Collectively, these results suggest that mitochondrial uncoupling, and not increased ATPCOST , is responsible for altering the regulation of skeletal muscle metabolism and oxygen consumption during maximal exercise. ABSTRACT: The relationship between skeletal muscle oxygen consumption and power output is augmented during exercise at workloads above the lactate threshold. Potential mechanisms for this response have been hypothesized, including increased ATP cost of force generation (ATPCOST ) and mitochondrial uncoupling, a process that reduces the efficiency of oxidative ATP synthesis (ATPOX ). To test these hypotheses, we used phosphorus magnetic resonance spectroscopy to non-invasively measure changes in phosphate concentrations and pH in the vastus lateralis muscle of nine young adults during repeated trials of maximal, all-out dynamic knee extensions (120°s-1 , 1 every 2 s) lasting 24, 60, 120, and 240 s. ATPOX was measured at each time point from the initial velocity of PCr resynthesis, and ATPCOST was calculated as the sum of ATP synthesized by the creatine and adenylate kinase reactions, non-oxidative glycolysis, ATPOX and net changes in [ATP]. Power output declined in a reproducible manner for all four trials. ATPCOST did not change over time (main effect P = 0.45). ATPOX plateaued from 60 to 120 s and then decreased over the final 120 s (main effect P = 0.001). The maximal capacity for oxidative ATP synthesis (Vmax ), as well as ADP-specific rates of ATPOX , also decreased over time (main effect P = 0.001, both). Collectively, these results demonstrate that prolonged maximal contraction protocols impair oxidative energetics and implicate mitochondrial uncoupling as the mechanism for this response. The causes of mitochondrial uncoupling are presently unknown but may offer a potential explanation for the dissociation between skeletal muscle power output and oxygen consumption during maximal, all-out exercise protocols.