Department of Integrative Physiology, University of Colorado, Boulder, CO, USA.
Department of Neurology, University of California, Irvine School of Medicine, Irvine, CA, USA.
Exp Neurol. 2021 Jun;340:113669. doi: 10.1016/j.expneurol.2021.113669. Epub 2021 Feb 27.
Persons living with incomplete spinal cord injuries (SCI) often struggle to regain independent walking due to deficits in walking mechanics. They often dedicate many weeks of gait training before benefits to emerge, with additional training needed for benefits to persist. Recent studies in humans with SCI found that daily bouts of breathing low oxygen (acute intermittent hypoxia, AIH) prior to locomotor training elicited persistent (weeks) improvement in overground walking speed and endurance. AIH-induced improvements in overground walking may result from changes in control strategies that also enhance intralimb coordination; however, this possibility remains untested. Here, we examined the extent to which daily AIH combined with walking practice (AIH + WALK) improved overground walking performance and intralimb motor coordination in persons with chronic, incomplete SCI.
We recruited 11 persons with chronic (> 1 year), incomplete SCI to participate in a randomized, double-blind, balanced, crossover study. Participants first received either daily (5 consecutive days) AIH (15, 90-s episodes of 10.0% O with 60s intervals at 20.9% O) or SHAM (15, 90s episodes at 20.9% O with 60s intervals at 20.9% O) followed by 30-min of overground walking practice. They received the second treatment after a minimum 2-week washout period. We quantified overground walking performance, in terms of speed and endurance, using the 10-Meter Walk Test (10MWT) and 6-Minute Walk Test (6MWT), respectively. We quantified intralimb motor coordination using kinematic variability measures of foot trajectory (i.e., endpoint variability, EV) and of inter-joint coupling between the hip and knee, as well as between the knee and ankle joints (i.e., angular coefficient of correspondence, ACC). We compared the changes in walking performance relative to baseline (BL) between daily AIH + WALK and daily SHAM+WALK on treatment day 5 (T), 1-week follow-up (F), and 2-weeks follow-up (F). We also compared these changes between participants who used bilateral walking aids (N = 5) and those who did not. To assess the effects of daily AIH + WALK on intralimb coordination, we compared potential treatment-induced changes in EV and ACC relative to BL at F and F.
Participants improved overground walking performance (speed and endurance) after daily AIH + WALK, but not SHAM+WALK. Following daily AIH + WALK, participants decreased their 10MWT time at T by 28% (95% CI 0.2-10.1 s, p = 0.04), F by 28% (95% CI 1.1-13.5 s, p = 0.01), and F by 27% (95% CI 1.4-13.9 s, p = 0.01) relative to BL. The greatest decreases in the 10MWT occurred in participants who used bilateral walking aids (p < 0.05). We also found daily AIH + WALK resulted in an increase in 6MWT distance at T by 22% (95% CI 13.3-72.6 m, p = 0.001), F by 21% (95% CI 13.1-72.5 m, p = 0.001), and F by 16% (95% CI 2.9-62.2 m, p = 0.02). However, measures of EV and ACC during self-selected walking conditions did not change following daily AIH + WALK (all p-values >0.50).
Consistent with prior studies, daily AIH + WALK triggered improvements in walking speed and endurance that persisted for weeks after treatment. Greatest improvements in speed occurred in participants who used bilateral walking aids. No change in EV and ACC may suggest that intralimb motor coordination was not a significant gait training priority during daily AIH + WALK.
在慢性、不完全性脊髓损伤（SCI）患者中，每日低氧通气（AIH）联合步行训练（AIH+WALK）是否比单独步行训练更能改善步行速度和耐力。
招募 11 名慢性（>1 年）、不完全性 SCI 患者参与随机、双盲、平衡、交叉研究。参与者首先接受每日（连续 5 天）AIH（15 次，每次 90s，10.0%O2，60s 间隔，20.9%O2）或 SHAM（15 次，每次 90s，20.9%O2，60s 间隔，20.9%O2），随后进行 30min 的地面步行训练。他们在至少 2 周的洗脱期后接受第二次治疗。我们使用 10 米步行测试（10MWT）和 6 分钟步行测试（6MWT）分别从速度和耐力方面量化地面行走表现。我们使用足部轨迹的运动学变异性指标（即端点变异性，EV）和髋关节与膝关节之间以及膝关节与踝关节之间的关节耦合角度系数（即角度一致性系数，ACC）量化了肢体间运动协调。我们比较了 AIH+WALK 治疗日 5（T）、1 周随访（F）和 2 周随访（F）相对于基线（BL）的步行表现变化，以及双侧助行器（N=5）和未使用双侧助行器的参与者（N=6）的这些变化。为了评估 AIH+WALK 对肢体间协调的影响，我们比较了 BL 时 EV 和 ACC 相对于 BL 的潜在治疗诱导变化。
AIH+WALK 后，参与者的地面行走速度和耐力均有改善，但 SHAM+WALK 无此效果。与 BL 相比，AIH+WALK 后参与者的 10MWT 时间在 T 时减少了 28%（95%CI 0.2-10.1s，p=0.04），F 时减少了 28%（95%CI 1.1-13.5s，p=0.01），F 时减少了 27%（95%CI 1.4-13.9s，p=0.01）。10MWT 最大的减少发生在使用双侧助行器的参与者中（p<0.05）。我们还发现，AIH+WALK 导致 6MWT 距离在 T 时增加了 22%（95%CI 13.3-72.6m，p=0.001），F 时增加了 21%（95%CI 13.1-72.5m，p=0.001），F 时增加了 16%（95%CI 2.9-62.2m，p=0.02）。然而，AIH+WALK 后，在自我选择的步行条件下，EV 和 ACC 的测量值没有变化（所有 p 值均>0.50）。
与先前的研究一致，每日 AIH+WALK 引发了步行速度和耐力的改善，这些改善在治疗后持续数周。速度的最大改善发生在使用双侧助行器的参与者中。EV 和 ACC 没有变化可能表明，在 AIH+WALK 期间，肢体间运动协调不是步行训练的一个重要重点。
