Daily acute intermittent hypoxia combined with walking practice enhances walking performance but not intralimb motor coordination in persons with chronic incomplete spinal cord injury

Abstract

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.

Methods: 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% O2 with 60s intervals at 20.9% O2) or SHAM (15, 90s episodes at 20.9% O2 with 60s intervals at 20.9% O2) 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 (T5), 1-week follow-up (F1), and 2-weeks follow-up (F2). 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 F1 and F2.

Results: 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 T5 by 28% (95% CI 0.2-10.1 s, p = 0.04), F1 by 28% (95% CI 1.1-13.5 s, p = 0.01), and F2 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 T5 by 22% (95% CI 13.3-72.6 m, p = 0.001), F1 by 21% (95% CI 13.1-72.5 m, p = 0.001), and F2 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).

Conclusions: 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.

Keywords: Acute intermittent hypoxia; Angular coefficient of correspondence; Endpoint variability; Incomplete spinal cord injury; Motor coordination; Rehabilitation; Walking; Walking aid.

Conflict of interest statement

Declaration of interests

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Copyright © 2021 Elsevier Inc. All rights reserved.

Figures

Figure 1.

(A) Acute intermittent hypoxia (AIH) treatment protocol. During a single session, participants received 15 episodes of 1.5 minutes of low oxygen (0.10 FiO2) alternating with 1 minute of room air (0.21 FiO2) as illustrated in (B). Abbreviations: Fraction inspired oxygen, FiO2; BP, blood pressure; HR, heart rate; SpO2, blood oxygen saturation.

Figure 2.

In (A), bars represent mean ± 1 standard error changes in the 10-meter walk test (10MWT) time (seconds) across all subjects at each time point for daily acute intermittent hypoxia (AIH, black) and normoxia (SHAM, white) combined with walking practice (WALK). Participant changes in 10MWT times (seconds) relative to BL across day 5 (D5) and follow-ups 1 (F1) and 2 (F2) during daily AIH+WALK (B). Decreases in time correspond to increases in walking speed. In (C), bars represent mean ± 1 standard error changes in the 6-meter walk test (6MWT) distance (meters) across all subjects at each time point for daily acute intermittent hypoxia (AIH, black) and normoxia (SHAM, white) combined with walking practice (WALK). Participant changes in 6MWT distance (meters) relative to BL across day 5 (D5) and follow-ups 1 (F1) and 2 (F2) during daily AIH+WALK (D). In A and C, single asterisks indicate significance relative to baseline (BL) at p<0.05 level, double asterisks indicate significance at p<0.01 level, and rackets with asterisks indicate significant differences between treatments.

Figure 3.

Representative data for footpath trajectory and interjoint coordination at baseline (BL) and follow-ups 1 (F1) and 2 (F2) during daily AIH+WALK. (A) Each line represents the footpath trajectory during swing phase of the gait cycle from one participant. The x-axis represents fore-aft position (cm) with zero indicating the reference point (posterior superior iliac spine) in the sagittal plane. The y-axis represents the vertical elevation in the sagittal plane (cm). We recorded multiple leg displacements during the swing phase of one gait cycle at baseline (BL) and follow-ups 1 (F1) and 2 (F2). We computed endpoint variability (EV) from these data. In (B), cyclogram graphs depict knee versus hip angles over the gait cycle from a single participant at each time point. Each overlaid trace represents one gait cycle. We computed angular coefficient of correspondence (ACC) from these data. Abbreviations: EV, endpoint variability, ACC, angular coefficient of correspondence; BL, baseline; F1, follow up visit 1; F2, follow up visit 2.

Figure 4.

Footpath trajectory and interjoint coordination variability do not change following rAIH and walking practice. (A) Data points represent the computed endpoint variability (cm2/cm) at each time point, baseline (BL) and follow-ups 1 and 2 (F1, F2). Each line corresponds to a single participant. Higher values indicate higher variability. (B) Data points represent the computed angular coefficient of correspondence (ACC) at each time point, BL, F1, F2. Each line corresponds to a single participant. An ACC value of 1 indicates perfect consistency of interjoint coordination for the hip and knee joints across multiple gait cycles.

Figure 5.

Bars represent mean ± 1 standard error changes in the 10-meter walk test (10MWT) time (seconds) following daily acute intermittent hypoxia combined with walking practice (AIH+WALK). Participants who used bilateral arm-driven walking aids correspond to white bars. Participants who did not use bilateral walking aids correspond to black bars. We compared changes in 10MWT times (seconds) relative to BL across day 5 (D5) and follow-ups 1 (F1) and 2 (F2). The circles correspond to the walking speed of individual participants. Asterisks indicate significance relative to baseline (BL) at p<0.05 level and rackets with asterisks indicate significant differences between treatments. Decreases in time correspond to increases in walking speed.