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

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.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Chronic Disease
  • Combined Modality Therapy / methods
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Humans
  • Hypoxia*
  • Male
  • Middle Aged
  • Psychomotor Performance / physiology*
  • Recovery of Function / physiology*
  • Spinal Cord Injuries / physiopathology
  • Spinal Cord Injuries / therapy*
  • Time Factors
  • Walking / physiology*
  • Young Adult