AI Insight
This randomized, double-masked crossover trial tested acute intermittent hypoxia (AIH) in 23 adults with multiple sclerosis, finding that five days of brief, repeated low-oxygen exposures significantly improved ankle plantarflexion strength by 17.5% immediately after treatment and 29.2% at follow-up, while also improving six-minute walk distance. The intervention was safe and well-tolerated, with no serious adverse events and no new MS activity detected on follow-up MRI. Cardiovascular parameters returned to baseline within minutes after each session.
Why it matters
Up to 75% of people with MS experience walking impairment, and current rehabilitation approaches are limited by reduced neuroplasticity in this population. This study demonstrates that AIH could serve as a safe primer to enhance rehabilitation outcomes when combined with gait training, potentially offering a new avenue to improve mobility in MS patients.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
BACKGROUND/OBJECTIVES Walking impairment affects up to 75% of persons with multiple sclerosis (MS), and the benefits of rehabilitation are constrained by limited capacity for training-induced neuroplasticity. Acute intermittent hypoxia (AIH), brief repeated exposures to low inspired oxygen, triggers serotonin-dependent spinal plasticity that enhances motor output. In spinal cord injury, daily AIH paired with walking training has produced larger walking gains than training alone, positioning AIH as a promising primer for rehabilitation. Before AIH can be combined with training in MS, its safety and stand-alone effects with repeated daily dosing must be established in a population with demyelinating disease. We therefore conducted the first multi-day AIH trial in persons with MS to characterize safety and tolerability and to evaluate preliminary effects on ankle strength and walking. METHODS Twenty-three ambulatory adults with MS (Expanded Disability Status Scale [EDSS] 3.0-6.5; 15 relapsing-remitting, 8 secondary-progressive) completed a randomized, double-masked, placebo-controlled crossover trial. Participants received AIH (15 x ~60 s episodes; FiO2 = 0.09; SpO2 target 84-88%) and Sham in a counterbalanced order, separated by a washout of at least 4 weeks. Assessments at pre-intervention, post-intervention, and follow-up included ankle plantarflexion and dorsiflexion torque, 6-Minute Walk Test (6MWT), Timed 25-Foot Walk (T25FW), and MS Walking Scale-12 (MSWS-12). Treatment effects were estimated using analysis of covariance (ANCOVA) with participant as a random effect. RESULTS No serious adverse events related to the intervention were reported, and follow-up MRI showed no new MS activity in either arm. Mean nadir SpO2 during AIH was 84.7 +/- 0.2%, and cardiovascular parameters returned to baseline within minutes of each session completion. Ankle plantarflexion torque was significantly greater following AIH than Sham (beta = 8.74 Nm, p < 0.001), with mean increases of 17.5% at post-intervention and 29.2% at follow-up. Six-minute walk distance was also significantly greater after AIH (beta = 10.14 m, p = 0.039). Dorsiflexion torque (p = 0.202), T25FW time (p = 0.239), and MSWS-12 score (p = 0.564) did not differ significantly between conditions. Greater elevation in heart rate during hypoxic episodes was associated with larger strength gains at follow-up (r = 0.58, p = 0.009). CONCLUSIONS: Daily AIH sessions are safe and well tolerated in persons with MS across a clinically heterogeneous disability range and produce significant improvements in ankle plantarflexion strength and walking endurance. These findings support combining AIH with task-specific gait training in future trials.