This interventional, randomized, sham-controlled study will examine whether Acute Intermittent Hypoxia (AIH) delivered immediately before Myoelectric Interface Neurorehabilitation Training (MINT)-based locomotor training improves gait in people with Multiple Sclerosis. The primary objectives are to evaluate changes in gait speed and endurance, with secondary objectives assessing spatiotemporal gait parameters, fatigue, and safety. Participants will receive AIH or sham priming followed by standardized treadmill and/or overground gait training, with outcome measures collected before and after the intervention across multiple sessions.

The study tests whether a brief breathing treatment, acute intermittent hypoxia (AIH), can make a computer-based muscle training program (MINT) more effective for people with MS who have difficulty walking. AIH involves breathing short alternating periods of low-oxygen air (about 9% oxygen versus the roughly 21% in room air) and normal room air. The premise, drawn from work in other neurological conditions like spinal cord injury, is that AIH delivered before movement training may improve strength and walking. Whether this benefits people with MS is not yet known, which is the gap the study addresses.

MINT itself uses surface EMG sensors on the leg muscles to capture muscle activity, which then controls game-like tasks on a screen. Participants practice activating the correct muscles for walking while suppressing unwanted activity.

Inclusion Criteria:

• Diagnosis of clinically definite multiple sclerosis
• Patient-Determined Disease Steps (PDDS) score between 3 and 6
• Relapse-free for at least 6 months prior to enrollment
• Age ≥ 18 years and ≤ 75 years
• Resting oxygen saturation (SpO₂) ≥ 95% on room air
• Systolic blood pressure between 85-140 mmHg and diastolic blood pressure between 55-90 mmHg
• Modified Ashworth Scale (MAS) score ≤ 3 at the ankle and knee
• Mini-Mental State Examination (MMSE) score ≥ 24
• Ability to walk at least 10 meters with or without an assistive device
• Ability to perform active ankle dorsiflexion and plantarflexion

Exclusion Criteria:

• Uncontrolled hypertension or hypotension outside the required ranges
• History of epilepsy or seizures
• Uncontrolled pulmonary, cardiovascular, or orthopedic disease
• Premorbid or ongoing major psychiatric illness (e.g., major depression, psychosis)
• Other neurological disease (e.g., stroke, traumatic brain injury, peripheral neuropathy)
• Illnesses with potential to cause brain injury
• Frequent or severe unexplained headaches
• Pregnancy
• Implanted medical devices (e.g., pacemakers, intrathecal pumps, brain stimulators)

We do not currently have a plan to share IPD.