High-Intensity Walking Training for Multiple Sclerosis

Inclusion Criteria: 1. Participants must have a clinical diagnosis of MS according to the revised McDonald Criteria. Participants with an EDSS score of 2.0-6.5 will be included but must have a stable disease course without worsening more than 1.0 EDSS point over the last 3 months and no MS exacerbation within the preceding 4 weeks, as determined by interview and review of medical records. 2. Participants will have stable MS disease treatments. All medications will be consistent for at least 1 month prior to enrollment. No corticosteroids for at least 1 month and no botulinum toxin injections above the knee for at least 3 months prior to enrollment. 3. Participants will be between the age of 18 and 65 and have a body mass of less than 135kg (maximum mass for treadmill equipment). 4. Participants will be able to follow three commands, as determined by the three step command test of the Mini Mental State Exam. 5. Participants must have had no myocardial infarction in the past month, must not have uncontrolled hypertension (blood pressure must be \< 190/110 mmHg at rest), must not have a symptomatic fall in blood pressure when standing and must not have documented, uncontrolled diabetes. 6. Participants will be medically stable, with absence of concurrent severe medical illness including: existing infection, known significant cardiovascular or metabolic disease that limits exercise participation, significant osteoporosis (as indicated by known history of fractures), known history of vascular claudication or pitting edema, and known history of pulmonary complications that limits exercise capacity, including significant obstructive and/or restrictive lung diseases. 7. All participants must be able to perform walking training with passive range of motion within the limits of normal locomotor function, including: 0-30 +/- 10 degrees ankle plantarflexion, knee flexion from 0 to 90 +/- 10 degrees, hip flexion to 0-90 +/- 10 degrees. 8. Individuals who are undergoing concurrent physical therapy or supervised exercise by a trained professional will be excluded from the study to eliminate confounding effects of additional physical interventions. Other therapies, such as occupational or speech therapies, will be allowed as prescribed by their physician. Individuals will be allowed and encouraged to continue their normal exercise routines during the course of the intervention. 9. Participants must have no other concomitant neurological diseases, no history of epileptic seizures, peripheral nerve injury in lower legs or traumatic brain injury. 10. Participants must have adequate hearing (whisper test) and vision (minimum 20/80 corrected vision on a Snellen chart). 11. Participants must be able to walk for 10 meters at their preferred walking speed. For participants that require assistive devices to walk overground, minimal assistance will be provided to enable training until participants recover enough that they are not needed. The use of braces or orthoses is allowed in the proposed study to assure orthopedic safety. Participants will be excluded if they have factors that preclude stepping exercise, such as severe spasticity, excessive fatigue or exercise intolerance. 12. Women of childbearing potential will not be excluded, although women who are pregnant or who are considering becoming pregnant will be excluded due to the trunk and pelvis restraints required for safety during treadmill training. 13. Participants must be willing to commit to the treadmill training program schedule and participate in all of the assessments. They must be able to provide informed written consent and willing to be randomized to any of the 4 study arms. Exclusion Criteria: See inclusion criteria.