A prospective, randomized controlled single-blind trial will test the hypotheses that a 6- week intervention that combines treadmill training (TT) with virtual reality (VR) significantly improves real-life, functional mobility and cognitive abilities, keys to health-related quality of life in patients with MS.

A prospective, single blinded,randomized controlled trial with 6 month follow-up will be employed to investigate the effects of treadmill training augmented with virtual reality on patients with MS. The study will include 200 participants. Participants will be randomized to either the intervention or active comparator. The intervention group will receive 18 sessions of Treadmill Training with Virtual Reality (TT+VR) and the active control comparison will receive 18 training sessions of treadmill training alone (TT) without the VR simulation All interventions will be delivered by therapists trained in the standard protocols. All subjects will be trained 3 times a week for 6 weeks, each session will last approximately 45 minutes.Training progression will be based on increasing both motor and cognitive challenges, individualized to the participant's level of performance.

Inclusion Criteria:

Patients will be included if:

• They are between 18-65 years of age.
• They have a confirmed diagnosis of relapsing remitting MS.
• They have a score between 2 and 6 on the Expanded Disability Status Scale (EDSS)
• They are free from dementia as determined using the Mini Mental State Exam (MMSE>=24)
• They can walk on the treadmill without partial body weight support harness for 5 minutes at their preferred walking speed; this is set as the smallest bout length at the start of training.
• They have no history of epileptic seizures.
• They have no MS exacerbation within the preceding 4 weeks, as determined by interview and medical notes review.
• They have stable MS disease treatments (e.g., last intake of steroids occurred at least 50 days before the enrolment, MS-specific drugs stable from at least 3 months, symptomatic drugs stable from at least 1 month before the enrolment).
• They have adequate hearing (as evaluated by the whisper test and adequate vision capabilities (as measured using a Snellen chart, 6.20 cut-off).
• They are willing to commit to treadmill training program week and participate in all of the assessments.
• They provide informed written consent and are willing to be randomized to any of the 2 study arms.

Exclusion Criteria:

• Patients will be excluded if:

  • They cannot follow safety or training instructions.
  • They have another neurological disorder, unstable cardiovascular disease, diabetes, lower limb arthritis, acute lower back or lower extremity pain, peripheral neuropathy, rheumatic or severe orthopaedic problems that may interfere with walking, or have diagnosed psychiatric problems.
  • They are pregnant.
  • They are undergoing any experimental drug or other kind of therapy.
  • Their medication regime is likely to change during the course of the study.
  • They are already participating in an intensive exercise program. The use of walking aids will not exclude participation.