The aim of the study is to set up a pilot study to investigate the effects of treadmill training in preventing the onset and worsening of walking impairments, balance deficits and fatigue.

As regards the of potential impact of exercises on functional decline at best of our knowledge no studies have been done on preventive interventions on walking, balance and fatigue disorders in early diagnosed PwMS. However, preliminary studies found that walking exercises can improve performances in PwMS with mild disability. van der Berg et al (van der Berg, 2006) investigated whether four weeks of aerobic treadmill training would improve mobility and fatigue in PwMS. They found that aerobic treadmill training is feasible and well tolerated and walking speed and endurance increased after training without changes in reported fatigue. In agreement with this study, Sabapathy et al (Sabapathy, 2011) reported improvements in mobility after endurance exercise training. Recent reviews (Dalgas, 2008 and Heine, 2015) and a recent paper by Sandroff et al (Sandroff, 2015) suggested that endurance training at low moderate intensity is well tolerated, has beneficial effects and reduces level of fatigue in MS patients having EDSS lower than 7.

Furthermore, the long-term effects of walking based aerobic endurance exercise on gait parameters were investigated by Wonnemberg et al (Wonnemberg, 2015). They found that step cadence decreased significantly and the step length increased significantly after 12 months suggesting that walking based aerobic endurance exercise may contribute to improved gait parameters in MS patients.

Walking exercises can be performed using treadmills. A Systematic review by Swinnen et al. (Swinnen, 2012) addresses the effect of different treadmill training (TT) modalities in PwMS. It showed that treadmill training improves walking skills and distance. In addition, Braendvik et al (Braendvik, 2015) revealed that TT was superior progressive strength training in improving walking in mild to moderate PwMS. Peruzzi et al. (Peruzzi, 2016) found similar results using Virtual Reality-based TT in PwMS with mild to moderate disability. After training, gait speed, stride length and the ability in negotiating obstacles were improved. Finally Gervasoni et al (Gervasoni, 2013) showed that 3-week of treadmill training reduced fatigue in PwMS.

The Hypothesis to be tested is that treadmill training can reduce subtle balance and gait impairments decreasing the impact of MS on the activities of daily living and, thereby, favorably impact on the disease progression.

Inclusion Criteria:

• Included will be patients residing in the centers' catchment areas
• Diagnosis of Multiple Sclerosis (Polman criteria)
• Stable disease course without worsening more than 1 Expanded Disability Status Scale (EDSS) point over the last 3 months
• EDSS < 2.5,
• Disease duration shorter than or equal to 5 years,
• Releasing a written informed consent.

Exclusion Criteria:

• Multiple Sclerosis relapse within the previous three months
• Cognitive impairment (MMSE score <27);
• Diagnosis of major depression (DSM-IV);
• Severe joint and/or bone disorders interfering with balance and gait (based upon clinical judgment);
• Cardiovascular diseases;
• Unconfirmed or uncertain diagnosis of MS (Polman criteria)
• Other concomitant neurological diseases;