The purpose of this study is to determine whether, in patients with multiple sclerosis presenting with marked asymmetry of strength, training the less-affected limb with a Cross-Training approach may induce a meaningful transfer of strength with neurophysiological, functional and clinical correlates, to the contralateral, more-impaired limb.

Muscle weakness is a major disability that is responsible for deeply reducing the overall quality of life (QoL) of patients with Multiple Sclerosis (MS). Research has shown that strength training (ST) has a significant positive effect on the performance of daily living activities in people with MS, resulting in an increased QoL. Several ST methods are currently employed for reducing strength impairment in MS but no one regimen has been portrayed as superior to others. When strength impairment is prominently lateralized to one limb, training is commonly addressed to the weaker side in order to balance the deficit. However, such ST may not always be applicable to a severely weakened limb that is too compromised to sustain it. For these selected patients we hypothesize that training the less affected limb with a Cross Training (CT) approach may overcome the problem, also avoiding patients' frustration and potential withdrawals from rehabilitation programs.

Aim of this project is to investigate and compare in two groups of selected MS patients, with a marked asymmetry of strength, the effects induced on dynamometric, neurophysiological, functional and clinical outcomes by a CT of the less-impaired leg (CT group) compared to a ST of the more-impaired leg (ST group). In order to make comparisons with a population which is not exposed to the condition MS, a third group composed of healthy subjects will also be included in the study.

The research plan will be articulated in 5 phases (recruitment, baseline assessment, 6 week-intervention phase, post-intervention assessment and follow up at 12 weeks).

Inclusion Criteria:

• Age: 18-65 years
• Expanded Disability Status Scale (EDSS) ≤6 (Pyramidal functional system ≥3)

Exclusion Criteria:

• Clinically relevant cognitive disorders;
• Disability caused by other diseases;
• Medication with corticosteroids within three months prior to enrolment;
• Medication with botulinum toxin within six months prior to enrolment;
• Clinically or radiologically documented exacerbation within six months prior to enrolment;
• Variations in disease-modifying drugs (DMD) within three months prior to enrolment;
• Severe ataxia and postural instability (assessed with Berg Balance Scale);
• Depression