Aims of the study:

This is a double-blind randomized-controlled trial to test the effects of a task oriented training combined with cerebellar transcranial direct current stimulation on locomotor function, mobility and balance in multiple sclerosis subjects with moderate gait impairments (EDSS 4-5,5).

Subjects and methods: 30 multiple sclerosis patients will be recruited in an outpatient rehabilitation clinic University Hospital Ferrara. Informed consent will be obtained. Participants enrolled will included in 2 different treatment groups: Task Oriented Circuit Training (TOCT) + anodal cerebellar transcranial direct current stimulation (experimental group) and TOCT + sham transcranial direct current stimulation over the cerebellum (control group). The group with anodal transcranial direct current stimulation will receive continuous stimulation with intensity of 2 mA during the first 15 minutes of functional circuit training. In the sham session, anodal transcranial direct current stimulation was applied for 30 s and then shut off. Each subject will receive 10 task-oriented training sessions over 2 weeks (5 sessions/week). 3 subjects with a supervisor physiotherapist will take part at the TOCT. During the stimulation sessions both the subject and the researcher, responsible for carrying out clinical tests, will be unaware of the type of stimulation set.

Treatment efficacy outcome measures will be clinical test for gait speed (Timed 25-Foot Walk), walking endurance (six minute walking test), balance (Dynamic Gait Index) and mobility (Time Up and Go Test); self-assessment questionnaire for motor fatigue (Fatigue Severity Scale FSS) and quality of life (Short Form (36) Health Survey).

Outcome measures will be assessed the week prior to treatment initiation (T0), the week after the end of treatment (T1) and at 3 months follow-up (T3) to evaluate treatments retention, by a clinician blinded to the treatment. At the end of each session, the subject will complete a questionnaire where report side effects due to stimulation (headache, neck pain, burning, redness and/or itching in the site of stimulation).

The inclusion criteria will be:

• males and females, community dwelling, age 18 or older;
• diagnosis of multiple sclerosis in a stable phase, which will be defined as a chronic progressive or relapsing-remitting pattern with no relapse during the last 3 months;
• moderate gait impairments referred to Expanded Disability Status Scale between 4 and 5,5 (this EDSS scores refers to people with restricted ambulation who do not need walking aids).

Inclusion Criteria:

• males and females, community dwelling, age 18 or older;
• diagnosis of multiple sclerosis in a stable phase, which will be defined as a chronic progressive or relapsing-remitting pattern with no relapse during the last 3 months;
• moderate gait impairments referred to Expanded Disability Status Scale between 4 and 5,5 (this EDSS scores refers to people with restricted ambulation who do not need walking aids).

Exclusion Criteria:

• neurologic conditions in addition to multiple sclerosis that may affect motor function;
• other medical conditions likely to interfere with the ability to safely complete the study protocol;
• impaired cognitive functioning (Mini Mental Status Examination < 24);
• contraindications to transcranial direct current stimulation: intracranial metal implants that can be stimulated, incorrectly positioned or over-heated by the electric current.