Inclusion criteria (stroke patients)

• - Age < 80.

• - Mini Mental State Examination > 24.

• - Modified Rankin Scale: 1-3.

• - Single hemisphere lesion.

• - Stabilized disease (> 6 months after the acute event) - Impairment in gait parameters (e.g. velocity, perceived fatigue etc) - Motor independence during walking (without orthotic devices and aids) but with pathological pattern (spasticity level: Ashworth < 2) Inclusion criteria (patients with Parkinson's disease) - Age < 80.

• - Mini Mental State Examination > 24.

• - Unified Parkinson Disease Rating Scale score (Parte III): < 28.

• - Stabilized disease and drug therapy.

• - Altered gait patterns.

• - Motor independence during walking (without orthotic devices and aids) but with pathological pattern.

Inclusion criteria (patients with multiple sclerosis):

• - Age < 60.

• - Mini Mental State Examination > 24.

• - Expanded Disability Status Scale score: 3-5.

• - Stabilized disease in the last 6 months (without relapse or disability progression) - Altered gait patterns (i.e., careening, slowing down, spasticity: Ashworth < 2, etc.) - Motor independence during walking.

Exclusion Criteria (stroke patients)

• - Multiple or bilateral lesions.

• - Neglect.

• - Equinism.

• - Spasticity: Ashworth >2.

• - Structured (non-elastic) Achilles tendon retraction.

• - Neurotoxin in the 3 months prior to the study.

• - Baclofen introduced or modified in the week before the start of the study.

• - Previous or concurrent diseases disabling the lower limb functions.

• - Rehabilitative treatments with music in the year before the study.

Exclusion criteria (patients with Parkinson's disease):

• - Previous or concurrent diseases disabling the lower limb functions.

• - Changes of drug therapy during the study.

• - Rehabilitative treatments with music in the year before the study.

Exclusion criteria (patients with multiple sclerosis):

• - Previous or concurrent diseases disabling the lower limb functions.

• - Neurotoxin in the 3 months prior to the study.

• - Baclofen introduced or modified in the week before the start of the study.

• - Spasticity: Ashworth >2.

• - Structured (non-elastic) Achilles tendon retraction.

- Rehabilitative treatments with music in the year before the study

Background: Music therapy is widely used in relational settings. The sound can engage limbic and paralimbic areas and a variety of other brain areas strictly connected with movement (motor cortex, supplementary motor area, cerebellum, basal ganglia, etc.). For this reason, music can be considered a useful tool in rehabilitation settings and, in particular, for neuromotor rehabilitation. The use of specific music-based techniques can induce plastic changes from childhood to elderly. These changes involve both brain motor and auditory sensory-motor areas thanks to the improved connectivity between brain areas induced by the sound and music that would not happen without the auditory stimuli. As suggested in previous studies the plastic changes induced by music in the nodal points of the cerebral network can cause effects that tend to persist even beyond the duration of rehabilitation training. The music also in the rehabilitation process determines an emotional involvement and creates a strong motivational basis reinforcing its action through the coupling of the auditory stimulus with sensory-motor component. Neurologic Music Therapy (NTM) could be defined as a codified use of music-based techniques aimed at recovering sensory, cognitive and motor deficits due to a neurological pathology. NMT consists in several specific techniques among which Rhythmic Auditory Stimulation (RAS) is one of the most used and well documented in scientific literature. RAS is based on the application of the rhythmic component of the music to gait and gait-related rehabilitation. Music effects in stroke rehabilitation are well documented: music can improve gait (velocity, cadence, stride length and balance), upper limbs movements , language, but also mood and psychological aspects. Gait rehabilitation studies for Parkinson's Disease (PD) and Multiple Sclerosis (MS) show similar results. Recent studies are related to the "sonification" technique: a properly selected set of sonorous-music stimuli are associated with patient movements mapping. The auditory-motor feedback can replace damaged proprioceptive circuits with a consequent improvement of the rehabilitation process. Interventions with "sonification" facilitate sensorimotor learning, proprioception and movements planning and execution improving global motor parameters. Studies related to "sonification" mainly concern upper limb rehabilitation and only a few of them concern the lower limbs rehabilitation. In particular, this study proposes the use of musical auditory cues which includes the melodic-harmonic component of the music. This kind of sonification makes the feedback pleasant and predictable as well as potentially effective. The investigators propose to apply this particular kind of sonification to gait training and other secondary outcomes in stroke, PD and SM population. Aims: 1. To assess the effectiveness of the sonification in the gait rehabilitation in stroke, PD and MS patients. 2. To assess the effectiveness of sonification on the level of fatigue perceived during the rehabilitation process. 3. To assess the impact of the sonification on the quality of life. Materials and methods: The study is a multicenter randomized controlled trial and will involve 120 clinically stabilized patients with stroke (n=40), Parkinsons' disease (n=40) and multiple sclerosis (n=40). Each of these three arms will be divided in two groups: a control group (n=20) will undergo standard motor rehabilitation and an experimental group (n=20) will undergo the same rehabilitation but with the sonification support. The gait training program includes 20 sessions, 30 minutes each 3 times a week (see next chapter for details). A unique randomization list will be generated according to the trial's design and managed by the Principal Investigator. Each subject will be associated with a unique identifier that will allow its identification throughout the duration of the study. The evaluation of the questionnaires and the statistical analysis will be carried out blindly. Assessment: The interventions will be evaluated at the baseline (T0), after 10 sessions (T1), after 20 sessions (T2, end of the treatment) and at follow-up (T3, one month after the end of the treatment). The scales used for the assessments will be the following: Functional evaluation:

• - Functional Independence Measure (FIM) Motor parameter evaluation: - 6 minutes Walking Test (velocity) - Mini BesTest (balance) - Dynamic Gait Index (dynamic balance, gait and risk of falls) - Timed Up & Go (mobility) Fatigue assessments, quality of life and perceived overall effect of the intervention: - VAS (Visual Analogue Scale, for assessing perceived fatigue at the end of each session) - McGill Quality of Life- it (quality of life assessment) - Global Perceived Effect (GPE) Statistics The collected data will be presented by descriptive statistics: continuous variables having a normal distribution as mean and standard deviation, continuous variables having a non-normal distribution as median and interquartile range.

Binary and categorical variables will be presented as a percentage or absolute number. For each group of patients involved in this study (stroke, Parkinson's disease, multiple sclerosis), the homogeneity of demographic data and outcome measures between the experimental subgroup and the control subgroup will be verified. Finally, for all outcome measures detected (6 minutes Walking Test, FIM, Dynamic Gait Index, Timed Up & Go, VAS fatigue, McGill Quality of Life-it and GPE) it is expected to perform the analysis of the variance or mixed linear model for repeated measurements (p<0.05) in order to evaluate the effects of the treatment type, time and their interaction. For those outcomes where the assumptions of applicability of the variance analysis will not be verified, non-parametric methods will be applied to assess the main effects and interaction separately. Patients will be asked to sign an Informed Consent before joining the study. Adverse events No indication of any risk associated with the protocol because the rehabilitative treatments will be performed according to the usual procedures laid down in clinical practice in accordance with the guidelines relating to the gait rehabilitation. Informed consent to participate in the study. All patients participating in the study will have to give their informed consent as required by the attachment for the execution of the study and for the processing of personal data. Insurance The activation of an additional insurance is not foreseen as the study and the procedures applied fall within the coverage of the insurance policy currently in force for the conduct of the clinical trial.

Arms

Experimental: Gait rehabilitation with "sonification"

The rehabilitation exercises with sonification are supported by the musical component (see "Interventions" section for details).

Active Comparator: Standard gait rehabilitation (without sonification)

The same rehabilitation exercises are performed without musical support.

Interventions

Device: - Gait rehabilitation with "sonification"

The sonification system is composed by 2 inertial sensors, a computer and a pair of bluetooth headphones connected with the computer. The sensors will be placed one per leg at the ankle and connected with Matlab software. An home-made ad-hoc software associates patient's movements with music patterns. The patient's natural rhythm is detected and used at the beginning of the intervention. The first part of each exercise is supported by a pre-recorded chord progression with a click on the background. In the second part (sonification approach) the software notices and records the contact of the heel with the ground. Each contact activates musical stimuli listened to via headphones. The steps succession will build a regular and predictable musical progression in relation to the correct sequence of steps. The exercises planned in this intervention are the same as those planned in the gait standard rehabilitation (see below).

Other: - Standard gait rehabilitation (without sonification)

The training will be carried out without any musical support. Exercises I Phase Load shift in anteroposterior standing in tandem position, left foot forward (3 minutes exercise with a short break in the middle) Load shift in anteroposterior standing in tandem position, right foot forward (3 minutes exercise with a short break in the middle) Left foot swing (3 minutes exercise with a short break in the middle) Right foot swing (3 minutes exercise with a short break in the middle) March in place (3 minutes exercise with a short break in the middle) Exercises II phase (15 minutes): the patient will perform 14 minutes of walking with a 1 minute of break in the middle (7 minutes of walking, 1 minute rest, 7 minutes of walking). In the second part of walking the patient will be asked to slightly increase the pace of the step up to the maximum possible speed.