Conventional Multidisciplinary Gait Rehabilitation VR Robotic Self-balancing Based Gait Rehabilitation

Aims Primary Aim: To compare the effect of Robot-Assisted Gait Training (RAGT) using the Atalante self-balance exoskeleton with conventional rehabilitation training (cRHB) for improving Walking speed measured by the Timed 10-meters walk test (10-MWT), considering a clinically relevant change an improvement of 20% of the velocity (m/s) with respect to the baseline assessment. Secondary Aims: * To compare the effect of RAGT using the Atalante self-balance exoskeleton with conventional Rehabilitation training (cRHB), for improving static balance, dynamic balance, mobility, and self-perception of gait impairment measured with: * Static Balance by the Berg Balance Scale (BBS), considering a clinically relevant change for improvement in balance as measured by BBS was +3 points, meaning that individuals are likely to perceive that as a reproducible and clinically important change in their balance performance. * Dynamic balance by the Timed Up and Go test (TUG) * Mobility measured by modified Rivermead Mobility Index (mRMI) * Self-perception of gait impairment by Multiple Sclerosis Walking Scale-12 (MSWS-12) * Instrumented gait analysis by the G-walk device (assessing gait cycle duration, step length, propulsion index, support phase percentage D/I, oscillation phase percentage D/I, double/unique support phase percentage). * To compare the effect of RAGT using the Atalante self-balance exoskeleton with conventional Rehabilitation training (cRHB) on quality of life, emotional status and fatigue measured at pre and post-intervention with: * Multiple Sclerosis Quality of Life-54 (MSQoL 54 Health Survey Spanish version) * Hospital Anxiety and Depression Scale (HADs) considering a clinically relevant change of 1.7 points at HADs * The Modified fatigue scale (MFIS) * The patient' physical effort of each session by means of the scale of perception of the effort R.P.E of Borg at the end of each training. * To evaluate the epigenetic blueprint of rehabilitation training by comparing the genome wide chromatin accessibility of peripheral blood mononuclear cells (PBMCs) before and after RAGT or cRHB, by Assay for Transposase-Accessible Chromatin sequencing (ATACseq). * To test the hypothesis that genome wide chromatin accessibility compared to clinical measures can be useful for identifying molecular mechanisms underlying rehabilitation therapies. * To compare the changes induced by RAGT versus cRHB on the overall chromatin accessibility, and specific genome regions and pathways. * Use the biological samples to provide additional functional and mechanistic information about the rehabilitation effects and subject health, disease or state. Materials And methods Design: This trial is a prospective, randomized, rater-blinded study (cRHB (N=30) vs RAGT (N=30)). For the control group, this protocol includes 24 one-hour sessions of cRHB training during 8 weeks three times per week, under the supervision of a qualified rehab team. For the intervention group (RAGT) this protocol includes 24 one-hour sessions of RAGT during 8 weeks three times per week, under the supervision of a qualified rehab team. Additionally, peripheral blood (6ml) will be taken from all subjects at three timepoints: at baseline (T1), after the 8 weeks of rehabilitation treatment (T2) and, if possible, one year after T4. Biological samples will then be given a unique identifier and transferred to researchers for analysis. Informed consent will be obtained from patients prior to inclusion in the study, which will be carried out in accordance with the Declaration of Helsinki. Enrollment and Screening Subjects will be evaluated for their eligibility from neurorehabilitation and neurology outpatient clinics at the Multiple Sclerosis Center of Catalonia (Cemcat). Potential subjects will be referred to the study via Cemcat Physicians. A member of the research team will screen the referral and confirm they meet the necessary inclusion and exclusion criteria. Following confirmation of criteria, potential subjects will be contacted by phone to schedule an initial visit for consent and baseline assessment. Additionally, peripheral blood (6ml) will also be taken from all subjects at baseline (T1). Prior to all testing