Traditional Versus Progressive Robot-assisted Gait Training in People With Multiple Sclerosis and Severe Gait Disability

Timed Up and Go (TUG) test

6-Minute Walk Test (6MWT)

Berg Balance Scale (BBS), a 5-point ordinal scale used to assess the ability to maintain balance statically and while performing functional movements. BBS comprises 14 tasks; the total score is calculated by summing the scores of each item (0-4). The maximum total score is 56. Higher totals reflect more balance impairment.

Modified Ashworth Scale (MAS), a 6-point measure of spasticity. The assessor will rate the perceived amount of resistance or tone at the flexor and extensor muscles of the hip, knee, and ankle. Higher scores reflect more spasticity

Multiple Sclerosis Impact Scale-29 (MSIS-29), a questionnaire that evaluates the impact of MS on physical and psychological functioning. It comprises 29 items, with 20 items assessing physical activity and 9 assessing psychological state. Each item can be rated from 0 to 5; the total score is the sum of all items. Higher score reflect higher impact of MS on quality of life.

Multiple Sclerosis Walking Scale-12 (MSWS-12), a questionnaire used to evaluate the impact of MS on walking ability. It comprises 12 items that inquire about the patient's perception of gait speed, running, confidence in ascending/descending stairs, balance, and fatigue. The total score is calculated by summing the scores of each item (0-5) and then converting it into a value ranging from 0 to 100. Higher score reflect higher impact of MS on walking ability.

Fatigue Severity Scale (FSS), a short questionnaire that requires the subject to rate their level of fatigue from 1 to 7 in different activities. Higher score reflect higher impact of fatigue

Beck Anxiety Inventory (BAI), a questionnaire used to measure anxiety levels, consisting of 21 items. Respondents indicate how severely each symptom affected them using a 4-point Likert scale, ranging from 0 (not at all) to 3 (severely). The sum of all responses provides an overall score, with higher totals reflecting more intense anxiety symptoms

Beck Depression Inventory - II (BDI-II), a questionnaire comprised of 21 multiple-choice questions. Respondents assign a score ranging from 0 to 3 to each answer, where higher cumulative scores signal a greater severity of depressive symptoms

Tampa Scale of Kinesiophobia (TSK), a 17-item self-evaluation checklist on a 4-point Likert scale to assess the fear of movement or potential re-injury. The scoring yields a total raw score that can range from 17 to 68 and higher cumulative scores reflect higher fear of movement.

Psychosocial Adjustment to Illness Scale-Self Report (PAIS-SR), a 46-item self-report tool designed to evaluate a patient's adaptation to either a current medical condition or the aftermath of a past illness. Each question within the PAIS-SR is scored on a scale from 0 to 3, where a higher score reflects a lower level of adjustment

Brief COPE, a self-report questionnaire used to evaluate coping strategies in facing stressful, unpredictable, and damaging events. It comprises 28 items grouped in 14 faced-scales which represent 14 different coping reactions. Respondents rate each item on a 4-point Likert scale, ranging from 1 (I haven't been doing this at all) to 4 (I've been doing this a lot). Total scores on each scale range from 2 (minimum) to 8 (maximum). Higher scores indicate increased utilization of that specific coping strategy.

The Near-infrared spectroscopy (NIRS) technology will evaluate muscle oxygen consumption. The patient, lying supine, will be fitted with a pair of NIRS sensors (transmitter and receiver) at the medial belly of the gastrocnemius to monitor changes in oxygenated and deoxygenated hemoglobin.

Hemodynamic cortical activation recorded during reaching and grasping activities performed with the most impaired (or not dominant) upper limb. Each patient will be equipped with a Near-infrared spectroscopy (NIRS) system composed of 16 sources and 16 detectors emitting two wavelengths of near-infrared light (760 and 850 nm). Hemodynamic signals will be recorded at a sampling rate of 3.81 Hz. A standard cap will be placed over each participant's scalp, and sources and detectors were positioned on the measuring cap according to the 10-20 international system with standard interoptode distances of approximately 3 cm. Optodes were placed over both hemispheres, resulting in 48 channels covering the regions of the primary motor and sensorimotor cortices. Data will be analyzed assessing the variations in oxygenated and deoxygenated hemoglobin

EEG recording during action observation task. Stimuli will consist in videos, filmed in the first person, in which a hand will show reaching for and grasping a can. The EEG will be recorded during the 20 minutes of the session: 3 minutes with open eyes, 3 minutes with closed eyes, and 14 minutes of video observation.

Urinary lab examination

Ad-hoc questionnaire with closed 1-10 Likert-scale and open-ended questions to assess patients' experience with the robot intervention. The questionnaire will specifically explore the usability, acceptability, perceived pleasantness, and safety of the intervention. Higher scores reflects higher satisfaction of the treatment.