A physiotherapist-to-patient ratio of 1:1 is provided for the treatment in all participating centres.

Patients will undergo a total of 25 sessions, each lasting 45 minutes, with the following frequency:

• 5 times a week for 5 weeks, for inpatients;
• 3 times a week for 8.3 weeks, for outpatients.

The Fugl-Meyer Assessment (FMA) is a stroke-specific, performance-based impairment index. It is designed to assess motor functioning, balance, sensation and joint functioning in patients with post-stroke hemiplegia. The upper extremity sensory function domain evaluates light touch on two surfaces of the arm, and position sense for upper limb joints. It ranges from 0 to 12 (normal sensory function).

The Fugl-Meyer Assessment (FMA) is a stroke-specific, performance-based impairment index. It is designed to assess motor functioning, balance, sensation and joint functioning in patients with post-stroke hemiplegia. The lower extremity motor function domain includes items assessing movement, coordination, and reflex action of the hip, knee, and ankle. It ranges from 0 (hemiplegia) to 34 (normal motor performance).

The Fugl-Meyer Assessment (FMA) is a stroke-specific, performance-based impairment index. It is designed to assess motor functioning, balance, sensation and joint functioning in patients with post-stroke hemiplegia. The lower extremity sensory function domain evaluates light touch on two surfaces of the leg, and position sense for lower limb joints. It ranges from 0 to 12 (normal sensory function).

The Berg Balance Scale (BBS) is used to objectively determine a patient's ability (or inability) to safely balance during a series of predetermined tasks. It is a 14-item scale designed to measure balance of the older adult in a clinical setting. It ranges from 0 to 56. A higher score indicates better balance.

The Symbol Digit Modalities Test evaluates information processing speed. It consists of a simple task of replacing symbols with numbers. Using a reference key, the patient has 90 seconds to match a sequence of symbols with the correspondent numbers as rapidly as possible. Both written or oral administration can be used. For each correct answer, a point is assigned. The higher the score, the faster the information processing speed.

The Modified Ashworth Scale (MAS) is a revised version of the original Ashworth Scale that measures spasticity in patients with lesions to the central nervous system. MAS is an assessment that is used to measure the increase in muscle tone. MAS assigns a grade of spasticity from a 0 to 4 ordinal scale. The grade is assigned by moving a joint/muscle through a high velocity quick stretch. The lower the score, the lower the spasticity. Upper and lower joints spasticity is assessed.

The Motricity Index (MI) is an ordinal method of measuring limb strength. For upper extremity test, shoulder abduction, elbow flexion, pinch grip are considered. It ranges from 0 (worse) to 100 (normal strength).

The Motricity Index (MI) is an ordinal method of measuring limb strength. For lower extremity test, hip flexion, knee extension, and ankle dorsiflexion are considered. It ranges from 0 (worse) to 100 (normal strength).

The Trunk control test (TCT) measures four simple aspects of trunk movement. Total score range from 0 (minimum) to 100 (maximum, indicating better performance).

The Numerical Rating Scale fo Pain (NRSP) is a subjective measure in which individuals rate their pain on an eleven-point numerical scale, from 0 (no pain) to 10 (worst pain imaginable).

The Neuropathic Pain 4 Questions (DN4) is a validated clinician-administered screening tool for neuropathic pain. It ranges from 0 to 10; higher values means higher neuropathic pain probability.

The Action Research Arm Test (ARAT) is a 19 item observational measure used to assess upper extremity performance (coordination, dexterity and functioning). The 19 items comprising the ARAT are scored using a 4 point ordinal scale. Scores on the ARAT may range from 0-57 points, with a maximum score of 57 points indicating better performance.

The 2 Minute Walk Test (2MWT) is a measure of self-paced walking ability and functional capacity. The person is encouraged to walk as fast as they can, safely, without assistance for two minutes and the distance is measured.

The 5-level EQ-5D (EQ-5D-5L) is a validated tool to assess health-related quality of life. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Index scores range from -0.59 to 1; 1 is the best possible health state. Negative values represent health states perceived as worse than dead, which is equal to 0.

The Brain Symmetry Index (BSI) is a quantitative electroencephalographic (qEEG) measure used to assess the degree of symmetry in brain activity between the two hemispheres. It is defined as the mean absolute difference in spectral power of the EEG signals from homologous channels pairs on the left and right hemispheres, in the frequency range from 1 to 25 Hz. A higher BSI value indicates greater asymmetry, which is often associated with poorer clinical outcomes in stroke patients.

The Delta/Alpha Ratio (DAR) is a quantitative electroencephalographic (qEEG) measure used to assess the balance between slow-wave (delta) and fast-wave (alpha) brain activity. It is calculated by dividing the power of delta waves (0.5-4 Hz) by the power of alpha waves (8-12 Hz). The DAR is particularly useful in evaluating brain function in stroke patients, as an increased DAR is often associated with greater brain dysfunction and poorer clinical outcomes.

Serum GFAP Concentration will be evaluated by "Ella" automated Immunoassay System method.

Serum NfL Concentration will be evaluated by "Ella" automated Immunoassay System method.

Serum BDNF Concentration will be evaluated by "Ella" automated Immunoassay System method.

The 10 Meter Walk Test is a performance measure used to assess walking or gait speed in meters per second over a distance of 10 meters

The Box and Block Test (BBT) measures unilateral gross manual dexterity. It is a quick, simple and inexpensive test. The individual is instructed to move as many blocks as possible, one at a time, from one compartment to the other of a test box with 150 blocks and a partition in the middle. The number of blocks transferred in 60 seconds is recorded. Both the affected and the not affected side are measured.

The Barthel Index for Activities of Daily Living is a validated ordinal scale which measures a person's ability to complete activities of daily living (ADL). Scores range from 0 (total dependence) to 100 (total independence).

The 5-level EQ-5D version (EQ-5D-5L) is a validated tool to assess health-related quality of life. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Index scores range from -0.59 to 1; 1 is the best possible health state. Negative values represent health states perceived as worse than dead, which is equal to 0.

The Cognitive Reserve Index questionnaire (CRIq) aims to collect and estimate the amount of cognitive reserve acquired during a person's lifetime. In a single index (CRI), the questionnaire conveys three main sources of cognitive reserve: education, working activity, and leisure time activities. The CRIq score fell into 1 of 5 ordered levels: low (less than 70); medium-low (70-84); medium (85-114); medium-high (115-130); and high (more than 130).

It is validated tool for assessing stroke severity. NIHSS scores range from 0 to 42, with higher scores indicating more severe neurological deficit.

The Cumulative Illness Rating Scale (CIRS) is a well-validated multidimensional test commonly used as part of the Comprehensive Geriatric Assessment. It offers a comprehensive disease assessment for 14 organ systems, based on a rating scale ranging from 0 (best) to 4 (worst) for each. The severity index (CIRS-SI) is the mean of the scores of the first 13 categories (excluding the category of psychiatric/behavioral pathologies), ranging then from 0 to 4.

The Cumulative Illness Rating Scale (CIRS) is a well-validated multidimensional test commonly used as part of the Comprehensive Geriatric Assessment. It offers a comprehensive disease assessment for 14 organ systems, based on a rating scale ranging from 0 (best) to 4 (worst) for each. The comorbidity index (CIRS-CI) is the number of categories in which a score greater than or equal to 3 is obtained (excluding the category of psychiatric/behavioral pathologies). This index ranges from 0 to 13, with 0 indicating no significant comorbidity and 13 indicating severe comorbidity in all categories.

It is a standardised measure of proprioception. It ranges from 0 (normal) to 3.

It measure the level of light touch sensation of the tips of the thumb and index finger. The Semmes Weinstein filament test kit consists of 20 flexible nylon monofilaments of constant length, but varying in diameter. They are labeled so as to give a linear scale of perceived intensity (1.65-6.65) using a logarithmic scale of applied force: labeled number = Log10 of (10 × force in milligrams). The more the labeled number increases, the thicker the filament becomes, and the more pressure is necessary to bend the filament, meaning lower level of light touch sensation.

The Fatigue Severity Scale(FSS) is a nine-item instrument designed to assess fatigue as a symptom of a variety of different chronic conditions and disorders. The scale addresses fatigue's effects on daily functioning, querying its relationship to motivation, physical activity, work, family, and social life, and asking respondents to rate the ease with which they are fatigued and the degree to which the symptom poses a problem for them. The items are scored on a 7 point scale with 1 = strongly disagree and 7= strongly agree. The minimum score is 9 and maximum score possible is 63. Higher score indicate greater fatigue severity.

It is a simple and easy to use instrument that explores some important risk factors, such as social support, functional status, number of active medical problems and number of drugs, to identify the risk of prolonged hospitalization and the need of discharge planning in individuals who are hospitalized. It comprises a 10-item scale that determines a score between 0 and 40: a result lower than 10 identifies patients which have few needs for discharge planning and a low demand for discharge planning resources.

The Montreal Cognitive Assessment (MoCA) is a widely used screening assessment for detecting cognitive impairment. It ranges from 0 (worst) to 30 (best).

The Intrinsic Motivation Inventory (IMI) is a questionnaire that provides qualitative information on the content and level of motivation that an user experiences during an intervention Each IMI item consists of a seven-point Likert scale, ranging from "not at all true" to "completely true", with a maximum score of 144. Higher scores mean a more positive result on motivation.

It is a self-assessment scale for detecting states of depression and anxiety in the setting of an hospital medical outpatient clinic. The Hospital Anxiety and Depression Scale (HADS) is a 14-question instrument that measures anxiety and depression. Each question is scored between 0 (no impairment) and 3 (severe impairment), with a maximum score of 21 for anxiety or depression.

The Beck Depression Inventory (BDI-II), is a 21-question multiple-choice self-report inventory, one of the most widely used psychometric tests for measuring the severity of depression. The range of possible scores is 0 to 63. BDI-II scores are classified as minimal (0-13), mild (14-19), moderate (20-28), and severe (29-63) depression.

It is a validated questionnaire for nutritional assessment. The total score range from 0 to 14 points, with scores of 12 to 14 points indicating normal nutritional status, scores between 8 and 11 points identifying patients at risk of malnutrition, and scores < 8 points diagnosing malnutrition.

The SARC-F questionnaire is a screening tool to identify probable sarcopenic patients. The questionnaire screens patients for self-reported signs suggestive of sarcopenia, which include deficiencies in strength, walking, rising from a chair, climbing stairs, and experiencing falls. Each of the self-reported parameters receives a minimum and maximum score of 0 and 2, respectively, with the greatest maximum SARC-F score being 10.

It is a tool to assess functional oral intake of food and liquids in patients with oropharyngeal dysphagia.specifically, it is a 7-point ordinal scale describing the functional level of oral intake of food and liquids. Level 7 represents a full oral diet with no restrictions, levels 6-4 indicate a full oral diet with restrictions, levels 3-2 describe a mixed oral and tube intake, while level 1 represents a totally tube-dependent intake.

It is an instrumented measure of grip strength.

It is a genetic analysis of BDNF polymorphism rs6265; it is performed using the HpyCH4IV restriction enzyme on DNA extracted from whole blood and amplified with PCR reaction. The polymorphism rs6265 identifies homozygous Valine/Valine, heterozygous Valine/Methionine and homozygous Methionine/Methionine.

The 5-level EQ-5D (EQ-5D-5L) is a validated tool to assess health-related quality of life. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Index scores range from -0.59 to 1; 1 is the best possible health state. Negative values represent health states perceived as worse than dead, which is equal to 0.

It is an ad-hoc questionnaire to assess computer skills.

It is a questionnaire used with the primary aim of identifying the determinants involved in the acceptance of Robotic and Allied Technology. The questionnaire consists of 4 sections (perceived usefulness, ease of use, compatibility, intention to use); each question includes a 7-point Likert scale, from 1 (worst) to 7 (best). The scoring is calculated for each section and is given by the average of the responses in that section, ranging from 1 (worst) to 7 (best).

This is an ad-hoc questionnaire designed to measure satisfaction with healthcare services. Each question uses a 5-point Likert scale, ranging from 1 (unsatisfied) to 5 (very satisfied).

It is an ad-hoc questionnaire for perception of problems and solution complexity. Each question utilizes a 5-point Likert scale, ranging from 1 (low complexity) to 5 (very complex).

Ad-hoc questionnaire to evaluate the costs (direct healthcare costs, direct non-healthcare costs, indirect costs ) incurred by the patient.

The incremental cost-utility ratio (ICUR) will serve as the key metric of the Cost-utility analysis, and it is calculated as the ratio between differences in costs and differences in utility across the analysis groups. Cost-utility analysis will assess and compare the efficiency of alternative rehabilitation interventions by measuring health outcomes in terms of utility, a measure of general well-being or quality of life (subjective measures), relative to the costs incurred to achieve these outcomes. Utilities will be evaluated using standardized measures based on quality of life. Each health condition identified through generic health-related quality of life questionnaires (EQ-5D-DL) will be associated with available utility scores specific to Italy.

The incremental cost-effectiveness ratio (ICER) is calculated by dividing the difference in costs between the alternative rehabilitation models tested in the clinical study by the difference in clinical outcomes (physical units - objective measures). It will be used as the key metric of the cost-effectiveness analysis, that will compare the costs and clinical outcomes of the alternative rehabilitation models being studied. The ICER represents the additional cost incurred to achieve an incremental unit of effectiveness, that will be assessed considering primary and secondary outcomes.

From the perspective of the payer, the expected outcome of the budget impact analysis is the assessment of the financial impact (differences in direct health costs) over a 3-5 year period for the diffusion of a mix of robotic-based rehabilitations, compared to conventional rehabilitation or a robotic solution. The financial impact will be assessed by considering the direct health costs associated with the different rehabilitation regimes, varying projections of robotic market uptake, and the degrees of substitutability between the compared rehabilitation regimes.