The FSMC is an assessment of MS-related cognitive and motor fatigue. A Likert-type 5-point scale (ranging from 'does not apply at all' to 'applies completely')produces a score between 1 and 5 for each scored question. Thus minimumvalue is 20 (no fatigue at all) and maximum value is 100 (severest grade offatigue). Two subscales (mental and physical fatigue) can be made. Items included in the subscale mental are 1-4-7-8-11-13-15-17-18-20 and items included in the subscale physical are 2-3-5-6-9-10-12-14-16-19.

The Timed Up and Go test (TUG) measures in seconds the time it takes a subjectto rise from a chair, walk a distance of 3 meters, turn, walk back to the chair andsit down.

The performance is rated on a scale of 1 to 5 (where 1 is normal and 5 is severelyabnormal) according to the observer's perception of the patient's risk of falling.

The timed part of the test records the mean time (in seconds) from initial gettingup to re-seating. Patients are compared with the mean time of adults in their agegroup, 60 to 69, 70 to 79, and 80 to 99 years of age.

Ambulation Index (AI) The Ambulation Index is a rating scale to assess mobility by evaluating the timeand degree of assistance required to walk 8 meters. Scores range from 0(asymptomatic and fully active) to 10 (bedridden). The patient is asked to walk amarked 8 meters course as quickly and safely as possible. The examiner recordsthe time and type of assistance (e.g., cane, walker, crutches) needed. Althoughthe patient's walking is timed, the time is not used directly but is utilized inconjunction with other factors to rate the patient on an ordinal scale with 11gradations.

0 = Asymptomatic; fully active. 10 = Bedridden

The Walking handicap scale (WHS) is an assessment tool that allows us toevaluate the quality of walking in the home and social environment through a ascale comprising six categories.

1 = Physiological walking: walking only as exercise 6 = Unrestricted walking insocial settings: independent in all activities, on uneven ground, in crowded places,shows complete independence in public places

The Functional Ambulation Categories (FAC) is a functional walking test thatevaluates ambulation ability. This 6-point scale assesses ambulation status bydetermining how much human support the patient requires when walking,regardless of whether or not they use a personal assistive device.

A score of 0 indicates that the patient is a non-functional ambulator (cannot walk);A score of 1, 2 or 3 denotes a dependent ambulator who requires assistance fromanother person in the form of continuous manual contact (1), continuous orintermittent manual contact (2), or verbal supervision/guarding (3).

A score of 4 or 5 describes an independent ambulator who can walk freely on:level surfaces only (4) or any surface (5=maximum score).

The 10mWT is used to assess walking speed in meters/second (m/s) over a shortdistance. The total time taken to ambulate 6 meters (m) is recorded to the nearesthundredth of a second. 6 m is then divided by the total time (in seconds) taken toambulate and recorded in m/s.

The time is measured for the middle 6 m to allow for patient acceleration anddeceleration.

The time is started when any part of the leading foot crosses the plane of the 2-mmark.

The time is stopped when any part of the leading foot crosses the plane of the 8-m mark.1 The time to walk the middle 6m, the level of assistance, and type ofassistive device and/or bracing used will be documented.

If a patient requires total assistance or is unable to ambulate at all, a score of 0m/s will be documented.

The six-minute walk test (6MWT) is a sub-maximal exercise test used to assesswalking endurance and aerobic capacity. Participants will walk around theperimeter of a set circuit for a total of six minutes. The score of the test is thedistance a patient walks in 6 minutes (measured in meters and can round to thenearest decimal point).

Distance (in meters) covered in six minutes is calculated by multiplying thenumber of total laps by 12 meters and adding the distance of the partial lapcompleted at the time the test ended.

The Multiple Sclerosis Walking Scale (MSWS-12) is a self-reported 12-item measure of an individual's ability to walk.

Each item can be assigned a score from 1 to 5, where 1 means "no limitation" and 5 means "extreme limitation".

The total score is obtained by summing the scores of the individual items; higher scores indicate a greater impact on walking than lower scores.

The modified Barthel Index (mBI) for activities of daily living is meant to be used in theassessment of patient performance (or degree of assistance required) with respect toself-care, sphincter management, transfers and locomotion. The index consist of 10items (each scored with a number of points) that relate to activities of daily living (ADLs)where the final score is calculated by summing the points awarded to each item. A five-point rating scales for each item to improve sensitivity to detecting change.

The 10 items assessed relate to help needed with feeding, bathing, grooming, dressing,transfers, walking, climbing stairs, presence or absence of fecal incontinence and urinaryincontinence.

The score ranges from 0 (maximum dependence) to 100 (maximum independence)

The 29-item Multiple Sclerosis Impact Scale (MSIS-29) is a self-administered questionnaire consisting of 20 physical and 9 psychological items to assess the impact of the disease on activities of daily living.

For each item, it is possible to assign a score ranging from 1, "Not at all", to a maximum of 5, "Extremely".

The total score is obtained by summing the scores for each item and can range from a minimum of 29, the minor impact of MS, to a maximum of 145, the extreme impact of MS.

The Beck Depression Inventory-II (BDI-II) is a scale consisting of 21 items identified in four increasing levels of severity, and is specifically designed to measure the 'behavioural manifestations of depression'. The quantification criteria are well defined for each item, and in fact, each severity level corresponds to a specific definition from which patients had to choose the one that best described their situation, taking into account the period including the last week before the test. At the end of the compilation, summing up the scores of the 21 items, which range from 0 to 3, gives four different degrees of depression:

• Scores between 0 and 10 indicate the absence of depressive content;
• Scores between 11 and 18 indicate mild depression;
• Scores between 19 and 29 indicate moderate depression;
• Scores between 30 and 63 indicate severe depression.

The State-Trait Anxiety Inventory (STAI-Y) is a scale used to assess state and trait anxiety. The STAI-Y is subdivided into two scales (Y1 and Y2), which respectively assess state anxiety, with questions that relate to how the subject feels at the time the questionnaire is administered, and trait anxiety, with questions that investigate how the subject habitually feels.

The STAI-Y consists of 40 items, 20 relating to state anxiety and 20 to trait anxiety. The patient's self-assessment is expressed in frequency using a Likert scale ranging from 0 to 4 points, where higher scores are positively correlated with higher levels of anxiety, while low scores indicate a mild form of anxiety.

The total score is between 20 and 80, with a threshold value predictive of anxiety symptoms of 40. Specifically, there are severity criteria: 40 to 50 mild form, 50 to 60 moderate, greater than 60 severe.

The Stroop Color and Word Test (SCWT) is a neuropsychological test extensively usedto assess the ability to inhibit cognitive interference that occurs when the processing of aspecific stimulus feature impedes the simultaneous processing of a second stimulusattribute, well-known as the Stroop Effect. The subject is asked to read the words in thefirst task, to name colors in the second and third tasks. It is necessary to mark both anymistakes made but also the time spent on each task. The cut-off for the error interferenceeffect is 4.24, while the cut-off for the time interference effect is 36.92.

The Symbol Digit Modalities Test (SDMT) is a test that assesses information processing speed and consists of a series of nine printed symbols to which nine numbers correspond. After a 'training' phase, patients are asked to match as many symbols as possible to the corresponding number in just 90 seconds. As the test persons can give written or oral answers, the test is suitable for people with motor disabilities or speech disorders.

The score is calculated by adding up the number of correct substitutions in the 90-second interval (maximum = 110). Interpretation results from normalising the categories of gender, age and education.