a validated questionnaire specifically developed for MS (22). It is a 20-items scales that allows graduation of fatigue severity, and separate evaluation of motor (10 items) and cognitive (10 items) fatigue components. The response pattern for each item consists in a five-point Likert scale; a total score higher than 43 indicates the presence of mild fatigue and the score increases proportionally to the severity of fatigue (> 53: moderate; >63 severe); the cut-off for both the cognitive and the motor subscales is 22. FSMC provides good reliability and correlates with both FSS and MFIS scores

a simple and quick measure of the patient's instant perception of fatigue on him/herself. It is a measurement of the impression at the moment of the interview. It consists of a graphic 10 cm wide line with "no fatigue" at one end and "very severe fatigue" on the other and the subject is asked to place a cross at the point that best express his/her answer to the question "how do you feel in this moment?"

it objectively explores somnolence in terms of ability to remain awake in sleep- promoting environmental conditions. It has to be performed after a nocturnal PSG recording because the knowledge of the previous sleep is essential for MWT interpretation. Recordings include only EEG, EMG and EOG from the previous PSG and are carried out in a dim room, with slight illumination. Patients are instructed to stay awake as long as possible. Four sessions are recorded every two hours, each lasting until the patient falls asleep or for 40 minutes of continuous awake state. The sleep latency is assessed in each of the four recordings and it is defined by the elapse time in minutes on each trial before sleep onset: the patient is considered asleep after three 30 seconds EEG epochs of stage N1 of non-REM sleep, or one 30-second epoch of any other sleep stage.

a self-administered questionnaire with 8 questions, which provide a measure of a subject's general level of daytime sleepiness (26). Subjects are required to indicate their chance to fall asleep in 8 different situations on a rating scale from 0 to 3, where 0 means no chance and 3 big chance. The total score is the sum of the eight items, and a score higher that 10 suggests an excessive daytime sleepiness, whose severity increases proportionally to the score. Most people can answer the questions with no assistance in less than 5 minutes.

a simple and quick measure of the patient's instant perception of somnolence on him/herself. It is a measurement of the impression at the moment of the interview. It consists of a graphic 10 cm wide line with "no sleepiness" at one end and "very severe sleepiness" on the other and the subject is asked to place a cross at the point that best express his/her answer to the question "how do you feel in this moment?".

a 21-item self-report of depressive symptomatology for individuals aged 13 to 80 years (32). It was developed to have clinical sensitivity for assessing depression criteria reported in the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) and intends to assess symptoms experienced in the 2 weeks prior to assessment, such as intense sadness, crying, or changes in sleep, appetite, or sexual interest. Items are on a 4-point scale ranging from 0 to 3, with a maximum score of 63. Higher total scores indicate more severe depression symptoms. Administration of the scale takes about 10 minutes.

is a 10-items questionnaire that is used to measure the core symptoms and cognitive features of clinical depression (33). An higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. The subject has to be interviewed by a trained psychologist or psychiatrist.

is a measure of attention and processing speed. It presents a series of nine symbols, each of which is paired with a single digit, labelled 1-9, in a key at the top of a sheet. The remainder of the page has a pseudorandomized sequence of the symbols and the subject must respond with the digit associated with each of these as quickly as possible. The score is the number of correct answers in 90 seconds.

is another measure of sustained attention and speed of information processing. The subject hears a series of single digit number from CD that are presented at the rate of one every 3 seconds in the first part of the test (PASAT 3"), or at the rate of one every 2 seconds in the second part (PASAT 2"). The subject is asked to add each consecutive digit to the one immediately preceding it. Sixty-one digits are presented for each part and each part has a maximum of 60 correct answers.

evaluates sustained attention and some aspects of executive functions, such as the ability to elaborate relevant and irrelevant dimensions in parallel and to inhibit an automatic response while performing a task based on conflicting stimuli. The procedure comprised of three trials. In the first trial, the subject is instructed to read a list of word indicating colours printed in black ink as quickly as possible; in the second trial the subject is instructed to name the colour of strings of dots as quickly as possible; in the third trial (interference condition), the subject has to name the colours of the ink of words indicating conflicting colours as quickly as possible. Performance will assess by calculating the time required to name the items and the number of the errors.

semi-structured interview for making the major DSM-IV Axis I diagnoses. It contains the following modules: Mood Episodes, Psychotic and Associated Symptoms, Psychotic Disorders, Mood Disorders, Substance Use Disorders, Anxiety Disorders, Somatoform Disorders, Eating Disorders, and Adjustment Disorder. Each criterion is coded as either ?,1,2, or 3 (?= inadequate information to code the criterion; 1= the symptom described in the criterion is clearly absent; 2= the threshold for the criterion is almost, but not quite, met; 3= the threshold for the criterion is just met.).

assess verbal learning and delayed recall. It include a list of 12 words and uses six consecutive learning trials and a delayed trials A word recalled on two consecutive trials is considered to have a long-term storage (LTS) on the first of these trials and scored as LTS on all following trials. The total sum of the words in LTS of all six trials is taken (SRT-LTS). If a word in LTS is consistently recalled on all subsequent trials, it is then scored as in Consistent Long Term Retrieval (CLTR). The total sum of the word in CLTR of all six trials is taken (SRT-CLTR). The Delayed Recall (SRT-D) is the total number of words recalled after the delayed period.

assess visuo-spatial learning and delayed recall. In the test, a checkerboard, with ten checkers arranged in a particular pattern, is shown to the subject for ten second. Then the subject is asked to reproduce the same pattern with ten checkers on an empty checkerboard. The test includes three consecutive trials and a delayed trials. The score is the number of correct responses for the three trials and a delayed recall trials (SPART-D).

explores verbal fluency on semantic stimulus by asking the subject to produce as many words as possible belonging to a semantic category within 90 seconds. The score is the number of correct words.

a self-rated questionnaire which differentiates "poor" from "good" sleepers by measuring seven domains: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction (27). Scoring of the answers is based on a 0 to 3 scale, where 3 reflects the negative extreme on the Likert Scale. The sum of the seven sub-scores generates the total score where 5 is the cut-off for distinguishing poor (higher) from good (lower) sleepers. The PSQI has internal consistency and a reliability coefficient (Cronbach's alpha) of 0.83 for its seven components.

it is a sustained-attention, reaction-timed task that is easily used to test the speed with which subjects respond to a visual stimulus, by pressing a button (28). It has become a standard laboratory tool in a variety of experimental conditions and in the sleep lab it is commonly used to assess the effects of sleep restriction on sustained performance (29-31). The PVT is a simple task where the subject is placed in front of a monitor where a light randomly appears every few seconds for 10 minutes and is asked to press a button as soon as the light appears. The main measurement is to see how many times the button is not pressed when the light is on. The test gives a numerical measure of sleepiness by counting the number of lapses in attention.

it is one of the most widely used MS-specific health related quality of life, instruments (34). This questionnaire includes 54 items distributed into multi-item scales (Physical health, Physical role limitations, Emotional role limitations, Pain, Emotional well-being, Energy, Social function, Cognitive function, Health perception, Health distress, Overall quality of life, Sexual function) and two single items (Change in health, Sexual function satisfaction). Two summary scores-physical health composite and mental health composite can be derived from a weighted combination of scale scores. MSQol-54 scale scores will create using the Likert method by averaging items within the scales, and then row scores will be linearly transformed into 0-100 scales. Higher values indicate better quality of life.