Investigation of Subclinical Markers of Multiple Sclerosis

TMS assessment of cortical silent period (CSP) change

时间窗: Baseline CSP, CSP change at 5 weeks taking the steroids

The neurophysiologic measure of CSP duration (expressed in milliseconds) will be evaluated with navigated TMS over the primary motor cortex in relapsing-remitting MS patients in 2 phases (before the intake of steroids, 5 weeks after taking the steroids).

EMNG assessment of distal motor latency (DML) and sensory nerve action potential latency (SNAP) change

时间窗: DML and SNAP latency before and 5 weeks after steroid intake in relapsing-remitting MS patients. DML and SNAP latency in relapsing-remitting MS group on immunomodulation.

* EMNG measures of DML and SNAP latency (expressed in milliseconds) of upper and lower extremities will be evaluated in relapsing-remitting MS patients receiving corticosteroid treatment in 2 phases (before the intake of steroids, 5 weeks after taking the steroids). * EMNG measures of DML and SNAP latency (expressed in milliseconds) of upper and lower extremities will be evaluated in relapsing-remitting MS receiving immunomodulation treatment patients at baseline.

EMNG assessment of muscle action potential amplitude (CMAP) and sensory nerve action potential amplitude (SNAP) change

时间窗: CMAP and SNAP amplitude before and 5 weeks after steroid intake in relapsing-remitting MS patients. CMAP and SNAP amplitude in relapsing-remitting MS group on immunomodulation.

* EMNG measures of CMAP and SNAP amplitude (expressed in millivolts) of upper and lower extremities will be evaluated in relapsing-remitting MS patients receiving corticosteroid treatment in 2 phases (before the intake of steroids, 5 weeks after taking the steroids). * EMNG measures of CMAP and SNAP amplitude (expressed in millivolts) of upper and lower extremities will be evaluated in relapsing-remitting MS patients receiving immunomodulation treatment at baseline.

EMNG assessment of motor and sensory conduction velocity (CV) change

时间窗: CV before and 5 weeks after steroid intake in relapsing-remitting MS patients. CV in relapsing-remitting MS group on immunomodulation.

* EMNG measures of CV (expressed in meters per second) of motor and sensory nerves of upper and lower extremities will be evaluated in relapsing-remitting MS patients treated with corticosteroids in 2 phases (before the intake of steroids, 5 weeks after taking the steroids). * EMNG measures of CV (expressed in meters per second) of motor and sensory nerves of upper and lower extremities will be evaluated in relapsing-remitting MS patients treated with immunomodulation treatment at baseline.

CD 14 expression on peripheral blood monocytes change

时间窗: CD 14 before and 5 weeks after steroid intake in relapsing-remitting MS patients. CD14 in relapsing-remitting MS group on immunomodulation and healthy control group.

* CD 14 expression on monocytes will be evaluated in relapsing-remitting MS patients treated with corticosteroids in 2 phases (before the intake of steroids, 5 weeks after taking the steroids). The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive monocytes. * CD 14 expression on monocytes will be evaluated in relapsing-remitting MS patients treated with immunomodulation at baseline.The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive monocytes. * CD 14 expression on monocytes will be evaluated in the healthy control group.The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive monocytes.

Psychological assessment change applying Multiple Sclerosis Impact Scale (MSIS-29).

时间窗: Baseline MSIS-29, and MSIS-29 change at 5 weeks and 6 months after taking the steroids.

* Relapsing-remitting MS patients treated with corticosteroids will be tested with MSIS before the intake of steroids, 5 weeks after taking the steroids and 6 months after taking the steroids. The total score is formed as the sum of the rounded answers to the two subscales (physical and psychological scale). * Relapsing-remitting MS patients treated with immunomodulation will be tested with MSIS at baseline. The total score is formed as the sum of the rounded answers to the two subscales (physical and psychological scale).

TMS assessment of motor evoked potentials (MEP) changes from upper and lower extremity muscles

时间窗: MEP (amplitude and latency) before and 5 weeks after steroid intake in relapsing-remitting MS patients. MEP (amplitude and latency) in relapsing-remitting MS group on immunomodulation.

The neurophysiologic measure of MEP (amplitude expressed in microvolts and latency expressed in milliseconds) will be evaluated with navigated TMS over the primary motor cortex for upper and lower extremity muscles: * in relapsing-remitting MS receiving corticosteroid treatment patients in 2 phases (before the intake of steroids, 5 weeks after taking the steroids). * relapsing-remitting MS receiving immunomodulation treatment patients at baseline

CD 16 expression on peripheral blood monocytes change

时间窗: CD 16 before and 5 weeks after steroid intake in relapsing-remitting MS patients. CD16 in relapsing-remitting MS group on immunomodulation and healthy control group.

* CD 16 expression on monocytes will be evaluated in relapsing-remitting MS patients treated with corticosteroids in 2 phases (before the intake of steroids, 5 weeks after taking the steroids). The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive monocytes. * CD 16 expression on monocytes will be evaluated in relapsing-remitting MS patients treated with immunomodulation at baseline. The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive monocytes. * CD 16 expression on monocytes will be evaluated in the healthy control group. The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive monocytes.

CD 40 expression on peripheral blood monocytes change

时间窗: CD 40 before and 5 weeks after steroid intake in relapsing-remitting MS patients. CD 40 in relapsing-remitting MS group on immunomodulation and healthy control group.

* CD 40 expression on monocytes will be evaluated in relapsing-remitting MS patients treated with corticosteroids in 2 phases (before the intake of steroids, and 5 weeks after taking the steroids). The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive monocytes. * CD 40 expression on monocytes will be evaluated in relapsing-remitting MS patients treated with immunomodulation at baseline. The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive monocytes. * CD 40 expression on monocytes will be evaluated in the healthy control group. The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive monocytes.

CD 4 expression on lymphocytes

时间窗: Determination of CD 4 at the beginning of study (study entry) in relapsing-remitting MS patients treated with immunomodulation and in healthy control group.

* CD 4 expression on lymphocytes will be evaluated in relapsing-remitting MS patients treated with immunomodulation at baseline. The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive lymphocytes. * CD 4 expression on lymphocytes will be evaluated in the healthy control group. The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive lymphocytes.

CD 25 expression on lymphocytes

时间窗: Determination of CD 25 at the beginning of study (study entry) in relapsing-remitting MS patients treated with immunomodulation and in healthy control group.

* CD 25 expression on lymphocytes will be evaluated in relapsing-remitting MS patients treated with immunomodulation at baseline. The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive lymphocytes. * CD 25 expression on lymphocytes will be evaluated in the healthy control group. The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive lymphocytes.

TMS assessment of resting motor threshold (RMT) change

时间窗: RMT before and 5 weeks after steroid intake in relapsing-remitting MS patients. RMT in relapsing-remitting MS group on immunomodulation.

Neurophysiologic measure of RMT (expressed in percentage of maximal stimulator output) will be evaluated with navigated TMS over the primary motor cortex: * in relapsing-remitting MS receiving corticosteroid treatment patients in 2 phases (before the intake of steroids, 5 weeks after taking the steroids). * relapsing-remitting MS receiving immunomodulation treatment patients at baseline

Change of CD 163 levels in blood serum samples

时间窗: CD 163 measured before and 5 weeks after taking the steroids.

CD 163 levels in serum will be evaluated in relapsing-remitting MS patients in 2 phases (before the intake of steroids, 5 weeks after taking the steroids). CD 163 levels will be measured with ELISA assay (expressed in micro mols per litre).

CTLA-4 expression on lymphocytes

时间窗: Determination of CTLA-4 at the beginning of study (study entry) in relapsing-remitting MS patients treated with immunomodulation and in healthy control group.

* CTLA-4 expression on lymphocytes will be evaluated in relapsing-remitting MS patients treated with immunomodulation at baseline. The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive lymphocytes. * CTLA-4 expression on lymphocytes will be evaluated in the healthy control group. The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive lymphocytes.

Cognitive assessment change applying Montreal Cognitive Assessment (MoCA).

时间窗: Baseline MoCA, and MoCA change at 5 weeks and 6 months after taking the steroids.

Relapsing-remitting MS patients will be tested with MoCA before the intake of steroids, 5 weeks after taking the steroids and 6 months after taking the steroids. MoCA is interpreted as the number of points (30 is maximal).

Psychomotor assessment change applying Lafayette O'Conner Finger Dexterity Test.

时间窗: Baseline O'Conner, and O'Conner change at 5 weeks and 6 months after taking the steroids.

Relapsing-remitting MS patients will be tested with O'Conner Finger Dexterity Test before the intake of steroids, 5 weeks after taking the steroids and 6 months after taking the steroids. The O'Connor Finger Dexterity Test requires hand placement of 3 pins per hole. Result (seconds) = time required to complete the first part of the test + (1.1 x time required to complete the second part of the test) / 2

TMS assessment of short afferent latency inhibition (SAI) change

时间窗: Baseline SAI, SAI change at 5 weeks after taking the steroids.

The neurophysiologic measure of SAI phenomena (expressed in milliseconds) will be evaluated with navigated TMS over the primary motor cortex with peripheral electrical stimulation over the median nerve at different interstimulus intervals (20-28 ms) in relapsing-remitting MS patients in 2 phases (before the intake of steroids, 5 weeks after taking the steroids).

EMNG assessment of F-wave change

时间窗: F-wave before and 5 weeks after steroid intake in relapsing-remitting MS patients. F-wave in relapsing-remitting MS group on immunomodulation.

-EMNG measures of F-wave (expressed in milliseconds) for motor nerves of upper and lower extremities will be evaluated in relapsing-remitting MS patients treated with corticosteroids in 2 phases (before the intake of steroids, 5 weeks after taking the steroids). --EMNG measures of F-wave (expressed in milliseconds) for motor nerves of upper and lower extremities will be evaluated in relapsing-remitting MS patients treated with immunomodulation at baseline.

CD 192 expression on peripheral blood monocytes change

时间窗: CD 192 before and 5 weeks after steroid intake in relapsing-remitting MS patients. CD 192 in relapsing-remitting MS group on immunomodulation and healthy control group.

* CD 192 expression on monocytes will be evaluated in relapsing-remitting MS patients treated with corticosteroids in 2 phases (before the intake of steroids, 5 weeks after taking the steroids and 6 months after taking the steroids). The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive monocytes. * CD 192 expression on monocytes will be evaluated in relapsing-remitting MS patients treated with immunomodulation at baseline. The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive monocytes. * CD 192 expression on monocytes will be evaluated in a healthy control group. The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive monocytes

FOXP3 expression on lymphocytes

时间窗: Determination of FOXP3 at the beginning of study (study entry) in relapsing-remitting MS patients treated with immunomodulation and in healthy control group.

* FOXP3 expression on lymphocytes will be evaluated in relapsing-remitting MS patients treated with immunomodulation at baseline. The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive lymphocytes. * FOXP3 expression on lymphocytes will be evaluated in the healthy control group. The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive lymphocytes.

Hand dominance assessment with Edinburgh Handedness Inventory test.

时间窗: Baseline measurement for single subject. The results for all subjects can be provided an average of 1 year of study duration.

The Edinburgh Handedness Inventory is a well known short questionnaire for determining objectively whether one is left , right handed, or ambidekster. The subjects determines whether he/she is using right or left hand for specific activities (ten activities). The total checks are given for right and left hand, than cumulative sume is given (total checks from right and left hand), difference between total checks for right minus left hand. Final result is the difference result subtracted from cumulative result x 100.

Psychological assessment change applying Depression, Anxiety, Stress (DASS-21) scale.

时间窗: Baseline DASS-21, and DASS-21 change at 5 weeks and 6 months after taking the steroids.

* Relapsing-remitting MS patients treated with corticosteroids will be tested with DASS-21 before the intake of steroids, 5 weeks after taking the steroids and 6 months after taking the steroids. * Relapsing-remitting MS patients treated with immunomodulation will be tested with DASS-21 at baseline. DASS-21 contains three scales for measuring emotional states of depression, anxiety and stress. Each scale contains 7 statements. The result on the depression, anxiety and stress scales is the sum of the rounded answers to specific statements.

Psychomotor assessment change of extremity muscles applying Lafayette Manual Muscle Tester Dynamometer.

时间窗: Baseline lower and upper extremity muscle strength, and muscle strength change at 5 weeks and 6 months after taking the steroids.

Relapsing-remitting MS patients will be tested with Lafayette Manual Muscle Tester Dynamometer before the intake of steroids, 5 weeks after taking the steroids and 6 months after taking the steroids. Muscle strength measured by Lafayette Manual Muscle Tester is recorded in kilograms and normalized to body-mass index (BMI). Handheld dynamometry will be used to measure ankle dorsiflexion; knee, flexion and extension; hip flexion, extension, abduction, and adduction; and trunk lateral flexion.

Cognitive assessment change applying Letter Digit Substitution Test (LDST).

时间窗: Baseline LDST, and LDST change at 5 weeks and 6 months after taking the steroids.

* Relapsing-remitting MS patients treated with corticosteroids will be tested with LDST before the intake of steroids, 5 weeks after taking the steroids and 6 months after taking the steroids. LDST is interpreted as the number of correct responses in 60 seconds. * Relapsing-remitting MS patients treated with immunomodulation therapy will be tested with LDST at baseline.

Psychological assessment change applying Fatigue Severity Scale (FSS).

时间窗: Baseline FSS, and FSS change at 5 weeks and 6 months after taking the steroids.

-Relapsing-remitting MS patients treated with corticosteroids will be tested with FSS before the intake of steroids, 5 weeks after taking the steroids and 6 months after taking the steroids. --Relapsing-remitting MS patients treated with immunomodulation will be tested with FSS at baseline. The subject is asked to read each statement and circle a number from 1 to 7, depending on how appropriate they felt the statement applied to them over the preceding week. A low value indicates that the statement is not very appropriate whereas a high value indicates agreement.The scoring is done by calculating the average response to the questions (adding up all the answers and dividing by nine).

Psychological assessment change applying Pain rating scale.

时间窗: Baseline Pain rating, and Pain rating change at 5 weeks and 6 months after taking the steroids.

Relapsing-remitting MS patients will be tested with numerical Pain Rating Scale before the intake of steroids, 5 weeks after taking the steroids and 6 months after taking the steroids. The result is interpreted as the total sum of points. The greater the results the more pain is detected.

Barthel Index for Activities of Daily Living (ADL) change.

时间窗: Baseline activities of daily living, and change in activities of daily living at 5 weeks and 6 months after taking the steroids.

Relapsing-remitting MS patients will be tested with Barthel Index for Activities of Daily Living (ADL) before the intake of steroids, 5 weeks after taking the steroids and 6 months after taking the steroids. The examiner is rank the patient's independence in the following areas:feeding, bathing, grooming, dressing, bowel control, bladder control, toilet use, transfers (bed to chair and back), mobility on level surfaces, and stairs. \* 0 - 20 = complete dependence; 21 - 60 = severe addiction; 61 - 90 = moderate dependence

Psychomotor assessment of hand grip change applying SAEHAN Squeeze Dynamometer.

时间窗: Baseline hand grip, and hand grip change at 5 weeks and 6 months after taking the steroids.

Relapsing-remitting MS patients will be tested with SAEHAN Squeeze Dynamometer before the intake of steroids, 5 weeks after taking the steroids and 6 months after taking the steroids. Six measurement results are recorded for each subject - three for the grip with the dominant hand and three for the grip with the non-dominant hand. The final result is the mean of the three measurements for each arm expressed in kilograms.