Transcranial Static Field Stimulation (tSMS) and Transcranial Direct Current Stimulation (tDCS) for the Treatment of Neurological Symptoms.

The Expanded Disability Status Scale (EDSS) is a clinician-administered assessment scale evaluating the functional systems of the central nervous system. The EDSS is used to describe disease progression in patients with multiple sclerosis MS and to assess the effectiveness of therapeutic interventions in clinical trials. It consists of ordinal rating system ranging from 0 (normal neurological status) to 10 (death due to MS) in 0.5 increments interval (when reaching EDSS 1).

Measurement of motor cortex plasticity (iTBS) through transcranial magnetic stimulation (TMS). The mean amplitudes of motor evoked potentials (MEP) will be recorded following iTBS, at each time point after iTBS (5, 15, and 30 minutes). The LTP-like effect will be expressed as percentage changes relative to the baseline MEPs.

The blood samples, immediately after collection, will undergo the necessary procedures for isolating the different components. These will then be used to analyze the levels of microRNA, cytokines, chemokines, cellular growth factors, markers of neuronal damage (tau, phosphorylated and truncated tau, neurofilaments), mitochondrial markers (lactate), and free d-amino acids. Genotyping studies will be conducted to identify single nucleotide polymorphisms (SNPs) in coding and/or regulatory regions of genes (microRNA or protein) that correlate with specific clinical parameters and the levels of the identified potential biomarkers.

The Brief Pain Inventory (BPI) is a self-administered measure of the sensory and reactive dimensions of pain that is the severity or intensity of the pain and the level of interference it has on various aspects of life. Interference is divided into activity and affective sub-dimensions. The BPI starts with a screening question, asking about the presence of pain and a body chart is used to indicate painful regions as well as the worst region. These items have not been evaluated. This is followed by the core BPI items: the rating scales for pain severity and interference. Numerical rating scales from 0 to 10 are used for all items. The anchors for pain severity scales are 0 = 'no pain' and 10 = 'pain as bad as you can imagine', whilst the interference anchors are 0 = 'no interference' and 10 = 'interferes completely'.

The Zung Self-Rating Anxiety Scale (SAS) is a 20-item self-report assessment device built to measure anxiety levels.

The total raw scores range from 20 to 80:

• 20-44 Normal Range
• 45-59 Mild to Moderate Anxiety Levels
• 60-74 Marked to Severe Anxiety Levels
• 75 and above Extreme Anxiety Levels

The Zung Self-Rating Depression Scale (SDS) is a short self-administered survey to quantify the depressed status of a patient. There are 20 items on the scale that rate the four common characteristics of depression: the pervasive effect, the physiological equivalents, other disturbances, and psychomotor activities. There are ten positively worded and ten negatively worded questions. Each question is scored on a scale of 1-4 (a little of the time, some of the time, good part of the time, most of the time).

The scores range from 25-100.

• 25-49 Normal Range
• 50-59 Mildly Depressed
• 60-69 Moderately Depressed
• 70 and above Severely Depressed

The Pittsburgh Sleep Quality Index (PSQI) is a widely used self-report questionnaire that assesses sleep quality over a one-month time interval. In scoring the PSQI, seven component scores are derived, each scored 0 (no difficulty) to 3 (severe difficulty). The component scores are summed to produce a global score (range 0 to 21). Higher scores indicate worse sleep quality.

The Short Form (36) Health Survey (SF-36) is a 36-item, patient-reported survey of patient health. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability, a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.

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, each answer being scored on a scale value of 0 to 3. Higher total scores indicate more severe depressive symptoms. The standardized cutoffs are the following:

• 0-13: minimal depression
• 14-19: mild depression
• 20-28: moderate depression
• 29-63: severe depression.

The State-Trait Anxiety Inventory (STAI) is a psychological inventory consisting of 40 self-report items on a 4-point Likert scale. The STAI measures two types of anxiety - state anxiety and trait anxiety. Each type of anxiety has its own scale of 20 different questions that are scored. Scores range from 20 to 80, higher scores are positively correlated with higher levels of anxiety.

The Toronto Alexithymia Scale (TAS-20) is a measure of deficiency in understanding, processing, or describing emotions. The current version has twenty statements rated on a five-point Likert scale. The total alexithymia score is the sum of responses to all 20 items, while the score for each subscale factor is the sum of the responses to that subscale.

The Fibromyalgia Impact Questionnaire (FIQ) is a brief 10-item, self-administered instrument that measures physical functioning, work status, depression, anxiety, sleep, pain, stiffness, fatigue, and well being. The FIQ is composed of 10 items. The first item contains 11 questions related to physical functioning - each question is rated on a 4 point Likert type scale. Items 2 and 3 ask the patient to mark the number of days they felt well and the number of days they were unable to work (including housework) because of fibromyalgia symptoms. Items 4 through 10 are horizontal linear scales marked in 10 increments on which the patient rates work difficulty, pain, fatigue, morning tiredness, stiffness, anxiety and depression. The FIQ is composed of ten questions with a maximum score of 100, higher scores reflecting greater impact.

The Modified Fatigue Impact Scale (MFIS) provides an assessment of the effects of fatigue in terms of physical, cognitive, and psychosocial functioning.Items on the MFIS can be aggregated into three subscales (physical, cognitive, and psychosocial), as well as into a total MFIS score. All items are scaled so that higher scores indicate a greater impact of fatigue on a person's activities.

• Physical Subscale: this scale can range from 0 to 36. It is computed by adding raw scores on the following items: 4+6+7+10+13+14+17+20+21.
• Cognitive Subscale: this scale can range from 0 to 40. It is computed by adding raw scores on the following items: 1+2+3+5+11+12+15+16+18+19.
• Psychosocial Subscale: this scale can range from 0 to 8. It is computed by adding raw scores on the following items: 8+9.
• Total MFIS Score: the total MFIS score can range from 0 to 84. It is computed by adding scores on the physical, cognitive, and psychosocial subscales

The Multiple Sclerosis Impact Scale (MSIS-29) is a 29-item self-report measure comprised of 20 items associated with a physical scale and 9 items associated with a psychological scale.1 Items question patients (or their proxies) about the impact of multiple sclerosis (MS) on day-to-day life in the last 2 weeks. All items have 5 response options from 1 (not at all) to 5 (extremely). Each of the 2 scales are scored by summing the responses across items, then converting to a 0 to 100 scale, where 100 indicates greater impact of disease on daily function (worse health).

The Multiple Sclerosis Quality of Life-54 (MSQOL-54) is a multidimensional health-related quality of life measure that combines both generic and multiple sclerosis MS-specific items into a single instrument. This 54-item instrument generates 12 subscales along with two summary scores, and two additional single-item measures. The subscales are: physical function, role limitations-physical, role limitations-emotional, pain, emotional well-being, energy, health perceptions, social function, cognitive function, health distress, overall quality of life, and sexual function. The summary scores are the physical health composite summary and the mental health composite summary. The single item measures are satisfaction with sexual function and change in health. The 54 items are divided into 12 multi-item and 2 single-item scales. The MSQOL-54 items are transformed linearly to 0-100 scores, and final scores are obtained by averaging items within the scales.

The Fatigue Severity Scale (FSS) is a 9-item scale which measures the severity of fatigue and its effect on a person's activities and lifestyle in patients with a variety of disorders. Answers are scored on a seven point scale where 1 = strongly disagree and 7 = strongly agree. This means the minimum score possible is nine and the highest is 63. The higher the score, the more severe the fatigue is and the more it affects the person's activities. It is simple to understand and takes an average of eight minutes to answer