Effect of Fingolimod on Neurodegeneration

Inclusion Criteria: 1. Diagnosed with RRMS as described in 2010 McDonald criteria (36) 2. Provided written informed consent prior to any intervention 3. Unresponsive to treatment with a beta interferon or glatiramer acetate for a minimum of one year at and at adequate dose and with high disease activity . (Unresponsive patients: patients with no changes in relapses, increased relapses, severer relapses with one-year treatment or those who had had at least one relapse during the past one year under previous treatments and one or multiple contrast enhancing lesions in cranial MRI or increased T2 lesions in successive MRIs) 4. EDSS score below 5.5 at screening Exclusion Criteria: * 1\. Patients with primary or secondary progressive or progressive relapsing MS. 2. Patients with known contraindications for fingolimod treatment. 3. Other coexistent autoimmune diseases including Hashimoto thyroiditis, systemic lupus erythematosus, rheumatoid anthiritis, psoriasis etc. 4\. Patients with any of the following cardiovascular conditions: * Resting heart rate \< 45 bpm/min * Cardiac failure at any time during the first study visit (Class III as per NYHA classification) or significant heart disease as judged by the physician * Myocardial infarction during the last 6 months * History of Mobitz Type II grade 2 AV block * Past or current grade 3 AV block * Confirmed history of sick sinus syndrome or sino-atrial heart block * arrhythmia requiring current treatment with Class Ia drugs (ajmaline, disopyramid, procainamide, quinidine) * hypertension uncontrolled with medication 5. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. 6\. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, detected by urinalysis and confirmed by a positive hCG laboratory test. 7\. Negative for varicella-zoster virus IgG antibodies at screening. Patients who have negative results for varicella-zoster virus IgG antibodies can be included in the study after vaccination for varicella-zoster virus. 8\. Active systemic bacterial, viral or fungal infections, or diagnosis of AIDS, Hepatitis B, Hepatitis C infection defined as a positive HIV antibody, Hepatitis B surface antigen or Hepatitis C antibody tests, respectively 9. History of previous fingolimod therapy 10. Patient who received any of the treatments below: 1. Corticosteroids or adrenocorticotropic hormone (ACTH) during the last 1 month 2. Immunosuppressive medications such as azathioprine or methotrexate etc. 3. Immunoglobulin treatment during the last 3 months 4. Cladribine, cyclophosphamide, mitoxantrone, natalizumab at any time