Background: Despite many benefits of the physical activity on physical and mental health of patients with Multiple Sclerosis (MS), the activity level in these patients is still very limited, and they continue to suffer from impairment in functioning ability. The main aim of this study is thus to closely examine exercise's effect on fatigue of patients with MS worldwide, with particular interest on Iran based on a comprehensive systematic review and meta-analysis. Methods: The studies used in this systematic review were selected from the articles published from 1996 to 2019, in national and international databases including SID, Magiran, Iranmedex, Irandoc, Google Scholar, Cochrane, Embase, ScienceDirect, Scopus, PubMed and Web of Science (ISI). These databases were thoroughly searched, and the relevant ones were selected based on some plausible keywords to the aim of this study. Heterogeneity index between studies was determined using Cochran's test and I 2. Due to heterogeneity in studies, the random effects model was used to estimate standardized mean difference. Results: From the systematic review, a meta-analysis was performed on 31 articles which were fulfilled the inclusion criteria. The sample including of 714 subjects was selected from the intervention group, and almost the same sample size of 720 individuals were selected in the control group. Based on the results derived from this meta-analysis, the standardized mean difference between the intervention group before and after the intervention was respectively estimated to be 23.8 ± 6.2 and 16.9 ± 3.2, which indicates that the physical exercise reduces fatigue in patients with MS. Conclusion: The results of this study extracted from a detailed meta-analysis reveal and confirm that physical exercise significantly reduces fatigue in patients with MS. As a results, a regular exercise program is strongly recommended to be part of a rehabilitation program for these patients.

The pattern of results suggests that for females with MS and treated with standard immune regulatory medication, exercise training programs such as yoga and aquatic exercising positively impact on core symptoms of MS, namely, fatigue, depression, and paresthesia. Exercise training programs should be considered in the future as possible complements to standard treatments.

Studies have shown an increase in the incidence of MS in Iran. The aim of our study was to evaluate the relationship between environmental exposure and MS in Iran. This case-control study was conducted on 660 MS patients and 421 controls. Many environmental factors are compared between the two groups. Our findings demonstrated that prematurity ([OR = 4.99 (95% CI 1.34-18.68), P = 0.017]), history of measles and mumps ([OR = 1.60 (95% CI 1.05-2.45), P = 0.029; OR = 1.85 (95% CI 1.22-2.78), P = 0.003, respectively]), breast feeding [OR = 2.90 (95% CI 1.49-5.65), P = 0.002], head trauma in childhood ([OR = 8.21 (95% CI 1.56-43.06), P = 0.013]), vaccination in adulthood ([OR = 4.57 (95% CI 1.14-18.41), P = 0.032, respectively]), migraine ([OR = 3.50 (95% CI 1.61-7.59), P = 0.002]), family history of MS, IBD, migraine, and collagen vascular diseases ([OR = 2.73 (95% CI 1.56-4.78), P < 0.001], [OR = 3.14 (95% CI 1.460-6.78), P = 0.004; OR = 3.18 (95% CI 1.83-5.53), P < 0.001; OR = 1.81 (95% CI 1.03-3.20), P = 0.040, respectively]), stressful events ([OR = 32.57 (95% CI 17.21-61.64), P < 0.001]), and microwave exposure ([OR = 3.55 (95% CI 2.24-5.63), P ≤0.001]) were more in the MS group. Sun exposure ([OR = 0.09 (95% CI 0.02-0.38), P = 0.001]), dairy and calcium consumption ([OR = 0.44 (95% CI 0.27-0.71), P = 0.001]), diabetes mellitus ([OR = 0.11 (95% CI 0.01-00.99), P = 0.049], and complete vaccination during childhood appeared to decreased MS risk. Our results investigated many risk factors and protective factors in Iran.

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Our results showed that administration of 25-mg cinnarizine every 12 hours can significantly decrease headache duration (p ≤ 0.001) and headache frequency (p ≤ 0.001) in patients with migraine. These results suggest that cinnarizine may be an appropriate substitution for first-line migraine prophylaxis such as valproate.

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Plasma homocysteine level and megaloblastic anemia status are two factors that can affect the quality of life of patients with multiple sclerosis (MS). We conducted this study to determine the effect of vitamin B12 and folic acid supplementation on serum homocysteine, megaloblastic anemia status and quality of life of patients with MS. A total of 50 patients with relapsing remitting multiple sclerosis (RRMS) included in this study which divided into 2 groups. The vitamin group received 5 mg folic acid tablet daily and 3 doses of vitamin B12 (1,000 mcg) injection and the other group received placebo and normal saline injection (same doses). The quality of life was measured by using Multiple Sclerosis Quality of Life-54 questionnaire (MSQOL-54). Fully automated fluorescence polarization immunoassay was used to measure serum homocysteine, vitamin B12 and folate. Complete blood count blood test was conducted to determine the anemia status. The mean homocysteine level reduced by 2.49 ± 0.39 µmol/L (p = 0.001), hemoglobin increased from 11.24 ± 1.54 to 13.12 ± 1.05 g/dL (p = 0.001), and mean corpuscular volume decreased from 95.50 ± 6.65 to 89.64 ± 4.24 in the vitamin group (p = 0.001). There was a significant improvement in the mental field of life quality in the placebo group (37.46 ± 19.01 to 50.98 ± 21.64; p = 0.001), whereas both physical and mental fields of quality of life were improved significantly in the vitamin group (40.38 ± 15.07 to 59.21 ± 12.32 and 29.58 ± 15.99 to 51.68 ± 18.22, respectively; p = 0.001). Serum homocysteine level decrease and anemia status improvement with vitamin B12 and folic acid supplementation reveal the potential role of these two vitamins in improving the life quality of MS patients.Trial RegistrationIranian Registry of Clinical Trials Identifier: IRCT2015100313678N7