Fampridine in multiple sclerosis patients with acute phase of cervical transverse myelitis: a double-blind, randomized placebo-controlled trial.

BACKGROUND: Fampridine is a potassium channel blocker drug used to improve walking ability in patients with multiple sclerosis (MS). We evaluated the effect of fampridine in patients with MS in the acute phase of transverse myelitis. METHODS: In a randomized, placebo-controlled trial, 30 patients who had their first episode of cervical myelitis with quadriparesis presentation, with the final diagnosis of MS, were randomly divided into two equal groups. The intervention group received intravenous methylprednisolone (IVMP) for 7 days plus fampridine. The placebo group received IVMP for 7 days plus placebo. To compare the treatment results, we compared the Barthel index (BI) scores of the groups at the start of the trial and the 21st day after the start of treatment. RESULTS: There was no significant difference in baseline characteristics between the intervention and placebo groups in terms of mean age, sex, and mean admission BI (p > 0.05). Mean (SD) admission BI in placebo and intervention groups was 27.20 (7.341) and 27.87(5.78), respectively (p = 0.784). The measured mean (SD) BI after treatment was 48.73 (15.54) in the placebo and 64.93 (11.81) in the intervention group (p = 0.003) after 3 weeks. CONCLUSION: Using fampridine plus IVMP in the acute phase of transverse myelitis in MS patients improved the disease's symptoms and increased the daily activity ability of patients.

Prevalence of Multiple sclerosis and its clinical and demographic characteristics in Kurdish populations in western Iran (2020).

BACKGROUND: Multiple Sclerosis (MS) is a costly burdensome nervous system disorder leading several disabilities in young and middle-aged people. Knowing MS clinical, epidemiologic and demographic characteristics may help to estimate and predict the required health services and medication facilities for the affected people. This study was aimed to determine the prevalence of MS and its demographic characteristic in about 2 million Kurdish populations in western Iran in 2020. METHODS: This cross-sectional study was conducted in 2020 on MS patients with Kurdish Ethnicity living in Kermanshah /western Iran which is a Mountainous area in. MS patients were registered and recruited to this study from several centers. The settings have been approved by the nationwide MS registry of Iran (NMSRI). Using two questioners, a questionnaire included sex, age, the age in which the MS symptoms onset, the age of diagnosis, family history of MS, and type of MS, and second one was the Expanded Disability Status Scale (EDSS) checklist. The demographic information of Kermanshah province was adopted from the Statistical Center of Iran. In addition to descriptive statistics, U-Mann-Whitney and Chi-square tests were also used. RESULTS: A total of 1557 MS patients with a mean age (±SD) of 38.66 ± 9.9 years were recruited in this study. Of them, 1216 (78.1%) were female. The majority of patients, 300 patients (19.3%), were in the age range 35-39 years, and the highest prevalence (184.82 per 100,000 populations) was observed in the age range 40-44 years. The prevalence of MS in Kermanshah province is estimated 79.50 per 100,000 people, 125.71 per 100,000 in female and 34.41 per 100,000 in male. This prevalence was higher in female (female to male was 3.65 to 1). The EDSS score was significantly higher in male than in female (3.06 ± 2.2 in male versus 2.42 ± 1.8 in female) (p = 0.001). The type of MS was significantly different between male and female, so that SPMS and PPMS were more common in male (31(10.3%), 22(7.3%)) than female (81(7.5%), 39(3.6%)) (p = 0.012). A positive family history of MS was found in 12.6% of patients. CONCLUSION: Given the information about prevalence of MS in Kermanshah (in 2012), the prevalence of MS in Kermanshah has increased during last decade. MS disabilities were more extensive in male rather than female.

Circulating mesenchymal stem cells, stromal derived factor (SDF)-1 and IP-10 levels increased in clinically active multiple sclerosis patients but not in clinically stable patients treated with beta interferon.

BACKGROUND: Mesenchymal stem cells (MSCs) have the capacity to migrate into the inflammatory regions in response to chemokines such as, IP-10 and SDF-1α and function as anti-inflammatory and immunomodulatory cells. METHODS: In this study we investigated the MSCs frequency in peripheral blood of Relapsing-Remitting Multiple Sclerosis (RRMS) patients in clinically active and not on disease-modifying therapy (DMT) (n = 22) and clinically stable on DMT (Interferon-ß (IFN-ß) therapy) for at least 6 months (n = 22) in comparison to sex and age-matched healthy controls (n = 25) using flow cytometry. The serum and gene expression levels of IP-10 and SDF-1a were also measured in studied groups by ELISA and Real time- PCR. RESULTS: We obtained significant high levels of circulating CD45-CD34- CD90+ and CD45-CD34- CD105+ cells in clinically active patients, not on DMT and patients under IFNß therapy compared with control group. Furthermore, a significant increase in the percentage of circulating CD45-CD34- CD105+ CD90+ cells was found in clinically active patients and not on DMT compared with control group. Serum analysis of IP-10 and SDF-1α showed a significant increase in IP10 concentration in both clinically active not on DMT (P = 0.02) and on DMT (P = 0.005) RRMS patients in comparison with controls. The expression level of SDF-1α mRNA significantly increased in clinically active not on DMT (P = 0.03), while decreased in patients under IFNß therapy (P = 0.04). The mRNA expression of IP-10 only increased in patients on DMT compared with controls (P = 0.05). CONCLUSION: Circulating MSCs, IP-10 and SDF-1α levels, increased in RRMS patients with clinically active not on DMT and IFN-ß therapy reduced circulating MSCs and SDF-1α levels.

Psychometric Evaluation of the Persian Version of the Chronic Illness Anticipated Stigma Scale (CIASS).

PURPOSE: The present study aimed to evaluate the cross-cultural validation and psychometric properties of the Persian version of the Chronic Illness Anticipated Stigma Scale (CIASS) among the patients with chronic illness in Iran. METHOD: Following standard procedures, the questionnaire was administered to a total sample of 186 patients with chronic illness who were recruited from the referral hospital, including hospitalized and clinic outpatients plus several referral clinics. Test-retest reliability and internal consistency were analyzed through intraclass correlation coefficient and Cronbach's alpha tests, respectively. Validity was evaluated in the areas of content and face validity, convergent, and also structural validity. RESULTS: Cronbach's alpha coefficient for the reliability of the scale was 0.88.The results of explanatory factor analysis confirmed extraction of all dimensions in three factors, consisting of family and friends, work colleagues, and healthcare workers. Evaluating convergent validity using Spearman's correlations showed satisfactory results; the correlation between the domains of the CIASS demonstrated internal agreement of the measure determining additional evidence to suggest the validity of the Persian CIASS. CONCLUSION: The preliminary study of the Persian version of the CIASS indicates good reliability and validity of the measure in Iranian patients with chronic illnesses.

Effect of Vitamin A Supplementation on fatigue and depression in Multiple Sclerosis patients: A Double-Blind Placebo-Controlled Clinical Trial.

Decreasing the population and activation of inflammatory T helper cells in multiple sclerosis (MS) patients using vitamin A derivatives (retinoic acids) has been well documented. The present study determined the effect of vitamin A supplementation on psychiatric signs in MS patients. The subjects were 101 relapsing-remitting MS patients enrolled in a placebo-controlled randomized clinical trial. The treatment group was administered 25000 IU/d retinyl palmitate (RP) for 6 months followed by 10000 IU/d RP for another 6 months. The results for baseline characteristics, modified fatigue impact scale and Beck Depression Inventory-II were recorded at the beginning and end of the one-year study. The non-normal distribution data was compared between groups using a nonparametric test and normal distribution data was analyzed using a parametric test. (ClinicalTrials.gov Identifiers: NCT01417273). The results showed significant improvement in the treatment group for fatigue (p=0.004) and depression (p=0.01). Vitamin A supplementation helped during interferon therapy in the treatment process and improved psychiatric outcomes for anti-inflammatory mechanisms.

Pregnancy and the Use of Disease-Modifying Therapies in Patients with Multiple Sclerosis: Benefits versus Risks.

The burden of multiple sclerosis (MS) in women of childbearing potential is increasing, with peak incidence around the age of 30 years, increasing incidence and prevalence, and growing female : male ratio. Guidelines recommend early use of disease-modifying therapies (DMTs), which are contraindicated or recommended with considerable caution, during pregnancy/breastfeeding. Many physicians are reluctant to prescribe them for a woman who is/is planning to be pregnant. Interferons are not absolutely contraindicated during pregnancy, since interferon-ß appears to lack serious adverse effects in pregnancy, despite a warning in its labelling concerning risk of spontaneous abortion. Glatiramer acetate, natalizumab, and alemtuzumab also may not induce adverse pregnancy outcomes, although natalizumab may induce haematologic abnormalities in newborns. An accelerated elimination procedure is needed for teriflunomide if pregnancy occurs on treatment or if pregnancy is planned. Current evidence supports the contraindication for fingolimod during pregnancy; data on other DMTs remains limited. Increased relapse rates following withdrawal of some DMTs in pregnancy are concerning and require further research. The postpartum period brings increased risk of disease reactivation that needs to be carefully addressed through effective communication between treating physicians and mothers intending to breastfeed. We address the potential for use of the first- and second-line DMTs in pregnancy and lactation.

Impact of Vitamin A Supplementation on Disease Progression in Patients with Multiple Sclerosis.

BACKGROUND: Many studies have shown that active vitamin A derivatives suppress the formation of pathogenic T cells in multiple sclerosis (MS) patients. The aim of the present study is to determine the impact of vitamin A on disease progression in MS patients. METHODS: A total of 101 relapsing-remitting MS (RRMS) patients were enrolled in a 1-year placebo-controlled randomized clinical trial. The treated group received 25000 IU/d retinyl palmitate for six month followed by 10000 IU/d retinyl palmitate for another six month. The results of the expanded disability status scale (EDSS) and multiple sclerosis functional composite (MSFC) were recorded at the beginning and the end of the study. The relapse rate was recorded during the intervention. Patients underwent baseline and follow up brain MRIs. RESULTS: The results showed "Mean ± SD" of MSFC changes in the treated group was (-0.14 ± 0.20) and in the placebo group was (-0.31 ± 0.19). MSFC was improved significantly (P < 0.001) in the treatment group. There were no significant differences between the "Mean ± SD" of EDSS changes in the treated (0.07 ± 0.23) and placebo (0.08 ± 0.23) groups (P = 0.73). There were also no significant differences between the "Mean ± SD" of annualized relapse rate in the treated group (-0.36 ± 0.56) and placebo (-0.53 ± 0.55) groups (P = 0.20). The "Mean ± SD" of enhanced lesions in the treatment (0.4 ± 1.0) and in the placebo (0.2 ± 0.6) groups were not significantly different (P = 0.26). Volume of T2 hyperintense lesions "Mean ± SD" was not significantly different between treatment (45 ± 137) and placebo (23 ± 112) groups after intervention (P = 0.23). CONCLUSION: Vitamin A improved total MSFC score in RRMS patients, but it did not change EDSS, relapse rate and brain active lesions.

Dietary intake of nutrients and its correlation with fatigue in multiple sclerosis patients.

BACKGROUND: The role of nutrition in the progression of multiple sclerosis (MS) and related complications such as fatigue has been reported by several studies. The aim of this study is the assessment of nutritional status and its relationship with fatigue in multiple sclerosis patients. METHODS: This is a cross-sectional study, in which 101 relapsing-remitting MS patients were enrolled. The fatigue status was determined using the validated Persian version of of the Modified Fatigue Impact Scale (MFIS). Dietary intake was assessed using a 3-day food record questionnaire and compared to dietary reference intake (DRI) values. Association between variables was determined using Pearson Correlation Coefficient. RESULTS: In the preset study, 25 men and 76 women (total = 101) were enrolled. Analysis of dietary intake showed that daily intake of vitamin D, folate, calcium, and magnesium were significantly lower than DRI in all of patients. In men, zinc intake was significantly lower than DRI; while, in women, iron was significantly below the DRI level. After adjusting for energy, MFIS and its physical subscale were highly correlated with intake of folate and magnesium. CONCLUSION: Our findings support that lower magnesium and folate diets are correlated with higher fatigue scores in MS patients.

Cost-effectiveness of different interferon beta products for relapsing-remitting and secondary progressive multiple sclerosis: Decision analysis based on long-term clinical data and switchable treatments.

BACKGROUND: Multiple sclerosis (MS) is a highly debilitating immune mediated disorder and the second most common cause of neurological disability in young and middle-aged adults. Iran is amongst high MS prevalence countries (50/100,000). Economic burden of MS is a topic of important deliberation in economic evaluations study. Therefore determining of cost-effectiveness interferon beta (INF ß) and their copied biopharmaceuticals (CBPs) and biosimilars products is significant issue for assessment of affordability in Lower-middle-income countries (LMICs). METHODS: A literature-based Markov model was developed to assess the cost-effectiveness of three INF ßs products compared with placebo for managing a hypothetical cohort of patients diagnosed with relapsing remitting MS (RRMS) in Iran from a societal perspective. Health states were based on the Kurtzke Expanded Disability Status Scale (EDSS). Disease progression transition probabilities for symptom management and INF ß therapies were obtained from natural history studies and multicenter randomized controlled trials and their long term follow up for RRMS and secondary progressive MS (SPMS). A cross sectional study has been developed to evaluate cost and utility. Transitions among health states occurred in 2-years cycles for fifteen cycles and switching to other therapies was allowed. Calculations of costs and utilities were established by attachment of decision trees to the overall model. The incremental cost effectiveness ratio (ICER) of cost/quality adjusted life year (QALY) for all available INF ß products (brands, biosimilars and CBPs) were considered. Both costs and utilities were discounted. Sensitivity analyses were done to assess robustness of model. RESULTS: ICER for Avonex, Rebif and Betaferon was 18712, 11832, 15768 US Dollars ($) respectively when utility attained from literature review has been considered. ICER for available CBPs and biosimilars in Iran was $847, $6964 and $11913. CONCLUSIONS: The Markov pharmacoeconomics model determined that according to suggested threshold for developing countries by world health organization, all brand INF ß products are cost effective in Iran except Avonex. The best strategy among INF ß therapies is CBP intramuscular INF ß-1a (Cinnovex). Results showed that a policy of encouraging accessibility to CBPs and biosimilars could make even high technology products cost-effective in LMICs.

Stroke modifies drug consumption in opium addicts: role of the insula.

INTRODUCTION: Addiction imposes a large medical, social and economic burden on societies. Currently, there is no effective treatment for addiction. Our struggle to decipher the different mechanisms involved in addiction requires a proper understanding of the brain regions which promote this devastating behavior. Previous studies have shown a pivotal role for insula in cigarette smoking. In this study we investigated the change in opium consumption after CVA. METHODS: This study took place in three referral academic hospitals affiliated to Tehran University of Medical Sciences. Patients who suffered a CVA and were addicted to opium were recruited during their hospitalization or visit to the neurology clinic in this study. Age, sex and the route and mean amount of opium use of each patient before CVA and 1, 3 and 6 months post-CVA was asked using a questionnaire. The patients were divided into three groups based on the location of brain ischemia (insula, basal ganglia and non-insula non-basal ganglia group). RESULTS: Seventy five percent of the patients with ischemia of the insula changed the route or amount of opium use after CVA and 37.5% of them stopped opium use after CVA. These values were significantly higher than patients with non-insula nonbasal ganglia ischemia (p values 0.005 and 0.03 for change in route or amount and stopping opium use, respectively). This was not true in patients with ischemia of the basal ganglia. Younger patients were more likely to change the route or amount of opium use and stop opium use after CVA (p values 0.002 and 0.026, respectively). DISCUSSION: The results of the present study indicate a possible role for the insula in opium addiction, especially in younger individuals.

The effect of vitamin A supplementation on stimulated T-cell proliferation with myelin oligodendrocyte glycoprotein in patients with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease whereby myelin sheath of the central nervous system is destroyed. Vitamin A is known to play a role in the immune system. It has been recognized that some metabolites of vitamin A can be used effectively to treat experimental autoimmune encephalomyelitis (EAE). AIMS: The effect of vitamin A as retinyl palmitate on T-cell proliferation in MS patients. SETTING AND DESIGN: This study is a double blind clinical trial of two test groups over a period of 6 months. MATERIALS AND METHODS: Thirty five multiple sclerosis (MS) patients were divided into two groups. One group received 25,000 IU/day vitamin A (as retinyl palmitate) and the other group were administered a placebo. The peripheral blood mononuclear cells (PBMCs) were separated and stimulated with myelin oligodendrocyte glycoprotein (MOG) and phytohemagglutinin (PHA) before and after the trial period. BrdU calorimetric assay was performed to measure cell proliferation. STATISTICAL ANALYSIS: Analysis of covariance (ANCOVA) and paired t-test were used to analyze the data. RESULTS: Observations showed statistical significant differences in the reduction of cell proliferation in the presence of MOG and fetal calf serum (FCS) in the culture medium, between patients receiving vitamin A and the placebo (P = 0.046). Although, this difference was not significant between the two vitamin A and placebo groups in MOG treatment with human serum, a decrease was observed in the group of patients taking vitamin A supplements (P = 0.019). Phytohemagglutinin did not cause any change in cell proliferation between the two groups. CONCLUSION: The results suggest supplementation with retinyl palmitate in patients with MS reduce MOG stimulatory effects on T-cells.

Variation in SNPs of the IL7Ra gene is associated with multiple sclerosis in the Iranian population.

Interleukin-7 receptor-alpha gene (IL7Ra) is a member of the type I cytokine receptor family located on 5p13 human chromosome. Some evidence associates multiple sclerosis and single nucleotide polymorphisms in the promoter and exonic region of IL7Ra gene. In an attempt to clarify this association, the frequency of 3 SNPs located in the promoter and 1 SNP located in the 6th exon of IL7Ra gene were analyzed in a population of 100 Iranian MS patients as well as 100 controls. Restriction enzyme digestion and a designed mismatch PCR-RFLP strategy were used for the SNP genotyping of our study groups. Considering allele, genotype and haplotype frequencies, no significant association was observed between MS and IL7Ra polymorphisms. Meanwhile, a significant difference was detected between control and primary progressive MS patients considering promoter SNPrs11567685 marker frequency. Also, a significant difference was detected considering exonic SNPrs6897932 for secondary progressive MS patients. Our analysis indicates that GCAC and GTAT haplotypes are less common in SP and PP MS groups, respectively. These differences support the concept that clinical phenotypes may have different etiologies and, therefore, require different therapy strategies.