Effects of long-term administration of Multi-Strain Probiotic on circulating levels of BDNF, NGF, IL-6 and mental health in patients with multiple sclerosis: a randomized, double-blind, placebo-controlled trial.

Background: Mental disorders is one of the main causes of disability and lower life expectancy among patients with Multiple Sclerosis (MS). The present trial aimed to examine the efficacy of multi-strain probiotic supplementation on circulating levels of BDNF, NGF, IL-6 and mental health in patients with MS.Methods: This trial was conducted among 70 patients with MS that referred to the MS Association. Patients were randomized into intervention and control groups to receive 2 multi-strain probiotic capsules or placebo, daily for six months. Serum BDNF, NGF and IL-6 was measured by ELISA kits. Mental health parameters were assessed by valid questionnaires in the baseline and end of the study.Results: Of the 70 patients enrolled in this study, 65 subjects were included in the final analysis. From baseline to 6 months, probiotic supplementation resulted in a significant increase in BDNF and a significant reduction in the IL-6 levels (P < 0.001). Our findings revealed that probiotic supplementation compared to placebo caused a significant improvement in the general health questionnaire-28 (GHQ-28) (-5.31 ± 4.62 vs. -1.81 ± 4.23; P = 0.002), Beck Depression Inventory-II (BDI-II) (-4.81 ± 0.79 vs. -1.90 ± 0.96; P = 0.001), Fatigue Severity Scale (FSS) (-3.81 ± 6.56 vs. 0.24 ± 5.44; P = 0.007) and Pain Rating Index (PRI) (-3.15 ± 4.51 vs. -0.09 ± 3.67; P = 0.004). However, we not found any significant difference between the two groups in other factors (P > 0.05).Conclusion: Overall, six months of probiotic supplementation resulted in greater improvement in mental health parameters.

Randomised trial of IV metoclopramide vs IV ketorolac in treatment of acute primary headaches.

INTRODUCTION: Headache is one of the most common neurological conditions among emergency department visits (ED), although the best therapy has not been identified yet. Therefore, in the current study, we aimed to compare the pain-relieving effect of metoclopramide and ketorolac in acute primary headaches patients. METHODS: This double-blind, randomised clinical trial was conducted at Golestan Hospital, Ahvaz, Iran. This research involved all adult patients with acute primary (migraine or tension-type) headaches presented to the ED. Pain intensity was assessed with 0 to 10 verbal Numeric Rating Scales (NRS). The subjects were randomised into 10 mg intravenous (IV) metoclopramide or 30 mg IV ketorolac groups. Pain score and drug adverse reactions were compared between the two groups at baseline, 15, 30, and 60 min after baseline. RESULTS: 108 patients completed this trial and were equally divided into two groups (mean age of 34 ± 8.54 years; 57.4% female). Before treatment, the mean pain score was 6.9 and 6.8 in metoclopramide and ketorolac groups, respectively (p > 0.05). Metoclopramide failed to provide more improvement in pain score at 30 min (p = 0.55) and 60 min (p = 0.15) from baseline. There were no serious adverse events in this study. Only five patients required rescue medication which four of them were in ketorolac group. CONCLUSION: We were unable to reject the null hypothesis that there would be no difference in pain outcomes between metoclopramide and ketorolac.

Long-term disability trajectories in primary progressive MS patients: A latent class growth analysis.

BACKGROUND: Several natural history studies on primary progressive multiple sclerosis (PPMS) patients detected a consistent heterogeneity in the rate of disability accumulation. OBJECTIVES: To identify subgroups of PPMS patients with similar longitudinal trajectories of Expanded Disability Status Scale (EDSS) over time. METHODS: All PPMS patients collected within the MSBase registry, who had their first EDSS assessment within 5 years from onset, were included in the analysis. Longitudinal EDSS scores were modeled by a latent class mixed model (LCMM), using a nonlinear function of time from onset. LCMM is an advanced statistical approach that models heterogeneity between patients by classifying them into unobserved groups showing similar characteristics. RESULTS: A total of 853 PPMS (51.7% females) from 24 countries with a mean age at onset of 42.4 years (standard deviation (SD): 10.8 years), a median baseline EDSS of 4 (interquartile range (IQR): 2.5-5.5), and 2.4 years of disease duration (SD: 1.5 years) were included. LCMM detected three different subgroups of patients with a mild ( n = 143; 16.8%), moderate ( n = 378; 44.3%), or severe ( n = 332; 38.9%) disability trajectory. The probability of reaching EDSS 6 at 10 years was 0%, 46.4%, and 81.9% respectively. CONCLUSION: Applying an LCMM modeling approach to long-term EDSS data, it is possible to identify groups of PPMS patients with different prognosis.

Effects of dual-task balance training on postural performance in patients with Multiple Sclerosis: a double-blind, randomized controlled pilot trial.

OBJECTIVE: To investigate the effects of dual-task balance training on postural performance in patients with multiple sclerosis as compared with single-task balance training. DESIGN: Double-blind, pretest-posttest, randomized controlled pilot trial. SETTING: Local Multiple Sclerosis Society. SUBJECTS: A total of 47 patients were randomly assigned to two equal groups labeled as single-task training and dual-task training groups. INTERVENTIONS: All patients received supervised balance training sessions, 3 times per week for 4 weeks. The patients in the single-task group performed balance activities, alone. However, patients in dual-task group practiced balance activities while simultaneously performing cognitive tasks. MAIN MEASURES: The 10-Meter Walk Test and Timed Up-and-Go under single-task and dual-task conditions, in addition to Activities-specific Balance Confidence, Berg Balance Scale, and Functional Gait Assessment were assessed pre-, and post intervention and also 6-weeks after the end of intervention. RESULTS: Only 38 patients completed the treatment plan. There was no difference in the amount of improvement seen between the two study groups. In both groups there was a significant effect of time for dual-10 Meter Walk Test (F1, 36=11.33, p=0.002) and dual-Timed Up-and-Go (F1, 36=14.27, p=0.001) but not for their single-tasks. Moreover, there was a significant effect of time for Activities-specific Balance Confidence, Berg Balance Scale, and Functional Gait Assessment ( P<0.01). CONCLUSIONS: This pilot study did not show more benefits from undertaking dual-task training than single-task training. A power analysis showed 71 patients per group would be needed to determine whether there was a clinically relevant difference for dual-task gait speed between the groups.

A national registry-based study of ethnic differences in people with multiple sclerosis in Iran.

OBJECTIVE: The relationship between MS and ethnicity has been understudied in the Middle East compared to the United States and Europe. As Iran as the highest prevalence of MS in the Middle East, we decided to investigate the demographic and clinical differences in people with MS (pwMS) from major ethnicities Iran. METHODS: In a cross-sectional study using data from National Multiple Sclerosis Registry in Iran. PwMS from six provinces were chosen and interviewed for determining their ethnicity. Persians (Fars), Kurds, Lurs, Azeris and Arabs with a clear ethnic background were included. Recorded data from the registry was used to compare the demographic and clinical features. RESULTS: A total of 4015 pwMS (74.2% female) were included in the study with an average age of 36.76 ± 9.68 years. Persians and Kurds had the highest percentage of pwMS in youngest and oldest age groups, respectively, with 2.9% and 5.7% (p<0.01). The highest average age of onset was seen in Persians (29.47 ± 8.89) and the lowest observed in Mazandaranis (26.82 ± 7.68, p<0.01). Azeris and Kurds had the highest proportions of pwMS diagnosed <18 and >55, at rates of 12% and 1.6%, respectively (p<0.01). There were statistically significant differences in distribution of phenotypes (p<0.01) and time to progression to secondary progressive MS (p<0.01) such that Persians had the highest rate of clinically isolated syndrome (CIS) at 19.3% and Arabs had highest rates of relapsing-remitting MS (86.2%) and secondary progressive MS (16.4%). Lurs, Azeris and Mazandaranis had significantly more patients progressing to secondary-progressive MS <5 years from diagnosis (p<0.01). There was a significant difference in number of relapses between the ethnicities (p<0.01) with Lurs having the highest proportion of participants reporting >4 relapses with 23.0% and Azeris having the highest percentage of pwMS reporting no relapse (53.0%). Kurds had the highest Expanded Disability Status Scale (EDSS) average at 2.93 ± 1.99 and Lurs had the lowest with 1.28 ± 1.25 (p<0.01). The differences in prevalence of positive family history for the whole cohort between ethnicities were significant (P=0.02), ranging from 12.8% in Kurds to 19.6% in Persians. CONCLUSION: We found Persians to have higher rates of pediatric MS and higher rates of CIS. Kurds and Lurs had higher and lower EDSS scores, respectively. Lurs and Persian had higher annual relapse rates. We also found lower rates of SPMS among Arabs and earlier progression to SPMS in Lurs, Azeris and Mazandaranis. Such differences highlight the importance of the potential role of ethnicities in diagnosis and prognosis of MS, especially considering their observation within the geographical limits of a single country.

Evaluating efficacy and safety of ocrelizumab biosimilar (Xacrel) compared to the originator (Ocrevus) in relapsing multiple sclerosis: a phase III, randomized, equivalency, clinical trial.

Multiple sclerosis is an inflammatory demyelinating disease and represents a global health concern. Ocrelizumab, a humanized IgG monoclonal antibody, selectively targets CD20 on B cells and CD20-expressing T cells. This study aimed to compare the efficacy and safety of the biosimilar ocrelizumab candidate (Xacrel) to the originator product (Ocrevus) in Relapsing Multiple Sclerosis (RMS) patients. In this randomized trial, patients received either Xacrel or Ocrevus for 96 weeks. The primary endpoint was the equivalency of the medications in reducing the annualized relapse rate (ARR) at week 48. The secondary endpoints included time to the onset of disability progression confirmed at 12 and 24 weeks, the proportion of relapse-free patients, magnetic resonance imaging (MRI) evaluations, safety assessments, and immunogenicity over 96 weeks. A total of 170 patients were randomized (1:1 ratio). In the per protocol analysis, the upper and lower limits of 95% two-sided confidence intervals of difference between treatments in the 48-week ARR rate were in the predefined margin of - 0.2 to 0.2 (- 0.002; 95% CI - 0.080 to 0.075). The two products were also comparable in terms of other efficacy parameters, safety, and immunogenicity. The results confirmed that Xacrel is equivalent to Ocrevus in terms of 48-week ARR in RMS patients, with no considerable difference in other efficacy parameters and the safety profile during the 96 weeks. The trial was registered in Iranian registry of clinical trials (IRCT) on 10/06/2019 with the registration number of IRCT20150303021315N13 and in Clinicaltrials.gov on 19/07/2021 with the registration code of NCT04966338.

Riboflavin supplementation to patients with multiple sclerosis does not improve disability status nor is riboflavin supplementation correlated to homocysteine.

BACKGROUND: Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system. Riboflavin is involved in myelin formation in nerve cells. Riboflavin is a precursor of flavin adenine D-nucleotide (FAD), which is a coenzyme of methylene tetrahydrofolate reductase (MTHFR), which is an important enzyme for remethylation of homocysteine. Riboflavin supplementation has been shown to affect the serum levels of homocysteine in healthy volunteers. The aim of the present study was to test the effect of riboflavin supplementation on the status and disability of patients with MS and whether this effect could be mediated by serum homocysteine levels. MATERIALS AND METHODS: This was a randomized, double-blind, controlled trial in which 29 MS patients with a mean age of 33 were tested with riboflavin, and the placebo group, with a mean age of 31, received either riboflavin supplementation (10 mg) or the placebo daily for six months. Disability, measured by the Expanded Disability Status Scale (EDSS) scores, erythrocyte glutathione reductase activity coefficient (EGRAC), and serum homocysteine levels were measured before and after the study. RESULTS: The mean ± SD of EDSS score was significantly decreased in both groups over the six months of the study (2.3 ± 0.7 vs. 1.6 ± 0.6 for the riboflavin group and 2.8 ± 1.1 vs. 2.3 ± 1.3 for the placebo groups. The comparison across both groups yielded a non-significant change (P = 0.001 and 0.02, respectively). No significant differences were observed between the two groups in terms of EGRAC, riboflavin deficiency levels by EGRAC category, and serum homocysteine levels before and after the study. CONCLUSION: Riboflavin supplementation (10 mg/day) to patients with MS does not improve disability status. It appears that this effect is not related to serum homocysteine levels.

Solifenacin versus posterior tibial nerve stimulation for overactive bladder in patients with multiple sclerosis.

Introduction: Overactive bladder (OAB) is one of the most common complications in patients with multiple sclerosis (MS). Choosing the effective treatment is very important in improving their quality of life (QOL). Therefore, the aim of this study was to compare solifenacin (SS) and posterior tibial nerve stimulation (PTNS) treatment effects in the MS Patients with OAB. Materials and methods: In total, 70 MS patients suffering from OAB enrolled in this clinical trial study. Patients with a score of at least 3 according to the OAB questionnaire were randomly divided into two groups (35 patients in each group). In one group, patients received SS (5 mg daily for 4 weeks and 10 mg/day for another 8 weeks) and in a second group, patients were treated by PTNS (12 weekly session, 30 min). Results: The mean (SD) age of patients participating in this study was 39.82 (9.088) and 42.41 (9.175) years for the SS group and the PTNS group, respectively. Patients in both groups showed statistically significant improvements in urinary incontinence, micturition, and daytime frequency (p < 0.001). Patients in the SS group had a better response for urinary incontinence after 12 weeks compared to the PTNS group. Also, patients in the SS group reported higher satisfaction and less daytime frequency compared to the PTNS group. Conclusion: SS and PTNS were effective for improving the OAB symptoms in patients with MS. However, patients demonstrated a better experience with SS in terms of daytime frequency, urinary incontinence, and treatment satisfaction rate.

Effects of N-acetylcysteine on oxidative stress biomarkers, depression, and anxiety symptoms in patients with multiple sclerosis.

AIM: N-acetylcysteine (NAC), a thiol-containing antioxidant and glutathione (GSH) precursor, attenuates oxidative stress, and possibly improves psychiatric disorders. This study aimed to evaluate the effects of oral NAC on oxidative stress, depression, and anxiety symptoms in patients with multiple sclerosis (MS). METHODS: This clinical trial was conducted on 42 MS patients randomly assigned to intervention (n = 21) and control (n = 21) groups. The intervention group received 600 mg of NAC twice daily for 8 weeks, and the control group received a placebo with the same prescription form. An analysis of serum malondialdehyde (MDA), serum nitric oxide (NO), and erythrocyte GSH was carried out on both groups, along with a complete blood count. The Hospital Anxiety and Depression Scale (HADS) was used to assess symptoms of depression (HADS-D) and anxiety (HADS-A). RESULTS: Compared to the control group, NAC consumption significantly decreased serum MDA concentrations (-0.33 [-5.85-2.50] vs. 2.75 [-0.25-5.22] µmol/L; p = 0.03) and HADS-A scores (-1.6 ± 2.67 vs. 0.33 ± 2.83; p = 0.02). No significant changes were observed in serum NO concentrations, erythrocyte GSH levels, and HADS-D scores (p > 0.05). CONCLUSIONS: Based on the findings of the present study, NAC supplementation for 8 weeks decreased lipid peroxidation and improved anxiety symptoms in MS patients. The aforementioned results suggest that adjunctive therapy with NAC can be considered an effective strategy for MS management. Further randomized controlled studies are warranted.

A case-control study of drinking beverages and the risk of multiple sclerosis in Iran.

BACKGROUND: There is no study in the world on the relationship between consuming black and green tea as beverages containing polyphenols and the risk of MS. This study aimed to determine the association between the consumption of green and black tea, coffee, non-alcoholic beer, milk, fruit juices and carbonated beverages with the risk of MS. METHODS AND MATERIALS: This case-control study was performed on 150 patients with MS and 300 healthy individuals as a control group among patients who were referred to the ophthalmology ward of a referral hospital in Ahvaz with the groups matching for age. The data collection tool was a researcher-made questionnaire including demographic information and beverage consumption. Analysis was performed using univariate and multiple logistic regression models. RESULTS: The mean age of patients at the time of diagnosis was 38.55 ± 8.88 years. The results showed that drinking milk (OR = 5.46), natural juice (OR = 2.49), and carbonated beverages (OR = 16.17) were associated with an increased chance of developing MS. However, drinking non-alcoholic beer (OR = 0.48), black tea (OR = 0.20), green tea (OR = 0.29) and coffee (OR = 0.07) were associated with a reduced chance of developing MS. CONCLUSION: The results show that drinking black and green tea, non-alcoholic beer, and coffee are associated with a decrease in the chance of developing MS. The results of this study can be used to design interventional research and to change people's lifestyles to prevent MS.

Effects of exergaming on cognition, lower limb functional coordination, and stepping time in people with multiple sclerosis: a randomized controlled trial.

PURPOSE: To compare the effects of exergaming versus conventional exercises on cognition, lower-limb functional coordination, and stepping time in people with multiple sclerosis (PwMS). METHODS: Thirty-six PwMS were randomly assigned to either intervention (n = 18) or control (n = 18) group and received 18 training sessions during six weeks. The intervention group performed exergames that required multidirectional timed-stepping, weight-shifting, and walking while the control group performed conventional matched exercises. Trail making test (TMT part A, B; TMT-A, TMT-B, TMT B-A), six-spot step test (SSST), and choice stepping reaction time (CSRT-including reaction time (RT), movement time (MVT), and total response time (TRT)) were assessed pre- and post-intervention (short-term), and after three-month follow-up (mid-term). RESULTS: The intervention group showed faster TMT-B (p = 0.003) and TMT B-A (p = 0.002) at post-intervention and faster SSST at both post-intervention (p = 0.002) and follow-up (p = 0.04). The CSRT components showed no between-group differences at post-intervention; however, at follow-up, the intervention group had lower TRT (p = 0.046) and MVT (p = 0.015). TMT-A and RT had no significant between-group differences. CONCLUSIONS: In short-term, exergames led to more improvements in complex attention, executive function, and lower-limb functional coordination comparing to the matched conventional exercises. In mid-term, exergaming was more effective for improving stepping time and lower-limb functional coordination. However, the two approaches did not show any superiority over each other for improving simple attention and RT.Implications for rehabilitationWhen designed properly, exergames have great potential to improve attention and executive function of people with multiple sclerosis (PwMS), at least in the short-term.Exergames seem like an appropriate option for improving lower limb coordination and decreasing choice stepping response time among PwMS in the mid-term.Exergames do not have superiority in improving the choice stepping reaction time compared to their matched conventional treatment.

Late-onset multiple sclerosis in Iran: A report on demographic and disease characteristics.

BACKGROUND: Today, it is estimated that around 5% of multiple sclerosis (MS) patients are in the late-onset category (age at disease onset ≥ 50). Diagnosis and treatment in this group could be challenging. Here, we report the latest update on the characteristics of Iranian patients with late-onset MS (LOMS). METHODS: This cross-sectional study used the information provided by the nationwide MS registry of Iran (NMSRI). The registrars from 14 provinces entered data of patients with a confirmed diagnosis of MS by neurologists. Patients with disease onset at or later than 50 years of age were considered LOMS. RESULTS: Of 20,036 records, the late-onset category included 321 patients (1.6%). The age-standardized LOMS prevalence was around 75 per 100,000 people. 215 patients (67%) were female. Median Expanded Disability Status Scale (EDSS) was 3 (interquartile range: 1.5-5). The majority of the cases (56%) suffered from relapsing-remitting (RR) course while 20% were diagnosed with primary progressive (PP) MS. Significantly higher proportion of male sex, PPMS, and higher EDSS were seen in the late-onset group compared with early-onset and adult-onset cases (p-value < 0.05). Seventy-five (23%) patients did not receive any disease-modifying treatment. DISCUSSION: The more prominent degenerative pathology of LOMS may be the underlying mechanism of the observed differences in comparison to non-LOMS. CONCLUSION: There are substantial differences and knowledge gaps regarding LOMS which could be the subject of further research.

Probiotic supplementation and systemic inflammation in relapsing-remitting multiple sclerosis: A randomized, double-blind, placebo-controlled trial.

Background: Multiple sclerosis (MS) is a complex inflammatory disease in which demyelination occurs in the central nervous system affecting approximately 2.5 million people worldwide. Intestinal microbiome changes play an important role in the etiology of chronic diseases. Objective: This study aimed to investigate the effect of probiotic supplementation on systemic inflammation in patients with MS. Methods: A 12-week double-blind clinical trial study was designed and seventy patients with MS were randomly divided into two groups receiving probiotics and placebo. Patients in the intervention group received two capsules containing multi-strain probiotics daily and patients in the control group received the same amount of placebo. Factors associated with systemic inflammation were assessed at the beginning and end of the study. Results: Sixty-five patients were included in the final analysis. There was no significant difference between the two groups in terms of baseline variables except for the duration of the disease (P > 0.05). At the end of the study, probiotic supplementation compared to the placebo caused a significant reduction in the serum levels of CRP (-0.93 ± 1.62 vs. 0.05 ± 1.74, P = 0.03), TNF-α (-2.09 ± 1.88 vs. 0.48 ± 2.53, P = 0.015) and IFN-γ (-13.18 ± 7.33 vs. -1.93 ± 5.99, P < 0.001). Also, we found a significant increase in the FOXP3 and TGF-ß levels in the intervention group (P < 0.05). Conclusion: The results of our study showed that supplementation with probiotics can have beneficial effects on serum levels of some factors associated with systemic inflammation. Clinical trial registration: [http://www.irct.ir], identifier [IRCT20181210041 918N1].

Validity, reliability, and responsiveness of Persian version of mini-balance evaluation system test among ambulatory people with multiple sclerosis.

BACKGROUND AND PURPOSE: Mini-Balance Evaluation Systems Test (mini-BESTest) is a widely used measure to assess balance impairments. This study aimed to assess the validity, reliability, responsiveness, and minimal clinically important change (MCIC) of the Persian mini-BESTest among ambulatory People with Multiple Sclerosis (PwMS). METHODS: Fifty ambulatory PwMS participated in this study. Persian mini-BESTest validated against Berg Balance Scale (BBS) and Timed-Up and Go (TUG) with/without a cognitive task. To assess the reliability, the Persian mini-BESTest was re-administered for a sample of 30 participants after 1 week. Also, 32 PwMS were tested before and after a 4-week of balance and gait training to assess the responsiveness. RESULTS: No floor/ceiling effect was found for the mini-BESTest total score. There were significant excellent correlations (p < .001) between mini-BESTest and BBS (r = 0.71), TUG (r = -0.76), and cognitive TUG (r = -0.73). No strong correlations were observed between the subscales (r = 0.37-0.55). Test-retest reliability and internal consistency of Persian mini-BESTest total score were excellent, with Intra-class Correlation Coefficient (ICC3,1 and Cronbach's alpha level of 0.89 and 0.80, respectively. The minimal detectable change was 4 points. The Persian mini-BESTest had acceptable responsiveness (AUC = 0.83), and MCIC was 5 points. CONCLUSION: The Persian mini-BESTest is a valid, reliable, and responsive measure of balance performance in Iranian ambulatory PwMS.

Corrigendum: Probiotic supplementation and systemic inflammation in relapsing-remitting multiple sclerosis: A randomized, double-blind, placebo-controlled trial.

[This corrects the article DOI: 10.3389/fnins.2022.901846.].

Prescription trends of disease-modifying treatments for multiple sclerosis in Iran over the past 30 years.

BACKGROUND: Iran, as a middle income country, is one of the places with high and rising prevalence of multiple sclerosis (MS). Regarding the substantial economic burden, reviewing the trend in prescribed disease modifying treatments (DMTs) could be of help. Here we studied the DMT information of nearly 14000 MS cases and its trends change for 30 years to improve health services to patients. METHODS: The population base of this descriptive-analytical (cross-sectional) study consisted of all MS patients in the nationwide MS registry of Iran (NMSRI), up to August 1, 2021. Registrars from 15 provinces, 24 cities, 13 hospitals,8 MS associations, 16 private offices, and 7 clinics had entered the data. RESULTS: Overall, 14316 cases were enrolled. The majority (76.1%) were female. The youngest and eldest patients were 5 and 78 years old, respectively. Diagnosis delay was under one year in most cases (median: 0, IQR: 0 - 1). Most (61.4%) had RRMS. Generally, platform injectables (IFN beta, glatiramer acetate) were the most used DMTs until 2010. It seems that introduction of newer agents (antiCD20s and oral DMTs) resulted in a decrease in the use of former drugs since around 2015. Some unusual practices are prominent such as using not approved DMTs for PPMS over the years, or administering high efficacy drugs like natalizumab for CIS. The results indicate the remaining popularity of first line injectable DMTs in female and pediatric patients. DISCUSSION: Mean age (SD) at onset in our study (29 ± 8.8) is near the statistics in Asia and Oceania (28 ± 0.7). Concerns about COVID-19 had a noticeable impact on administering high efficacy drugs like rituximab and fingolimod. However, in male patients this approach has not been the case. It may be related to more aggressive disease course in this group. The other possible explanation could be planning for pregnancy in female cases. The popularity of platform injectable drugs in pediatric MS may be related to its favorable safety profile over the years. Another point in this group, is the superiority of rituximab over other highly efficient medications.

Does atorvastatin have augmentative effects with sodium valproate in prevention of migraine with aura attacks? A triple-blind controlled clinical trial.

BACKGROUND: Migraine is a painful and disabling nervous disorder which negatively affects the quality of life. Migraineurs may suffer from a generalized vasomotor dysfunction. Statins improve vasomotor and vascular function, with their pleiotropic effects. We aimed to assess efficacy and safety of adding Atorvastatin to prophylactic regimen in better control of migraine with aura. METHODS: This triple-blind controlled clinical trial was on 68 patients with migraine with aura. An interval of at least 1 month was given to evaluate vitamin D3 level and eligibility. In patients with vitamin D3 deficiency, the correction with vitamin D supplementation was provided. The patients were randomly assigned to receive atorvastatin 20 mg plus sodium valproate 500 mg or placebo plus sodium valproate 500 mg once a day for 2 months. The patients were evaluated based for the number of attacks and pain severity based on Visual Analogue Scale. RESULTS: There was a significant (p = 0.0001) improvement in severity of pain and number of migraine attacks by adding Atorvastin to the prophylactic regimen of patients with migraine with aura. After controlling for variable parameters, the differences between two arms of the study was yet statistically significant (p = 0.0001). A significant number of participants in intervention group were satisfied by their treatment (p = 0.001) with no remarkable side effects (P = 0.315). CONCLUSIONS: Adding atorvastatin to migraine with aura preventive regimen may help reduce the number of acute attacks and pain severity without causing considerable side effects and led to a better patient satisfaction. TRIAL REGISTRATION: IRCT20180106038242N1 . Registered: 7 February 2018.

Association of HLA-DR2-Related Haplotype (HLA-DRB5*01-DRB1*1501-DQB1*0602) in Patients with Multiple Sclerosis in Khuzestan Province.

OBJECTIVE: Multiple sclerosis (MS) is a partially heritable autoimmune disease. HLA-DR2 is the largest identified genetic risk factor for MS. The largest identified genetic risk factor is haplotype from the MHC class II HLA-DR2, which increases the disease risk. The HLA-DR2 distribution in MS patients has been confirmed, but contradictory outcomes have been found. Moreover, the HLA-DR2 effect on ethnicity and gender is unclear. There are no data regarding the HLA-DR2 (HLA-DRB1*1501-DRB5*01-DQB1*0602) association with MS in Khuzestan Province, Iran. This study aimed to investigate the association of HLA-DR2 with MS regarding both sex and ethnicity in this province. MATERIALS & METHODS: A total of 399 individuals were recruited. HLA typing was conducted using the polymerase chain reaction amplification with sequence-specific primers technology. The HLA-DR2 association with MS was analyzed, and also its probable association with gender, ethnicity, the expanded disability status scale (EDSS), and MS clinical course was examined using the Chi-square test. RESULTS: HLA-DRB5*01 - -DQB1*0602 - as the most common HLA haplotype was found in both patient and control groups. In contrast, the DRB5*01 + -DRB1*1501 + -DQB1*0602 - frequency was very low in the groups. It was observed that haplotypes had no association with MS susceptibility. Most of the haplotypes showed no association with ethnicity, sex, EDSS, and MS course except for the HLA-DRB5*01 + -DRB1*1501 + -DQB1*0602 - haplotype that was positively associated with EDSS steps 5 to 10 (p=0.014) and non-RRMS (p=0.023). CONCLUSION: There was no association between HLA-DR2 and MS susceptibility. However, the higher HLA-DRB5*01 + -DRB1*1501 + -DQB1*0602 - frequency may play a role in MS development. Also, HLA-DR2 did not increase significantly concerning clinical course, ethnicity, sex, and EDSS. This study further supports the importance of replication studies as susceptible loci that might differ in various ethnicities. Therefore, it is concluded that the association between HLA-DR2 and MS is more allelic than haplotypic in Khuzestan.

Prevalence of Sexual Dysfunction and Related Risk Factors in Men with Multiple Sclerosis in Iran: A Multicenter Study.

INTRODUCTION: Sexual dysfunction (SD) is a common complaint in patients with multiple sclerosis (MS). The aim of this study was to assess the prevalence of SD and its related risk factors in men with MS in Iran. METHODS: In this cross-sectional study, 320 men who had been diagnosed with MS according to the McDonald revised criteria were recruited from January to June 2019, from the north, south, east, west, and central parts of Iran. Patients were assessed using the Male Sexual Health Questionnaire (MSHQ), International Index of Erectile Function (IIEF), The Multiple Sclerosis Intimacy and Sexuality Questionnaire-(MSISQ 19), Sexual Quality of Life-Men (SQOL-M), and Standard General Health Questionnaire (GHQ). RESULTS: Sexual dysfunction, defined as total IIEF score ≤ 45 was present in 114 patients (35.6%). The results of univariate logistic regression showed that there were significant direct relations between age (OR 1.050, 95% CI 1.02-1.08), Expanded Disability Status Scale (EDSS) (OR 1.45, 95% CI 1.24-1.7), duration of MS (OR 1.005, 95% CI 1.002-1.009), MSISQ-19 (OR 1.103, 95% CI 1.078-1.128), GHQ (OR 1.04, 95% CI 1.03-1.06), SQOL-M (OR 0.930, 95% CI 0.914-0.947), smoking (OR 1.941, 95% CI 1.181-3.188), non-MS chronic disease (OR 1.91, 95% CI 1.20-3.04), having a main sexual partner (OR 2.56, 95% CI 1.32-4.94), and significant inverse relations between exercise (OR 0.584, 95% CI 0.364-0.936) and regular sexual activity (OR 0.241, 95% CI 0.15-0.40), with the prevalence of SD. The results of multiple logistic regression indicated that the age, MSISQ-19, and SQOL-M were the only independent predictive factors for SD in these patients. CONCLUSION: The prevalence of SD in men with MS in Iran is relatively high. These patients should be screened, diagnosed, and treated for SD and influencing factors.

Safety and efficacy of fingolimod in Iranian patients with relapsing-remitting multiple sclerosis: An open-label study.

BACKGROUND: Fingolimod was the first oral therapy approved for treating relapsing-remitting multiple sclerosis (RRMS) in 2010. This open-label study evaluated the safety and efficacy of fingolideR, 0.5 mg in Iranian MS patients during one-year follow-up. METHODS: A multicenter, open-label, longitudinal was designed to evaluate the safety and efficacy of fingolideR, 0.5 mg over a one-year follow-up period across 11 centers. The patients were visited by their neurologists every two months to evaluate possible adverse events and clinical disease activity considered by recording Kurtzke's Expanded Disability Status Scale (EDSS). RESULTS: A total of 252 patients with the mean treatment duration of 343±45.70 days were. 20 patients experienced adverse events (AEs) and serious adverse events (SAEs) such as resistant urinary tract infection (UTI), premature atrial contraction (PAC), skin allergic reaction, macular edema, chicken pox, zona, panic attacks, and exacerbations associated with steroids treatment, all of which led to FingolideR discontinuation. The mean EDSS decreased from (2.15±1.29, 95%CI: 1.99to2.32) at baseline to (1.85±1.22, 95%CI: 1.68to2.02) at 12th month (final visit) while a p-value revealed significant differences comparing baseline and final EDSS (p<0.001). Mean annualized relapse rate (ARR) of the patients in one year prior to the study was (0.006±0.016, 95%CI: 0.004to0.008) which changed to (0.005±0.016, 95%CI: 0.003to0.007) at the end of the study period. Patients with a 12-month period of fingolideR treatment experienced sustained ARR and disease progression (p<0.001). CONCLUSION: The obtained findings suggest that the administration of FingolideR, 0.5 mg (Fingolimod, Osvahpharma, Tehran, Iran) is safe and efficient for Iranian MS patients.