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• This study aimed to explore the sleep quality in MS patients. • Thirteen studies were included in this systematic review. • The limited available evidence suggests that subjective sleep quality is affected by MS. Sleep quality is individual satisfaction with the sleep experience and the Pittsburgh Sleep Quality Index (PSQI), one of the most reliable subjective measurements of sleep quality, assesses the quality of sleep over the previous month. This study aimed to explore the sleep quality in multiple sclerosis (MS) patients in comparison to healthy controls (HCs). Following the Joanna Briggs Institute (JBI) methods and PRISMA statement, a systematic search was conducted through PubMed, Web of Science, Scopus, and Embase online databases and studies that assessed the sleep quality based on the PSQI, in MS patients and HCs were included. The risk of bias in the included studies was assessed using the JBI critical appraisal tools and meta-analysis was conducted by the third version of Comprehensive Meta-Analysis (CMA3) software. Out of 1574 identified records, 13 studies were included. Regarding the PSQI scores, the difference was statistically significant between patients with MS and HCs (10 studies; I2:94.59%; Standard difference in means: 1.056; 95%CI: 0.758–1.372; p-value < 0.001). MS patients were found to have more prevalence of poor sleep quality (PSQI > 5); however, the difference was not statistically significant (4 studies; I2: 87.08%; odds ratio: 2.31;95% CIs: 0.82–6.35; p-value: 0.113). The limited available evidence suggests that subjective sleep quality is affected by MS and it should be considered by the clinicians for prevention of sleep-related symptoms such as depression and anxiety. Future well-designed prospective studies are needed to reach a comprehensive conclusion in this regard. This study was supported by the Student Research Committee, Tabriz University of Medical Sciences (Registration Code: 70999). [ABSTRACT FROM AUTHOR]

• Coenzyme Q10 (CoQ10) is a potent antioxidant. • CoQ10 may ameliorating oxidative stress and inflammation in multiple sclerosis (MS). • CoQ10 may have a positive therapeutic impact on fatigue, depression, and neurological symptoms in MS. Multiple Sclerosis (MS) is a chronic and progressive inflammatory disease of the central nervous system (CNS). Oxidative stress is a crucial mediator in multiple conditions, including the MS. Coenzyme Q10 (CoQ10) is a potent antioxidant, present in enzyme complexes of mitochondria, and involved in oxidative phosphorylation to produce adenosine triphosphate (ATP). The objective of this systematic review was to investigate the outcomes of CoQ10 supplementation in oxidative stress, inflammatory, and clinical status of patients with MS. Following the Cochrane and PRISMA methods, a comprehensive search was conducted in PubMed, Scopus, Embase, and Web of Science databases, and clinical studies that reported the outcomes of CoQ10 supplementation in MS patients, are included. The risk of bias was assessed using the revised Cochrane risk-of-bias tool for randomized trials (RoB2). The initial search yielded 237 articles, of which eight reports from six studies (total n = 195), including three RCTs, two semi-experimental studies, and one retrospective analysis were included. The effects of 2–3 months of CoQ10 supplementation on inflammatory factors, antioxidant enzyme system, and lipid peroxidation remain controversial in 200mg/day dose; however, 500mg/day of CoQ10 supplement can improve oxidative stress and inflammation, along with depression and fatigue amelioration in MS patients. This study concludes that CoQ10 might exert dose-dependent beneficial effects on ameliorating oxidative stress and inflammation in MS, and also sheds light on its possible utility in relieving clinical symptoms of MS; however, limitations of the evidence such as the small number of included studies, suggested future studies for clinical recommendations. The research protocol was approved and supported by the Student Research Committee, Tabriz University of Medical Sciences (grant number: 71910). This study was registered in International prospective register of systematic reviews (PROSPERO ID: CRD42023461877) [Display omitted] [ABSTRACT FROM AUTHOR]

The development of oral disease-modifying therapies (DMTs) like dimethyl fumarate (DMF) has shifted treatment preferences in relapsing–remitting multiple sclerosis (RRMS) due to their convenience and potential to improve adherence. Patient-reported outcomes (PROs) in MS provide crucial insights into treatment impact, capturing the patient's perspective on disease burden, symptom management, and overall quality of life. PROFIT was a phase 4, open-label, prospective, single-arm observational study following patients treated with DMF over 12 months. Outcomes were assessed at baseline, 6 months, and 12 months, focusing on changes in PRO scores and treatment satisfaction. A total of 419 RRMS patients were enrolled, with 305 completing the study. Paired t-test analysis was used to evaluate changes in satisfaction and clinical outcomes. Among 419 patients (72.8% female; mean age 34.0 ± 7.7 years), significant improvements were observed in treatment satisfaction across all TSQM-14 dimensions, including effectiveness (change: 13.01, p<0.001), side effects (change: 24.61, p<0.001), convenience (change: 35.21, p<0.001), and global satisfaction (change: 15.75, p<0.001). QoL improvements were reflected in the EQ-5D VAS score (change: 3.37, p=0.045). Sleep quality (PSQI) also improved significantly, with reductions in global sleep score (change: 1.6, p<0.001) and sleep disturbances (change: 0.33, p=0.003). WPAI-MS scores showed significant reductions in absenteeism and work impairment, while depression levels (BDI-7) improved at 12 months (change: 1.29, p=0.006). DMF treatment over 12 months demonstrated significant improvements in treatment satisfaction, QoL, sleep quality, and depression in RRMS patients. These findings suggest that DMF offers meaningful benefits for patient well-being, particularly for those transitioning from injectable therapies. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). Several findings show that cognitive impairment in the early stages of the disease may appear as the first symptom or MS. Cognitive disorders can affect up to 70% of patients and are present in 40-20% of patients in the early stages of the disease. Memory, processing speed, attention, visuospatial and executive unctions are the cognitive domains which are mostly impaired in MS patients. In this cross-sectional study, 124 MS patients who visited the outpatient neurology clinics of Tabriz University of Medical Sciences between 2022-2023 were included. CANTAB was used for cognitive evaluation of the patients. In addition to motor Screening Task (MOT), four nonverbal cognitive subtests from the CANTAB, paired-associate learning (PAL), rapid visual information processing (RVP), reaction time (RTI), and the Spatial Working Memory test (SWM) were used. Impaired functions in at least 3 domains were defined as cognitive Impairment. The statistical analysis was done through 23th version of SPSS. Among 124 MS patients with a median age of 31 (26.25 – 37.75) years old, 93 (75%) of them were female 49 (39.5%) of them were cognitively impaired. The disease phenotype was RRMS in 112 (90.3%) of patients. In terms of sex, there wasn't any significant difference between the two groups of cognitively impaired (females: 40 (81.6%)) and cognitively intact patients (females: 53 (70.7%)) (p-value: 0.16). there was a significant difference in age of patients between the two groups (cognitively impaired: 37 (24 – 44), cognitively not impaired: 28 (24 – 34.5), p-value<0.01). Also, the progressive form of the disease was more frequent in the cognitively impaired group (16.3% vs 5.3%, p-value: 0.04). we couldn't find statistically significant difference in terms of disease duration between the two groups of study (cognitively impaired: 120 (36 – 165) months, cognitively not impaired: 48 (21 – 108), p-value: 0.08). SWM was mostly impaired in patients (76 patients, 61.3%). MS patients with an older age and progressive form of the disease have more prevalence of neuropsychiatric dysfunctions, however, gender doesn't attect them. We couldn't find a relation between the disease duration and cognitive impairment in this study which can be due to the small sample size. [ABSTRACT FROM AUTHOR]

Cognitive dysfunction is prevailing among multiple sclerosis (MS) patients. This study was conducted following the Joanna Briggs Institute (JBI) Manual for Evidence Synthesis and PRISMA 2020 statement. A systematic search was performed in PubMed, Scopus, Web of Science, and Embase in October 2023, and updated via handsearching in March 2024. JBI's critical appraisal tools were utilized to scrutinize the risk of bias. Out of 297 screened records, four studies were eventually found to meet our inclusion criteria. A single-blind crossover trial (n=12) showed short-term caffeine abstinence increased errors on the Stroop cognitive test and also a retrospective cohort study (n=124) found higher coffee intake was associated with subjectively better concentration and attention in MS patients. A small pilot cohort study (n=63) reported better verbal learning and memory performance among MS patients with higher daily coffee consumption, however, a cross-sectional study (n=126) study did not find significant effects of coffee/caffeine intake on other cognitive test measures. Evidence indicates an association between caffeine and coffee consumption, and improved cognitive outcomes, which suggests a domain-specific cognitive effectiveness for this substance in MS. Considering the small number of examinations and great diversity in assessed outcomes, the findings of this study should translate to clinical practice with great notice. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a disabling disease of the central nervous system. Poor sleep quality is prevalent among MS patients. On the other side, impaired information process speed (IPS) is the predominant form of cognitive dysfunction in MS. This study followed the Joanna Briggs Institute's (JBI) and PRISMA guidelines. PubMed, Scopus, Embase, and Web of Science databases were searched and original studies delineating the relationship between sleep quality, based on the Pittsburgh Sleep Quality Index (PSQI) questionnaire, and auditory and/or visual IPS, based on Paced Auditory Serial Addition Test (PASAT) and/or Symbol Digit Modalities Test (SDMT) in MS patients were included. Two independent reviewers selected the articles based on predefined eligibility criteria and performed data extraction. The risk of bias was assessed using the JBI critical appraisal tools and quantitative synthesis was conducted using the correlation coefficients, using the fourth version of CMA software, with 95% confidence intervals (CIs) and 0.05 level of significance for p-value. Out of 1635 screened records, seven studies [1-7] (total sample size: 484) were included in this systematic review, and six studies were included in the meta-analysis. There was a considerable risk of bias in two of the included studies. Based on the quantitative synthesis; there was no significant correlation between PSQI and PASAT scores (6 studies; correlation coefficient: 0.090; 95% CI: -0.006 to 0.184; p-value: 0.065; heterogeneity: I2: 72.70%; p-value: 0.003). Also, there was no significant correlation between PSQI and SDMT scores (3 studies; correlation coefficient: -0.025; -0.164 to 0.114; p-value: 0.726; heterogeneity: I2: 62.91%; p-value: 0.067). The overall correlation between sleep quality and IPS was not significant (9 studies; correlation coefficient: 0.053; 95% CI: -0.026 to 0.132; p-value: 0.186; heterogeneity: I2: 68.60%; p-value: 0.001). Evidence did not support a significant correlation between self-reported sleep quality in one prior month and IPS in patients with MS, which can be due to the subjective assessment of sleep condition in the included studies. [ABSTRACT FROM AUTHOR]

• Lipids are considered to be associated with MS progression through different pathways. • Evidence suggested an association between serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) with cognitive outcomes. • This study's quantitative synthesis only revealed a correlation between TC and the MoCA scores. Cognitive impairment is highly prevalent in multiple sclerosis (MS) with poorly understood underlying mechanisms. Lipids are considered to be associated with MS progression through the inflammatory and oxidative stress pathways, brain atrophy, cellular signaling, and tissue physiology. In addition, serum lipids are proposed as a modifiable factor affecting the neuropsychiatric condition; therefore, this study aims to assess the association between serum lipid levels and cognitive outcomes in MS. This study was carried out following the PRISMA 2020 statement. A systematic search was conducted in PubMed, Scopus, Web of Science, and Embase in March 2023, and the Joanna Briggs Institute (JBI)'s critical appraisal tools were utilized for risk of bias (RoB) assessments in the included studies. The quantitative synthesis was performed with the comprehensive meta-analysis (CMA3) software. Out of 508 screened records, 7 studies were eventually found to meet our inclusion criteria. In two studies, the course of MS in the sample of the study was only Relapsing-Remitting MS (RRMS), whereas the other five studies' sample was a combination of different phenotypes. Studies utilized different scales such as Minimal Assessment of Cognitive Function in MS (MACFIMS), Brief International Cognitive Assessment for MS (BICAMS), Montreal Cognitive Assessment (MoCA), Brief Repeatable Battery of Neuropsychological Tests (BRB-N) for cognitive evaluations. Dealing with possible confounders such as age, disease duration and level of disability was the most common possible source of bias in the included studies. One study revealed an inverse relationship between serum levels of apolipoproteins (including ApoA-I, ApoB, and ApoB/ApoA-I) and Symbol Digit Modalities Test (SDMT) scores. Also, a correlation between 24S-hydroxycholesterol (24OHC) serum concentrations and SDMT score was reported in one study. The association between serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) and different aspects of cognitive function was reported in the studies; however, serum levels of high-density lipoprotein cholesterol (HDL) were not found to be associated. The quantitative synthesis revealed a significant correlation between TC and the MoCA scores (r =-0.238; 95 %CI: -0.366 to -0.100; p-value = 0.001); however, the correlation between TG levels and MoCA were not statistically significant (r:-0.070; 95 %CI: -0.209 to 0.072; p-value: 0.334). In addition, the mata-analyses were not associated with significant findings regarding the correlation between lipid profiles (including HDL, LDL, TG, and TC) and other cognitive assessment scales including SDMT, Brief Visuospatial Memory Test (BVMT), and California Verbal Learning Test (CVLT) (p-values>0.05). Available evidence suggested a link between TC and LDL with cognitive outcomes of MS patients which was not evident in our quantitative synthesis. The limited number of studies, high RoB, different cognitive assessment scales and reporting methods, and the cross-sectional design of the included studies, were the main limitations that alleviate the clinical significance of the findings of this study and suggested further investigations on this topic. The research protocol was approved and supported by the Student Research Committee, Tabriz University of Medical Sciences (grant number: 71,909). This study is registered in the international prospective register of systematic reviews (PROSPERO ID: CRD42023441625). [ABSTRACT FROM AUTHOR]

Highlights • MtDNA G15927A or G15928A variation is said to be associated with MS. • Using PCR-RFLP, we tested this association in an Iranian population. • We found no association between the mtDNA variation and MS. Abstract Background Modern genetics has offered a fresh perspective on the pathology of Multiple Sclerosis (MS). As mitochondrial DNA (mtDNA) variations are held to be potential contributors to the complex pathobiology of MS, the present study tests the claim that mtDNA G15927A or G15928A variations, or both, are associated with MS in an Iranian population. Materials and methods Following DNA extraction from blood samples of 100 subjects with relapsing-remitting MS, and 100 healthy unrelated control subjects, PCR-RFLP analyses was carried out by HpaII restriction enzyme reaction. Electrophoresis was then performed with 3% Agarose gel. As the restriction enzyme did not differentiate between two neighboring nucleotide positions (G15927A and G15928A), all PCR products with a variant allele were sequenced to determine the exact position of the variation. Results The MtDNA G15927A or G15928A variations were observed in 11 of all 100 cases of MS (11%) and in 7 of 100 healthy control subjects (7%) (P = 0.3, OR = 1.6, 95% CI = 0.5–5.2). Having sequenced all the PCR products with the variant allele (11 cases and 7 controls), the mtDNA G15927A variation was found in one of the 100 cases (1%) and 3 of 100 controls (3%) (P = 0.3, OR = 0.3, 95% CI = 0.0–4.1). Therefore, the mtDNA G15928A variation was present in 10 of the 100 cases (10%) and in 4 of 100 controls (4%) (P = 0.09, OR = 2.6, 95% CI = 0.7–12.0). Conclusion Neither mtDNA variation, G15927A or G15928A, was associated with MS in the studied Iranian population. There was a non-significant association of the G15927A and the G15928A variations separately with MS. [ABSTRACT FROM AUTHOR]

Lower urinary tract symptoms (LUTS) is prevalent among patients with multiple sclerosis (MS). This study was conducted following the PRISMA statement. Systematic review studies which reported the efficacy and/or safety of a method for LUTS in MS are considered for inclusion in this study. A systematic search was conducted in PubMed, Scopus, Embase, Web of Science, and Cochrane databases with ("Multiple Sclerosis") AND (bladder OR urine) AND ("systematic review") keywords in March 2023. The risk of bias was assessed using the Joanna Briggs Institute (JBI) critical appraisal checklist for systematic reviews. Out of 348 results of database searches, 31 systematic reviews were included in this umbrella review. There is little evidence that reported appropriate efficacy and safety for alpha-blockers (indoramin, phenoxybenzamine, and tamsulosin), anticholinergics, desmopressin, intravesical vanilloids, mirabegron, stem cell therapies, neurotoxin treatments, cannabinoids, transcranial magnetic stimulation, and craniosacral therapy, and catheterization. In addition, peripheral nerve stimulations (sacral neuromodulation, spinal cord stimulation, tibial nerve stimulation) and pelvic floor muscle training are also found to be effective and safe in MS patients. Although, a high prevalence of LUTS in MS patients, there is a lack of well-designed randomized controlled trials (RCTs) regarding the management of MS-related LUTS, which makes evidence inconclusive. There is a need for future multi-center studies on this topic. [ABSTRACT FROM AUTHOR]

Multiple Sclerosis (MS) is a neuroinflammatory disease with an autoimmune etiology. Cognitive impairment is one of the most prevalent symptoms of MS which affect nearly 40% to 70% of patients. Apolipoprotein E (ApoE) genotype is known to have a significant association with cognitive disorders. The E4 allele of ApoE has shown a significant relation with the increased risk of Alzheimer's Disease (AD) and has been detected in 40–80% of patients with AD. Following the PRISMA statement, a systematic search was conducted though Medline via PubMed, Scopus, and ISI web of science and studies which assessed the association between ApoE and cognitive impairment based on the Brief Visuospatial Memory Test - Revised (BVMT-R), the California Verbal Learning Test- II (CVLT-II), and the Delis-Kaplan Executive Function System (DKFES) tests, in MS patients included in this study. Risk of bias was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools and the meta-analysis was conducted with Comprehensive Meta-Analysis (CMA.2) software. Out of 224 identified records, 16 records were screened in the title/abstract stage and finally, 3 studies were included. Considering a low risk of bias in these 3 studies, evaluating the cognitive impairment in MS patients showed that, based on BVMT-R (OR: 1.59, 95% CI: 0.88 - 2.86, p=0.12), CVLT-II (OR: 1.59. 95% CI: 0.84 - 3,p=0.15) and DKEFS (OR: 1.54, 95% CI: 0.66 - 3.59, p=0.32) tests, ApoE4 allele doesn't have a significant role in cognitive impairment of MS patients. ApoE4 doesn't have a specific association with cognitive impairment in MS patients. [ABSTRACT FROM AUTHOR]

The development of oral treatments for relapsing–remitting multiple sclerosis (RRMS) may alter patient satisfaction and quality of life (QoL). Additionally, patient-reported outcomes (PRO) offer a comprehensive assessment of the RRMS disease and its treatment. PROFIT is a phase 4, open-label, prospective single-arm (treatment with DMF), 12-month observational study was applied. Primary endpoints were evaluated at baseline and month 6 of follow-up including the mean changes in PRO score in terms of Qol, depression, productivity, sleep disorders in naïve and switchers, and the mean changes in treatment satisfaction in switchers. To achieve the end point, enrolled patients were asked to complete the Treatment Satisfaction Questionnaire for Medication-14 (TSQM-14), the European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3L), the Beck's Depression Inventory-7 (BDI-7), the Work Productivity and Activity Impairment Questionnaire: Multiple Sclerosis (WPAI-MS), and the Pittsburgh Sleep Quality Index (PSQI). Factors associated with the mentioned questionnaires and scores were evaluated using paired t-test analysis. Four Hundred and Ten patients (79.5% females and 20.5% male, mean age 34.0 ± 7.7 years) receiving DMF were recruited of which 340 (82.9%) completed the study. No correlation existed between drop rate (17.1%) and age, gender, education and history of treatment (naive or switcher). Patient satisfaction improved from baseline to month 6 in all dimension including TSQM effectiveness (change: -10.94, 95% CI: -17.06 to -4.82, p<0.001), TSQM side effect (change: -6.54, 95% CI: -10.40 to -2.68, p=0.001), TSQM Convenience (change: -34.40, 95% CI: -40.44 to -28.36, p<0.001) and TSQM Global Satisfaction (change: -13.64, 95% CI: -18.14 to -9.13, p<0.001). Additionally, EQ-5D-3L VAS satisfaction improvement was noted (change: -2.87, 95% CI: -4.86 to -0.88, p=0.005). Regarding PSQI, significant improvement including 0.16 change in the sleep quality score (95% CI: 0.05-0.28, p=0.007) and 99.0 change in PSQI Global score were reported. In terms of WPAI-MS, from baseline to month 6, significant reduction was reported. The 6-month treatment showed significant improvements in various dimensions of TSQM, including effectiveness, side effects, convenience, and global satisfaction. In addition, sleep quality and work productivity were increased. These data suggest potential benefits in the DMF treatment in MS patients, concerning their work and activity functionality. [ABSTRACT FROM AUTHOR]

• In this systematic review and meta-analysis, we collected the current evidence to evaluate the association between the ApoE genotype and the cognitive outcomes in patients with MS. • 13 studies were included in our systematic review, and 5 of them were included in the quantitative synthesize. • ApoE4 may have a domain-specific association with cognitive impairment in MS patients; so that ApoE4 patients had more delayed responses to stimuli, but the rate of impaired visuospatial perception is lower in these patients. • There is a doubt about the clinical significance of the association between ApoE and cognitive outcomes of MS patients. Multiple sclerosis (MS) is a neuroinflammatory disorder commonly seen in young female adults. Cognitive impairment is one of the widespread symptoms of MS. In recent years multiple studies sought the possible risk factors for MS-related cognitive deficit. Apolipoprotein E (ApoE) genotype is one of the genetic factors which correlated significantly with cognitive status and it is a well-known risk factor for Alzheimer's Disease. In this systematic review and meta-analysis, we collected the current evidence to evaluate the association between the ApoE genotype and the cognitive outcomes in patients with MS. Results of searches through Medline via PubMed, Scopus, and ISI web of science, as well as hand searching, were screened in the title/abstract and full-text stages. English observational studies in which the association between ApoE and cognitive outcomes, in patients with MS were included in this systematic review. Animal studies, conference abstracts, reviews, clinical trials, case reports, letters and withdrawn studies, were not included. Risk of bias was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools and the meta-analysis was conducted with Comprehensive Meta-Analysis (CMA.2) software. The numbers of patients with impairment in both ApoE4+ and ApoE4- groups were utilized for the calculation of the odds ratios (ORs) with 95% confidence intervals (CI) and a 0.05 level of significance for p-value. Out of 224 results of searching, 13 studies met the eligibility criteria and were included in our systematic review, and 5 of them were included in the quantitative synthesis. Eleven studies assessed the cognitive status of patients with MS in two groups of ApoE4+ and ApoE4- while 2 rests, reported the rate of ApoE4+ patients in cognitively impaired and non-impaired groups. The phenotype of MS was only Relapsing-remitting multiple sclerosis (RRMS) in 3 studies and in the other 10 studies, it was a mixture of RRMS, clinically isolated syndrome (CIS), and progressive MS. Most of the reports did not find a significant association between ApoE genotype and cognitive outcomes in patients with MS. Contrary to the expectations, patients in ApoE4- group were more likely to have impairment in Judgment of Line Orientation (JLO) (OR: 0.405; 95% CI: 0.173 to 0.949, p-value:0.038), while ApoE4+ patients had more rate of impairment in SRT (OR:1.901; 95%CI: 1.237 to 2.920; p-value:0.003). Appropriate identifying and dealing with cofounding factors were the most common source of bias in our included studies. ApoE may have a domain-specific association with cognitive impairment in MS patients. ApoE4 patients had more delayed responses to stimuli, but the rate of impaired visuospatial perception is lower in these patients. Based on the current evidence, there is a doubt about the clinical significance of this association. [ABSTRACT FROM AUTHOR]

• Oxidative stress (OXS) is a major basis of the pathogenesis of MS. • Neither endogenous antioxidant factors including catalase activity (CAT), glutathione peroxidase 1 and 2 (GPX1, GPX2), reduced glutathione (GSH), total antioxidant capacity (TAC), and superoxide dismutase (SOD) nor malondialdehyde (MDA), as an OXS biomarker, are associated with the cognitive function or physical disability in MS patients. • The level of CAT and TAC in male MS patients is higher than in females. Type of MS is associated with levels of GPX1, 2, and SOD. Multiple sclerosis (MS) is the most common non-traumatic cause of disability in younger adults. MS can be presented with a wide range of symptoms such as cognitive impairment (CI). Oxidative stress (OXS) is a major basis of the pathogenesis of MS. There is a positive correlation between OXS factors and the progression of the disease in MS patients. There are limited studies regarding the role of OXS in MS-related CI. In this study, as an exploratory analysis, we assess the role of endogenous antioxidants and OXS factors in cognitive function, the severity of disability due to MS, and demographic findings in a sample of MS patients. Adult (>18 years old) patients with a definite diagnosis of MS based on 2017 revised MacDonald criteria were included in this study. The neurophysiological assessment was conducted, using the validated Persian version of minimal assessment of cognitive function in multiple sclerosis (MACFIMS) battery, which is composed of seven different tests. Based on the structure of the battery, CI was defined as a failure in at least two different components of the MACFIMS battery. The patients were separated into two groups of CI and non-CI. Examined antioxidant factors included catalase Activity (CAT), Glutathione Peroxidase 1 (GPX1), Glutathione Peroxidase 2 (GPX2), Reduced Glutathione (GSH), Superoxide Dismutase (SOD), and serum total antioxidant capacity (TAC). Malondialdehyde (MDA) was also measured as an OXS marker. 71 patients were involved in this study. The type of MS was relapsing-remitting MS (RRMS) in 80.28% of the participants. Disease duration (P <0.01), type of MS (p <0.01), and EDSS score (p <0.01) were different between CI and non-CI groups, but there were not any significant differences in CAT (p = 0.80), GPX1 (p = 0.71), GPX2 (p = 0.41), GSH (p = 0.96), TAC (p = 0.13), SOD (p = 0.37), and MDA (p = 0.82). A significant difference between RRMS and progressive MS (PMS) patients in the levels of GPX1 (p = 0.01), GPX2 (p = 0.01), and SOD (p = 0.01) was observed. Also, we found higher circulatory levels of CAT (p = 0.02) and TAC (p <0.01) in male MS patients. We found significant correlations between aging and CAT (R = 0.28; p = 0.01), GPX1 (R = 0.36; p <0.01), GPX2 (R = 0.34; p <0.01), and SOD (R = 0.40; p <0.01). EDSS, the duration of the disease, relapse rate, and the number of impaired cognitive tasks were not correlated with any of investigated OXS or antioxidant factors (p >0.05). In terms of a detailed investigation of associations between MACFIMS battery components and levels of OXS and antioxidant factors, there were no significant relations in this regard (p >0.05). Based on the logistic regression multivariate analysis, only disease duration (p = 0.03) and GPX1 (p = 0.01) were independently associated with CI in MS patients in our sample. The circulatory levels of GPX1, GPX2, and SOD are significantly different between RRMS and PMS patients. Neither endogenous antioxidants nor MDA, as an OXS biomarker, are associated with the cognitive function or level of physical disability in MS patients. Limitations of this study suggest a need for future studies in a larger sample of MS patients. [ABSTRACT FROM AUTHOR]

• The prevalence of MS in East-Azerbaijan was 75.72 by the end of 2017, so northwest of Iran is located in the high prevalence of the MS region in Asia. • The age group of 25-29 with the prevalence of 148.8 was the most involved age. • There is significant increment in MS annual incidence especially in women. • The positive family history of MS was 13.9%. Incidence and prevalence of multiple sclerosis (MS) is postulated to be rising in recent decades. Therefore, updating and completing the information of patients is essential, especially in high population areas. East-Azerbaijan is the largest and most populous province in the northwest of Iran. This study aimed to determine the prevalence and annual incidence of MS from 2008 to 2017 in East-Azerbaijan. We evaluated the data of all patients who had registered at the MS center in the university hospital. The data include nearly all MS patients in the East-Azerbaijan region, because it is the only referral site in the area. All of the reported rates were calculated in 100,000 of the total population. By the end of 2017, the number of MS patients was 2995 (residing in the, with 769 (25.67%) men and 2226 (74.32%) women. The prevalence rate was 75.72/100,000 (95 % CI: 73.06-78.48), 38.2 in men (95% CI: 35.5-41.0), and 114.61 for women (95% CI: 109.9-119.4), with a female to male (F/M) ratio of 3:1. The mean annual incidence rate was 7.63/100,000 (95% CI: 5.6-9.3), and this rate was higher in women than men. During the nine years, the incidence rate increased. The patients' mean age was 32.33 ± 8.92, with a peak prevalence in 25-29 years for both genders. In this study, 13.9% of patients had a positive MS family history. This study showed a high prevalence of MS in the region. There is a significant increase in the incidence of MS during the nine years in East-Azerbaijan. The increment of incidence was more prominent in women. Also, considering the increasing incidence rate, it is concluded that the risk of MS is increasing in this region. [ABSTRACT FROM AUTHOR]

• In about 5% of cases, Multiple sclerosis (MS) can be diagnosed at ages above 50 years old. Although the proportion of females is still more than males in Late-onset multiple sclerosis (LOMS); but there is a trend to increase in male cases with aging. • There is an increasing concern of a more progressive form of MS in LOMS cases. Also, we found a 65.00% proportion of spinal involvements in LOMS. • The most prevalent first disease presentation of LOMS is motor dysfunction followed by sensory problems, visual symptoms, and brainstem dysfunctions. • Understanding the proportion and clinical features of LOMS will help clinicians with the diagnosis of MS in this age group and prevention of wrong management plans and complications in these patients. Multiple sclerosis (MS) commonly affects young adults at the ages 20 to 40 years old, but it can onset at each age. Late-onset multiple sclerosis (LOMS) is defined as symptoms initiating after the age of 50. Misdiagnosis and a remarkable gap in diagnosis of LOMS is a challenge of the elderly population so in this article we described the proportion of LOMS and the clinical features and phenotype of the disease in this age group. After registration of the study protocol, an electronic search was performed in 3 databases and for full coverage of the published studies, we also checked the references of each related article. Two independent researchers screened the records in title/abstract and full-text stages and extracted the data using a data extraction table. The risk of bias was assessed using Joanna Briggs Institute checklist and meta-analysis was conducted by CMA 2. Only the studies with 50 years old cut-off and using McDonald or Poser diagnostic criteria were included in the meta-analysis. After removing duplicated studies, out of 733 results of electronic and hand searching, 31 studies met our inclusion criteria for the systematic review, and 11 of them were included in the quantitative synthesis. With different cut-offs and diagnostic methods 1.1% to 21.3% proportion of LOMS, has been reported in the studies. Meta-analysis reached a 5.01% (95% CI: 3.78% to 6.57%), proportion of LOMS in total MS cases. The female cases were more than males (range between 57.7% to 70.2%) and 64.46% (95% CI: 61.94% to 66.91%) proportion of females has been found in this study. 65.00% (95% CI: 44.71% to 81.02%) proportion of spinal cord involvements and 49.80% (95% CI: 39.28% to 60.24%) proportion of relapsing-remitting multiple sclerosis (RRMS) was also observed in LOMS cases. In 4 of included studies, the progressive form was the predominant phenotype. The most prevalent first disease presentation of LOMS was motor dysfunction (ranges between 100% to 35.4%) followed by sensory problems (ranges between 94% to 5%), visual symptoms (ranges between 22.9% to 5%), and brainstem dysfunction (ranges between 25% to 12.3%). The proportion of positive oligoclonal band (OCB), was varied from 46% to 98% in different studies and positive immunoglobulin G (IgG) index also was seen in 45.04% and 66% of the patients. 2.2% - 12.5% of the LOMS cases had a positive family history. In about 5% of cases, MS can be diagnosed at ages above 50 years old. There is an increasing concern of a more progressive form of MS in LOMS cases. Unlike the adult-onset MS, the first presentation of LOMS is usually motor dysfunction. Understanding the proportion and clinical features of LOMS will help clinicians with the diagnosis of MS in this age group and prevention of wrong management plans and complications in these patients. Although the proportion of females is still more than males in LOMS cases; but there is a trend to increase in male cases with aging. [ABSTRACT FROM AUTHOR]

• SDMT, PASAT, COWAT, and CVLT are the most frequently used tasks in cognitive evaluations of MS patients. • Acetylcholine esterase inhibitors, CNS stimulants, fampridine, and herbal remedies are frequently reported therapeutic categories in MS studies. • The currently proposed therapeutic agents have no beneficial effects on cognitive impairments in MS patients. • Fampridine has slight beneficial effects on improvement of SDMT task outcomes in MS patients. Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) commonly complicated by cognitive impairment. Unfortunately, no medical therapy has been proved to improve cognitive problems in these patients. This meta-analysis investigated the effectiveness of different categories of drugs on the minimal assessment of cognitive function in MS (MACFIMS)-related tasks outcome in MS patients. To this end, a systematic evaluation was conducted using PubMed, Google Scholar, and Scopus databases. Among a total of 128 publications, 31 studies met our inclusion criteria, and 22 included in the meta-analysis. We found that symbol digit modalities test (SDMT), paced auditory serial addition test (PASAT), controlled oral word association test (COWAT), and California verbal learning test (CVLT) were the most frequently reported tasks in included studies. The frequently reported drugs were classified into five main groups of acetylcholine esterase inhibitors, CNS stimulants, fampridine, herbal remedies, and miscellaneous. Overall heterogeneity of the studies was modest. The treatments did not affect cognitive function in any of the tasks (p >0.05). However, in subgroup analysis, we found significant improvement in SDMT task outecomes after treatment by fampridine (0.283 SMD, 95%CI, 0.015 to 0.550, p = 0.039, I2=11.7%). Our meta-analysis highlighted that the currently proposed therapeutic agents had no beneficial effects on the alleviation of MS-induced cognitive impairment. [ABSTRACT FROM AUTHOR]

• CANTAB can discriminate cognitively impaired from cognitively normal patients in MS. • The optimal threshold of CANTAB tasks for detection of cognitive impairment was reported. • MACFIMS and CANTAB might be interchangeably used in detection of cognitive impairment. We determined how the Cambridge Neuropsychological Test Automated Battery (CANTAB) compared to the Minimal Assessment of Cognitive Function in multiple sclerosis (MACFIMS) in terms of sensitivity, specificity, and predictive values in detecting cognitive impairment in multiple sclerosis (MS) patients. Sixty MS patients were recruited, 2 of whom were lost to follow-up. On the first day of the neuropsychological examination, the standard MACFIMS battery and the day after, the CANTAB (paired-associate learning (PAL), reaction time (RTI), rapid visual information processing (RVP), and spatial working memory tasks (SWM)) were completed by the patients. The sensitivity, specificity, and predictive values of the CANTAB in the differentiation of cognitively impaired (CI) patients from not cognitively impaired (NCI) ones were compared with those of the MACFIMS battery using appropriate statistical tests. Fifty-eight patients were categorized into two groups of CI (n=16 (27.58%)) and NCI (n=42 (72.41%)) based on the MACFIMS battery standard criteria. The best reporter indices and their cut-off scores for differentiation of CI from NCI patients in each task of the CANTAB were "total errors=13" for PAL, "between errors=26" for SWM, "five-choice reaction time=368.57" for RTI, and "mean latency=522.14" for RVP. The optimal cut-off point for distinguishing CI from NCI in the CANTAB was found to be an impaired function in 3 or more tasks [(AUC (95% CI): 0.97 (0.94–1.00); p<0.001)]. Accordingly, 36.20% of the patients were CI based on the CANTAB criteria. The inter-test agreement (CANTAB and MACFIMS batteries) was found to be the highest (Cohen's κ (95% CI): 0.80 (0.64–0.96)). Results confirm that the CANTAB can discriminate CI from NCI MS patients with high accuracy, and its results are comparable to those of the MACFIMS battery; thus, they might be interchangeably used in the clinical practice. [ABSTRACT FROM AUTHOR]