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Background: Cognitive impairment (CI) is common in people with MS (PwMS). Evidence is lacking for the self-reported CI's mediation effect on employment status and objective cognitive performance. Self-reported CI was found to be unreliable and seemed to be more associated with depression rather than formal cognitive performance. We hypothesized that the link between subjective and objective assessments of cognitive functions, mood, and employment status may be more complex in PwMS than previously reported., Objective: The aims of this study are the following: (Romero-Pinel et al., 2022) to determine whether employment status could affect performance in cognitive function testing and (Rao et al., 1991) whether their relationship may be mediated by self-reported CI; and (Deluca et al., 2013) to determine whether self-reported depression interacts with self-reported CI in influencing performance in various cognitive domains in PwMS., Methodology: A retrospective study was performed involving PwMS who completed the self-report Multiple Sclerosis Neuropsychological Questionnaire (MSNQ), Hospital Anxiety and Depression Scale-depression scale (HADS-D), Minimal Assessment of Cognitive Function in MS (MACFIMS) and had data regarding employment status. Included PwMS were classified as employed or unemployed. A structural equation modeling (SEM) approach was taken due to the advantage of examining multiple cognitive outcomes simultaneously while accounting for shared associations. First, a latent factor of memory and executive functioning modeled the error-free associations between both factors and a processing speed task (SDMT). Next, the model tested for the indirect effect of self-reported cognition (MSNQ) on employment status differences in each outcome (memory, speed, and executive functioning). Finally, we tested interactions between MSNQ and HADS-D on each of the outcomes., Results: We included 590 PwMS: 72.5% female, mean age 44.2 years (SD = 10.5), mean disease duration 8.6 years (SD 9.0). The majority (n = 455, 77.1%) had relapsing MS; 357 (60.5%) were employed. About half (n = 301, 51%) did not report CI on the MSNQ; of those, 213 (70.8%) were employed. The mean MSNQ for employed PwMS was 24.5 (SD = 10.7) and 29.8 (SD = 11.2) for unemployed PwMS. Employed PwMS had significantly better memory (β = .16, p < .05), executive functioning (β = .25, p < .05), and processing speed (β = .22, p < .05). MSNQ partially indirectly mediated the effect of employment status on memory (Δβ = .03, p < .05) and executive functioning (Δβ = .03, p < .05) and processing speed (Δβ = .04, p < .05), indicating that self-report CI partially explains the influence of employment status on these cognitive domains. The association between MSNQ with both memory and executive functioning was moderated by depression, meaning that in PwMS with high HADS-D scores, MSNQ was more strongly related to worse memory and executive functioning. The final model was an acceptable fit to the data (χ 2 (87) = 465.07, p < .05; CFI = .90, RMSEA = .08, 90% CI [.06, .09], SRMR = .05) explaining 41.20%, 38.50% and 33.40% of the variability in memory, executive functioning, and processing speed, respectively., Conclusion: Self-reported CI partially explains the associations between employment status and objective cognitive assessment in PwMS. Depression may moderate the relationship between self-reported cognitive assessment and objective cognitive performance. Thus, employment status and mood may guide the interpretation of self-reported CI., Competing Interests: Declaration of competing interest AE, YS, MB, JS: have no disclosures. CC: in the past 3 years, has served on advisory boards for: Biogen Idec, Alexion, EMD Serono. Novartis, Roche, Sanofi Genzyme; has received Investigator Initiated Grant Funds from: Biogen Idec, and has acted as site PI for multi-center trials funded by: Novartis, and Roche. JM: has in the past 3 years served on advisory boards for Biogen Idec, EMD Serono, Novartis, Roche; Received Investigator Initiated Grant Funds from Biogen Idec. SAM: in the past 3 years, has served on advisory boards for: Biogen Idec, Celgene, EMD Serono. Novartis, Roche, Sanofi Genzyme and Teva Neurosciences; has received Investigator Initiated Grant Funds from: Biogen Idec, Novartis, Roche and Sanofi Genzyme and has acted as site PI for multi-center trials funded by: AbbVie, Celgene, EMDSerono, Novartis, Roche and Sanofi Genzyme., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Performing routine brain magnetic resonance imaging (MRI) is widely accepted as the standard of care for disease monitoring in multiple sclerosis (MS), but the utility of performing routine spinal cord (SC) MRI for this purpose is still debatable., Objective: This study aimed to measure the frequency of new isolated cervical spinal cord lesions (CSLs) in people with MS (pwMS) undergoing routine brain and cervical SC-MRI for disease monitoring and determine the factors associated with the development of new CSLs and their prognostic value., Methods: We retrospectively identified 1576 pwMS who underwent follow-up 3T brain and cervical SC-MRI over a 9-month period. MRI was reviewed for the presence of new brain lesions (BLs) and CSLs. Clinical records were reviewed for interval relapses between sequential scans and subsequent clinical relapse and disability worsening after the follow-up MRI., Results: In 1285 pwMS (median interval: 13-14 months) who were clinically stable with respect to relapses, 73 (5.7%) had new CSLs, of which 49 (3.8%) had concomitant new BLs and 24 (1.9%) had new isolated CSLs only. New asymptomatic CSLs were associated with ⩾ 3 prior relapses ( p  = 0.04), no disease-modifying therapy (DMT) use ( p  = 0.048), and ⩾ 3 new BLs ( p  < 0.001); ⩾ 3 new BLs (OR: 7.11, 95% CI: 4.3-11.7, p  < 0.001) remained independently associated with new CSLs on multivariable analysis. Having new asymptomatic CSLs was not independently associated with subsequent relapse or disability worsening after the follow-up MRI (median follow-up time of 26 months)., Conclusion: Routine brain and cervical SC-MRI detected new isolated CSLs in only < 2% of clinically stable pwMS. Developing new asymptomatic CSLs was associated with concomitant new BLs and did not confer an independent increased risk of relapse or disability worsening. Performing SC-MRI may not be warranted for routine monitoring in most pwMS, and performing only brain MRI may be sufficient to capture the vast majority of clinically silent disease activity., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: T.R.U.L., S.P.K., S.S., A.I.E., A.J., and A.W.L. have nothing to disclose. J.O. holds the Waugh Family Chair in MS Research; has received research funding from the MS Society of Canada, the National MS Society, National Institutes of Health (NIH), Brain Canada, the Barford/Love MS Fund of St. Michael’s Hospital, Biogen Idec, Roche, and EMD Serono; and has received compensation for consulting or speaking from EMD Serono, Sanofi Genzyme, Biogen Idec, Novartis, Bristol Myers Squibb (BMS), and Roche. A.B. has received compensation for consulting or speaking from Roche and Novartis.

Background: Biotin may activate the acetyl-CoA-, 3-methylcrotonyl-CoA-, propionyl-CoA-, and pyruvate carboxylases to increase myelin repair and/or synthesis, and may enhance the production of adenosine triphosphate (ATP), which may be essential to prevent neurodegeneration. The purpose of this review was to determine the effectiveness and safety of high-dose biotin (HDB) in multiple sclerosis via a systematic review of randomized controlled trials., Methods: We searched the following electronic databases for relevant articles: MEDLINE, CENTRAL, EMBASE, Scopus, and ClinicalTrials.gov website until April 2021. We considered randomized clinical trials (RCTs) that involved adult patients diagnosed with any phenotype of multiple sclerosis that conforms with the McDonald 2010/2017 criteria or the Lublin 2014 criteria. We included studies employing high-dose biotin or "MD1003" administered orally for at least 300 mg/day and given for at least three months. The methodological quality assessment of the included studies was done using the Cochrane Risk of Bias (RoB) tool. The GRADE approach was used to assess the certainty of evidence [COE]., Results: Out of 366 records identified, three RCTs involving 889 individuals diagnosed with MS (830 participants had progressive MS (PMS); 59 had RRMS) were pooled for analyses. The overall female:male ratio was 1.16:1. All included trials used HDB as an adjunctive treatment. The risks of bias in the three studies were low across the domains. At 12 to 15 months, there is insufficient evidence that the HDB and placebo arms differed in terms of composite improvement of MS-related disability (relative risk (RR) 2.87; 95% CI 0.29-28.40; 2 trials; 796 participants; I 2  = 66%) [low COE], improvement in expanded disability status scale (IEDSS) (RR 2.27; 95% CI 0.25-20.98; 2 trials; 796 participants; I 2  = 63%) [low COE], and both IEDSS and improvement in 25-foot walk time (ITW25) (IEDSS-ITW25) (RR 0.58; 95% CI 0.17-2.00; 2 trials; 796 participants; I 2  = 13%) [moderate COE] among patients with PMS. Pooled data for ITW25 at 12 to 15 months yielded statistical significance (RR 2.06; 95% CI 1.04-4.09; 2 trials; 796 participants; I 2  = 0%) [moderate COE] favoring HDB among patients with PMS. At 12 to 15 months, no significant differences were found in terms of mean change in EDSS (MD -0.06; 95% CI -0.14-0.02; 2 studies; 796 participants; 889 participants; I 2  = 68%) among patients with PMS. Synthesized data on incidence of any AEs (RR 0.98; 95% CI 0.92-1.04; 3 trials; I 2  = 0%) [high COE] and any serious AEs (RR 0.98; 95% CI 0.77-1.24; 3 trials; 889 participants; I 2  = 0%) [moderate COE] were not significantly different between HDB and placebo groups. Out of 662 pooled patients in the HDB group, 31 patients (4.7%) were found to have laboratory test interference compared to zero event in the pooled placebo group [high COE]., Conclusions: A moderate certainty of evidence suggests a potential benefit in favor of HDB administered for 12 to 15 months in terms of ITW25 in patients with PMS. However, an important trade-off of this benefit is the high certainty of evidence suggesting an increased incidence of laboratory test interference when HDB is taken., (Copyright © 2021. Published by Elsevier B.V.)

Background: Fatigue is a debilitating symptom of multiple sclerosis (MS) affecting at least 75% of patients. Amantadine has been tested for MS-related fatigue treatment but efficacy and safety remain unclear. Materials & methods: We performed a systematic review and meta-analysis of qualified literatures searched until 30 April 2020. Results: A total of 11 clinical trials were included. The meta-analysis revealed improvement of MS-related fatigue with amantadine treatment using the patients' subjective responses and validated fatigue scales. Conclusion: Amantadine is the most studied drug that has shown improvement of MS-related fatigue, with mild side effects and good tolerability. Larger studies using a standard measurement for MS-related fatigue are recommended to improve the quality of evidence. Safety and efficacy on long-term use needs further investigation.

Background: The provision of adequate services for individuals living with multiple sclerosis (MS) is an important issue since MS has a chronic and debilitating course., Objective: We aimed to review the literature on health service delivery for individuals with MS in the Philippines and identify the gaps in adequate provision of healthcare in these individuals., Methods: We reviewed data from relevant local and international repositories on health service delivery for individuals with MS in the Philippines., Results: The epidemiology of MS in the Philippine setting remains unknown. Approximately 1 neurologist caters to 175,000 Filipinos aged 15 and above, and nearly half are practicing in the National Capital Region. Physical access to magnetic resonance imaging is severely limited at 0.8 MRI unit per million Filipinos. Household out-of-pocket payment and voluntary health care payment schemes contributed 53.9% and 12.2%, respectively, to the current health expenditures. The average monthly income of a Filipino household is only 519 USD which may not be enough to cover treatment of a single relapse let alone costly disease-modifying treatments., Conclusion: The Philippines faces challenges in terms of the availability of accurate epidemiologic information, resource allocation, access to services and provision of therapies for individuals with MS., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Scientific productivity in the Southeast Asian (SEA) region in the field of multiple sclerosis and neuromyelitis optica spectrum disorder (MS/ NMOSD) was hypothesized to be low in magnitude. The aim of this study was to determine and compare MS/ NMOSD research outputs among the SEA countries in terms of established bibliometric indices. The association between these productivity indices and relevant country-specific socioeconomic factors was also determined., Methods: A systematic review was conducted to include all relevant published MS/ NMOSD studies in the SEA indexed in MEDLINE, Embase, Scopus and CENTRAL from the inception of these databases to August 1, 2019. Quantity of research productivity was measured in terms of the total published documents. Quality of research impact was evaluated by assessing the study designs of the published reports, publications in journals with impact factor (IF) and PlumX Metrics (citations, usage, captures, mentions and social medias). Population size, gross domestic product (GDP) per capita, percentage (%) of GDP allocated to research and development (R&D), and the total number of neurologists reported in each country were obtained from reliable published data., Results: Out of 3,547 articles identified, only 142 articles fulfilled the eligibility criteria; therefore, the total number of publications in the SEA region related to MS/ NMOSD was deemed low in quantity. Most studies were cross-sectional and case reports/ series; hence, most studies offered low level of evidence. Since the aggregate scores in citations, usage, captures, mentions, and social medias in PlumX Metrics and publications in journals with IF were low, the overall quality of the published articles was considered low. Thailand (57 articles), Malaysia (40) and Singapore (29) contributed to the majority of publications on the topic-. GDP per capita was statistically correlated with usage. Percent GDP for R&D was positively correlated with total publications, usage, captures and social mediaindices., Conclusion: In conclusion, the scientific impact of MS/ NMOSD in the SEA was considered low in quantity and quality. This study must encourage researchers in the SEA to produce greater volumes of high-quality publications in this particular field and motivate governments to increase % GDP for R&D for the benefit of patients suffering fromthese rare and disabling conditions., Competing Interests: Declaration of Competing Interest The authors have nothing to disclose., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives The objectives of this study were to investigate the incidence of demyelinating disease (DD) among SpA patients and to identify risk factors that predict DD in this patient population. Methods Axial SpA (axSpA) and PsA patients were identified from a longitudinal cohort database. Each group was analysed according to the presence or absence of DD. Incidence rates (IRs) of DD were obtained, with competing risk analysis. Cox regression analysis (with Fine and Gray's method) was used to evaluate predictors of DD development. Results Among 2260 patients with follow-up data, we identified 18 DD events, corresponding to an average IR of 31 per 100 000 persons per year for SpA. The IR of DD at 20 years was higher in axSpA than in PsA (1.30% vs 0.13%, P  = 0.01). The risk factors retained in the best predictive model for DD development included ever- (vs never-) smoking [hazard ratio (HR) 2.918, 95% CI 1.037–8.214, P  = 0.0426], axSpA (vs PsA) (HR 8.790, 95% CI 1.242–62.182, P  = 0.0294) and presence (vs absence) of IBD (HR 5.698, 95% CI 2.083–15.589, P  = 0.0007). History of TNF-α inhibitor therapy was not a predictor of DD. Conclusion The overall incidence of DD in this SpA cohort was low. Incident DD was higher in axSpA than in PsA. A diagnosis of axSpA, the presence of IBD, and ever-smoking predicted the development of DD. History of TNF-α inhibitor use was not found to be a predictor of DD in this cohort. [ABSTRACT FROM AUTHOR]

Background: Performing routine brain magnetic resonance imaging (MRI) is widely accepted as the standard of care for disease monitoring in multiple sclerosis (MS), but the utility of performing routine spinal cord (SC) MRI for this purpose is still debatable. Objective: This study aimed to measure the frequency of new isolated cervical spinal cord lesions (CSLs) in people with MS (pwMS) undergoing routine brain and cervical SC-MRI for disease monitoring and determine the factors associated with the development of new CSLs and their prognostic value. Methods: We retrospectively identified 1576 pwMS who underwent follow-up 3T brain and cervical SC-MRI over a 9-month period. MRI was reviewed for the presence of new brain lesions (BLs) and CSLs. Clinical records were reviewed for interval relapses between sequential scans and subsequent clinical relapse and disability worsening after the follow-up MRI. Results: In 1285 pwMS (median interval: 13–14 months) who were clinically stable with respect to relapses, 73 (5.7%) had new CSLs, of which 49 (3.8%) had concomitant new BLs and 24 (1.9%) had new isolated CSLs only. New asymptomatic CSLs were associated with ⩾ 3 prior relapses (p = 0.04), no disease-modifying therapy (DMT) use (p = 0.048), and ⩾ 3 new BLs (p < 0.001); ⩾ 3 new BLs (OR: 7.11, 95% CI: 4.3–11.7, p < 0.001) remained independently associated with new CSLs on multivariable analysis. Having new asymptomatic CSLs was not independently associated with subsequent relapse or disability worsening after the follow-up MRI (median follow-up time of 26 months). Conclusion: Routine brain and cervical SC-MRI detected new isolated CSLs in only < 2% of clinically stable pwMS. Developing new asymptomatic CSLs was associated with concomitant new BLs and did not confer an independent increased risk of relapse or disability worsening. Performing SC-MRI may not be warranted for routine monitoring in most pwMS, and performing only brain MRI may be sufficient to capture the vast majority of clinically silent disease activity. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS), a disabling demyelinating disease of the central nervous system, is associated with cognitive impairment, spasticity, and fatigue. There are still no established guidelines on the management of MS-related sequela. Memantine has the potential to reduce glutamate toxicity, thereby reducing consequent cognitive impairment, spasticity, and fatigue. Objectives: This study aims to determine the efficacy and safety of memantine in preventing cognitive impairment, reducing spasticity and fatigue, and controlling disability in MS patients through a review of relevant randomized trials. Methods: MEDLINE, CENTRAL, Scopus, Embase, LILACS, ClinicalTrials.gov, and HERDIN were searched from inception to May 2020 for relevant trials. Results: The search yielded 203 articles; four studies were included in the analysis. Pooled evidence shows that memantine compared with placebo does not significantly improve PASAT, ASS, MFIS, and EDSS scores of patients with MS. Memantine is associated with mild adverse drug events such as dizziness, fatigue, and anxiety. Conclusion: There is not enough evidence to support the efficacy of memantine in preventing cognitive decline, controlling spasticity, reducing fatigue, and preventing disability. Future researches should consider the different MS subtypes, effect of co-administration of disease-modifying therapies, longer duration of administration, and more sensitive outcome measures to evaluate the potential benefit of memantine in MS. [ABSTRACT FROM AUTHOR]