Multiple Sclerosis Journal - Experimental, Translational and Clinical最新文献

Background: Work ability index (WAI) is an instrument that measures work ability in workplace surveys and health examinations in occupational health and research. It has been used in different population groups. But research is limited among people with multiple sclerosis (PwMS).

Objective: To determine the factors associated with work ability among PwMS in Sweden.

Methods: A total of 4103 PwMS who answered a web-based survey were included in the analysis. Work ability was assessed using the work ability score (WAS) component of WAI. Univariable and multivariable linear regression analyses were performed to assess the association of sociodemographic, clinical, and self-reported health variables with WAS.

Results: Just over half of the PwMS reported good (37.0%) or excellent (16.3%) WAS. The overall mean WAS was 6.9 (standard deviation = 2.8). Health-related quality of life (R-squared = 31.6%), fatigue (28.3%), occupation (22.6%), and expanded disability status scale (EDSS) score (18.1%), explained the highest proportions of variation in WAS, individually. In the adjusted model, occupation, EDSS score, and fatigue had the strongest associations with WAS with significantly lower scores in those with no occupation, higher EDSS score, and severe fatigue levels.

Conclusion: Work ability among PwMS was lower than in the general population in Sweden. Occupation, EDSS score and fatigue were among the most important factors associated with work ability.

Background: In Denmark, specialized multiple sclerosis (MS) clinics offer free-of-charge treatment to people with MS. However, not all people with MS attend regular clinical follow-up.

Objective: To identify people with MS who do not attend Danish MS clinics and identify barriers to treatment.

Methods: The Danish Multiple Sclerosis Registry was linked to other national Danish registries with follow-up from 2000-2020. We used a time-dependent Cox regression to rank factors associated with low attendance to clinical follow-up visits based on the magnitude of hazard ratios (HRs).

Results: We included 10,175 adults with MS, of which 3862 (38%) had less than one visit annually. The five top-ranked factors that reduced the risk of visits occurring included never having received diseases modifying treatment (HR: 0.48; 95%CI: 0.46-0.49), been diagnosed with MS before 2009 (0.79; 0.78-0.81), association with MS center in an outer region of Denmark (0.82; 0.80-0.84), having progressive MS type (0.88; 0.86-0.91) and not having received symptomatic treatment at diagnosis (0.91; 0.89-0.93).

Conclusion: Our results highlight disease-specific and geographic inequalities in the management of people with MS in Denmark. Strategies to prevent this inequality, especially for people with progressive phenotypes and those who need supportive and non-medical treatment and care, should be implemented.

The prodromal features of multiple sclerosis (MS) are non-specific and are prevalent in the general population. Several studies indicate an increased use of healthcare resources by individuals with MS in the years preceding their diagnosis, suggesting a trend of deteriorating health prior to the clinical manifestation of MS. This study aimed to capture the possible associations of sick leave with the timing of the diagnosis of MS. Our findings suggest that sick leave with neurological diagnoses - excluding MS, and other diagnoses during the year before MS onset is associated with a shorter time to MS diagnosis.

Background: Cognitive dysfunction in multiple sclerosis (MS) occurs early. Locally adapted neuropsychological data from India in MS is scarce.

Objectives: We aimed to identify the pattern of cognitive impairment in relapsing MS (RMS) with mild disability using a regionally-adapted MS-specific cognitive battery.

Methodology: The study included 59 persons with MS (pwMS) with expanded disability status scale (EDSS)≤ 4 and 62 controls. The battery had 8 neuropsychological tests (Paced Auditory Serial Addition Test [PASAT], Symbol Digit Modalities Test [SDMT], Rey Auditory Verbal Learning Test [RAVLT], Brief Visuospatial Memory Test-Revised [BVMT-R], verbal fluency [VF], Judgement of Line Orientation Test [JOLOT], Wisconsin Card Sorting Test [WCST] and Trail Making Test-B [TMT-B]) with 11 measures. The scores were compared between the groups for pattern and associations of cognitive impairment.

Results: The pwMS cohort had 39 (66.1%) females; mean age of 32.56 (±8.17) years. Scores were significantly worse for pwMS in 10 of 11 tests (except JOLOT). Cohen's-d test showed the largest effect sizes for PASAT, SDMT, VF and TMT-B. Cognitive impairment (defined as ≥2 abnormal tests) were noted in 41 (69.5%) pwMS. Male sex was associated with cognitive impairment (p = 0.002).

Conclusions: In pwMS with mild disability, nearly two-thirds had cognitive abnormalities, predominantly involving processing speed, working memory, executive function, and VF.

Intermediate uveitis (IU) may be associated with multiple sclerosis (MS), with both conditions possibly sharing pathogenic mechanisms. Two patients presented with bilateral IU. Despite targeted uveitis treatment with corticosteroids and methotrexate, both had ongoing disease activity with symptoms, and fluorescein angiographic abnormalities. Both were subsequently identified to have radiologically isolated MS in the absence of clinical demyelination. Treatment with natalizumab in isolation, led to rapid and sustained resolution of uveitis, enabling discontinuation of other immunosuppression. This case series adds evidence supporting use of alpha-4 integrins in the treatment of MS-associated uveitis, in addition to its known high-efficacy in MS.

Background: There is heterogeneity of aerobic fitness (VO_2peak) changes with a standardized exercise training stimulus in the general population (i.e. some participants demonstrate improvements, others no change, and some a reduction in VO_2peak).

Objectives: This secondary, exploratory analysis of data examined the heterogeneity of VO_2peak responses and possible correlates among persons with progressive multiple sclerosis (PMS) from the CogEx trial.

Methods: CogEx was a multi-site, multi-arm, randomized, double-blinded, and sham-controlled trial undertaken by 11 sites in six different countries. Participants were randomized into one of four conditions with different combinations of exercise training and cognitive rehabilitation including respective sham conditions. The analysis focuses primarily on VO_2peak change for the pooled exercise training intervention conditions compared with the pooled sham exercise control conditions.

Results: Waterfall plots for change in VO_2peak suggested greater heterogeneity with exercise training than sham, and the proportions of difference in VO_2peak change (i.e. improvement/worsening) were significantly different between exercise training and sham conditions(p < 0.05). The multivariable analysis indicated that lower baseline VO_2peak (p < 0.001) was the only statistically significant correlate of increases in VO_2peak with exercise training.

Conclusion: Our results highlight the heterogeneity of change in VO_2peak with exercise training that is correlated with initial aerobic capacity in PMS, and such results may inform hypothesis testing in future clinical trials of exercise training.

Background: Individuals with neuromyelitis optica spectrum disorder (NMOSD) often suffer from severe, disabling, and treatment-refractory neuropathic pain. Transcutaneous electrical nerve stimulation (TENS) therapy is a non-invasive, pain-modifying device.

Objective: To determine whether TENS therapy is safe, tolerable, and effective for neuropathic pain in patients with NMOSD.

Methods: We conducted a four-week, randomized, double-blind, sham-controlled, remote trial of TENS in patients with NMOSD who have neuropathic pain, followed by a 12-week open-label extension period. The difference in the Numeric Rating Scale current pain scores between 0 weeks and 4 weeks was the primary outcome measure.

Results: Forty-six patients (23 per arm) were enrolled in this trial, of which 40 were included in the primary analysis (four in the intervention arm and two in the sham arm withdrew prior to assessment of the primary outcome). Both the sham and intervention arms demonstrated significant decreases in average pain, worst pain, and current pain rating between baseline and 4 weeks, but there was no significant difference between the two arms.

Conclusions: In conclusion, there was no demonstrated benefit of TENS over sham TENS treatment, however, both arms demonstrated significant decreases in reported pain between baseline and 4 weeks. This trial is registered with ClinicalTrials.gov, NCT04614454.

Background: Multiple sclerosis (MS) is an autoimmune condition characterized by inflammatory and neurodegenerative traits. Recently, DNA methylation has emerged as a promising field of investigation for elucidating dynamics characterizing MS development and progression.

Objectives: This study aimed to comprehensively investigate the role of epigenetics in MS by analyzing the methylation profiles from blood and brain tissues from public datasets.

Methods: Employing a meta-analytical framework for differential methylation analyses, the study extended beyond conventional analyses to explore additional dimensions of epigenetic regulation, including epigenetic drift, age acceleration, and rare epivariations.

Results: Results of the differential methylation analysis were in line with previously reported findings. No significant differences were observed in age acceleration or global epigenetic drift between MS cases and controls. However, upon closer analysis at the gene level, distinctive patterns of epigenetic drift emerged, particularly within genes implicated in neural biological functions.

Conclusions: These findings underscore the role of epigenetic modifications in shaping MS pathology. Furthermore, the study unveiled the exclusive presence of rare epivariations within the MS cases, some of which involved genes previously linked to MS or other autoimmune diseases. This highlights the potential significance of rare genetic aberrations in driving MS susceptibility and progression.

Background: Few studies have examined B cells among patients with anti-myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), including brain pathology.

Objective: To describe cases of tumefactive MOGAD with B-cell dominant central nervous system (CNS) infiltration.

Methods: In this study, we reviewed three cases with clinical and brain histopathological features with tumefactive MOGAD.

Results: Forty-nine cases of tumefactive brain lesions (TBL) between January 2003 and December 2023 were included; of these, seven had MOGAD. Three underwent a brain biopsy. B-cell dominant CNS infiltration was observed in two cases. In two cases with B-cell dominant CNS infiltration, symptoms included fever, headache, nausea, somnolence, and focal neurological deficits. Cerebrospinal fluid examination revealed both mild pleocytosis and negative oligoclonal IgG bands. Magnetic resonance imaging of the brain revealed large abnormal lesions extending from the basal ganglia to the parietotemporal lobe in both cases. These cases showed a good response to steroids; however, one case relapsed. Brain pathology showed demyelination and perivascular lymphocytic infiltration. One showed small vessel vasculitis. Deposition of the activated complement component was absent or rarely observed. Loss of MOG was observed in two cases.

Conclusion: MOGAD could exhibit B-cell dominant CNS infiltration and small vessel vasculitis. MOGAD should be considered in differential diagnosis of TBL.

Background: The prevalence of multiple sclerosis (MS) in Latin America is generally considered low to moderate. However, accurate data regarding MS epidemiology in Colombia is lacking.

Objective: This study aims to discuss the situation of MS in Colombia.

Results: Analysis reveals a lack of accurate data regarding MS epidemiology in Colombia, however, there have been notable improvements in diagnosis and ultimately leading to better access to treatment for MS patients. While ethnic diversity may potentially influence MS prevalence, there is currently no strong data supporting this claim. MS treatment in Colombia, focuses on early disease-modifying therapy, nevertheless, MS is considered an orphan disease in Colombia, contributing to MS patients not receiving comprehensive evaluation in MS centers. Regional efforts are ongoing to improve diagnostic access and access to treatment for MS patients.

Conclusion: Despite the challenges in accurately defining MS epidemiology in Colombia, an increase in neurological training, diagnostic capabilities, and access to treatment has been observed. However, the status of MS as an orphan disease in Colombia poses challenges to comprehensive care for affected individuals. Further studies are needed to elucidate risk factors and improve care conditions for MS patients in the region.