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

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.

Background: One of the most disabling symptoms of patients with multiple sclerosis (MS) is spasticity which affects their quality of life. Nowadays, cannabinoids are used for spasticity control in patients with MS, while the efficacy and safety are not clearly understood. So, we designed this systematic review and meta-analysis to assess the efficacy of cannabinoids for controlling MS-related spasticity.

Methods: PubMed, Scopus, EMBASE, Web of Science, and Google Scholar were systematically searched by two independent researchers on 1 May 2023. They also searched gray literature (references of included studies, as well as conference abstracts).

Results: A literature search revealed 6552 records, 95 full-texts were evaluated, and finally, 31 studies remained for systematic review. Among included studies, six randomized trials were included. Nabiximols was the most commonly used medication for controlling MS-related spasticity. Mean Expanded Disability Status Scale ranged between 4.6 and 7. Most studies (17 studies) were done in Italy, followed by Germany (4 studies). The pooled standardized mean difference (SMD) of NRS (Numeric Rating Scale) (after-before) is estimated as -1.41 (95% confidence interval (CI): -1.65, -1.17) (I² = 97%, p < 0.001). The pooled standardized mean difference (SMD) of Ashworth (after-before) is estimated as -0.39 (95% CI: -0.72, -0.06) (I² = 69.9%, p = 0.005).

Conclusion: The results of this systematic review and meta-analysis showed that nabiximols was the most common cannabinoid which was used to control MS-related spasticity, and it was effective in controlling MS-related spasticity (significantly decreased SMD of NRS, and Ashworth after treatment).

Background: This meta-analysis aimed to assess the treatment effects of immunotherapies in subgroups of adults with clinically isolated syndrome or relapsing forms of multiple sclerosis (MS) and the effect of potential treatment effect modifiers (TEMs).

Methods: Phase 2 and 3 RCTs with a placebo comparator were analyzed. Risk of bias was assessed. Random-effects meta-analyses were conducted to summarize treatment effects within subgroups and differences in treatment effects between subgroups.

Results: Thirty-one studies were included. Age < 40 years was the strongest TEM for relapse rate across DMTs with a ratio of rate ratios (RRR) of 1.44 (95% CI 1.09-1.90; 7 studies). Disability progression was influenced by age (ratio of hazard ratios, RHR 1.59, 95% CI 1.11-2.29; 4 studies). Dichotomizing patients based on EDSS cut-offs (EDSS 2.0 and 3.0) also showed a significantly higher benefit for those less disabled for relapse rate (RRR 1.35, CI 1.03-1.76; 8 studies). Sex, baseline MRI parameters, previous immunotherapy, and clinical presentation showed no effect in this meta-analysis.

Conclusion: Age < 40 is a robust TEM for a lower relapse rate as well as less disability progression across six MS immunotherapies. Additionally, a lower baseline EDSS was predictive of the relapse rate.

Background: An increasing number of women with multiple sclerosis (wMS) are considering pregnancy. Prior studies suggest increased rate of elective cesarian sections (C-sections) in wMS.

Methods: The Canadian Multiple Sclerosis Pregnancy Study (CANPREG-MS) is a prospective study on pregnant wMS. This report shows comparisons between (i) CANPREG-MS wMS delivered by C-section and the general population and (ii) C-section and vaginal deliveries in this study cohort.

Results: CANPREG-MS has resulted in 170 deliveries with 63 by C-section. The proportion with C-sections in CANPREG-MS (37.1%) was significantly higher than that for the Canadian population (28%) (p = .0085). The majority (66.7%) of C-sections were not planned, and typically were performed for obstetrical indications. C-sections were performed at an earlier gestational age than vaginal deliveries, although birthweight did not differ by mode of delivery in wMS. MS relapses (3.2%) and pseudo-relapses (3.2%) were rare in the first month after C-section deliveries, regardless of disease modifying therapy decisions during gestation and postpartum.

Conclusions: C-sections were more common in wMS than the general population, but few were because of maternal MS. CANPREG-MS provides informative data for pregnancies in wMS with well-managed and relatively mild disease. This information is helpful to obstetrical and MS healthcare providers.

Background: Although healthcare practitioners (HCPs) are a valuable source of social support, research on support provided by neurologists to older persons with multiple sclerosis (pwMS) remains limited.

Objectives: To explore expectations of pwMS aged 55 years or older regarding MS care and to identify support types, met and unmet needs within their relationship with neurologists.

Methods: Utilizing a mixed-methods approach, we analyzed survey data from Swiss Multiple Sclerosis Registry participants. Quantitative data included Likert scales gauging the importance of various aspects of MS care for pwMS both in and out of neurological care. Qualitative data were derived from three open-ended questions, focusing on neurologist-provided support for pwMS in neurological care. Data underwent descriptive and deductive thematic analysis, using Cutrona and Suhr framework for coding social support.

Results: Among the 286 participants (median age 61.0 years, interquartile range (IQR) 57.0-66.0; median disease duration 23.5 years, IQR 15.0-31.0), 84.6% (N = 244) were under neurological care. Quantitative findings highlighted the significance of HCP expertise and consultation time. Qualitative analysis identified all social support domains in the neurologist-pwMS relationship, with informational support being most prevalent, followed by emotional support. Neurologists' expertise, availability, comprehensive advising, listening, and validation emerged as key themes. Unmet needs were relatively infrequent and concerned insufficient information on complementary medicine, empathy, and understanding of symptoms like fatigue.

Conclusions: Older pwMS see neurologists as adequate providers of comprehensive support and particularly value neurologists' sufficient availability, informational and emotional support. Areas for improvement include attention to complementary medicine and empathy.

Background: The development of personalized interventions aimed at coping with multiple sclerosis is enriched by the understanding of patients' representations of the illness.

Objective: The aim of this study was to investigate the association between patients' illness representations versus contextual factors (i.e. presence/absence and type of caregiver, engagement, frequency and type of rehabilitation), fatigue, pain, and neurological impairment.

Methods: Interviews of 28 patients were analysed through an automated text analysis procedure. After a systematic labelling procedure four illness representations were identified: daily life, search for meaning of the disease, relationship to people and the diagnosis, coping and physical growth.

Results: Findings showed that the representation of the relational aspects of the illness was associated with the caregiver's presence, while the representation related to coping and growth tended to be associated with participation in rehabilitation programs. Moreover, the representation related to daily life was associated with lower levels of fatigue compared to the representation related to coping and growth, and with higher levels of neurological impairment compared to the representations related to coping and growth and the relational aspects of the illness.

Conclusion: Exploring illness representations is a key step that can help health professionals to get an integrated perspective that could be useful in designing and calibrating interventions according to specific patient needs.