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

Background: Comorbidities are a critical concern for clinicians in both the treatment and diagnosis of multiple sclerosis. Autoimmune diseases, including multiple sclerosis, often co-occur within individuals. However, most studies examining the incidence or prevalence of autoimmune diseases in persons with multiple sclerosis compared to healthy controls have used relatively small sample sets, with only a few being population-based.

Objectives: To analyze the co-occurrence of other autoimmune diseases in persons with multiple sclerosis and determine whether common genetic susceptibility factors contribute to the co-occurrence of autoimmune diseases.

Methods: We conducted a population-based study using administrative health records to include all residents of Piedmont, an Italian Region with about 4.3 million inhabitants, identifying individuals with multiple sclerosis and 14 other autoimmune diseases. For a subset of persons with multiple sclerosis with available genome-wide genotyping data, we investigated the influence of their genetic backgrounds using a polygenic risk score.

Results: The prevalence of all 14 tested autoimmune diseases was higher in persons with multiple sclerosis compared to those without multiple sclerosis. Furthermore, persons with multiple sclerosis with autoimmune disease comorbidities had a higher polygenic risk score compared to persons with multiple sclerosis without comorbidities.

Conclusion: Our findings confirm the co-occurrence of multiple sclerosis with several autoimmune diseases, and suggest that shared genetic susceptibility factors may influence this association.

Background and objectives: Cardiovascular diseases (CVD) and their risk factors supposedly occur frequently in patients with multiple sclerosis (pwMS). We investigated prevalence of comorbidity particularly CVD among pwMS.

Methods: Two cohorts from Tehran and Isfahan were investigated retrospectively with longitudinal follow up and were invited to participate prospectively with measurement of biomedical parameters including determination of metabolic syndrome (MetS), and insulin resistance (IR). The 10-year office-based Framingham risk score (FRS) was calculated.

Results: Out of 856 pwMS 329 (38.4%) had at least one comorbidity and 97 (11.3%) had > 2 diseases, i.e., multiple comorbidity. PwMS and comorbidity were older (p < 0.0001) and had higher age at MS onset (p < 0.0001) compared to the non-comorbidity group. The prevalence of comorbidity increased from 24.0% at age 15-29 years to 37.3% at 30-49 and to 52.6% at 50-76 years (p < 0.0001) and was associated with odds of EDSS ≥ 4. FRS was for men 7.1 (4.2, 10.5) and for women 2.0 (1.3, 3.4). Of 255 with prospective blood testing, 35 (13.7%) had MetS, and 106 (41.6%) had IR.

Conclusion: A high prevalence of comorbidity, associated with disability and high FRS was observed in pwMS. Our data suggest that MetS and IR occur frequently in this population.

Background: Patients with multiple sclerosis (PwMS) could suffer from frequent and disabling motor symptoms, including balance and mobility problems, spasticity, weakness and fatigue, with an impact on patients' quality of life. Current treatments have limited efficacy or significant side effects. The EXOPULSE Mollii Suit, a transcutaneous electrical nerve stimulation system, provides simultaneous stimulation to 40 muscle groups and may offer a therapeutic alternative.

Objectives: This study evaluated the effects of this device on balance, other motor symptoms and quality of life in PwMS.

Methods: A randomized, crossover, sham-controlled, double-blind study (phase 1) evaluated the effects of a 60-min single session of active versus sham stimulation. An open-label phase 2 evaluated the effects of stimulation over four weeks. Balance (Berg Balance Scale) was the primary outcome, with secondary measures including spasticity, mobility, pain, fatigue and quality of life.

Results: Thirty-two patients completed phase 1, and 30 completed phase 2. The intervention was well tolerated. Significant improvements in balance (p < 0.001), spasticity (p < 0.001) and fatigue (p = 0.007) were observed in phase 1. Phase 2 showed sustained improvements in balance, spasticity, mobility and quality of life (p < 0.05).

Conclusions: The EXOPULSE Molii Suit demonstrated significant benefits for motor symptoms, warranting further large-scale research into long-term effects.This clinical trial was prospectively registered on clinicaltrials.gov as 'EXOPULSE Mollii Suit, Motor Function & Multiple Sclerosis (EXOSEP)' (NCT06702137). https://clinicaltrials.gov/study/NCT06702137?term=NCT06702137&rank=1.

Background: The present review aimed to identify published studies that reported the validation of the Brief Cognitive Assessment for Multiple Sclerosis (BICAMS) in Latin America (LATAM).

Methods: To compile a comprehensive list of available validation studies, we performed a systematic review of the literature via an electronic search of PubMed and Web of Science via the keywords "Validation," "Brief Cognitive Assessment for Multiple Sclerosis," "BICAMS," and "Latin America."

Results: Twenty-seven sources of validation studies for the BICAMS were identified. Of the 27 citations identified, only four provide validation of the BICAMS in LATAM. These studies include a comparison of cognitive performance between multiple sclerosis (MS) patients and healthy controls (HCs) across all three BICAMS tests. Overall, the studies included a greater proportion of patients with RRMS and middle-aged adults and included participants with wide ranges of education levels.

Conclusion: We provide a detailed description of the BICAMS validation currently available for people living in LATAM. Although the validation of tests in diverse populations has gained interest in the field, there is still a need for more studies among people from LATAM countries.

Background: Dynamic contrast-enhanced magnetic resonance imaging is a promising biomarker allowing for in vivo quantification of blood-brain barrier permeability.

Objectives: To explore the relationship between blood-brain barrier permeability, optic neuritis disease severity, and multiple sclerosis conversion in optic neuritis.

Methods: Gjedde-Patlak models from dynamic contrast-enhanced magnetic resonance imaging were used to estimate blood-brain barrier permeability (K_i ) in 78 optic neuritis patients. The 2017 McDonald criteria were used to diagnose multiple sclerosis with a minimum follow-up time of 2 years.

Results: Normal-appearing white matter K_i correlated with the number of magnetic resonance imaging criteria for dissemination in space (Spearman's ρ = 0.3, p = 0.0074), but not with visual acuity, color vision, and inter-eye difference in retinal nerve fiber layer thickness. Normal-appearing white matter K_i did not differ between patients with and without oligoclonal bands (p = 0.067), but patients with brain contrast-enhancing lesions had higher normal-appearing white matter K_i than those without (p = 0.04). Early multiple sclerosis-converters diagnosed at optic neuritis onset (n = 36) had higher normal-appearing white matter K_i than non-converters (n = 29) (p = 0.01), but this was not the case for late multiple sclerosis-converters (n = 13) (p = 0.57). Normal-appearing white matter K_i did not significantly predict overall multiple sclerosis conversion (p = 0.068, AUC = 0.652).

Conclusions: Normal-appearing white matter K_i was associated with magnetic resonance imaging biomarkers of multiple sclerosis, but not with biomarkers of optic neuritis disease severity. Normal-appearing white matter K_i was increased at, but not before, the multiple sclerosis diagnosis.

Background: Cholesterol is an essential and major component of myelin. Brain cholesterol turnover in humans can be studied noninvasively by metabolic labeling of the brain-specific cholesterol metabolite, 24S-hydroxycholesterol (24-OHC), which is released into blood.

Objectives: We examined the effects on brain cholesterol turnover in healthy individuals and in multiple sclerosis (MS) following treatment with placebo or the remyelinating monoclonal antibody, rHIgM22, which binds to oligodendrocytes and myelin.

Methods: In vivo synthesis rates of brain cholesterol were measured by label incorporation and die-away of 24-OHC sampled from blood during and after heavy water (D₂O) intake in age- and sex-matched non-MS and clinically stable relapsing-remitting MS subjects.

Results: Incorporation and die-away of labeled 24-OHC revealed biphasic kinetics, with two kinetically distinct pools of brain cholesterol: a large, slow turnover pool and a smaller, metabolically more active pool of newly synthesized cholesterol. The latter showed significantly higher turnover rates in MS compared to non-MS subjects, which was significantly reduced in patients with MS treated with rHIgM22.

Conclusions: Plasma 24-OHC kinetics provide a minimally invasive biomarker of brain cholesterol metabolism and revealed differences between healthy and clinically stable MS subjects, with increased turnover of the metabolically active 24-OHC pool that normalized in response to rHIgM22 therapy.

Background and objectives: The genetic basis of adult-onset multiple sclerosis (MS) is well-studied, but less is known about pediatric-onset MS (pedMS), comprising approximately 5% of all MS onsets. Mendelian randomization (MR) studies have demonstrated evidence for a causal association between MS and both 25-hydroxyvitamin D [25(OH)D] serum levels and genetic variation related to vitamin D receptor (VDR) binding. The objective was to identify whether VDR binding variants (VDR-BVs) previously implicated in adult-onset MS were associated with pedMS using genetic instrumental variables (GIVs).

Methods: Using previously identified VDR-BVs to construct individual GIVs with two-sample MR, we investigated associations with pedMS in 725 cases and 592 controls of European ancestry from the US Network of Pediatric MS Centers. Associations between each VDR-BV and pedMS were estimated using logistic regression adjusting for the first three genome-wide principal components. A significant interaction between a VDR-BV and 25(OH)D GIV provided evidence for a causal association unbiased by pleiotropy.

Results: One VDR-BV, rs2531804, previously associated with adult-onset MS, was also significantly associated with pedMS after multiple testing correction.

Discussion: This study is the first to use VDR-BVs from previous MR studies to demonstrate causal differences in VDR binding at a locus contributing to pedMS susceptibility.

Background: Multiple sclerosis (MS) may have a major impact on the physical, social and psychological wellbeing of people with multiple sclerosis (pwMS) and their family members/partners.

Aim: To measure the impact of a person's MS on the quality of life of their family members/partner, and the associates of impact among family members, using a validated generic family-specific quality of life instrument, the Family Reported Outcome Measure (FROM-16).

Methods: An online cross-sectional study was conducted to recruit family members/partners of pwMS through UK patient support groups.

Results: A total of 219 family members/partners (mean age = 49.3 years, SD = 13.7; females = 55.3%) of pwMS (mean age = 50.1, SD = 12.5; females = 56.6%) completed the FROM-16. The FROM-16 mean total score was 16.9 (SD = 7.8), indicating 'a very large effect' on family members' quality of life. The increasing age of pwMS, being a male person with MS, and being a female carer were significant predictors of family impact. 50.7% of family members had FROM-16 scores ≥17. Spouses/partners (170/219) of pwMS reported a significant impact on their sex life compared to other relationships (p < 0.001).

Conclusion: MS substantially impacts the quality of life of family members/partners of pwMS, indicating a need to assess this impact routinely. The FROM-16 could be used to measure the MS family impact in routine practice to support family members appropriately and to include this impact in health economic appraisal and therapeutic clinical trials.

Background: Optical coherence tomography (OCT) allows evaluation of inter-eye differences (IEDs) in peri-papillary retinal nerve fiber layer (pRNFL) and macular ganglion cell-inner plexiform layer (GCIPL) thicknesses to identify unilateral optic nerve involvement (UONI), which is included in the 2024 revised McDonald diagnostic criteria for multiple sclerosis (MS).

Objectives: To evaluate the test-retest reliability of pRNFL and GCIPL thicknesses/IEDs in people with MS, other neurological disorders, and healthy controls using Cirrus HD-OCT.

Methods: 509 participants underwent Cirrus HD-OCT, acquiring two macular and optic disc scans per eye within each session. Scans meeting OSCAR-IB quality control criteria were included in final analyses (959 eyes), with no clinical/demographic exclusions (reflecting a real-world clinical setting). Reliability was assessed using coefficients of variation (COVs), intraclass correlation coefficients (ICCs), and Bland-Altman limits of agreement (LOA). IED consistency was evaluated using difference-in-differences (DiDs) of test-retest measurements.

Results: GCIPL demonstrated superior reliability (ICC: 0.998, COV: 0.40%, LOA: -1.29 to 1.35 μm) to pRNFL (ICC: 0.989, COV: 1.18%, LOA: -3.59 to 3.70 μm) thickness. Inter-eye absolute DiDs [pRNFL: 2.00 μm (standard deviation (SD) 1.73); GCIPL: 0.64 μm (SD 0.67)] were lower than IED thresholds proposed for identifying UONI.

Conclusions: The excellent reliability of GCIPL and pRNFL thicknesses/IEDs support OCT for identifying UONI to diagnose MS.

Background: Multiple sclerosis is a neurodegenerative and neuroinflammatory disease causing a variety of symptoms, involving physical and cognitive domains. Previous research has demonstrated that racial disparities are prevalent in multiple sclerosis neurological outcomes, with Black individuals facing worse disease outcomes than their White counterparts.

Objective: To examine the race- and place-based differences in experiences with multiple sclerosis care among Black and White participants.

Methods: Qualitative data were collected from 20 adults with multiple sclerosis during four focus groups and ten individual semi-structured interviews. Focus groups and interviews were audio-recorded, transcribed, and coded in NVivo. Thematic analysis was used to identify dominant themes.

Results: Thematic analysis resulted in the following themes: health care quality, health literacy, patient-provider communication, multiple sclerosis, place, and race. Similarities and differences between Black and White participants were identified that may be fruitful areas for intervention to reduce existing disparities.

Conclusions: Both Black and White participants described positive experiences they have had with their multiple sclerosis care. However, only Black participants discussed the role of health insurance and facing discrimination. Only White participants reported residing in an area with access to many providers.