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

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.

Background: This study aimed to evaluate the impact of ellagic acid (EA) on fatigue, depression, and anxiety in patients with multiple sclerosis (MS) who have moderate disability.

Methods: A triple-blind, placebo-controlled clinical trial was conducted. Fifty-eight MS patients were randomly allocated to receive EA or placebo. Measurements of fatigue, depression, and anxiety were taken at the beginning and end of the study. Data analysis was performed via SPSS.

Results: Significant improvements were observed in the EA group across several measures: the State-Trait Anxiety Inventory (STAI), the Quick Inventory of Depressive Symptomatology (QIDS), the Hospital Anxiety and Depression Scale (HADS) for both depression and anxiety subscales, and the Modified Fatigue Impact Scale (MFIS), which includes total, cognition, psychosocial, and physical scores (P < 0.001). At the end of the study, significant differences between the EA and placebo groups were noted. Within the EA group, significant changes from baseline were found in EDSS, STAI (p = 0.003), QIDS (p = 0.041), HADS-D (p = 0.032), HADS-A (p = 0.012), total MFIS (p = 0.004), MFIS-Cognition (p = 0.001), MFIS-Psychosocial (p = 0.049), and MFIS-physical (p = 0.001) scores. In the EA group, significant changes from baseline were observed in EDSS, STAI (p = 0.003), QIDS (p = 0.041), HADS-D (p = 0.032), HADS-A (p = 0.012), total MFIS (p = 0.004), MFIS-Cognition (p = 0.001), MFIS-Psychosocial (p = 0.049), and MFIS-physical (p = 0.001) scores.

Conclusions: EA appears to significantly alleviate fatigue, depression, and anxiety in MS patients.

Background: Research cohort data suggest diagnostic delay in multiple sclerosis (MS) has diminished in tandem with MS diagnostic criteria revisions, yet other studies have not replicated this finding. Recent data indicate misdiagnosis of initial symptoms of MS is a frequent contributor to diagnostic delay.

Objectives: This survey study assessed diagnostic delay and misdiagnosis in an MS patient registry.

Methods: Participants completed the survey study between November 12, 2021, through December 22, 2021.

Results: There were 428 participants. Diagnostic delay was a median of 2.0 months (mean of 22.8 months, range: 0-32.9 years); 173/428 (40.4%) reported misdiagnosis of symptoms later attributed to MS, and this was associated with longer diagnostic delay (p < 0.001). Diagnostic delay decreased over time proximal to revisions to MS diagnostic criteria. 217/428 (50.7%) reported earlier symptoms retrospectively recognized as referable to MS that were not clinically evaluated, resulting in a diagnostic delay median of 5.4 years (mean 8.9 years, range: 0-47.4 years).

Conclusions: Diagnostic delay was prevalent and associated with frequent misdiagnosis of initial symptoms of MS and earlier unevaluated symptoms later attributed to MS. Studies tracing the diagnostic journey of patients with MS are needed to understand and prevent causes of diagnostic delay.

Background: Blood-based biomarkers have emerged as promising tools to optimize treatment decisions in multiple sclerosis (MS) including initiation, switch, or cessation of disease modifying therapies.

Objectives: The clinically validated MS disease activity (MSDA) test measures 18 proteins to derive a disease activity score. This study tests the clinical utility of MSDA in real-world practice.

Methods: Twenty clinicians from 14 clinics conducted a chart review utilizing a retrospective, longitudinal design, with a pre-post component. Chart reviews captured clinician decision-making before and after receipt of each MSDA result, while separate clinician assessments also captured the perceived impact of MSDA on MS management.

Results: A total of 352 charts were reviewed. The overall rate of clinical decision changes after MSDA testing (19.4%) exceeded predefined benchmarks. The proportion of patient time points where clinicians "strongly agreed" or "agreed" that MSDA results influenced their decision-making was greater when multiple longitudinal MSDA results were available compared to a single result: 69.2% (95%CI: [60.2%, 78.3%) vs. 59.8% (95%CI: [43.7%, 76.0%]), respectively.

Conclusion: When used in addition to standard of care, MSDA demonstrates clinical utility for real-world decision-making in MS management, based on objective changes in treatment plan and clinician-reported impact, which increases with longitudinal use.