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

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.

Introduction: Cognitive rehabilitation includes a set of programs to train the brain, which leads to the improvement of mental and neuro-psychological functions. This meta-analysis was conducted with the aim of investigating the effectiveness of cognitive rehabilitation in comparison with routine rehabilitation methods in patients with multiple sclerosis (MS).

Methods: The Cochrane Library, ProQuest, PubMed, PsycINFO, and Web of Science databases were searched from inception to August 2022. Google Scholar was used to find relevant sources and complete the search coverage. Two authors independently selected studies based on predefined inclusion criteria. Data analysis was performed using RevMan (version 5.3).

Results: Out of the 578 studies found, 20 studies were finally included in this review. The results of the meta-analysis on four outcomes (Paced Auditory Serial Addition Test (PASAT), Brief Visuospatial Memory Test (BVMT), MS Neuropsychological Screening Questionnaire (MSNQ), and Beck Depression Inventory (BDI)) indicated that the outcome was significant in favor of the cognitive rehabilitation group. However, for five outcomes (Controlled Oral Word Association Test (COWAT), California Verbal Learning Test (CVLT), Everyday Memory Questionnaire (EMQ), Symbol Digit Modalities Test (SDMT), and Expanded Disability Status Scale (EDSS)), the differences between the two groups were not significant.

Conclusion: The results of this meta-analysis showed that cognitive rehabilitation has an effect on improving the performance of patients with MS. However, further studies with more accurate methodologies are required to determine which of the outcomes cognitive rehabilitation has a greater effect on.

Background: Health disparities in adult-onset multiple sclerosis have been identified in the Black/African American (AA) population. A higher relapse rate has been suggested in Black/AA patients with pediatric-onset MS (POMS), but little work explores healthcare utilization and social determinants of health (SDOH).

Objective: To evaluate racial, ethnic, and socioeconomic disparities in POMS outcomes.

Methods: Retrospective chart review identified 31 eligible patients diagnosed with POMS at Children's of Alabama between 2013 and 2023. Demographics, outcomes, and healthcare utilization over 2 years from diagnosis were collected. Patient addresses were connected to SDOH measures from the US Census. Bivariate analysis was performed using Fisher's Exact Test, Wilcoxin Test, and 2-sided t-test.

Results: Black/AA children had a higher Expanded Disability Status Scale (EDSS) at first presentation (p = 0.0276) and were more likely to initiate fingolimod vs. glatiramer acetate (p = 0.0464). Living further from Children's of Alabama was associated with a higher most recent EDSS (p = 0.0301) and fewer neurology appointments (p = 0.0167). Families living in more socioeconomically deprived census tracts had significantly more hospital admissions.

Conclusion: Black/AA POMS patients had a more severe initial presentation and were started on higher efficacy medication. We identified disparities in EDSS and healthcare utilization based on SDOH data linked to a child's home address.

Background: Serum neurofilament light chain (sNfL) is a marker of neuroaxonal injury, and serum glial fibrillary acidic protein (sGFAP) reflects reactive astrogliosis. In adult multiple sclerosis (MS), sNfL correlates with relapsing disease activity while sGFAP correlates with progressive disease.

Objectives: We evaluate sNfL and sGFAP as biomarkers in pediatric-onset MS (POMS) compared to pediatric healthy controls (PHC), and correlations with the disease course.

Methods: In this single-center observational cross-sectional study, we extracted data from a longitudinal database and measured NfL and GFAP from bio-banked serum using single-molecule array technology.

Results: The analysis included 61 POMS patients and 45 PHC. Controlling for age and BMI, sNfL was 414% higher and sGFAP was 42.3% higher in POMS. Disability (EDSS) is associated with higher sNfL (β = 0.32, p = 0.002) and higher sGFAP (β = 0.11, p = 0.03). sNfL is associated with MRI lesion burden, recent disease activity (β =0.95, p < 0.001), and untreated status (β = 0.5, p = 0.006).

Conclusion: sNfL and sGFAP are elevated in POMS compared to PHC. Both biomarkers are associated with clinical disability. Elevated sGFAP may reflect early neurodegeneration in POMS, while sNfL reflects disease activity and DMT response. Elevated sNfL among some clinically and radiographically stable POMS patients suggests ongoing neuroaxonal injury with a potential role for sNfL monitoring disease stability.

Background: There is a paucity of studies examining quality of life (QoL) in people with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).

Methods: A cross-sectional, online, self-administered survey was distributed. Data elements included demographic and clinical characteristics, and QoL in Neurological Disorders (Neuro-QoL) short form questionnaires. Neuro-QoL domain scores were compared to reference populations, yielding standardized T-scores. Symptom severity was categorized as mild, moderate, or severe, using standard Neuro-QoL cut points.

Results: A total of 259 participants completed the survey. Neuro-QoL domain impairment was present in a significant proportion of respondents (anxiety: 58.1%, depression: 30.7%, stigma 29.8%, cognition: 58.5%, social function: 57.7%). T-scores were significantly worse than the reference population for anxiety (p<0.001), stigma (p=0.005), cognitive function (p<0.001) and social interactions (p<0.001). There was no clear association between QoL domains and demographics, disease-modifying therapy class, or type of clinical presentation. A relapsing vs monophasic disease course was associated with worse anxiety, stigma, cognition, and social interactions (p<0.05).

Conclusion: People with MOGAD may exhibit impairment in multiple domains of QoL. Practicing clinicians should be aware of this burden in MOGAD. Further research is needed to better understand factors associated with QoL impairment in MOGAD.

Background: Myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD) is a relatively new disease entity in the field of demyelinating disorders. Its first diagnostic criteria have recently been published.

Objectives: We evaluated the positive predictive value (PPV) for MOG-IgG testing and report the clinical and radiologic features with respect to the recently published criteria.

Methods: A retrospective study was conducted at three centers in Dallas, Texas. Patients with positive MOG-IgG testing on cell-based assays at any time were included. Positive cases were reviewed by at least two neuroimmunologists for fulfillment of the criteria.

Results: We included 235 patients. The PPV of seropositivity at any time was 78.3% overall, 52.6% for low titer, and 90.1% for high titer. Children had a higher PPV than adults (93.9% versus 67.2%). Positive predictive value was 6.3% in those without a core clinical demyelinating attack. Children more often have the typical imaging features of MOGAD in optic neuritis than adults.

Conclusions: We report a PPV of 78.3% for MOG-IgG testing using the 2023 MOGAD diagnostic criteria. Children had higher PPV and frequency of supporting imaging features. Careful consideration is necessary when assigning patients with no core demyelinating event and low titers a MOGAD diagnosis.