Multiple Sclerosis Journal最新文献

Background: The age of multiple sclerosis (MS) onset coincides with fertile age, and both improved prognosis and treatment may influence birth rates in people with MS (pwMS).

Objectives: To investigate birth rates over time in pwMS compared with controls.

Methods: This cohort study included pwMS from three hospitals in the southeast of Norway. Clinical data were collected prospectively. Statistics Norway provided year of live births and marital status in pwMS and controls matched for age, sex, and place of residence at age 16.

Results: We included 1599 pwMS (1118 women with MS (wMS) and 481 men with MS (mMS)) and 23,855 controls. The mean number of live births was 1.5 (standard deviation (SD) 1.2) for pwMS versus 1.8 (SD 1.2) for controls (p < 0.001). Birth rates in wMS declined significantly starting 3 years before onset, with 4.5% giving birth versus 8.4% of controls 2 years before onset (p = 0.046). Birth rates were also lower 1 year after onset (p = 0.002). mMS showed a dip 2 years before onset (p = 0.002), but otherwise had rates similar to controls. There were no differences in marital status.

Conclusion: wMS have reduced rates of childbirth compared with controls. This is significant already in the prodromal phase.

Background: The circulating metabolome incorporates multiple levels of biological interactions and is an emerging field for biomarker discovery. However, few studies have linked metabolite levels with quantitative neurologic function assessments in people with multiple sclerosis (pwMS).

Objectives: We quantified metabolomic differences between pwMS and healthy controls (HCs) and assessed the association of metabolites with disease severity.

Methods: We profiled 517 metabolites using liquid chromatography-mass spectrometry (Biocrates Inc.) for participants from the MS Partners Advancing Technology and Health Solutions (MS PATHS). We conducted a multicenter cross-sectional study and applied linear regression to assess the association between metabolites and neurological function measures in multiple sclerosis (MS), including walking speed, manual dexterity, and processing speed.

Results: Among 1010 participants (837 MS; 71.2% relapsing-remitting MS; 173 HC; mean age: 44.5 (standard deviation (SD): 11.4); 73.9% female; 12.7% non-white), pwMS showed decreased levels of phosphatidylcholines (PCs) and different amino acids (AAs) but increased triglycerides (TGs). Metabolites showed an association with worse neurologic function; for instance, a 1-SD decrease in PC aa C36:6 was associated with 21.36% (95% confidence interval (CI): 11.07-30.46; p = 1.35E-04) slower walking speed.

Conclusions: This large study identified lipid alterations linked to MS severity. Future longitudinal studies will evaluate if these metabolite levels predict MS outcomes.

Background: Neurostatus-Expanded Disability Status Scale (EDSS) is the standard measure used to assess impairment and disability in multiple sclerosis (MS) trials but requires trained expert neurologists.

Objectives: This study aims to evaluate the concordance of Neurostatus-EDSS assessments from specially trained health care professionals (HCPs) and standardized trained neurologists.

Methods: A Swiss multicenter, randomized, cross-over study with 100 people with MS. HCPs were trained to assess the Neurostatus-EDSS based on the newly developed SMARTCARE-EDSS training method.

Results: The concordance rate between HCPs and neurologists was 0.87 (95% confidence interval (CI) = 0.815-0.925).

Conclusion: Trained HCPs can reliably perform Neurostatus-EDSS assessments, supporting broader implementation and improved trial access.

Trigeminal neuralgia (TN) is commonly associated with multiple sclerosis (MS). Whether TN should be considered a clinical relapse or evidence of active disease lacks consensus. TN was diagnosed in 0.9%-1.9% (n = 171) of people with multiple sclerosis (pwMS) at three international sites. In 9.9%, TN was their first potential demyelinating symptom. In 86%, TN onset occurred a median of 13-16 years after MS diagnosis. A clinical relapse occurred within 6 months of TN onset in 20% of pwMS. These data suggest TN onset should be evaluated as active disease and incorporated in diagnostic and therapeutic decisions in MS.

Background: Predicting treatment response and disease progression in multiple sclerosis (MS) is challenging. Treatment Response Scoring Systems (TRSS) are potentially useful, but their utility in patients receiving high-efficacy therapies and very high-efficacy therapies (HET/vHET) remains unclear.

Objective: This study aimed to evaluate the performance of TRSS in patients treated with HET/vHET.

Methods: We retrospectively studied MS patients treated with HET/vHET in an MS specialized centre. TRSS, including the Rio Score, modified Rio Score and MAGNIMS score, were applied to assess response to treatment. We evaluated the predictive value of the TRSS on disease activity and disability progression.

Results: TRSS effectively predicted disease activity and progression of disability in patients treated with HET/vHET. Patients with high TRSS scores at 12 months post-HET/vHET initiation had a significantly increased risk of relapses, new lesions on magnetic resonance imaging (MRI) scans and progression of disability at 4 years.

Discussion: Our findings highlight the importance of personalized treatment strategies in MS. TRSS are valuable tools for monitoring treatment response, guiding clinical decision-making and optimizing patient care.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disorder that occurs in children and adults.

Case: We report a case of a 10-year-old female with AQP4+ NMOSD who presented with paraparesis from longitudinally extensive transverse myelitis (LETM) from C2 to the conus medullaris. The patient showed gradual improvement in strength and sensation with solumedrol and plasma exchange therapy. Given her severe presentation, eculizumab therapy was also initiated acutely. She had near complete recovery, although she developed a myelitis relapse during transition to rituximab treatment.

Conclusion: This case demonstrates the role of eculizumab as a safe and effective treatment option in treating an acute attack of pediatric AQP4+ NMOSD. More data are needed to understand the risk of relapse if transitioning off of these highly effective medications.

Background: Spinal cord volume loss is associated with clinical disability in multiple sclerosis (MS). Aerobic capacity may mitigate the impact of central nervous system (CNS) damage accumulation, exerting beneficial effects on MS-related disability.

Objectives: We investigated whether aerobic capacity could moderate the association between spinal cord atrophy and clinical disability in MS.

Methods: In this cross-sectional analysis, expanded disability status scale (EDSS), peak of oxygen consumption (VO₂peak), brain volumetric measures, and the normalized mean upper cervical cord area (nMUCCA) were collected from 51 MS patients and 33 healthy controls (HCs). Low aerobic capacity was defined as having a VO₂peak z-score less than -1.64 standard deviations. In MS patients, we explored whether the association between nMUCCA and EDSS is moderated by the level of aerobic capacity.

Results: The relationship between nMUCCA and EDSS was moderated by aerobic capacity, with a significant nMUCCA × aerobic capacity interaction (β = -0.099, 95% bootstrapped confidence interval [CI] = [-0.172; -0.014], p = 0.012). Lower nMUCCA was significantly associated with higher EDSS score in MS patients with low aerobic capacity (β = -0.073, p < 0.001), but not in those with high aerobic capacity (β = 0.026, p = 0.417).

Conclusions: In MS patients with mild disability, higher aerobic capacity can potentially mitigate the negative impact of spinal cord damage on clinical disability.

Background: Real-world studies are needed to expand our knowledge concerning populations underrepresented in clinical trials.

Objective: This study aimed to evaluate the safety and effectiveness of ocrelizumab in Hispanic/Latino people with multiple sclerosis (pwMS).

Methods: Prospective longitudinal observational study including pwMS who received at least one dose of ocrelizumab between June 2018 and October 2023.

Results: A total of 305 pwMS (223 relapsing-remitting MS (RRMS), 29 secondary progressive MS (SPMS), and 53 primary progressive MS (PPMS)), 67% female, mean age 38.7, mean disease duration 7 years, and median Expanded Disability Status Scale (EDSS) 2.0 (range 0-7). Median follow-up under ocrelizumab 29.5 (range 6-65) months. Only 1 patient had a relapse, 12-week-confirmed disability worsening was observed in 12.4% of the full cohort. Survival analysis showed higher risk of 12-week-confirmed disability worsening in SPMS compared with RRMS and PPMS (p = 0.0009). Magnetic resonance imaging (MRI) activity was significantly reduced from baseline across all disease phenotypes. Serious infections were observed in 4.6%, and two patients died during follow-up (one serious COVID-19 and one metastatic cancer). Notably, 22 pregnancies were reported, with 11 newborns and 6 pregnancies still on course.

Conclusion: This study supports the effectiveness of ocrelizumab in a real-world cohort of individuals from traditionally underrepresented groups, such as the Latin American population, with a consistent safety profile in patients receiving care at a specialized MS Unit.

Radiologically isolated syndrome (RIS) is the earliest documented stage in the disease continuum of multiple sclerosis (MS). It is discovered incidentally in individuals who are asymptomatic but have typical lesions in the brain or spinal cord suggestive of autoimmune inflammatory demyelination. The revised 2023 RIS criteria aim to secure an accurate and timely diagnosis due to the presence of imaging mimics. These criteria require having at least one T2-weighted hyperintense lesion in one of the four suggestive MS locations along with two of the following three features: spinal cord lesion, cerebrospinal fluid (CSF)-restricted oligoclonal bands, or new T2 or gadolinium-enhancing lesion observed on a subsequent magnetic resonance imaging (MRI) study. Once the diagnosis is confirmed, established risk factors, including age, lesion location and CSF, significantly improve prognostic stratification, which is crucial for immunoactive interventions. Recent clinical trials have shown that oral disease-modifying treatments can delay or prevent the first clinical event in RIS patients. Consulting with an MS team for each RIS case is strongly recommended to enhance care and disease surveillance. The revised 2024 McDonald criteria will classify individuals with additional CSF and advanced MRI biomarkers as having preclinical MS, highlighting the importance of vigilance in this area.