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

Background: Neuromyelitis optica spectrum disorder (NMOSD) primarily affects women of childbearing age.

Objectives: Studying the potential relationship between NMOSD and pregnancy characteristics and outcomes.

Subjects and methods: This is a retrospective cohort study that was conducted on 66 married female patients diagnosed with NMOSD. All patients underwent a thorough review of their demographic and clinical history through their medical records and personal interviews. Additionally, a complete neurological examination was performed, along with the expanded disability status scale (EDSS) and a pregnancy registry questionnaire.

Results: After comparing married patients before and after disease onset, there was a significant increase in the number of abortions and the percentage of cesarean sections, as well as a decrease in the percentage of breastfeeding after disease onset. The p values were .02, <.001, and <.001, respectively, with odds ratios of 2.03, 5.13, and 6.17. Additionally, there was a rise in the occurrence of postpartum relapses, which accounted for 66% of all relapses after the disease onset. Most of these relapses (88.7%) occurred within the first 3 months postpartum.

Conclusion: Presence of NMOSD increased the percentage of miscarriage, delivery by cesarean section, and decreased the chance of breastfeeding. In addition, pregnancy increases NMOSD relapse and subsequent disability.

We describe the case of a gentleman with relapsing-remitting multiple sclerosis and chronic lymphocytopenia secondary to treatment with fingolimod who presented with disseminated histoplasmosis after receiving the third dose of the Moderna coronavirus disease 2019 (mRNA-1273) vaccine. Following the vaccination the patient noted fatigue which worsened over time along with gradual weight loss. A few months later he noted low-grade fever and finally shortness of breath. A diagnosis of disseminated histoplasmosis was performed based on urine, blood, and imaging data. He responded well to prolonged antifungal treatment. Fingolimod was discontinued and replaced with glatiramer acetate. He has been clinically stable until the time of this report, 33 months following symptom onset.

Background: Cladribine shows efficacy in multiple sclerosis (MS), but Latin American (LATAM) real-world data is limited, despite potential sociodemographic variations.

Objective: Investigate baseline characteristics and clinical response in highly active MS patients in Mexico, identifying predictors of early treatment response.

Method: A multicenter cohort study analyzed retrospective data from individuals with "highly active" MS in the Cladribine Patient Support Program across 11 Mexican clinics. Criteria included one-year prior treatment with another disease-modifying treatment and recent relapse with specific MRI findings. Primary outcomes focused on achieving NEDA-3 status after 12 months.

Results: In the follow-up, 67.5% maintained NEDA-3 status. Baseline EDSS scores decreased significantly from 1.50 to 1.00 (p = 0.011), with no confirmed disability worsening. No significant differences were observed between NEDA-3 achievers and non-achievers in demographic and clinical variables. No severe adverse events were reported.

Conclusion: Cladribine showed early and effective control of active MS in Mexican patients, demonstrating a secure profile with minimal adverse events. This study provides valuable real-world evidence in the LATAM context.

Background: Multiple sclerosis (MS) shares clinical/radiological features with several monogenic diseases that can mimic MS.

Objective: We aimed to determine if exome sequencing can identify monogenic diseases in patients diagnosed with MS according to the McDonald criteria thus uncovering them as being misdiagnosed.

Methods: We performed whole exome sequencing in a cohort of 278 patients with MS, clinically or radiologically isolated syndrome without cerebrospinal fluid-specific oligoclonal bands (CSF-OCBs) (n = 228), a positive family history of MS (n = 44), or both (n = 6), thereby focusing on individuals potentially more likely to have underlying monogenic conditions mimicking MS. We prioritized 495 genes associated with monogenic diseases sharing features with MS.

Results: A disease-causing variant in NOTCH3 was identified in one patient without CSF-OCBs, no spinal lesions, with non-response to immunotherapy, and a family history of dementia, thereby converting the diagnosis to cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Moreover, 18 patients (6.5% of total) carried variants of unclear significance.

Conclusion: Monogenic diseases being misdiagnosed as MS seem rare in patients diagnosed with MS according to the McDonald criteria, even in CSF-OCB negative cases. The detected pathogenic NOTCH3 variant emphasizes CADASIL as a rare differential diagnosis and highlights the relevance of genetic testing in selected MS cases with atypical presentations.

Background: Previous investigations of multiple sclerosis (MS)-related healthcare have focused on utilisation of specific individual health services (e.g. hospital care, office-based neurologists) by people with MS (PwMS). Meanwhile, little is known about possible patterns of utilisation across health services and their potential differences across patient characteristics.

Objective: To comprehensively analyse and identify patterns of MS-related health service utilisation and detect patient characteristics explaining such patterns.

Methods: In 2021, we invited all PwMS insured by the largest insurance company in Lower Saxony, Germany, to take part in an online survey. We merged respondents' survey and health insurance claims data. We analysed MS-related health service utilisation and defined individual characteristics for subgroup analyses based on Andersen's Behavioural Model. We executed non-parametric missing value imputation and conducted hierarchical clustering to find patterns in health service utilisation.

Results: Of 6928 PwMS, 1935 responded to our survey and 1803 were included in the cluster analysis. We identified four distinct health service utilisation clusters: (1) regular users (n = 1130), (2) assistive care users (n = 443), (3) low users (n = 195) and (4) special services users (n = 35). Clusters differ by patient characteristics (e.g. age, impairment).

Conclusion: Our findings highlight the complexity of MS-related health service utilisation and provide relevant stakeholders with information allowing them to tailor healthcare planning according to utilisation patterns.

Background: Decision-making about treatment when planning a pregnancy (family planning) is complex for women living with multiple sclerosis (MS). Decision tools can help this process, in 2016 MS Trust launched their online digital treatment decision tool to support people with MS.

Objectives: To evaluate user-experience of this tool by exploring women's opinions about its content, interface, and usefulness in the context of family planning; and to synthesize recommendations to improve the tool.

Methods: Thirty participants qualitatively evaluated the tool using Think Aloud methodology. Sessions were conducted online using Microsoft Teams and were video recorded. Transcription was automated and data were thematically analyzed.

Results: Women's first impression was that the tool presented a lot of information at once, which was difficult to take in, and they found it difficult to navigate. Although the tool was helpful in allowing them to compare treatment options, the filters were confusing, and the information related to pregnancy sometimes contradicted advice from their healthcare practitioners. They suggested rewording the pregnancy recommendations and filters, updating some content, and making some changes to the interface to meet users' cognitive needs.

Conclusion: The MS Trust treatment decision tool is excellent in helping women with treatment choices at initial diagnosis. However, it is not currently as useful when considering family plans. Recommendations were conveyed to MS Trust where some are now applied to the new live version and the rest are to be considered for future updating projects.

Background: Eye movements can reflect brain alterations and inform on the presence of motor disabilities and cognitive impairments in people with multiple sclerosis (pwMS).

Objective: The aim of the study was to determine the correlation between motor and cognitive measurements and eye movement parameters when performing the n-back task (NBKT).

Methods: This was a cross-sectional study carried out at Ramos Mejía Hospital, a center specialized in demyelinating diseases in Buenos Aires, Argentina. The study population consisted of 66 patients with relapsing-remitting multiple sclerosis (RRMS) and 5 patients with secondary progressive multiple sclerosis (SPMS). pwMS performed the n-back test while using a device head mounted display (HMD) with eyetracking capabilities in order to capture eye movement. Clinical motor and cognitive measures were assessed with Expanded Disability Status Scale (EDSS), Nine Hole Peg Test (NHPT), Timed 25-Foot Walk (T25FW), and Symbol Digit Modalities Test (SDMT).

Results: pwMS showed strong and statistically significant correlations between gaze duration; number of fixations, saccade amplitude and motor disabilities and cognitive impairments as measured by EDSS, NHPT, T25FW, and SDMT.

Conclusion: This study found significant correlations between eye movement behavior and motor and cognitive disability in pwMS. These findings suggest that eye movements have the potential to be used as a surrogate biomarker in MS progression.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing, autoimmune, inflammatory astrocytopathy. Rituximab for B-cell suppression is a common treatment for NMOSD; however, large-scale randomised controlled trials are lacking.

Objective: Evaluate long-term efficacy and safety of rituximab for NMOSD.

Methods: Retrospective observational study of patients with NMOSD treated with rituximab. Annualised relapse rates (ARRs) before and during rituximab treatment were evaluated; Modified Rankin Scores (mRS) were measured as a marker of disability.

Results: In total, 37 patients were included: 27 aquaporin-4-IgG-seropositive and 10 seronegative NMOSD. The predominant rituximab dosing regimen was an initial 1000 mg, split over two 500 mg infusions, two weeks apart, followed by single 500 mg doses. Over a median follow-up of 54 months, ARR for the whole cohort was 0.136 (95% CI 0.088-0.201), significantly lower than the pretreatment ARR of 0.366 (95% CI 0.271-0.483, p < 0.001). There was a significant reduction in ARR for the seropositive subgroup, but not seronegative. Significant improvement in mRS was seen post-treatment. Infections were reported in 32% of patients during follow-up; most were mild.

Conclusion: Rituximab, at doses lower than traditionally used, may be an efficacious therapy for NMOSD, with a favourable safety profile.

Background: Fatigue is the most debilitating symptom in patients with multiple sclerosis (MS). Natalizumab and rituximab are the most used MS disease modifying therapies in Sweden, but comparative data on the effect on fatigue is sparse.

Objective: Primary objective was to compare fatigue levels between patients on natalizumab and rituximab. As secondary objective, we assessed processing speed, an attention domain quality, between treatment groups.

Method: In this Swedish multicentre cross-sectional study, patients with relapsing-remitting MS and >24 months treatment duration were identified in the Swedish MS-registry. Fatigue was assessed using the Fatigue Scale for Motor and Cognitive functions (FSMC) and processing speed using Symbol Digit Modalities Test (SDMT).

Results: 128 patients were enrolled (natalizumab: 56, rituximab: 72). No significant differences in FSMC were found when adjusting for potential confounders (p = 0.936), with age having the biggest impact, correlating with increased fatigue. Individuals on natalizumab performed significantly better on SDMT at cross-section (natalizumab 64.7, rituximab 56.2; p = 0.003), with an improvement from treatment initiation, compared to rituximab (change: natalizumab 8.9, rituximab -1.0; p = 0.002).

Conclusion: We found no difference in fatigue levels between natalizumab and rituximab cohorts. Patients treated with natalizumab showed significantly better results on SDMT than patients on rituximab.

Background: The use of non-specific immunosuppressants (NSIS) to treat multiple sclerosis (MS) remains prevalent in certain geographies despite safety concerns, likely due to resource limitations.

Objective: To use MSBase registry data to compare real-world outcomes in adults with relapsing-remitting MS (RRMS) treated with dimethyl fumarate (DMF) or NSIS (azathioprine, cyclosporine, cyclophosphamide, methotrexate, mitoxantrone or mycophenolate mofetil) between January 1, 2014 and April 1, 2022.

Methods: Treatment outcomes were compared using inverse probability of treatment weighting (IPTW) Cox regression. Outcomes were annualized relapse rates (ARRs), time to discontinuation, time to first relapse (TTFR) and time to 24-week confirmed disability progression (CDP) or 24-week confirmed disability improvement (CDI; in patients with baseline Expanded Disability Status Scale [EDSS] score ≥2).

Results: After IPTW, ARR was similar for DMF (0.13) and NSIS (0.16; p = 0.29). There was no difference in TTFR between cohorts (hazard ratio [HR]: 0.98; p = 0.84). The DMF cohort experienced longer times to discontinuation (HR: 0.75; p = 0.001) and CDP (HR: 0.53; p = 0.001), and shorter time to CDI (HR: 1.99; p < 0.008), versus the NSIS cohort.

Conclusion: This analysis supports the use of DMF to treat patients with relapsing forms of MS, and may have implications for MS practices in countries where NSIS are commonly used to treat RRMS.