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

Background: Recent studies support the need for early and intensive disease-modifying treatment (DMT) for patients with multiple sclerosis (PWMS). Abrupt DMT withdrawal may risk disease reactivation. Recent studies showed that MS disease activity was not rare after DMT withdrawal for PWMS aged >45/55 y. Immune reconstitution therapy (IRT) with cladribine tablets (CladT), may be an option for older PWMS who wish to stop DMT.

Objective: We retrospectively analysed PWMS aged >45 y who initiated CladT in 6 MS centers in Europe.

Results: One hundred and twenty nine PWMS (95 women/34 men, mean age 55.0 +/-7.5y initiated CladT; 83 (64.3%) previously received platform DMT, 35 (27.2%) previously received high efficacy DMT and 11 (8.5%) received CladT as a 1^st DMT due to a late onset of MS or to a delayed therapy decision. Mean follow-up was 2.4 y (1-5) on CladT. Only three patient experienced 4 relapses. The first one had 2 relapses after switching from fingolimod with a 2-month interval between treatments. The 2 remaining were naïve patients that had a relapse between the 2 courses of CladT.

Conclusion: Last/exit therapy with CladT seems to avoid MS disease reactivation in older PWMS and may be an interesting alternative solution to continue immunosuppression/immunomodulation.

Background: This scoping review aimed to identify existing information and gaps in knowledge regarding the diversity characteristics of the multiple sclerosis (MS) population in Canada.

Methods: We searched MEDLINE, EMBASE, Cumulated Index in Nursing and Allied Health Literature (CINAHL), SCOPUS and ProQuest's global dataset of theses and dissertations from 2010 to January 12, 2024. Data sources were case reports/series, cohort studies, case-control studies, analytical cross-sectional studies, randomized clinical trials, qualitative, mixed methods, participatory studies and systematic reviews conducted in Canada, published in English or French, that included participants with clinically isolated syndrome or MS. Sample characteristics were extracted applying Cochrane's PROGRESS-Plus framework.

Results: We included 259 studies, most often studying disease-modifying therapy (24.3%) and access to care (20.9%). Among primary data collection studies 40% used one recruitment strategy, usually MS Clinics and MS Canada. Age (92.7%) and sex (86.9%) were reported most often, ≤10% of studies reported race or ethnicity; religion, sexual orientation and language were not reported.

Conclusions: We lack an understanding of characteristics of people living with MS in Canada relevant to health equity. Existing research has been insufficiently inclusive. Better reporting of diversity characteristics is needed, along with specific efforts to recruit and retain more diverse samples.

Background: Impact of changing diagnostic criteria for the population-based incidence of multiple sclerosis (MS) has not been investigated.

Objective: To assess the effect of changing diagnostic criteria on national MS incidence and prevalence in Finland from 1974 to 2021.

Methods: We identified patients with MS (pwMS) through the National MS registry and the national Care Register for Healthcare and divided them into four groups based on the year of MS diagnosis: 1) Schumacher criteria (1974-1982), 2) Poser criteria (1983-2000), 3) Earlier McDonald criteria (2001-2016), and 4) Current McDonald criteria (2017-2021). Age-adjusted incidence and prevalence were calculated.

Results: Age-adjusted incidence per 10⁵ person years increased from 3.7 (95% CI 3.5-3.8) during the Schumacher criteria period to 9.2 (95% CI 9.0-9.4) during the earlier McDonald criteria. During the Current McDonald criteria incidence stabilized to 8.6 (95% CI 8.3-9.0). Prevalence increased from 24.3 (95% CI 22.8-25.8) to 241.5 (95% CI 237.3-245.6) per 10⁵ person years.

Conclusion: Both incidence and prevalence of MS increased significantly. Incidence showed a sharp increase when entering the twenty-first century, after which it stabilized. Increasing incidence was likely related to incorporation of MRI in the diagnostic criteria. Current diagnostic criteria did not further increase the incidence.

Objective: To determine the efficacy of a safety program designed for monitoring infusion disease-modifying therapies (DMTs) prescribed for multiple sclerosis (MS).

Background: Infusion-based high-efficacy DMTs represent a major advance in the treatment of MS. However, safe administration requires close monitoring. Non-adherence to safety monitoring can lead to DMT-related complications.

Methods: A safety nurse navigator reviewed charts for infusion DMT patients from November 2020 to December 2022, and contacted them to address incomplete safety monitoring. Patients were screened for the primary outcome of incomplete safe infusion, including outdated safety labs, imaging, and/or recent follow-up with their neurologist. Logistic regression was performed for predictors of incomplete safety monitoring and of successful safety intervention.

Results: Three hundred and forty-three patients were on infusible DMTs over the study time period: 75 natalizumab, 31 rituximab, and 237 ocrelizumab. Two hundred and eighty-six (83%) patients did not meet the criteria for safe infusion; 64% lacked safety labs, 47% prescriber follow-up, and 26% an MRI. The nurse succeeded in 82% of interactions. B-cell depletion was linked to outdated lab monitoring, whereas natalizumab use was associated with outdated appointments and imaging.

Conclusions: This safety initiative identified gaps for managing infusion-based MS DMTs. Our safety nurse navigator successfully identified incomplete safety monitoring and intervened to avoid drug-related complications.

Background: Persistence to B cell depleting therapies (BCDT) like ocrelizumab and rituximab may be higher compared with other disease-modifying therapies (DMT) in multiple sclerosis (MS). Clinical trials directly comparing these treatments are lacking.

Objective: To compare the risk of treatment discontinuation, relapse, and confirmed disability worsening in patients starting BCDT vs other DMT within real-world settings.

Methods: In a longitudinal cohort study, patients with relapsing MS starting BCDT (ocrelizumab/rituximab, n = 269) after enrolment into the Swiss MS Cohort (SMSC) were evaluated for treatment discontinuation, occurrence of relapses, and disability worsening in comparison with platform (n = 57) and oral (n = 454) DMT, or natalizumab (n = 73) using Cox regression with double robust adjustment for baseline covariates.

Results: Patients starting BCDT were less likely to discontinue treatment than all other DMT combined (HR = 0.26, 95% CI = 0.18-0.36, p < .01), oral DMT (HR = 0.28, 95% CI = 0.20-0.39, p < .01) and natalizumab (HR = 0.35, 95% CI = 0.21-0.58, p < .01). BCDT were associated with lower risk of relapses as compared to oral DMT HR = 0.59, 95% CI = 0.39-0.88, p < .01), but not to natalizumab (HR = 0.90, 95% CI = 0.45-1.82, p = .778). Disability worsening was not significantly different between treatment groups.

Conclusion: We provide real-world evidence for patients being more persistent to BCDT than to other treatments, and better clinical outcomes may partly explain this.

Introduction: Fatigue is a highly prevalent symptom in people with multiple sclerosis. It demands careful assessment and prompt intervention to improve their quality of life and overall burden of disease. This scoping review aims to provide a comprehensive synthesis and update of the existing evidence on the effectiveness of different pharmacological and nonpharmacological interventions for multiple sclerosis (MS)-related fatigue.

Methods: To ensure the transparency and quality of the articles chosen for this scoping review, the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols extension for Scoping Reviews was used. Exclusively randomized controlled trials published between 2016 and 2023 were included.

Results: Twenty-eight articles were analyzed. We found that pharmacological interventions are few and have included the use of Amantadine, Ondansetron, Methylphenidate, and Modafinil, with little effects on fatigue. Nonpharmacological interventions are diverse and include cognitive behavioral therapy, guided imagery, phototherapy, exercise, brain stimulation, and lavender administration with evidence of a statistically significant decrease in fatigue.

Conclusions and discussion: Current evidence on the effectiveness of pharmacological and nonpharmacological interventions is inconclusive. Lack of knowledge of the pathophysiology of fatigue limits its prevention, control, and management recommendations. A comprehensive and interdisciplinary approach is required to manage this symptom in patients with MS.

Background: Comorbidities in people with multiple sclerosis (PwMS) can affect disease course and quality of life.

Objectives: To investigate comorbidities in the five years after diagnosis, timing of comorbidity occurrence, age and sex effects, and differences between multiple sclerosis (MS) and other chronic autoimmune diseases (AIDs).

Methods: In this retrospective cohort study, we systematically assessed differences in diagnosis frequencies in newly diagnosed PwMS (n = 9,880) compared to matched controls (noAID, n = 29,640) and individuals with other AIDs (psoriasis, n = 29,640; Crohn's disease, n = 9,880).

Results: Some comorbidities of PwMS are similarly frequent in other AIDs, while others, such as depression, are more prevalent in PwMS (odds ratio (OR) vs noAID = 2.03(1.94-2.13)). We found that personality disorders are more frequently recorded in PwMS before (OR  = 1.34(1.21-1.49)) and after MS diagnosis (OR  = 1.32(1.16-1.5)), especially in women (OR  = 1.39(1.2-1.6)). PwMS are more frequently diagnosed with Lyme disease (OR  = 1.98(1.69-2.33)), which was predominantly recorded by general practitioners after presentation with neurological symptoms. We observed lower acute tonsillitis frequencies in PwMS (OR  = 0.8(0.75-0.85)).

Conclusions: Our results suggest that PwMS might have a generally increased risk for specific personality disorders. More frequent Lyme disease recordings for PwMS suggest misdiagnoses of MS symptoms. Lower tonsillitis frequencies suggest a link between MS and protection from specific infections.

Few controlled trials of disease-modifying therapies (DMTs) have been conducted on the pediatric-onset multiple sclerosis (PoMS) population, leading to extensive off-label use of therapies approved only for adults. This highlights the need for real-world evidence to guide clinical practice. Clinical registries can offer high-quality data, but limitations such as missing and erroneous information must be considered. This validation study compared Swedish Multiple Sclerosis registry data from 122 PoMS patients to medical records. Generally (≥89%), data were confirmed. However, missing data exceeded 30% for rituximab infusions, magnetic resonance imaging, and relapses. Overall, the registry provides valid, real-world data on DMT use in PoMS.

Background: Diffusion tensor imaging (DTI) in adults with multiple sclerosis (MS) has identified marked volume and diffusion abnormalities of the fornix, the main white matter (WM) output tract of the hippocampus.

Objective: To determine if the fornix is affected in pediatric-onset MS (POMS) using the same DTI protocols used in adult-onset MS (AOMS), which would suggest its early involvement in the disease course.

Methods: High-resolution, fluid-suppressed diffusion tractography was used to identify the fornix in 11 POMS patients (13-19 years old) and 26 controls. Fornix volume and diffusion metrics were compared between groups and with other total/regional brain volumes, and then correlated with cognitive/clinical scores.

Results: POMS showed lower fornix volumes (-26%) compared to controls, which was greater than proportional losses in total and other regional brain volumes. Notably, the hippocampus volume was not lower in POMS. DTI yielded lower fractional anisotropy (-7%) and higher mean (+12%), axial (+7%), and radial (+16%) diffusivities in POMS. There were no significant correlations between fornix volume/diffusion metrics and cognitive/clinical scores.

Conclusion: Diffusion tractography showed marked injury to the fornix in POMS that precedes injury to connected gray matter such as hippocampus, implicating the fornix as an early brain region affected in MS.

Background: SLIPPERS (Supratentorial Lymphocytic Inflammation with Parenchymal Perivascular Enhancement Responsive to Steroids) is a rare variant of a syndrome called CLIPPERS (Chronic Lymphocytic Inflammation with Ponsine Perivascular Enhancement Responsive to Steroids). SLIPPERS is characterized by distinct supratentorial lesions that share radiological and pathological characteristics with CLIPPERS. The ongoing issue is whether these syndromes should be considered as a distinct disease entity or simply a form for a variety of underlying conditions such as granulomatosis, vasculitis, and infectious diseases.

Case: We present a unique case of SLIPPERS observed in a 26-year-old woman with no notable medical or familial background. Laboratory findings ruled out certain diseases from the list of differentials and cranial MRI showed T2 hyperintense areas with linear-patchy enhancements, a pattern consistent with SLIPPERS syndrome. Consequently, patient was diagnosed with SLIPPERS syndrome and received methylprednisolone therapy.

Conclusion: Both SLIPPERS and CLIPPERS are complicated syndromes posing diagnostic challenges and requiring careful investigation to avoid misdiagnosis. Following a thorough differential diagnosis, appropriate treatment can be initiated, and follow-up is required.