Multiple Sclerosis Journal最新文献

Background: A latent period of variable length elapses between multiple sclerosis (MS) biological onset and the occurrence of the first clinical episode reflecting a central nervous system (CNS) demyelinating event. Factors affecting the duration of such interval are unknown.

Objective: To explore whether brain reserve, which moderates the impact of structural damage along MS course, could also affect the timing of MS clinical onset.

Methods: We conducted a time-to-event analysis in 326 relapsing-onset multiple sclerosis patients to ascertain the effect of brain reserve, that is, larger maximal lifetime brain growth (MLBG) estimated as intracranial volume, on the risk of an earlier disease onset. For this purpose, we carried out a Cox proportional hazards regression model stratified by sex and adjusted by site and pre-morbid MS risk factors. All patients reached the event (i.e. the disease onset) with no censored case; the age (years) at disease onset was set as the main time variable.

Results: We identified a protective effect of brain reserve on the time to disease onset (HR = 0.11, 95% CI = 0.02-0.83, p = 0.032), unchanged when accounting for MS risk factors.

Conclusion: Brain reserve might counteract the pathological mechanisms ongoing after biological initiation, thus delaying the disease overt clinical manifestation.

Introduction: Multiple sclerosis (MS) is an immune-mediated central nervous system disorder and a growing global health challenge affecting nearly 3 million people worldwide. Incidence and prevalence continue to increase with no known cause or cure. Globally governments and non-profit organizations fund research toward better understanding of and treatments for multiple sclerosis.

Methods: This study identified MS research projects funded between 2021 and 2023 by government and non-profit organization sources. Projects were described by type of scientific approach, Pathways to Cure research category (i.e. Stop, Restore, End), and other key characteristics.

Results: Over 2,300 MS research projects were identified through 16 non-profit MS organizations and 18 government databases. The overall global portfolio of these projects is valued at nearly one and a half billion Euros. The majority of projects were classified in the Stop category (60%). Research collaboration occurs in many forms among the research community; around 272 projects were reported to be co-funded.

Conclusion: Global MS research collaboration will accelerate progress toward increased knowledge, effective treatments, improved health outcomes, and ultimately cures for MS. This landscape analysis highlights the current distribution of MS research investment between topics and begins to suggest where the MS community should focus to increase potential impact for current and future endeavors.

Background: Conflicting data exist around oral contraceptive exposure and subsequent multiple sclerosis (MS).

Objective: To use routinely collected primary healthcare data to explore the potential association between oral contraceptive exposure and subsequent MS in females at population level.

Methods: We performed a nested case-control study using electronic primary care data, with complete electronic ascertainment from 1990. Logistic regression was used to evaluate associations between contraceptive exposure and MS, without and with adjusting for age, ethnicity and deprivation.

Results: A total of 4455 females were included: 891 cases and 3564 controls. No association was seen between oral contraceptive exposure and subsequent MS, or between any contraceptive, combined oral contraceptive pill (COCP) or progesterone-only pill (POP) use 0-2, 2-5 or >5 years prior to MS. Conclusions: In the largest population-based study to date, we find no evidence of an association between oral contraceptive exposure and subsequent MS diagnosis.

Background: People with multiple sclerosis (pwMS) are at risk of concurrently using multiple central nervous system (CNS)-active drugs, yet the prevalence of CNS-active polypharmacy remains unmeasured in pwMS.

Objective: The objective is to measure the prevalence of CNS-active polypharmacy in pwMS.

Methods: This serial, cross-sectional study measured CNS-active polypharmacy in people with MS in the United States from 2008 to 2021 using insurance claims data. CNS-active polypharmacy was defined as the concurrent prescription of ⩾3 CNS-active drugs for >30 continuous days. CNS-active drugs included antidepressants, antiepileptics, antipsychotics, benzodiazepines, nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants.

Results: The number of subjects included at each time point ranged from 23,917 subjects in 2008 to 55,797 subjects in 2021. In 2021, subjects with CNS-active polypharmacy were more likely to be 46-65 years of age and have CNS-related comorbidities compared to those without CNS-active polypharmacy. From 2008 to 2021, the age-adjusted prevalence of CNS-active polypharmacy among female subjects increased from 19.8% (95% confidence interval (CI) = 19.1-20.4) to 26.4% (95% CI = 25.9-26.8) versus 15.9% (95% CI = 14.8-17.0) to 18.6% (95% CI = 17.9-19.2) in male subjects.

Conclusion: The prevalence of CNS-active polypharmacy has increased among people with MS with a growing disparity by sex.

Background: Current guidance on the selection of appropriate contraception for people with multiple sclerosis (PwMS) is lacking.

Objective: To address this gap, an expert-led consensus program developed recommendations to support clinicians in discussing family planning and contraception with women and men with multiple sclerosis (MS).

Methods: A multidisciplinary steering committee (SC) of 13 international clinical experts led the program, supported by an extended faculty of 32 experts representing 18 countries. A modified Delphi methodology was used for decision-making and consensus-building. The SC drafted 15 clinical questions focused on patient-centered care, selection of contraception, and timing of stopping/starting contraception and disease-modifying therapies (DMTs). Statements addressing each question were drafted based on evaluation of published evidence and the experts' clinical experience. Consensus was reached if ⩾75% of respondents agreed (scoring 7-9 on a 9-point scale) with each recommendation.

Results: Consensus was reached on 24 of 25 proposed recommendations, including how and when to discuss contraception, types and safety of contraceptives, and how to evaluate the most appropriate contraceptive options for specific patient groups, including those with significant disability or being treated with DMTs.

Conclusion: These expert recommendations provide the first practical, relevant, and comprehensive guidance for clinicians on the selection of contraception in PwMS.

Background: Employing a rebaselining concept may reduce noise in retinal layer thinning measured by optical coherence tomography (OCT).

Methods: From an ongoing prospective observational study, we included patients with relapsing multiple sclerosis (RMS), who had OCT scans at disease-modifying treatment (DMT) start (baseline), 6-12 months after baseline (rebaseline), and ⩾12 months after rebaseline. Mean annualized percent loss (aL) rates (%/year) were calculated both from baseline and rebaseline for peripapillary-retinal-nerve-fiber-layer (aLpRNFL_baseline/aLpRNFL_rebaseline) and macular-ganglion-cell-plus-inner-plexiform-layer (aLGCIPL_baseline/aLGCIPL_rebaseline) by mixed-effects linear regression models.

Results: We included 173 RMS patients (mean age 31.7 years (SD 8.8), 72.8% female, median disease duration 15 months (12-94) median baseline-to-last-follow-up-interval 37 months (18-71); 56.6% moderately effective DMT (M-DMT), 43.4% highly effective DMT (HE-DMT)). Both mean aLpRNFL_baseline and aLGCIPL_baseline significantly increased in association with relapse (0.51% and 0.26% per relapse, p < 0.001, respectively) and disability worsening (1.10% and 0.48%, p < 0.001, respectively) before baseline, but not with DMT class. Contrarily, neither aLpRNFL_rebaseline nor aLGCIPL_rebaseline was dependent on relapse or disability worsening before baseline, while HE-DMT significantly lowered aLpRNFL_rebaseline (by 0.31%, p < 0.001) and aLGCIPL_rebaseline (0.25%, p < 0.001) compared with M-DMT.

Conclusions: Applying a rebaselining concept significantly improves differentiation of DMT effects on retinal layer thinning by avoiding carry-over confounding from previous disease activity.