Persistent progression independent of relapse activity in multiple sclerosis.

Patients with relapsing-remitting multiple sclerosis (RRMS) may experience disability progression independent of relapse activity (PIRA), which can be an early sign of secondary progressive MS (SPMS). We defined persistent PIRA as ongoing sustained disability over the entire available follow-up period. However, PIRA events can regress over time.

Haematopoietic stem cell transplant versus immune-reconstitution therapy in relapsing multiple sclerosis.

In the treatment of relapsing-remitting multiple sclerosis, autologous hematopoietic stem cell transplant and immune-reconstitution therapies show several similarities. These treatment strategies have not yet been compared head-to-head. This study emulated pairwise trials of comparative effectiveness of stem cell transplant vs.

Corticosteroid treatment of multiple sclerosis relapses is associated with lower disability worsening over 5 years.

Background: Corticosteroid treatment of multiple sclerosis (MS) relapses is assumed to improve the speed of relapse recovery, without modifying long-term disability risk. We aimed to re-evaluate this assumption in a large cohort of individuals with MS.

Methods: Individuals with clinically definite MS and ≥3 Expanded Disability Status Scale (EDSS) measurements over ≥12 months were identified within the international neuroimmunology registry MSBase.

Personalized federated learning for predicting disability progression in multiple sclerosis using real-world routine clinical data.

Early prediction of disability progression in multiple sclerosis (MS) remains challenging despite its critical importance for therapeutic decision-making. We present the first systematic evaluation of personalized federated learning (PFL) for 2-year MS disability progression prediction, leveraging multi-center real-world data from over 26,000 patients. While conventional federated learning (FL) enables privacy-aware collaborative modeling, it remains vulnerable to institutional data heterogeneity.

Ponesimod as add-on treatment in patients with active relapsing multiple sclerosis under dimethyl fumarate (POINT): A phase 3, randomized, placebo-controlled clinical trial.

Background: Combining two oral therapies with different mechanisms could be an attractive treatment strategy for multiple sclerosis (MS) to increase efficacy; however, evidence of such efficacy and safety is lacking.

Objectives: The phase 3 randomized, double-blind, placebo-controlled POINT study evaluated efficacy and safety of ponesimod 20 mg versus placebo as an add-on therapy to ongoing dimethyl fumarate (DMF) treatment in patients with active relapsing MS despite DMF monotherapy.

Methods: Patients (18-55 years) were randomized (1:1) to ponesimod+DMF or placebo+DMF orally once-daily for ≤156 weeks.

Four years on: Pregnancy and birth outcomes reported in the MSBase pregnancy, neonatal outcomes, and Women's Health Registry (2020-2024).

Background: Family planning is an important aspect of multiple sclerosis (MS), and neuromyelitis optica spectrum disorder (NMOSD) management. Knowledge gaps remain, including optimal perinatal management strategies, and fetal risks associated with disease-modifying therapy (DMT) exposure.

Objective: To describe perinatal DMT use, together with pregnancy and neonatal outcomes prospectively recorded in the International MSBase Pregnancy and Women's Health Registry.

Steroidomic Changes in the Cerebrospinal Fluid of Women with Multiple Sclerosis.

Multiple sclerosis (MS) is a long-term disease that causes inflammation and damage to the nervous system. This study evaluated steroidomic alterations related to MS in 57 female MS patients during the follicular phase and 17 during the luteal phase, as well as in age- and phase-matched controls. The data showed that (1) unconjugated and conjugated steroids were strongly linked between the blood and CSF.

SARS-CoV-2 Is Linked to Brain Volume Loss in Multiple Sclerosis.

Objective: The impact of SARS-CoV-2 infection on brain and spinal cord pathology in patients with multiple sclerosis (pwMS) remains unclear. We aimed to describe changes in brain lesion activity and brain and spinal cord volumes following SARS-CoV-2 infection.

Methods: We included 177 pwMS (570 MRI scans) diagnosed with and tested positive for SARS-CoV-2 infection between August 2020 and May 2021.

Standardized Definition of Progression Independent of Relapse Activity (PIRA) in Relapsing-Remitting Multiple Sclerosis.

Importance: Progression independent of relapse activity (PIRA) is a significant contributor to long-term disability accumulation in relapsing-remitting multiple sclerosis (MS). Prior studies have used varying PIRA definitions, hampering the comparability of study results.

Objective: To compare various definitions of PIRA.

Clinical risk stratification: Prague validation of the DAAE score, a clinical tool for estimating risk of disesase progression in multiple sclerosis.

Background: Secondary progressive MS is associated with a worse prognosis, warranting the need for early predictive tools. The DAAE score estimates the five-year risk of transition to clinical diagnosis of SPMS, showing a 38 % risk in high-risk patients in Amsterdam and Buffalo data. The DAAE score remains to be validated against objective disease progression criteria.

Effect of Treatment on Steroidome in Women with Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease of the central nervous system. The manifestation of MS is related to steroid changes during the menstrual cycle and pregnancy. As data focusing on the effect of anti-MS drug treatment on steroidome are scarce, we evaluated steroidomic changes (79 steroids) in 61 female MS patients of reproductive age 39 (29, 47) years (median with quartiles) after treatment with anti-MS drugs on the GC-MS/MS platform and immunoassays (cortisol and estradiol).

Explainable time-to-progression predictions in multiple sclerosis.

Background: Prognostic machine learning research in multiple sclerosis has been mainly focusing on black-box models predicting whether a patients' disability will progress in a fixed number of years. However, as this is a binary yes/no question, it cannot take individual disease severity into account. Therefore, in this work we propose to model the time to disease progression instead.

Treatment De-escalation in Relapsing-Remitting Multiple Sclerosis: An Observational Study.

Background: In relapsing-remitting multiple sclerosis (RRMS), extended exposure to high-efficacy disease modifying therapy may increase the risk of side effects, compromise treatment adherence, and inflate medical costs. Treatment de-escalation, here defined as a switch to a lower efficacy therapy, is often considered by patients and physicians, but evidence to guide such decisions is scarce. In this study, we aimed to compare clinical outcomes between patients who de-escalated therapy versus those who continued their therapy.

Lysate of prevents severe forms of experimental autoimmune encephalomyelitis by modulating the priming of T cell response.

The gut microbiota influences the reactivity of the immune system, and has emerged as an anti-inflammatory commensal. Here, we investigated whether its lysate could prevent severe forms of neuroinflammation in experimental autoimmune encephalomyelitis (EAE) in mice and how this preventive strategy affects the gut microbiota and immune response. Lysate of anaerobically cultured (Pd lysate) was orally administered to C57BL/6 mice in four weekly doses.

Altered Steroidome in Women with Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) mainly afflicting young women. Various steroids can influence the onset and development of the disease or, on the contrary, mitigate its course; however, a systematic review of steroidomic changes in MS patients is lacking. Based on the gas chromatography tandem mass spectrometry (GC-MS/MS) platform and, in the case of estradiol, also using immunoassay, this study performed a comprehensive steroidomic analysis in 25 female MS patients aged 39(32, 49) years compared to 15 female age-matched controls aged 38(31, 46) years.

Lipid and brain volumetric measures in multiple sclerosis patients: findings from a large observational study.

Objectives: This study aimed to investigate relationships between cholesterol profile, brain volumetric MRI, and clinical measures in a large observational cohort of multiple sclerosis (MS) patients.

Materials And Methods: We included 1.505 patients with 4.

Multiple sclerosis: emerging epidemiological trends and redefining the clinical course.

Multiple sclerosis is a chronic, inflammatory, and neurodegenerative disease of the central nervous system and a major cause of neurological disability in young adults. Its prevalence and incidence are increasing, and it has been estimated at over 2.8 million cases worldwide, in addition to recent trends towards a shift in MS prevalence to older ages, with peak prevalence estimates in the sixth decade of life.

Disease Activity in Pregnant and Postpartum Women With Multiple Sclerosis Receiving Ocrelizumab or Other Disease-Modifying Therapies.

Background And Objectives: Women with multiple sclerosis (MS) are at risk of disease reactivation in the early postpartum period. Ocrelizumab (OCR) is an anti-CD20 therapy highly effective at reducing MS disease activity. Data remain limited regarding use of disease-modifying therapies (DMTs), including OCR, and disease activity during peripregnancy periods.

Lipid measures are associated with cognitive functioning in multiple sclerosis patients.

Background: An association between lipid measures and cognitive decline in patients with multiple sclerosis (MS) has been suggested.

Objectives: This study aimed to investigate relationships between lipid profile and cognitive performance in a large observational cohort of MS patients.

Materials And Methods: We included 211 patients with 316 available pairs of lipid and cognitive measures performed over follow-up.

Patients with multiple sclerosis who develop immunogenicity to interferon-beta have distinct transcriptomic and proteomic signatures prior to treatment which are associated with disease severity.

Anti-drug antibodies (ADA) reduce the efficacy of immunotherapies in multiple sclerosis (MS) and are associated with increased disease progression risk. Blood biomarkers predicting immunogenicity to biopharmaceuticals represent an unmet clinical need. Patients with relapsing remitting (RR)MS were recruited before (baseline), three, and 12 (M12) months after commencing interferon-beta treatment.

Real-world effectiveness of cladribine as an escalation strategy for MS: Insights from the Czech nationwide ReMuS registry.

Background: Cladribine, a selective immune reconstitution therapy, is approved for the treatment of adult patients with highly active multiple sclerosis (MS).

Objectives: Provide experience with cladribine therapy in a real-world setting.

Methods: This is a registry-based retrospective observational cohort study.