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Live Attenuated Measles-Mumps-Rubella and Varicella Vaccinations and Multiple Sclerosis Activity.

IMPORTANCE: Live attenuated measles-mumps-rubella (MMR) and varicella vaccines are recommended for immunocompetent people with multiple sclerosis (MS) lacking immunity. However, concerns about postvaccination relapses may contribute to vaccine hesitancy, and robust data addressing this risk remain limited. OBJECTIVE: To assess whether the risk of MS relapse within 1 year after MMR or varicella vaccination is not unacceptably worse than risk after no such vaccination based on a predefined noninferiority margin. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used prospectively collected …

Disentangling verbal learning performance in multiple sclerosis: Dissociating strategy initiation and maintenance.

Objectives: Performance in verbal learning tests conflates two distinct executive mechanisms: the ability to generate a semantic strategy and the ability to maintain it over time. Deconstructing verbal learning performance may help in the design of personalized cognitive rehabilitation interventions. Methods: We analyzed verbal learning performances of 558 people with MS and 501 healthy controls. The initiation index (first successful semantic cluster) and the cessation index (trial where clustering was permanently abandoned) were calculated. Linear and multinomial logistic regressions adjuste

Targeting pyruvate kinase M2 (PKM2) reduces T cell pathogenicity in multiple sclerosis.

BACKGROUND: Pyruvate kinase M2 (PKM2) is an enzyme with moonlighting activities that controls murine T cell pro-inflammatory potential in a mouse model of multiple sclerosis (MS). However, no study analysed in detail the expression of PKM2 in human T cell subsets, and whether targeting PKM2 may limit the inflammatory potential of T cells from patients with MS is unknown. METHODS: In this observational, case control study we evaluated the expression of PKM2 in circulating T cells of healthy control individuals (HCs) and patients with MS, as well as its isomerisation in peripheral blood mononuc…

Assessing nonlinear gait characteristics in multiple sclerosis: Insights from a systematic review.

BACKGROUND: Multiple sclerosis is a chronic neurodegenerative disease that often compromises gait, a key determinant of independence and quality of life. Nonlinear gait analysis may provide useful information about motor control alterations in people with multiple sclerosis, yet current evidence remains limited and fragmented. This systematic review synthesized research on nonlinear gait variables in this population, focusing on entropy, Lyapunov exponents, and detrended fluctuation analysis. METHODS: This systematic review followed PRISMA guidelines and included studies retrieved from PubMed…

From emergency myelopoiesis to chronic myeloid reprogramming: hematopoietic dysregulation in multiple sclerosis.

Multiple sclerosis (MS) is classically understood through pathogenic T and B cell responses, while increasing evidence indicates that altered myelopoiesis and bone marrow-derived myeloid programs also contribute to disease initiation and progression. This review summarizes the dynamic evolution of hematopoietic dysregulation in MS, proposing a pathological mechanism spanning from transient emergency myelopoiesis to persistent chronic myeloid reprogramming. Driven by sustained inflammatory stress, hematopoietic stem and progenitor cells (HSPCs) undergo epigenetic remodeling to acquire a stable …

Neuropathic pain in multiple sclerosis: discrepancies between DN4 screening and neurophysiological measures.

BACKGROUND: Pain is a common and disabling symptom in multiple sclerosis (MS), yet its pathophysiological mechanisms remain poorly understood. Clinical assessment of neuropathic pain relies largely on subjective screening tools such as the DN4 questionnaire. This study aimed to characterize pain phenotype in MS using the DN4 score and to determine its relationship with objective neurophysiological markers of nociceptive and non-nociceptive pathway function assessed by laser-evoked (LEPs) and somatosensory evoked potentials (SEPs). METHODS: Fifty MS patients reporting pain underwent standardiz…

A Pre-symptomatic phase of tumefactive multiple sclerosis mirrors radiologically isolated syndrome.

INTRODUCTION: Tumefactive multiple sclerosis (TMS) is characterized by large brain demyelinating lesions, often with severe, disabling attacks. While MS can be preceded by a radiologically isolated syndrome (RIS), a pre-symptomatic phase in TMS is not well described. AIM: To characterize pre-symptomatic TMS and compare its frequency and symptomatic evolution to a non-tumefactive MS (nTMS) cohort. METHODS: Adults (≥18 years) with ≥1 tumefactive demyelinating lesion (TDL; ≥2 cm), fulfilling 2024 McDonald Criteria were included. Pre-symptomatic TMS was defined as an incidental TDL fulfilling th…

Rethinking EDSS-based ambulation assessment in multiple sclerosis using continuous variable monitoring.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by relapses and progressive disability. The Expanded Disability Status Scale (EDSS), used to quantify disability, is based on single, discretely assessed and potentially inaccurate patient-estimated walking ability, whereas digital health technologies (DHTs) enable continuous activity monitoring and more objective assessment of real-world functional performance. METHODS: In this prospective observational study conducted at two German centers, patients with relapsing-remittin…

Global overview of multiple sclerosis care units: an international cross-sectional survey.

BACKGROUND: Multiple sclerosis care units (MSCUs) are a reference model for multidisciplinary MS care, yet comparable global data on their structure, resources, and performance remain limited. OBJECTIVE: To characterize the global landscape of MS centers and evaluate compliance with multidisciplinary standards using a simplified, scalable classification framework. METHODS: An international cross-sectional survey (2020-2021) collected validated responses from 198 MS centres across 38 countries. Comparative analyses focused on 168 hospital-based centres. MSCUs were initially classified as type…

Impact of multiple sclerosis disease-modifying therapies on chronic lesion tissue expansion.

BACKGROUND: Chronic lesion tissue expansion (CLTE) reflects slow, concentric growth of established multiple sclerosis (MS) lesions and is linked to central brain atrophy and disability progression. Whether existing MS disease-modifying therapies (DMTs) differentially influence this aspect of progressive MS biology remains unclear. OBJECTIVES: To compare the effect of current DMTs on CLTE in a multicentre, real-world MS cohort. METHODS: We conducted a retrospective, observational study using linked clinical data from MSBase and the MSBase Imaging Repository. Data from patients aged ⩾18 years …

Choroid plexus morphological and microstructural changes across inflammatory phenotypes in multiple sclerosis.

BACKGROUND: Growing evidence supports choroid plexus (CP) involvement in MS pathophysiology, but phase-specific associations according to recent inflammatory activity and longitudinal dynamics remain unclear. OBJECTIVE: To characterize CP alterations in MS using volumetric and quantitative magnetic resonance imaging (MRI) and explore associations with neuroinflammation and neurodegeneration. METHODS: We analyzed cross-sectional and 2-year longitudinal data from 101 patients with active relapsing MS (RMS), 83 with inactive progressive MS (PMS), and 100 controls, with MS groups stratified by i

Treatment escalation after clinically silent MRI lesions in relapsing-remitting multiple sclerosis.

Clinically silent MRI lesions occur frequently in people with relapsing-remitting multiple sclerosis (RRMS) despite disease modifying therapy (DMT). Guidelines only routinely recommend DMT escalation after multiple silent lesions, and adherence is variable. We explored outcomes and the effect of treatment escalation following single and multiple on-treatment silent lesions. This cohort study and emulated target trial used MSBase registry data from 99 clinics in 26 countries between 2007 and 2025. Clinically stable participants receiving any DMT for RRMS with silent lesions versus without silen…

Genome-wide association analyses highlight the neuronal contribution to multiple sclerosis susceptibility.

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease. Previous genetic studies have identified susceptibility loci that primarily impact immune cells and microglia. Here we performed a multi-ancestry genome-wide association study of 20,831 MS cases and 729,220 controls and identified 236 susceptibility variants outside of the major histocompatibility complex, including four novel genomic loci. We also derived a polygenic score for MS; while optimized for European ancestry, it is informative for African American and Latino individuals. Integrating single-cell data fro…

Optimizing rituximab dosing in multiple sclerosis: Real-world outcomes with interval extension.

BACKGROUND: Rituximab is highly effective in multiple sclerosis (MS), but optimal dosing intervals are unclear; extended interval dosing (EID) may preserve disease control while reducing treatment burden and cost. OBJECTIVE: To prospectively evaluate whether structured, progressive extension of rituximab infusion intervals after initial treatment could be implemented without an increase in disease activity, and to assess B-cell kinetics and infection risk. METHODS: In this single- centre prospective study,126 patients received 655 rituximab infusions. Initial standard (SD) and non-standard (…

Коэффициент активации талонов при множественном склерозе: от периферической воспаления до центральной нейродегенерации.

Множественный склероз (MS) представляет собой хроническое воспалительное и нейродегенеративное заболевание, при котором периферическая иммунная активация, дисфункция мозгового барьера (BBB) и повреждение центральной нервной системы (CNS) тесно взаимосвязаны. Фактор активации талонов (PAF) является мощным посредником, занимающимся воспалением фосфолипида, активацией тромбоцитов, окислительным стрессом и нейронным сигналом. Повышение уровней PAF в плазме и цереброспиновой жидкости (CSF) пациентов с MS свидетельствует о их вовлеченности как в периферийные, так и в центральные процессы заболеваний

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease in which peripheral immune activation, blood-brain barrier (BBB) dysfunction, and central nervous system (CNS) injury are closely interconnected. Platelet-activating factor (PAF) is a potent phospholipid mediator involved in inflammation, platelet activation, oxidative stress, an…

Смолдинг нейроинфламмации в прогрессивном множественном склерозе: механизмы, визуальные биомаркеры и терапевтические возможности.

Прогрессивный множественный склероз (MS) по-прежнему является серьезной терапевтической проблемой, поскольку инвалидность часто продолжает накапливаться, несмотря на эффективный контроль за рецидивами и новыми головными провокационными повреждениями. Эта диссоциация говорит о том, что прогресс определяется не только острым воспалением, но и отдельным процессом, который все чаще называется задушающим нейро-воспалением. Последние данные подтверждают, что хронические активные повреждения являются важным, но не эксклюзивным патологическим субстратом этого процесса. Эти повреждения характеризуются

Совпадение в аннотации оригинала
Progressive multiple sclerosis (MS) remains a major therapeutic challenge because disability often continues to accumulate despite effective control of relapses and new focal inflammatory lesions. This dissociation suggests that progression is driven not only by acute inflammation, but also by a distinct process increasingly termed smoldering neuroinflammati…

Boundary-anchored thalamic ADC profiling shows spatially structured abnormalities in multiple sclerosis.

PURPOSE: Diffusion MRI is sensitive to tissue abnormalities in multiple sclerosis (MS), but conventional region-of-interest measures reduce spatially structured signal patterns to a single summary value. We evaluated boundary-anchored thalamic apparent diffusion coefficient (ADC) profiling in MS using line-based edge-anchored profiling (LEAP). MATERIALS AND METHODS: In this retrospective matched-control study, age- and sex-matched controls (CTRL, n = 28) and participants with relapsing-remitting MS (RRMS, n = 14) or secondary progressive MS (SPMS, n = 14) were analyzed on the same 3T MRI scan…

Воображаемые подтипы обнаруживают различные биологические субстраты и профили инвалидности в множестве склерозов.

Множественный склероз характеризуется ярко выраженной биологической неоднородностью, которая лишь частично улавливается традиционными клиническими фенотипами и возрастными категориями. МРТ может выявлять фокусные повреждения, диффузные микроструктурные повреждения и атрофию, однако эти меры обычно рассматриваются отдельно. Поэтому мы намеревались использовать подтип и стадию < < Происхождение > > ( < < SuStaIn > > ), неконтролируемую систему машинного обучения, для выявления биологически значимых подтипов МРТ с множественным склерозом и определения их связей с инвалидно

Совпадение в аннотации оригинала
Multiple sclerosis is characterized by marked biological heterogeneity that is only partly captured by conventional clinical phenotypes and age-at-onset categories. MRI can detect focal lesions, diffuse microstructural damage and atrophy, but these measures are usually considered separately. We therefore aimed to use Subtype and Stage Inference (SuStaIn), an…

Дефекты цереброспинальной жидкости, приводимые в движение эпендимальной мотиловой килии, связаны с множественным склерозом.

Множественный склероз (MS) — расстройство CNS, в котором автоматически реактивные иммунные клетки мигрируют через поврежденный мозговый барьер, приводящий к повреждениям мозга. Помимо основных повреждений, существуют также диффузные "поверхностные" градиенты патологии в MS, где повреждения являются наиболее серьезными непосредственно рядом с контактными поверхностями CSF, такими как подпиальные и перивентные зоны. Это наблюдение свидетельствует о том, что наличие и/или эволюция градиентов поверхностных частиц способствуют воздействию токсичных факторов в рамках РСФ. Прямое отделение CSF от пер

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a disorder of the CNS in which autoreactive immune cells migrate through a damaged blood-brain barrier, resulting in focal demyelinating lesions. Beyond focal lesions, there are also diffuse 'surface-in' gradients of pathology in MS, wherein damage is most severe directly adjacent to CSF-contacting surfaces, such as the subpial and…