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B cell tolerance checkpoint function in multiple sclerosis and transient CD52 depletion.

Transient CD52 immune cell depletion with the monoclonal antibody alemtuzumab is highly effective in treating relapsing-remitting multiple sclerosis but often leads to secondary autoimmunity. Whether these effects are linked to an alteration of B cell tolerance mechanisms is currently not known. To evaluate peripheral B cell tolerance checkpoint integrity in patients and controls, we constructed 138 recombinant mAbs from single mature naïve B cells and tested their poly- and autoreactivity. We examined three healthy donors (HDs), three immunotherapy-naïve MS patients, and six patients treated …

Hematopoietic stem cell transplantation for multiple sclerosis: Improving understanding and addressing misconceptions.

Autologous hematopoietic stem cell transplantation (HSCT) for multiple sclerosis (MS) is the technique of administrating a short immunosuppressive regimen over 4-6 days (depending on the drug regimen) followed by intravenous infusion of one's own hematopoietic stem cells to hasten hematopoietic recovery. The toxicity and efficacy of the procedure depend on the regimen and on patient selection and, to a lesser extent, on center experience. MS-specific nonmyeloablative regimens are less toxic and safer than myeloablative regimens that were initially developed for cancer. To date, there have been…

Shared Genetic Effects and Antagonistic Pleiotropy Between Multiple Sclerosis and Common Cancers.

OBJECTIVE: Epidemiologic studies have reported inconsistent altered cancer risk in individuals with multiple sclerosis (MS). Factors such as immune dysregulation, comorbidities, and disease-modifying therapies may contribute to this variability. This study aimed to assess the potential causal effects and shared genetic risk between MS and 12 common cancers. METHODS: We used large-scale genetic studies for MS (47,429 cases, 68,374 controls) and 12 cancers (sample size 85,716 to 417,127). Two-sample Mendelian randomization (MR) was performed to estimate the causal effect of genetic liability to…

Steps to Health: Backward Walking Predicts Physical Activity Levels in Multiple Sclerosis.

BackgroundPhysical activity (PA) supports physical, cognitive, and mental health, yet is often limited in persons with multiple sclerosis (PwMS) due to mobility, cognitive, and psychological factors. Practical methods to identify those meeting PA recommendations are needed. This study aimed to develop a clinically useful approach combining patient-reported outcomes and objective measures to determine whether PwMS meet step count goals.MethodsParticipants completed mobility assessments (static balance, reactive balance, forward walking [FW], and backward walking [BW]), cognitive testing, and se…

Multiple Sclerosis-Specific Reference Curves for Brain Volumes to Explain Disease Severity.

In the Research Article “Multiple Sclerosis–Specific Reference Curves for Brain Volumes to Explain Disease Severity” by van Nederpelt et al.,1 the confidence intervals in the first sentence of the MS-Specific Brain Volume Reference Model section and the penultimate sentence of the Predictive Value of Reference Quartiles section have been corrected. Figure 1 has been replaced to include data points that were mistakenly omitted. In addition, D.R. van Nederpelt and L. Bos should be noted as sharing first authorship, and M.M. Schoonheim and H. Vrenken should share senior authorship. The article ha…

Immune Checkpoint Signatures Reveal Stage-Specific Biomarkers for High-Activity Multiple Sclerosis.

The early identification of patients with highly active multiple sclerosis (HAMS) is crucial for guiding therapeutic decisions and initiating high-efficacy treatment strategies. This study aimed to characterize peripheral immune profiles that can distinguish between patients who are candidates for intensive therapy at disease onset and in later stages. Using spectral flow cytometry, we identified distinct immune signatures to differentiate early-stage patients from those with refractory, long-standing disease. In newly diagnosed individuals, decreased herpesvirus entry mediator (HVEM) expressi…

Optical Coherence Tomography Angiography-Derived Peripapillary Vessel Density Findings in Multiple Sclerosis.

Background/Objectives: Multiple sclerosis (MS)-related optic neuritis (ON) results in thinning of the peripapillary nerve fiber layer (pRNFL) which tends to be temporal quadrant-predominant. Optical coherence tomography angiography (OCTA) enables visualization of the retinal vasculature. Prior studies have shown reduced peripapillary vessel density (VD) in MS but data on the quadrantic pattern of peripapillary VD loss are limited. Our objective was to investigate the pattern of OCTA-derived peripapillary VD reduction in MS. Methods: People with MS (PwMS) and healthy controls (HC) underwent opt…

Genetic Determinants of Multiple Sclerosis Susceptibility in People From Diverse Ancestral Backgrounds.

BACKGROUND AND OBJECTIVES: The genetic basis of multiple sclerosis (MS) susceptibility has been studied extensively in European (EUR) ancestry populations. The aim of our study was to determine the genetic architecture of MS susceptibility in people of South Asian (SAS) and African (AFR) genetic ancestral backgrounds. METHODS: We recruited and genotyped a cohort of ancestrally diverse people with MS (pwMS) from across the United Kingdom. Cases were combined with controls from the UK Biobank (UKB). After genetic ancestry inference, we performed within-ancestry case-control genetic association …

Time-Varying Brain Functional Reconfiguration Patterns Associated With Fatigue in Multiple Sclerosis.

Fatigue affects between 36.5% and 78% of people with multiple sclerosis (pwMS) and significantly impairs daily life. The neurobiological mechanisms underlying fatigue remain poorly understood and information about the time-varying communication between brain regions and the networks they form may offer new insights into the complex pathology of MS-related fatigue. Brain regions continuously reconfigure how they communicate within distinct networks (i.e., time-varying reconfigurations) and aberrant time-varying reconfigurations may contribute to the perception of fatigue in pwMS. This study aim…

Ocular Manifestations of Multiple Sclerosis: A Retrospective, Population-Based Single-Center Study.

Background and objective Multiple sclerosis (MS) is an autoimmune disease that affects the central nervous system by causing inflammation and damage to myelinated axons. It often impacts the visual pathways, and optic neuritis (ON) is commonly the first symptom people notice. Eye movement disorders, including internuclear ophthalmoplegia (INO) and nystagmus, may result in double vision, oscillopsia, and reading fatigue. MS is also linked to ocular inflammation, such as pars planitis and retinal periphlebitis. This study aimed to identify the most common eye-related symptoms of MS and to determ…

Evidence of skull bone translocator protein overexpression linked to multiple sclerosis progression.

The skull bone marrow contributes to brain immune homeostasis via recently discovered skull-meningeal channels, enabling the bidirectional trafficking of immune cells between skull bone and underlying dura mater. In multiple sclerosis, autoreactive T cells migrate to the bone marrow and shift its haematopoietic output towards myeloid differentiation, contributing to disease progression. However, the role of the skull bone marrow in multiple sclerosis pathophysiology, and its relationship to brain damage and clinical disability remain largely unexplored. We utilized simultaneous MR-PET with the…

AI-enabled Living Labs: Accelerating innovation in multiple sclerosis care and research.

The rapid rise of artificial intelligence (AI) and digital health technologies presents new opportunities for personalized care in multiple sclerosis (MS). However, implementation in routine practice is limited by regulatory hurdles, fragmented infrastructure and a lack of agile real-world evaluation methods. Living Labs (LLs) emerge as dynamic environments for advancing MS care and research, supporting early testing and iterative development of digital tools, while fostering structured collaboration among patients, clinicians, researchers and regulators. In this review, we conceptually frame …

Calprotectin reveals distinct innate immune signatures in NMOSD, MOGAD, and multiple sclerosis.

BACKGROUND: Granulocyte-mediated injury contributes to the immunopathology of aquaporin-4 neuromyelitis optica spectrum disease (AQP4-NMOSD) and myelin oligodendrocyte glycoprotein-associated disease (MOGAD), yet calprotectin, a myeloid-derived inflammatory marker, has not been evaluated in these disorders. OBJECTIVE: To assess the diagnostic and activity-related potential of cerebrospinal fluid (CSF) and serum calprotectin concentrations in AQP4-NMOSD, MOGAD, seronegative or double-negative NMOSD (DNNMOSD) and RRMS. METHODS: In this observational study, CSF and serum calprotectin were measu

Patient experiences with systematically-administered patient-reported outcome measures in multiple sclerosis.

INTRODUCTION: There have been limited studies on the views of persons with MS (PwMS) around the systematic use of Patient Reported Outcome Measures (PROMs). The objective of this study was to explore the perspectives of PwMS on the integration of PROMs into clinical practice as part of a randomized trial. METHODS: We conducted a qualitative substudy of our previous randomized controlled trial (RCT)(Clinicaltrials.gov NCT0497954), which was conducted from November 2021 to April 2024 and evaluated the effect of the systematic use of PROMs on depression and anxiety in PwMS. In this sub-study tha

Immersive Virtual Reality Assessment in Multiple Sclerosis: Patient-Reported Experience and Correlates.

Background: Immersive virtual reality (VR) has emerged as a promising tool for standardized, engaging assessment of motor and cognitive function in people with multiple sclerosis (pwMS). However, patient-reported experiences with immersive VR tasks have not been systematically evaluated. Objective: To characterize patient-reported experience measures (PREMs) after a multidomain immersive VR task and explore relationships with clinical characteristics, therapeutic history, and task performance. Methods: In this prospective cross-sectional study, participants completed a seated immersive VR task…

Understanding Late-Stage Clinical Trial Failure in Multiple Sclerosis: Insights from ClinicalTrials.gov.

INTRODUCTION: Clinical trial failure - when a study is withdrawn or terminated for reasons unrelated to safety or efficacy - wastes resources and exposes patients to unnecessary risks. We examined such failures in the field of multiple sclerosis (MS). METHODS: We searched <ext-link ext-link-type="uri" xlink:href="http://ClinicalTrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">ClinicalTrials.gov</ext-link> for phase III and IV MS drug trials conducted in 2008-2024. Trials were classified as normally ended or failed based on recruitment status and reported reasons. When information was mi…

Relapse-associated worsening in apolipoprotein E ε4 carriers with relapsing multiple sclerosis.

BACKGROUND: In multiple sclerosis (MS), disability accrual can arise from relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA). While genetic variants associated with increased MS severity have been identified, little is known on apolipoprotein E (ApoE) gene. This study aims to investigate the impact of the ApoE ε4 allele (ApoE4) on disability accrual in relapsing MS patients. METHODS: Patients with relapsing MS, aged >18 years, consecutively referred to the MS centre at the University of Florence, Italy, were recruited (n=160). Patients were classified as…

Accelerated Brain Aging Identifies Functional Vulnerability Beyond Chronological Age in Multiple Sclerosis.

Chronological age incompletely captures neurodegenerative burden and functional vulnerability in multiple sclerosis (MS). Brain-predicted age difference (Brain-PAD; predicted minus chronological age) provides an MRI-derived index of accelerated brain aging, but links to mobility and real-world behavior remain unclear. Forty-three adults with MS completed structural MRI, mobility testing, and six months of free-living physical activity monitoring. Brain age was estimated using PyBrainAge applied to FreeSurfer-derived cortical thickness and subcortical volumes. Hierarchical regressions tested wh…

Ultra-processed food consumption and multiple sclerosis incidence: A prospective cohort study.

BACKGROUND & AIMS: Emerging evidence suggests an association between ultra-processed food (UPF) consumption and neurodegenerative diseases, but there is limited evidence for multiple sclerosis (MS). Diets rich in UPFs promote inflammation and oxidative stress that both play an important role in modulating the immune system, and thereby, potentially the pathogenesis of MS. This study aimed to investigate the longitudinal association between UPF consumption and MS onset in middle-aged and older adults. METHODS: The study included 185,788 adults who completed at least one valid dietary assessmen…

Ручная обработка против методов извлечения глубоких признаков для диагностики множественной скlerоза на основе МРТ.

Фон: Несмотря на значительные продвижения в анализе медицинских изображений, автоматический диагноз множественной скlerоза (МС) на основе магнитно-резонансной томографии (МРТ) остается сложной задачей из-за сложности 3D-данных мозга и вариабельности вида плоскостей поражений. Цель: В этой работе мы предлагаем эффективную и оптимизированную систему извлечения признаков для автоматического диагноза МС с использованием МРТ с весом FLAIR, T1 и T2. Предложенный подход улучшает Декимальные Дескрипторные Паттерны (DDP) за счет интеграции локальной информации градиента, создавая 3D-представление текст

Совпадение в аннотации оригинала
Background: Despite significant advances in medical image analysis, automated diagnosis of Multiple Sclerosis (MS) from magnetic resonance imaging (MRI) remains challenging due to the complexity of 3D brain data and the variability of lesion appearance. Objective: In this work, we propose an efficient and optimized feature extraction framework for automated …