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Impaired myelination in multiple sclerosis organoids: p21 links oligodendrocyte dysfunction to disease subtype.

Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system. The cause of the disease is unknown but both genetic and environmental factors are strongly involved in its pathogenesis. We derived cerebral and spinal cord organoids from induced pluripotent stem cells (iPSC) from healthy controls as well as from primary progressive MS (PPMS), secondary progressive MS (SPMS) and relapsing-remitting MS (RRMS) patients to investigate and compare oligodendrocyte differentiation and myelination capacity. In MS organoids, particularly in PPMS, we observed a decrease in p2…

Histamine H4 receptor in neuroinflammation: Dual roles in multiple sclerosis and Parkinson's disease.

Neuroinflammation plays a pivotal role in the progression of neurodegenerative disorders such as multiple sclerosis (MS) and Parkinson's disease (PD), primarily through a self-amplifying positive feedback loop between inflammation and neurodegeneration. The histamine H4 receptor (H4R), expressed on both peripheral immune cells and central microglia, serves as a critical molecular interface linking peripheral immunity to central nervous system inflammation. This review provides a systematic analysis of the context-dependent, dual roles of H4R in neuroinflammatory processes underlying MS and PD.…

Prediagnostic prescription patterns in multiple sclerosis: a UK-based longitudinal linked data study.

BACKGROUND: Early detection of multiple sclerosis (MS) could improve patient outcomes. Changes in clinical activity before MS diagnosis may represent 'diagnostic windows' for earlier detection. AIM: To determine whether certain prescriptions are more common in patients with MS and examine prescription patterns prediagnosis in the UK. DESIGN AND SETTING: Case-control study using routinely collected primary care data. Patients in the case group had an MS diagnosis (2001-2022) and patients in the control group were matched by birth year. METHOD: Multivariable conditional logistic regression ad…

Emerging CSF and Serum Biomarkers in Multiple Sclerosis: Cytokines, MOG, GFAP, and Beyond.

BACKGROUND AND OBJECTIVES: Accurate biomarkers that reflect disease activity, severity, and molecular pathophysiology in multiple sclerosis (MS) remain an unmet diagnostic need. We compared the performance of the established biomarkers, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), with emerging candidates in CSF and serum. METHODS: We measured 21 analytes using Olink proximity extension assay technology, NfL and GFAP using Simoa, and soluble triggering receptor expressed on myeloid cells (sTREM2) and neuronal pentraxin 2 (NPTX2) using Fujirebio platforms in pair…

T cell-mediated immunodysregulation in multiple sclerosis: from pathogenic subsets to therapeutic advances.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) caused by chronic inflammation. It is the leading cause of neurologic symptoms in young people and leads to progressive neurodegenerative disability. Accumulating evidence indicates that MS arises from the coordinated and co-dominant actions of peripheral immune cells, meningeal tertiary lymphoid structures (TLS), and CNS-resident immune compartments. Within this complex immunopathological network, dysregulated T-cell-mediated adaptive immune responses play a pivotal role in initiating and organizing autoimm…

Impact of modern central nervous system radiation on multiple sclerosis relapse and progression.

BACKGROUND: Central nervous system (CNS) radiation is associated with primary demyelination and neurotoxicity in patients with existing demy … blastoma and 2 meningioma). CONCLUSIONS: Modern-day ionizing radiation to the CNS in patients with multiple sclerosis was not associated with clinical worsening but can potentially be associated with an increased risk of asymptomatic inflammatory MS disease activity.

Refining neuropsychological assessment strategies in multiple sclerosis: insights from long-term cognitive trajectories.

OBJECTIVE: Cognitive evolution in people with multiple sclerosis (pwMS) may follow different trajectories. This study investigated long-term cognitive evolution in pwMS while controlling for methodological factors and psychological variables, to refine neuropsychological monitoring. METHODS: A cohort of pwMS (n = 148) underwent neuropsychological evaluations at three time points: baseline (BL), re-baseline (RBL; ~ 1 year later), and long-term follow-up (LTFU; ~ 6 years after BL). Annualized cognitive change scores were analyzed to compare changes during BL-RBL interval with those in RB-LTFU. …

A novel multiplexed biomarker panel reveals key molecular pathways in progressive multiple sclerosis.

Progressive multiple sclerosis is characterized by gradual neurological decline, often occurring independently of relapses or MRI activity-a phenomenon known as progression independent of relapse and MRI activity (PIRMA). Despite the effectiveness of disease-modifying therapies in controlling inflammatory activity, identifying individuals at risk of PIRMA remains an unmet clinical need. The objective of this exploratory study was to identify biomarkers and underlying molecular pathways associated with multiple sclerosis progression and especially PIRMA. Using the NUcleic acid Linked Immuno-San…

Fluid biomarkers in multiple sclerosis: Indicators of disease activity, progression, and treatment response.

Multiple sclerosis (MS) is a chronic immune-mediated CNS disorder marked by inflammation, demyelination, and neurodegeneration. Standard clinical evaluation, neurological exams, disability scoring, and MRI often miss subclinical activity and poorly predict progression. Fluid biomarkers in cerebrospinal fluid (CSF) and blood provide objective, quantifiable indicators of disease activity, progression, and therapeutic response. Essential fluid biomarkers for monitoring MS include neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), Chitinase-3-like protein 1 (CHI3L1), C-X-C Mo…

Plumbagin ameliorates multiple sclerosis by inducing DDX3X-mediated stress granule assembly in mice.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) with limited therapeutic options. Stress granules (SGs), membraneless organelles formed via liquid-liquid phase separation (LLPS) in response to cellular stress, function as a cytoprotective mechanism against stress induced apoptosis and pyroptosis. SGs can counteract NLRP3 inflammasome by sequestering dead-box helicase 3 X-linked (DDX3X), thereby promoting the survival of pyroptotic cells. Here, we identified that plumbagin (PL), a natural naphthoquinone with antioxidant and anti-inflam…

First Reported Coexistence of Plasma Cell Gingivitis and Multiple Sclerosis: A Case Report.

BACKGROUND: Plasma cell gingivitis (PCG) is a rare, benign inflammatory condition of the oral mucosa characterized histologically by a dense plasmacytic infiltrate. Its etiology remains uncertain, with proposed triggers including allergens, infectious agents, and idiopathic immune reactions. Multiple sclerosis (MS), on the other hand, is a chronic autoimmune demyelinating disorder of the central nervous system that may indirectly influence oral health due to neurological impairment, altered immunity, or long-term medication use. However, the coexistence of PCG and MS is extremely rare, and to …

Disability profiles in progressive multiple sclerosis reflect pathology distribution, independent of clinical phenotype.

Multiple sclerosis (MS) is a clinically heterogeneous disease affecting both neurological and cognitive functions. In this study, we defined clinical profiles based on combined cognitive and motor assessments in progressive MS patients, examined their overlap with classical progressive phenotypes and linked each profile to MRI measures of network disconnection and grey matter atrophy. We analyzed baseline data from 580 participants [277 primary progressive (PP)MS, 303 secondary progressive (SP)MS] in the phase 3b CONSONANCE (NCT03523858) study. Clinical assessments included Expanded Disability…

Multimodal benefits of VR-based treadmill training in multiple sclerosis: A systematic review.

BACKGROUND: Motor and cognitive impairments in multiple sclerosis are progressive in nature and impair independence and overall quality of life. Although the use of a treadmill improves gait and endurance, there is limited benefit in regard to cognitive motor integration. Virtual reality offers multi-sensory, task-oriented environments that can enhance engagement and combine motor and cognitive rehabilitation. OBJECTIVES: This systematic review assessed the effectiveness of VR-enhanced treadmill training versus conventional treadmill training on gait, endurance, balance, and cognitive-motor p…

TSPO-PET-measurable neuroinflammation associates with information processing speed decline in multiple sclerosis.

BACKGROUND: Impaired information processing speed (IPS) is a common and disabling cognitive deficit in multiple sclerosis (MS). OBJECTIVES: To assess whether glial activation measured using translocator protein-positron emission tomography (TSPO-PET) predicts performance and long-term change on the Symbol Digit Modalities Test (SDMT). METHODS: Forty-eight people with MS underwent [¹¹C]PK11195 TSPO-PET, magnetic resonance imaging (MRI), diffusion tensor imaging and SDMT at baseline; 34 repeated SDMT a median (first to third quartile) 4.9 (3.7-5.2) years later. Glial activation was quantified …

Cognitive and structural brain changes in ofatumumab-treated multiple sclerosis: A longitudinal study.

Anti-CD20 therapies control inflammatory activity in multiple sclerosis (MS), but their effects on neurodegeneration and cognition in real-world settings remain uncertain. We conducted a longitudinal observational study of relapsing MS (RMS) patients treated with ofatumumab. Cognitive performance was assessed using the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS), with processing speed as the primary outcome, and Magnetic Resonance Imaging (MRI) measures included thalamic volume, deep gray matter (DGM) volume, and cortical thickness (CTh). Longitudinal changes and s…

TLR3 polymorphism protects against multiple sclerosis onset but not progression in Egyptian patients.

INTRODUCTION: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the CNS that results from complex interactions between the peripheral and the central immune systems through proinflammatory cytokine secretion. AIMS: The present study aimed to 1: estimate the associated risk of single nucleotide polymorphisms (SNPs) in genes regulating the immune responses, namely, Toll like receptor 3 (TLR3), TLR7, and Suppressor of cytokine signaling 3 (SOCS3), with MS incidence, 2: correlate the SNPs frequencies with some patient demographics. MATERIALS AND METHODS: A total of 192 M…

Long-Term IFN-β Therapy Enhances and Prolongs IFN Responses in Multiple Sclerosis.

Multiple sclerosis (MS) is a central nervous system (CNS) disease with autoimmune inflammation, demyelination, and neurodegeneration. Untreated MS patients exhibit subnormal activation of the p-Ser-STAT1 transcription factor in peripheral blood mononuclear cells (PBMCs), causing weak interferon (IFN) signaling and low expression of some IFN-stimulated genes (ISGs). IFN-β therapy reduces MS exacerbations, delays progression, and largely corrects abnormal gene expression in PBMC. We hypothesize that long-term IFN-β therapy improves weak IFN responses and regulates MS immunity through a priming e…

Tear CHI3L1 in multiple sclerosis: a non-invasive biomarker linked to disease progression.

OBJECTIVE: To evaluate tear CHI3L1 (tCHI3L1) as a minimally invasive biomarker in multiple sclerosis (MS), compare it with serum and cerebrospinal fluid (CSF) CHI3L1, and assess associations with clinical phenotype and disease measures. METHODS: This cross-sectional study included 111 MS patients (71 relapsing-remitting MS [RRMS] and 40 progressive MS [PMS]) and 23 healthy controls (HC). tCHI3L1 was quantified by optimized ELISA and normalized to tear volume (tCHI3L1 ratio). Paired tear-serum samples were available for 99 patients to measure sCHI3L1, sGFAP, and sNFL. Associations with age, Ex…

Multical Sclerosis Severity Alle res10191329A и Когнитивная функция: UK Biobank Study.

В рамках исследования, проведенного в рамках всей ассоциации генома по вопросу о жесткости множественных склерозов, генетический вариант rs10191329A увязывался с долгосрочной инвалидностью и в качестве одного из определяющих факторов исхода учитывала устойчивость мозга. Мы гипотезали, что rs10191329A может повлиять на когницию других неврологических заболеваний и здоровый контроль. Мы изучили связь между rs10191329A и когницией с использованием времени реакции, жидкого интеллекта и возможных тестов памяти в Биобанке Великобритании. Мы наблюдали слабые, но последовательные связи между rs1019132

Совпадение в аннотации оригинала
The genome-wide association study of Multiple Sclerosis severity linked the genetic variant rs10191329A to long-term disability and implicated brain resilience as a determinant of outcome. We hypothesised that rs10191329A might influence cognition in other neurological diseases and healthy controls. We explored the relationship between rs10191329A and cognit…

Infectious Agents in Multiple Sclerosis: Viral Triggers, Antibody-Mediated Autoimmunity, and Parasitic Immunomodulation.

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system characterized by demyelination, neuroinflammation, and progressive neurodegeneration. While there is a small component of genetic susceptibility to MS risk, environmental factors, including infectious exposures, are gaining increased recognition as playing a critical role in MS initiation and progression. Viral infections, especially by Epstein-Barr virus (EBV), have emerged as strong candidates and triggers of MS symptoms, through antibody-mediated molecular mimicry and B-cell dysregulation. In contrast…