Age Matters in Multiple Sclerosis

Neurology, Journal Year: 2025, Volume and Issue: 104(4)

Published: Feb. 4, 2025

Language: Английский

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A New Perspective on Mechanisms of Neurodegeneration in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis: the Early and Critical Role of Platelets in Neuro/Axonal Loss

Journal of Neuroimmune Pharmacology, Journal Year: 2025, Volume and Issue: 20(1)

Published: Feb. 4, 2025

Abstract Multiple sclerosis (MS) is a central nervous system (CNS) autoimmune disorder, with limited treatment options. This disease characterized by differential pathophysiology between grey matter (GM) and white (WM). The predominant WM hallmark the perivascular plaque, associated blood brain barrier (BBB) loss of function, lymphocytic infiltration, microglial reactivity, demyelination axonal injury adequately addressed immunomodulatory drugs. By contrast, mechanisms underlying GM damage remain obscure, consequences for neuroprotective strategies. Cortical pathology already significant in early MS reduced BBB disruption infiltration relative to WM, but highly inflammatory environment, neuro/axonal loss. There no satisfactory explanation occurrence neurodegeneration without large-scale cell influx cortical GM. A candidate mechanism suggests that it results from soluble factors originating meningeal aggregates, which diffuse into tissue trigger activation. However, recent literature highlights role platelets inflammation, together relationship coagulation factors, particularly fibrinogen, MS. Using experimental encephalomyelitis (EAE) model, we identified as drivers neuroinflammation platelet-neuron associations pre-symptomatic stage. We propose fibrinogen leakage across signal platelet represent major participant neurodegeneration. concept compatible new appreciation immune cells neuronal driven sequestered meninges. Graphical

Language: Английский

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Persons with multiple sclerosis reveal distinct kynurenine pathway metabolite patterns: a multinational cross-sectional study

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 24, 2025

Abstract Neuroaxonal damage in multiple sclerosis (MS) results from an interplay of neurotoxic pathomechanisms combined with a reduced neuroprotective capacity neurons and glia to resist damage. Kynurenine pathway (KP) imbalance resembles some the molecular mechanisms central incompletely understood MS pathophysiology. To study role KP MS, we performed targeted metabolomics on serum samples 353 persons 111 healthy individuals, detected MS-specific differences concentrations most kynurenines. Using exploratory factor analysis, then identified two distinct metabolite patterns: inflammation-driven pattern „NeuroTox“ „NeuroPro“. Our show that greater lower „NeuroPro“ were associated higher disease severity. The novelty our data-driven approach patterns advocates for future studies using comparable approaches investigate whether follows similar disease-specific diseases other than MS.

Language: Английский

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Body Composition and Its Outcomes and Management in Multiple Sclerosis: Narrative Review

Nutrients, Journal Year: 2025, Volume and Issue: 17(6), P. 1021 - 1021

Published: March 14, 2025

Background: There is emerging interest in obesity and its prevalence, outcomes, management people with multiple sclerosis (MS). Body mass index (BMI) the traditional marker of MS, whereas body composition, inclusive specific tissue compartments (e.g., fat, bone, muscle), often overlooked despite relevance. Objective: This narrative review (a) underscored use utility dual-energy X-ray absorptiometry (DEXA) as an accurate reliable measure composition; (b) thematically analyzed synthesized current evidence regarding composition (using DEXA); (c) determined gaps to be addressed future research. Methods: The structure reporting this followed guiding criteria outlined Scale for Assessment Narrative Review Articles (SANRA). relevant literature was identified via a PubMed search utilizing combined terms such ‘body composition’ ‘multiple sclerosis’. research then organized by authors into major themes sub-themes. articles described within were based on saturation Results: Three identified, namely (1) comparison between MS non-MS controls (2 meta-analyses); (2) examination relationships range outcomes (14 cross-sectional studies); (3) interventions that report and/or target (11 clinical trials). Conclusions: mapped existing posits novel, informative, targeted concept population. underscores importance randomized controlled trials focus significant modifiable outcome. Such could improve understanding poor identify useful recommendations diagnosis management.

Language: Английский

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Advances in neuroimaging of multiple sclerosis

Current Opinion in Neurology, Journal Year: 2025, Volume and Issue: unknown

Published: March 19, 2025

Purpose of review To summarize recent advancements in understanding multiple sclerosis (MS) pathophysiology, predicting disease course, and monitoring treatment responses using MRI. Recent findings Paramagnetic rim lesions (PRLs) are highly specific to MS clinically relevant. Detected from the earliest phases, PRLs aid distinguishing other conditions, improving diagnostic accuracy. Moreover, associated with more severe disability measures brain damage may predict progression. Similarly, slowly expanding (SELs) a course. Disease-modifying therapies have limited effectiveness reducing or SELs. Choroid plexus (CP) enlargement is structural clinical predicts evolution. Enlarged perivascular spaces (ePVS) suggest microangiopathic changes rather than direct MS-related inflammation. Glymphatic dysfunction, evaluated diffusion tensor image analysis along space, emerges early correlates disability, cognitive impairment, damage. Aging comorbidities exacerbate damage, complicating diagnosis treatment. Emerging technologies, such as brain-age paradigms, aim disentangle aging MS-specific neurodegeneration. Summary Advances MRI highlighted significance chronic inflammation glymphatic dysfunction contributors progression well interplay between aging, MS.

Language: Английский

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Should we stay or should we go? Recent insights on drug discontinuation in multiple sclerosis

Neurological Research and Practice, Journal Year: 2025, Volume and Issue: 7(1)

Published: April 20, 2025

Abstract Background The decision to discontinue disease-modifying therapies (DMTs) in patients with multiple sclerosis (PwMS) is a critical clinical challenge. Historically, DMTs were discontinued due side effects, treatment limitations, or progression secondary progressive MS. However, advancements MS therapies, particularly high-efficacy (HE-DMTs) and the increased knowledge on disease courses phenotypes have resulted more personalized approaches introduced discussion scheduled DMT discontinuation. This review explores current evidence discontinuation, focusing its implications for aging populations interplay between cardiovascular diseases (CVD) Current CVD Randomized trials such as DISCOMS DOT-MS provided insights into discontinuing stable patients. In summary, both randomized highlight risk of reactivation following Due limited sample size, neither study was able conduct subgroup analyses based age groups. Additionally, terminated prematurely, direct comparisons other studies should be avoided. While older observational data (e.g., OFSEP) shown relapse risks associated drugs like natalizumab fingolimod, there HE-DMT discontinuation outcomes. Comorbidities, CVDs, further complicate decisions regarding continuation adults. bear higher burden CVD, which also unfavorable courses. optimizing profiles appears advisable, it remains unclear whether themselves positive impact CVDs. Conclusion Given complexities patients, essential balance avoidance polypharmacy potential comorbidities, especially progression. highlights importance holistic assessment when considering

Language: Английский

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Randomized controlled trials for multiple sclerosis: integrating pathology-driven outcomes to capture therapeutic efficacy

Journal of Neurology, Journal Year: 2025, Volume and Issue: 272(6)

Published: May 10, 2025

Language: Английский

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B- and T-cell Specific Responses to Vaccination against SARS-CoV-2 in Anti-CD20 Treated Patients with Relapsing-Remitting or Progressive Form of Multiple Sclerosis Reveal Immunosenescent Features

Published: July 4, 2024

Clinical, pathological, and imaging evidence in multiple sclerosis (MS) shows that inflammation starts early progresses with age. B cells play a central role this process, contributing to cytokine production, defective regulatory functions, abnormal immunoglobulin even the nervous system. Anti-CD20 (aCD20) therapies, which deplete CD20+ cells, are effective for both relapsing-remitting (RR) progressive-relapsing (PR) MS. While against MS symptoms lesions detectable by magnetic resonance imaging, aCD20 therapies can reduce immune response COVID-19 vaccination. By using high-parameter flow cytometry, we examined antigen-specific (Ag+) six months post-third mRNA-vaccination patients RR PR forms on therapy. Despite lower Ag+ cell responses levels of anti-SARS-CoV2, total neutralizing antibodies, developed strong T responses. We observed similar percentages numbers CD4+ high proportion CD8+ slight differences phenotype functionality, however suggested presence driven age disease severity.

Language: Английский

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SARS-CoV-2 Vaccination Responses in Anti-CD20-Treated Progressive Multiple Sclerosis Patients Show Immunosenescence in Antigen-Specific B and T Cells

Vaccines, Journal Year: 2024, Volume and Issue: 12(8), P. 924 - 924

Published: Aug. 17, 2024

Clinical, pathological, and imaging evidence in multiple sclerosis (MS) shows that inflammation starts early progresses with age. B cells play a central role this process, contributing to cytokine production, defective regulatory functions, abnormal immunoglobulin even the nervous system. Anti-CD20 (aCD20) therapies, which deplete CD20+ cells, are largely used treatment of both relapsing remitting (RR) progressive (PR) forms MS. Although effective against MS symptoms lesions detectable by magnetic resonance imaging, aCD20 therapies can reduce immune response COVID-19 vaccination. By using high-parameter flow cytometry, we examined antigen-specific (Ag+) six months post-third mRNA vaccination patients RR PR on therapy. Despite lower Ag+ cell responses levels anti-SARS-CoV2, total neutralizing antibodies, developed strong T responses. We observed similar percentages numbers CD4+ high proportion CD8+ slight differences phenotype functionality; this, however, suggested presence driven age disease severity.

Language: Английский

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Disability worsening outcome in multiple sclerosis based on EDSS: does half a point matter?

Journal of Neurology, Journal Year: 2024, Volume and Issue: 272(1)

Published: Dec. 12, 2024

Language: Английский

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