Biomarkers of Intrathecal Synthesis May Be Associated with Cognitive Impairment at MS Diagnosis

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 826 - 826

Published: Jan. 19, 2025

The pathophysiology of cognitive impairment (CI) in multiple sclerosis (MS) remains unclear. Meningeal B cell aggregates may contribute to cortical grey matter pathology. Cerebrospinal fluid (CSF), kappa free light chains (KFLC), and KFLCs-Index (kappa-Index) are reliable quantitative markers intrathecal synthesis, but few data have been presented exploring the association with CI, no present for lambda FLC (LFLC) MS. We evaluated cognition using Brief International Cognitive Assessment MS (BICAMS) battery collected serum CSF at diagnosis newly diagnosed drug-naïve patients. observed that patients impaired verbal memory overall CI showed increased KFLCs (respectively p: 0.0003 0.003) kappa-Index 0.01 0.02) compared those normal CI. Patients also displayed lower LFLCs (p: 0.04) lambda-Index 0.001); however, only KFLC negatively correlated normalized results (for age, sex, educational levels), even after correction EDSS (r: −0.27 0.01). Finally, FKLC were significant predictors a multivariate analysis. Our results, suggest activity might development

Language: Английский

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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 Window into New Insights on Progression Independent of Relapse Activity in Multiple Sclerosis: Role of Therapies and Current Perspective

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 884 - 884

Published: Jan. 21, 2025

In multiple sclerosis (MS), there is significant evidence indicating that both progression independent of relapse activity (PIRA) and relapse-related worsening events contribute to the accumulation progressive disability from onset disease throughout its course. Understanding compartmentalized pathophysiology MS would enhance comprehension mechanisms, overcoming traditional distinction in phenotypes. Smoldering thought be maintained by a continuous interaction between parenchymal chronic processes neuroinflammation neurodegeneration intrathecal compartment. This review provides comprehensive up-to-date overview neuropathological immunological related mechanisms underlying PIRA phenomena MS, with focus on studies investigating impact currently available therapies these complex mechanisms.

Language: Английский

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Attitudes of Neurologists Toward Serum Neurofilament Light-Chain Testing in the Management of Relapsing–Remitting Multiple Sclerosis with Cognitive Impairment

Journal of Personalized Medicine, Journal Year: 2025, Volume and Issue: 15(2), P. 69 - 69

Published: Feb. 14, 2025

Background: Cognitive impairment has an impact upon the function and quality of life patients with multiple sclerosis (MS). High-serum neurofilament light-chain (sNfL) levels predict disease progression are also associated impaired cognitive performance. This study aimed to assess attitudes neurologists toward sNfL testing as regards making therapeutic decisions in clinically radiologically stable experiencing decline. Methods: A web-based observational was conducted among caring for MS. The role assessed through a simulated case scenario describing 31-year-old woman relapsing-remitting MS four years on glatiramer acetate. Her partner reported increased distractibility difficulties organizing daily activities over past 18 months. There no history new relapses, follow-up brain MRI scan showed lesions. performance Symbol Digit Modalities Test decreased by 8 points from previous year, 46 correct answers. patient had level 21 pg/mL, other identified factors that could have altered this value. participants were tasked deciding either escalate treatment or continue current schedule reassessment 6-12 months (defined misaligned emerging evidence [DMEE]). Multivariate regression analysis determine DMEE. Results: One hundred sixteen participated study. Almost 50% (n = 57) opted not despite high levels. more common fully dedicated care (60.5% vs. 43.6%). multivariate being neurologist (odds ratio [OR] 2.35, 95% confidence interval [CI] 1.01-5.50; p 0.04) having poor perception benefits (OR 1.02, CI 1.00-1.04; 0.01) Conclusions: Neurologists' lack full dedication limited sNfL's clinical utility key suboptimal decline elevated sNfL. These findings underscore need education improve evidence-based decision-making management.

Language: Английский

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CSF biomarkers of B-cell activation in multiple sclerosis: a clinical perspective

Journal of Neurology, Journal Year: 2025, Volume and Issue: 272(3)

Published: Feb. 17, 2025

Abstract The role of B cells in the pathophysiology multiple sclerosis (MS) extends beyond antibody synthesis, also involving modulation T lymphocytes and myeloid cells. B-cell activation within Central Nervous System is associated with release various antibodies, cytokines, chemokines, measurable biofluids, thereby serving as biomarkers immune processes responsible for MS. To this purpose, a biomarker-based characterization disease through combination well-established markers, e.g., immunoglobulin (Ig) G index, IgG oligoclonal bands, Ig free light chains, new promising namely chemokine (C–X–C motif) ligand 13, activating factor/A proliferation-inducing ligand, might represent significant improvement management people

Language: Английский

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High efficacy therapy to prevent the formation of meningeal tertiary lymphoid organs after CXCL13 index screening in early multiple sclerosis

Frontiers in Neuroscience, Journal Year: 2025, Volume and Issue: 19

Published: March 17, 2025

Postmortem studies have shown the presence of subpial inflammation with tertiary lymphoid organs (TLO) in meninges patients progressive multiple sclerosis, playing an important role pathophysiology disease. The chemokine (C-X-C motif) ligand 13 (CXCL13) induces formation these organs, thus promoting activity progression to disability sclerosis has been reduced, thanks effect disease modifying therapy. However, despite advances treatment immunomodulatory agents, we still lack specific laboratory biomarkers that could indicate state disease, either at time diagnosis or when escalation therapy seems be mandatory. In MRI not demonstrated TLO CNS, so far. determination CXCL13 index (ICXCL 13), clinical specimens, become a reliable biomarker for verification and TLO, contributing improving outcome, high efficacy therapy, setting.

Language: Английский

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Monitoring multiple sclerosis: digital and fluid phase biomarkers

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

Published: March 30, 2025

Purpose of review Monitoring disease activity and treatment response in multiple sclerosis (MS) currently relies on the integration qualitative clinical radiological data that is limited predictive value. An array quantitative digital fluid biomarkers, many cusp broad translation, expected to herald a new era data-driven therapeutic strategy, particularly with respect sequencing disease-modifying therapies (DMTs). Available highly-effective DMTs, which largely abolish acute inflammatory early, relapsing MS, have impact progressive MS biology. However, robust biomarkers progression independent relapse (PIRA) emerged as major unmet need, fuelled by imminent availability treatments target pathomechanisms such chronic active or smouldering brain inflammation. Recent findings The criteria for diagnosis incorporate both imaging cerebrospinal (CSF) disease, lacks single diagnostic ‘test’. recent validation objective CSF k-FLC index, promises improve accuracy, patients atypical minor changes. Precision monitoring therapy being transformed advent clinically integrated, tools; wearables patient reported outcomes, including cognitive batteries delivered personal devices; an ultra-sensitive, readily-obtained serum indicate severity tissue injury MS. promise strategy further explored multimodal digital/fluid twin biomarker studies artificial intelligence algorithms. Summary Here, we key near-term will guide individualised people targeting no evidence (NEDA) early established disease. In medium term, composite integrated outcomes underpinned transformative effect management

Language: Английский

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Do Nitrosative Stress Molecules Hold Promise as Biomarkers for Multiple Sclerosis?

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3412 - 3412

Published: April 5, 2025

Multiple sclerosis (MS), an auto-immune disease of the central nervous system (CNS) with inflammatory and neurodegenerative properties, remains insufficiently understood despite more than 150 years research. In contrast to diseases from other medical fields such as, for instance, oncology, a description its clinical non-clinical features based on readouts as biomarkers is still in infancy. While, this regard, neurofilament light chain (NfL) seems be promising new tool, significant intra- interindividual variation serological marker somewhat limits widespread applicability everyday reality. This has sparked novel studies which glial fibrillary acidic protein (GFAP) was proposed on-top serving improve overall specificity. context, it found that MS progression significantly often associated increased levels both NfL GFAP compared alone. highlights complexity while also emphasizing potential benefits introducing additional markers enhance current options. We propose nitrosative stress markers, nitrate, nitrite, nitrotyrosine (3NT), could serve purpose effectively.

Language: Английский

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Success stories: impactful applications of cancer biomarkers

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 297 - 331

Published: Jan. 1, 2025

Language: Английский

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Emerging MRI and biofluid biomarkers in the diagnosis and prognosis of multiple sclerosis

The Lancet Regional Health - Europe, Journal Year: 2024, Volume and Issue: 44, P. 101023 - 101023

Published: Aug. 23, 2024

Language: Английский

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