Unraveling Microstructural and Macrostructural Brain Age Dynamics in Multiple Sclerosis.

Background And Objectives: In multiple sclerosis (MS), neurodegeneration results from the interplay between disease-specific pathology and normal aging. Conventional MRI captures morphologic changes in neurodegeneration, while quantitative MRI (qMRI) provides biophysical measures of microstructural alterations. Combining these modalities may reveal how aging and pathology interact and contribute to disability progression in people with MS.

Serum Neurofilament Light Chain in Multiple Sclerosis: Superiority of Age- and BMI-Corrected Z Scores/Percentiles Over Absolute Cutoff Values for Prediction of Treatment Response.

Objective: Prognostication of disease course and prediction of treatment response in multiple sclerosis is an unmet need. We compared the performance of serum neurofilament light chain Z scores (age- and BMI-adjusted) with absolute concentrations for the prediction of response to disease-modifying therapy.

Methods: Observational cohort study including the first serum sample of participants after the start of fingolimod therapy.

Treatment Strategies and Disease Activity During Pregnancy and Postpartum: Real-World Data From the Swiss Multiple Sclerosis Cohort.

Backgrounds And Objectives: Managing multiple sclerosis (MS) during pregnancy and postpartum is a therapeutic challenge. We aim to describe therapy regimens, clinical and MRI disease activity, and serum neurofilament light chain (sNfL) levels in all pregnancies observed between 2012 and 2023 among participants of the Swiss MS cohort.

Methods: We assessed the treatment strategies during pregnancy and 1 year postpartum in all included pregnancies.

Comparative effectiveness of teriflunomide and ocrelizumab on smoldering activity in multiple sclerosis: an observational study in the Swiss Multiple Sclerosis Cohort.

Background: This study aimed to compare the effects of teriflunomide and ocrelizumab on clinical and MRI endpoints related to smoldering activity in relapsing-remitting multiple sclerosis (RRMS).

Methods: In this observational, longitudinal, multicenter study, we included 128 people with RRMS (pwRRMS) treated with teriflunomide and 495 treated with ocrelizumab. Outcomes included time to progression independent of relapse activity (PIRA).

Retinal neuronal loss and progression independent of relapse activity in multiple sclerosis.

Background: In multiple sclerosis (MS), inner retinal thinning measured by optical coherence tomography (OCT) is related to lesional and gray matter changes of the brain.

Objective: To evaluate the association between OCT markers and progression independent of relapse activity (PIRA).

Methods: Analysis within the Swiss MS Cohort Study, in patients with ≥ 1 OCT.

Prognostic Factors for Multiple Sclerosis Symptoms in Radiologically Isolated Syndrome.

Importance: Understanding the risk factors for symptom development will allow clinicians to stratify people with radiologically isolated syndrome (pwRIS) more effectively and tailor their management strategies accordingly.

Objective: To identify prognostic factors at radiologically isolated syndrome (RIS) diagnosis associated with the development of multiple sclerosis (MS) symptoms.

Design, Setting, And Participants: This cohort study was performed in samples collected between July 2004 and September 2022 and included 33 MS centers.

Personalized treatment decision algorithms for the clinical application of serum neurofilament light chain in multiple sclerosis: A modified Delphi Study.

Background: Serum neurofilament light (sNfL) chain levels, a sensitive measure of disease activity in multiple sclerosis (MS), are increasingly considered for individual therapy optimization yet without consensus on their use for clinical application.

Objective: We here propose treatment decision algorithms incorporating sNfL levels to adapt disease-modifying therapies (DMTs).

Methods: We conducted a modified Delphi study to reach consensus on algorithms using sNfL within typical clinical scenarios.

Integrating TSPO-PET imaging with metabolomics for enhanced prognostic accuracy in multiple sclerosis.

Background: Predicting disease progression in multiple sclerosis (MS) remains challenging. PET imaging with 18 kDa translocator protein (TSPO) radioligands can detect microglial and astrocyte activation beyond MRI-visible lesions, which has been shown to be highly predictive of disease progression. We previously demonstrated that nuclear magnetic resonance (NMR)-based metabolomics could accurately distinguish between relapsing-remitting (RRMS) and secondary progressive MS (SPMS).

Treatment persistence and clinical outcomes in patients starting B cell depleting therapies within the Swiss MS Cohort.

Background: Persistence to B cell depleting therapies (BCDT) like ocrelizumab and rituximab may be higher compared with other disease-modifying therapies (DMT) in multiple sclerosis (MS). Clinical trials directly comparing these treatments are lacking.

Objective: To compare the risk of treatment discontinuation, relapse, and confirmed disability worsening in patients starting BCDT vs other DMT within real-world settings.

Modulator of VRAC Current 1 Is a Potential Target Antigen in Multiple Sclerosis.

Background And Objectives: Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disease of the CNS. Highlighted by the success of B-cell-depleting therapies such as the monoclonal anti-CD20 antibodies rituximab, ocrelizumab, and ofatumumab, B cells have been shown to play a central role in the immunopathology of the disease. Yet, the target antigens of the pathogenic B-cell response in MS remain unclear.

Serum Glial Fibrillary Acidic Protein and Neurofilament Light Chain Levels Reflect Different Mechanisms of Disease Progression under B-Cell Depleting Treatment in Multiple Sclerosis.

Objective: To investigate the longitudinal dynamics of serum glial fibrillary acidic protein (sGFAP) and serum neurofilament light chain (sNfL) levels in people with multiple sclerosis (pwMS) under B-cell depleting therapy (BCDT) and their capacity to prognosticate future progression independent of relapse activity (PIRA) events.

Methods: A total of 362 pwMS (1,480 samples) starting BCDT in the Swiss Multiple Sclerosis (MS) Cohort were included. sGFAP levels in 2,861 control persons (4,943 samples) provided normative data to calculate adjusted Z scores.

MultiSCRIPT-Cycle 1-a pragmatic trial embedded within the Swiss Multiple Sclerosis Cohort (SMSC) on neurofilament light chain monitoring to inform personalized treatment decisions in multiple sclerosis: a study protocol for a randomized clinical trial.

Background: Treatment decisions for persons with relapsing-remitting multiple sclerosis (RRMS) rely on clinical and radiological disease activity, the benefit-harm profile of drug therapy, and preferences of patients and physicians. However, there is limited evidence to support evidence-based personalized decision-making on how to adapt disease-modifying therapy treatments targeting no evidence of disease activity, while achieving better patient-relevant outcomes, fewer adverse events, and improved care. Serum neurofilament light chain (sNfL) is a sensitive measure of disease activity that captures and prognosticates disease worsening in RRMS.

Association of Spinal Cord Atrophy and Brain Paramagnetic Rim Lesions With Progression Independent of Relapse Activity in People With MS.

Background And Objectives: Progression independent of relapse activity (PIRA) is a crucial determinant of overall disability accumulation in multiple sclerosis (MS). Accelerated brain atrophy has been shown in patients experiencing PIRA. In this study, we assessed the relation between PIRA and neurodegenerative processes reflected by (1) longitudinal spinal cord atrophy and (2) brain paramagnetic rim lesions (PRLs).

Neurofilament Light Chain Elevation and Disability Progression in Multiple Sclerosis.

Importance: Mechanisms contributing to disability accumulation in multiple sclerosis (MS) are poorly understood. Blood neurofilament light chain (NfL) level, a marker of neuroaxonal injury, correlates robustly with disease activity in people with MS (MS); however, data on the association between NfL level and disability accumulation have been conflicting.

Objective: To determine whether and when NfL levels are elevated in the context of confirmed disability worsening (CDW).

Serum neurofilament light chain reference database for individual application in paediatric care: a retrospective modelling and validation study.

Background: Neurological conditions represent an important driver of paediatric disability burden worldwide. Measurement of serum neurofilament light chain (sNfL) concentrations, a specific marker of neuroaxonal injury, has the potential to contribute to the management of children with such conditions. In this context, the European Medicines Agency recently declared age-adjusted reference values for sNfL a top research priority.

Granulocyte activation markers in cerebrospinal fluid differentiate acute neuromyelitis spectrum disorder from multiple sclerosis.

Background: Granulocyte invasion into the brain is a pathoanatomical feature differentiating neuromyelitis optica spectrum disorder (NMOSD) from multiple sclerosis (MS). We aimed to determine whether granulocyte activation markers (GAM) in cerebrospinal fluid (CSF) can be used as a biomarker to distinguish NMOSD from MS, and whether levels associate with neurological impairment.

Methods: We quantified CSF levels of five GAM (neutrophil elastase, myeloperoxidase, neutrophil gelatinase-associated lipocalin, matrixmetalloproteinase-8, tissue inhibitor of metalloproteinase-1), as well as a set of inflammatory and tissue-destruction markers, known to be upregulated in NMOSD and MS (neurofilament light chain, glial fibrillary acidic protein, S100B, matrix metalloproteinase-9, intercellular adhesion molecule-1, vascular cellular adhesion molecule-1), in two cohorts of patients with mixed NMOSD and relapsing-remitting multiple sclerosis (RRMS).

Serum Glial Fibrillary Acidic Protein Compared With Neurofilament Light Chain as a Biomarker for Disease Progression in Multiple Sclerosis.

Importance: There is a lack of validated biomarkers for disability progression independent of relapse activity (PIRA) in multiple sclerosis (MS).

Objective: To determine how serum glial fibrillary acidic protein (sGFAP) and serum neurofilament light chain (sNfL) correlate with features of disease progression vs acute focal inflammation in MS and how they can prognosticate disease progression.

Design, Setting, And Participants: Data were acquired in the longitudinal Swiss MS cohort (SMSC; a consortium of tertiary referral hospitals) from January 1, 2012, to October 20, 2022.

Corrigendum: Determination of CSF GFAP, CCN5, and vWF levels enhances the diagnostic accuracy of clinically defined MS from non-MS patients with CSF oligoclonal bands.

[This corrects the article DOI: 10.3389/fimmu.2021.

Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and neurodegeneration: a prospective cross-sectional study.

Growing evidence links COVID-19 with acute and long-term neurological dysfunction. However, the pathophysiological mechanisms resulting in central nervous system involvement remain unclear, posing both diagnostic and therapeutic challenges. Here we show outcomes of a cross-sectional clinical study (NCT04472013) including clinical and imaging data and corresponding multidimensional characterization of immune mediators in the cerebrospinal fluid (CSF) and plasma of patients belonging to different Neuro-COVID severity classes.

Association of Brain Atrophy With Disease Progression Independent of Relapse Activity in Patients With Relapsing Multiple Sclerosis.

Importance: The mechanisms driving neurodegeneration and brain atrophy in relapsing multiple sclerosis (RMS) are not completely understood.

Objective: To determine whether disability progression independent of relapse activity (PIRA) in patients with RMS is associated with accelerated brain tissue loss.

Design, Setting, And Participants: In this observational, longitudinal cohort study with median (IQR) follow-up of 3.

Intrathecal IgM Synthesis Is Associated with Spinal Cord Manifestation and Neuronal Injury in Early MS.

Objective: Intrathecal Immunoglobulin M synthesis (IgM ) and spinal MRI lesions are both strong independent predictors of higher disease activity and severity in multiple sclerosis (MS). We investigated whether IgM is associated with spinal cord manifestation and higher neuroaxonal damage in early MS.

Methods: In 122 patients with a first demyelinating event associations between (1) spinal versus (vs) non-spinal clinical syndrome (2) spinal vs cerebral T2-weighted (T2w) and (3) contrast-enhancing (CE) lesion counts with IgG (vs IgG ) or IgM (vs IgM ) were investigated by logistic regression adjusted for age and sex, respectively.

Determination of CSF GFAP, CCN5, and vWF Levels Enhances the Diagnostic Accuracy of Clinically Defined MS From Non-MS Patients With CSF Oligoclonal Bands.

Background: Inclusion of cerebrospinal fluid (CSF) oligoclonal IgG bands (OCGB) in the revised McDonald criteria increases the sensitivity of diagnosis when dissemination in time (DIT) cannot be proven. While OCGB negative patients are unlikely to develop clinically definite (CD) MS, OCGB positivity may lead to an erroneous diagnosis in conditions that present similarly, such as neuromyelitis optica spectrum disorders (NMOSD) or neurosarcoidosis.

Objective: To identify specific, OCGB-complementary, biomarkers to improve diagnostic accuracy in OCGB positive patients.