De-escalating and discontinuing disease-modifying therapies in multiple sclerosis.

The development of disease-modifying therapies (DMTs) for the treatment of multiple sclerosis (MS) has been highly successful in recent decades. It is now widely accepted that early initiation of DMTs after disease onset is associated with a better long-term prognosis. However, the question of when and how to de-escalate or discontinue DMTs remains open and critical.

Neurofilament Light Chain as a Discriminator of Disease Activity Status in MOG Antibody-Associated Disease.

Background And Objectives: In patients with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), acute disease activity is generally identified through medical history, neurologic examination, and imaging. However, these may be insufficient for detecting disease activity in specific conditions. This study aimed to investigate the dynamics of serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) after clinical attacks and to assess their utility in discriminating attacks from remission in patients with MOGAD.

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.

Targeting cytokine networks in neuroinflammatory diseases.

In neuroinflammatory diseases, systemic (blood-borne) leukocytes invade the central nervous system (CNS) and lead to tissue damage. A causal relationship between neuroinflammatory diseases and dysregulated cytokine networks is well established across several preclinical models. Cytokine dysregulation is also observed as an inadvertent effect of cancer immunotherapy, where it often leads to neuroinflammation.

Contrast-Enhancing Lesion Segmentation in Multiple Sclerosis: A Deep Learning Approach Validated in a Multicentric Cohort.

The detection of contrast-enhancing lesions (CELs) is fundamental for the diagnosis and monitoring of patients with multiple sclerosis (MS). This task is time-consuming and suffers from high intra- and inter-rater variability in clinical practice. However, only a few studies proposed automatic approaches for CEL detection.

Presentation and Outcome in S1P-RM and Natalizumab-Associated Progressive Multifocal Leukoencephalopathy: A Multicenter Cohort Study.

Background And Objectives: Progressive multifocal leukoencephalopathy (PML) is a severe neurologic disease resulting from JC virus reactivation in immunocompromised patients. Certain multiple sclerosis (MS) disease-modifying therapies (DMTs) are associated with PML risk, such as natalizumab and, more rarely, sphingosine-1-phosphate receptor modulators (S1P-RMs). Although natalizumab-associated PML is well documented, information on S1P-RM-associated PML is limited.

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).

B cell depletion attenuates CD27 signaling of T helper cells in multiple sclerosis.

Multiple sclerosis is a chronic inflammatory disease of the central nervous system. Whereas T cells are likely the main drivers of disease development, the striking efficacy of B cell-depleting therapies (BCDTs) underscore B cells' involvement in disease progression. How B cells contribute to multiple sclerosis (MS) pathogenesis-and consequently the precise mechanism of action of BCDTs-remains elusive.

Harmonizing Definitions for Progression Independent of Relapse Activity in Multiple Sclerosis: A Systematic Review.

Importance: Emerging evidence suggests that progression independent of relapse activity (PIRA) is a substantial contributor to long-term disability accumulation in relapsing-remitting multiple sclerosis (RRMS). To date, there is no uniform agreed-upon definition of PIRA, limiting the comparability of published studies.

Objective: To summarize the current evidence about PIRA based on a systematic review, to discuss the various terminologies used in the context of PIRA, and to propose a harmonized definition for PIRA for use in clinical practice and future trials.

Optical coherence tomography versus other biomarkers: Associations with physical and cognitive disability in multiple sclerosis.

Background: Optical coherence tomography (OCT) is a biomarker of neuroaxonal loss in multiple sclerosis (MS).

Objective: The objective was to assess the relative role of OCT, next to magnetic resonance imaging (MRI) and serum markers of disability in MS.

Methods: A total of 100 patients and 52 controls underwent OCT to determine peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell-inner plexiform layers (GCIPL).

Comparative analysis of dimethyl fumarate and teriflunomide in relapsing-remitting multiple sclerosis.

Background And Purpose: In relapsing-remitting multiple sclerosis (RRMS), analyses from observational studies comparing dimethyl fumarate (DMF) and teriflunomide showed conflicting results. We aimed to compare the effectiveness of DMF and teriflunomide in a real-world setting, where both drugs are licensed as first-line therapies for RRMS.

Methods: We included all patients who initiated DMF or teriflunomide between 2013 and 2022, listed in the Swiss National Treatment Registry.

Immunoglobulin A Antibodies Against Myelin Oligodendrocyte Glycoprotein in a Subgroup of Patients With Central Nervous System Demyelination.

Importance: Differential diagnosis of patients with seronegative demyelinating central nervous system (CNS) disease is challenging. In this regard, evidence suggests that immunoglobulin (Ig) A plays a role in the pathogenesis of different autoimmune diseases. Yet little is known about the presence and clinical relevance of IgA antibodies against myelin oligodendrocyte glycoprotein (MOG) in CNS demyelination.

A structured evaluation of cryopreservation in generating single-cell transcriptomes from cerebrospinal fluid.

Single-cell transcriptomics allows characterization of cerebrospinal fluid (CSF) cells at an unprecedented level. Here, we report a robust cryopreservation protocol adapted for the characterization of fragile CSF cells by single-cell RNA sequencing (RNA-seq) in moderate- to large-scale studies. Fresh CSF was collected from twenty-one participants at two independent sites.

Cerebrospinal Fluid HIV-1 Escape in Patients With Neurocognitive Symptoms: Pooled Data From a Neuro-HIV Platform and the NAMACO Study.

Background: Despite modern antiretroviral therapy, human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) escape into the cerebrospinal fluid (CSF) may occur. We examined the prevalence of and factors associated with CSF HIV-1 escape among people living with HIV (PLWH) in Switzerland.

Setting: The Neurocognitive Assessment in the Metabolic and Aging Cohort study is an ongoing, prospective, longitudinal, multicenter study within the Swiss HIV Cohort Study.

Evaluation of frequency, severity, and independent risk factors for recurrence of disease activity after fingolimod discontinuation in a large real-world cohort of patients with multiple sclerosis.

Background: Clinical and radiological signs of recurring disease activity (RDA) have been described in patients with multiple sclerosis (pwMS) after discontinuation of fingolimod (FGL).

Objective: To describe frequency, severity and potential risk factors for RDA after FGL discontinuation in a large real-world cohort of pwMS.

Methods: Post-FGL RDA was defined as evidence of clinical and/or radiological activity within 6 months after FGL discontinuation.

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.

Natalizumab in cerebrospinal fluid and breastmilk of patients with multiple sclerosis.

Background: Natalizumab is a highly effective monoclonal antibody for the treatment of multiple sclerosis (MS), which can diffuse in different anatomical compartments, including cerebrospinal fluid (CSF) and milk.

Objectives: Starting from incidental detection of natalizumab in the CSF of MS patients, the objective of this study was to develope a flow-cytometry-based assay and apply it to quantify natalizumab in body fluids, including milk collected from nursing patients over 180 days and in patients with neutralizing antibodies against natalizumab.

Methods: CSF, milk and sera samples from patients with multiple sclerosis were tested by flow-cytometry for binding to a VLA-4 expressing cell line or to a control cell line.

A Multicenter Longitudinal MRI Study Assessing LeMan-PV Software Accuracy in the Detection of White Matter Lesions in Multiple Sclerosis Patients.

Background: Detecting new and enlarged lesions in multiple sclerosis (MS) patients is needed to determine their disease activity. LeMan-PV is a software embedded in the scanner reconstruction system of one vendor, which automatically assesses new and enlarged white matter lesions (NELs) in the follow-up of MS patients; however, multicenter validation studies are lacking.

Purpose: To assess the accuracy of LeMan-PV for the longitudinal detection NEL white-matter MS lesions in a multicenter clinical setting.