De-escalation from anti-CD20 to cladribine tablets in multiple sclerosis: A pilot study.

Prolonged treatment with anti-CD20 antibodies can lead to hypogammaglobulinemia and increased infection risk in multiple sclerosis (MS). We investigated switch from anti-CD20 to cladribine as a strategy to prevent immunoglobulin reduction while preserving efficacy. We prospectively analysed serum IgG, IgM, neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) in 44 patients, 14 who were switched from anti-CD20 to cladribine and 30 continuing anti-CD20.

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.

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.

Persistent longitudinal T cell responses after SARS-CoV-2 mRNA vaccines in MS patients on different disease modifying treatments.

Few data are available regarding vaccine induced SARS-CoV-2 specific T cell responses over time and after booster doses in multiple sclerosis (MS) patients on different disease modifying treatments. We measured SARS-CoV-2 specific CD4 T cell responses in 72 samples collected from 36 MS patients. The percentage of CD4 CTV CD25 ICOS T cells after stimulation with Spike Recombinant Protein was 29.

Effectiveness, Safety and Patients' Satisfaction of Nabiximols (Sativex) on Multiple Sclerosis Spasticity and Related Symptoms in a Swiss Multicenter Study.

Cannabinoid oro-mucosal spray nabiximols is approved for patients with moderate to severe multiple sclerosis spasticity (MSS) resistant to other antispastic medications. Few real-world data are available on the effectiveness, safety and patients' satisfaction in MS patients treated with nabiximols as monotherapy. To investigate the effectiveness, tolerability and satisfaction of nabiximols in a real-life multicentric Swiss cohort as monotherapy or with stable doses of other antispastic medications, and explore clinical features which may predict treatment response.

Tolerability and Acceptance of Switching from Brand to Generic Glatiramer Acetate in Multiple Sclerosis.

The costs of disease-modifying therapies (DMTs) for multiple sclerosis (MS) have increased interest in generic alternatives. This prospective and observational study aims to investigate the safety, tolerability, and acceptance of switching from brand glatiramer acetate (GA) 40 mg/mL three times per week (Copaxone) to generic GA 40 mg/mL three times per week (Glatiramyl). Conducted at the Neurocenter of Southern Switzerland from September 2020 to September 2021, the study enrolled 27 patients; 21 completed the study.

Memory B cell-guided extended interval dosing of ocrelizumab in multiple sclerosis.

Background: Ocrelizumab (OCR) is an anti-CD20 monoclonal antibody approved for the treatment of relapsing-remitting and primary-progressive multiple sclerosis (MS). We aimed to evaluate the effectiveness of an individualized OCR extended interval dosing (EID), after switching from standard interval dosing (SID).

Methods: This was a retrospective, observational, single-centre study including MS patients regularly followed at the Neurocenter of Southern Switzerland.

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).

Efficacy and safety of the implantable, magnetic resonance imaging-compatible StimRouter neuromodulation system in the treatment of refractory lower urinary tract symptoms in multiple sclerosis patients.

Background And Purpose: Lower urinary tract symptoms (LUTS) significantly affect quality of life (QoL) of multiple sclerosis (MS) patients, and pharmacotherapy has limited efficacy. We investigated efficacy and safety of the implantable StimRouter neuromodulation system for treating refractory LUTS in MS.

Methods: This prospective, single-center, clinical trial was conducted at the Multiple Sclerosis Center of Lugano, Switzerland, involving MS patients treated with self-administered percutaneous tibial nerve stimulation delivered by StimRouter over 24 weeks.

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).

Interplay between age and disease-modifying treatments in influencing infection risk in multiple sclerosis.

Background: Disease-modifying treatments (DMTs) can increase the risk of infections in multiple sclerosis (MS). Aged individuals are usually excluded from clinical trials, and there is uncertainty regarding safety of immunosuppressive DMTs in these patients.

Objective: To investigate the association of DMTs, ageing and other clinical variables with risk of infections in MS patients.

Longitudinal serum neurofilament light kinetics in post-anoxic encephalopathy.

Serum neurofilament light (sNfL) is a promising marker of outcome after cardiac arrest, but its kinetics are unclear. We prospectively measured sNfL concentrations in 62 patients at 0, 1, 3, 5, 7 and 10 days after cardiac arrest. Survivors and non-survivors had similar sNfL at admission (14.

Influence of Disease Modifying Treatment, Severe Acute Respiratory Syndrome Coronavirus 2 Variants and Vaccination on Coronavirus Disease 2019 Risk and Outcome in Multiple Sclerosis and Neuromyelitis Optica.

Patients suffering from neuro-inflammatory diseases such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) remain vulnerable to COVID-19. We investigated the risk of COVID-19 in MS and NMOSD patients over time, considering the impact of disease-modifying treatments (DMTs), vaccinations, and the spread of new SARS-CoV-2 variants. We retrospectively collected clinical information regarding all MS and NMOSD consecutive patients seen at the Neurocenter of Southern Switzerland.

Endovascular therapy outcome in isolated posterior cerebral artery occlusion strokes: A multicenter analysis of the Swiss Stroke Registry.

Purpose: There is little data on the safety and efficacy of endovascular treatment (EVT) in comparison with intravenous thrombolysis (IVT) in acute ischemic stroke due to isolated posterior cerebral artery occlusion (IPCAO). We aimed to investigate the functional and safety outcomes of stroke patients with acute IPCAO treated with EVT (with or without prior bridging IVT) compared to IVT alone.

Methods: We did a multicenter retrospective analysis of data from the Swiss Stroke Registry.

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.

Real-world evaluation of ocrelizumab in multiple sclerosis: A systematic review.

Across its clinical development program, ocrelizumab demonstrated efficacy in improving clinical outcomes in multiple sclerosis, including annualized relapse rates and confirmed disability progression. However, as with any new treatment, it was unclear how this efficacy would translate into real-world clinical practice. The objective of this study was to systematically collate the published real-world clinical effectiveness data for ocrelizumab in relapsing remitting multiple sclerosis and primary progressive multiple sclerosis.

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.

Longitudinal Postvaccine SARS-CoV-2 Immunoglobulin G Titers, Memory B-Cell Responses, and Risk of COVID-19 in Multiple Sclerosis Over 1 Year.

Background And Objectives: Some disease-modifying treatments impair response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in multiple sclerosis (MS), potentially increasing the risk of breakthrough infections. We aimed to investigate longitudinal SARS-CoV-2 antibody dynamics and memory B cells after 2 and 3 messenger RNA (mRNA) vaccine doses and their association with the risk of COVID-19 in patients with MS on different treatments over 1 year.

Methods: Prospective observational cohort study in patients with MS undergoing SARS-CoV-2 mRNA vaccinations.

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.

Fatigue, sleepiness and depression in multiple sclerosis: defining the overlaps for a better phenotyping.

Background And Objectives: To define the boundaries and the overlaps between fatigue, sleepiness and depression in patients with multiple sclerosis (MS) by using different tools for each dimension, including instrumental sleep analysis.

Methods: In this cross-sectional, observational study, 71 MS patients (males/females: 20/51; mean age: 48.9 ± 10.

Monitoring of safety and effectiveness of cladribine in multiple sclerosis patients over 50 years.

Clinical trial data regarding efficacy and safety of cladribine in MS are limited to young individuals, and the overall risk-benefit profile does not necessarily applies to elderly patients. We investigated effectiveness and safety outcomes in MS patients initiating cladribine at ≥50 years (n=35) and <50 years (n=62), over a median follow-up of 12.4 months.

Alpha-synuclein oligomers and small nerve fiber pathology in skin are potential biomarkers of Parkinson's disease.

The proximity ligation assay (PLA) is a specific and sensitive technique for the detection of αSyn oligomers (αSyn-PLA), early and toxic species implicated in the pathogenesis of PD. We aimed to evaluate by skin biopsy the diagnostic and prognostic capacity of αSyn-PLA and small nerve fiber reduction in PD in a longitudinal study. αSyn-PLA was performed in the ankle and cervical skin biopsies of PD (n = 30), atypical parkinsonisms (AP, n = 23) including multiple system atrophy (MSA, n = 12) and tauopathies (AP-Tau, n = 11), and healthy controls (HC, n = 22).

Development, validation and clinical usefulness of a prognostic model for relapse in relapsing-remitting multiple sclerosis.

Background: Prognosis for the occurrence of relapses in individuals with relapsing-remitting multiple sclerosis (RRMS), the most common subtype of multiple sclerosis (MS), could support individualized decisions and disease management and could be helpful for efficiently selecting patients for future randomized clinical trials. There are only three previously published prognostic models on this, all of them with important methodological shortcomings.

Objectives: We aim to present the development, internal validation, and evaluation of the potential clinical benefit of a prognostic model for relapses for individuals with RRMS using real-world data.