Multiple Sclerosis Journal - Experimental, Translational and Clinical

People with multiple sclerosis (pwMS) have an increased risk of infection. As disease-modifying therapies (DMTs) and other treatments may interact with the immune system, there may be concerns about vaccine efficacy and safety. Therefore, it is important to evaluate possible interactions between DMTs and vaccines. The fumarates, dimethyl fumarate, diroximel fumarate, and monomethyl fumarate, are approved for the treatment of relapsing multiple sclerosis. This review assesses the evidence on vaccine response in pwMS treated with fumarates, with a particular focus on COVID-19 vaccines...

Fingolimod is a multiple sclerosis disease-modifying therapy which sequestrates lymphocytes in the lymph nodes, thereby reducing peripheral blood lymphocytes. Cryptococcal infection is an important adverse effect which should be recognised. We report a case of cutaneous and central nervous system infection who presented with isolated cutaneous symptoms in the absence of neurological or systemic manifestations.

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BACKGROUND: Multiple sclerosis (MS) comparative effectiveness research needs to go beyond average treatment effects (ATEs) and post-host subgroup analyses. OBJECTIVE: This retrospective study assessed overall and patient-specific effects of dimethyl fumarate (DMF) versus teriflunomide (TERI) in patients with relapsing-remitting MS. METHODS: A novel precision medicine (PM) scoring approach leverages advanced machine learning methods and adjusts for imbalances in baseline characteristics between patients receiving different treatments...

BACKGROUND: Functional connectome fingerprinting can identify individuals based on their functional connectome. Previous studies relied mostly on short intervals between fMRI acquisitions. OBJECTIVE: This cohort study aimed to determine the stability of connectome-based identification and their underlying signatures in patients with multiple sclerosis and healthy individuals with long follow-up intervals. METHODS: We acquired resting-state fMRI in 70 patients with multiple sclerosis and 273 healthy individuals with long follow-up times (up to 4 and 9 years, respectively)...

Sleep disturbance is common in people with multiple sclerosis and may worsen fatigue; however, the assessment of sleep-fatigue relationships varies across studies. To better understand sleep-fatigue relationships in this population, we conducted a systematic review and random effects meta-analyses for the associations between fatigue and 10 sleep variables: Sleep-disordered breathing, daytime sleepiness, sleep quality, insomnia, restless legs, number of awakenings, sleep efficiency, sleep latency, sleep duration, and wake after sleep onset...

BACKGROUND: Multiple sclerosis (MS) is a progressively debilitating neurologic disease that poses significant costs to the healthcare system and workforce. OBJECTIVE: To evaluate the impact of MS disease progression on societal costs and quality of life (QoL) using data from the German NeuroTransData (NTD) MS registry. METHODS: Cross-sectional cohort study. The cost cohort included patients with MS disability assessed using Expanded Disability Status Scale (EDSS) in 2019 while the QoL cohort included patients assessed using EDSS and EuroQol-5 Dimension 5-Levels between 2009 and 2019...

BACKGROUND: In high-income countries, four anti-CD20 monoclonal antibodies (mAbs) are used or in the pipeline for relapsing MS: ocrelizumab, ofatumumab (both registered), ublituximab (awaiting registration) and rituximab (off-label). List prices differ significantly between registered and off-label drugs. OBJECTIVE: Comparing differences in benefits between anti-CD20 mAbs from a health-economic and societal perspective. METHODS: To reflect lifetime use of DMTs, we used a treatment-sequence model to compare ocrelizumab/ofatumumab and eight other drug classes in terms of health (lifetime relapses, time to Expanded Disability Status Scale [EDSS] 6, lifetime quality-adjusted life years) and cost-effectiveness (net health benefit)...

BACKGROUND: Comorbidity is a current area of interest in multiple sclerosis (MS) and is essential for multidisciplinary management. Although recent studies suggest that patients with MS have an elevated risk of developing inflammatory bowel diseases (IBD), this systematic review and meta-analysis aimed to estimate the overall risk of developing ulcerative colitis (UC), specifically in patients with MS. METHODS: In 2021, a comprehensive literature search was performed on PubMed, Scopus, Embase, and Web of Science to identify studies investigating the association between UC and MS...

BACKGROUND: Differences in pain between subtypes of multiple sclerosis are understudied. OBJECTIVE: To compare the prevalence of pain, and the association between pain and: (a) pain interference and (b) social participation in people with relapsing-remitting multiple sclerosis and progressive multiple sclerosis. METHODS: Participants completed the McGill Pain Questionnaire Short-Form-2, Pain Effects Scale and Ability to Participate in Social Roles and Activities-V2...

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) has a high incidence of debilitating spasticity. Central Nervous System (CNS) intrafusal settings have an impact on spasticity level. Mechanoreceptors of the Peripheral Nervous System (PNS) communicate monosynaptically with the central nervous system (CNS). This case series assesses feasibility of multimodal treatment of individuals with MS using a direct current electrical stimulation (DC) to influence mechanoreceptors. CASE DESCRIPTION AND INTERVENTION: Seven MS diagnosed participants with Expanded Disability Status Scale (EDSS) = 6...

BACKGROUND: Despite tremendous development in the treatment of neuromyelitis optica spectrum disorder (NMOSD), less is known about the characteristics of hospitalized patients and inpatient care utilization. OBJECTIVE: To investigate the development of inpatient NMOSD case numbers and implemented immunotherapies in the last decade in Germany. METHODS: We conducted a nationwide retrospective study using an administrative database of all hospitalized NMOSD patients between 2010 and 2021...

BACKGROUND: Anti-CD20 agents are commonly used in MS, NMOSD, and MOGAD. Few studies have compared strategies to address hypogammaglobulinemia. OBJECTIVE: To compare strategies to manage secondary hypogammaglobulinemia in neuroimmunology patients, including reducing anti-CD20 dose and dosing frequency, IVIG/SCIG, anti-CD20 cessation, and DMT switches. METHODS: All MS, NMOSD, and MOGAD patients at our institution with hypogammaglobulinemia on anti-CD20 agents from 2001 to 2022 were analyzed...

BACKGROUND: New interventions for multiple sclerosis (MS) commonly require a demonstration of cost-effectiveness using health-related quality of life (HRQoL) utility values. The EQ-5D is the utility measure approved for use in the UK NHS funding decision-making. There are also MS-specific utility measures - e.g., MS Impact Scale Eight Dimensions (MSIS-8D) and MSIS-8D-Patient (MSIS-8D-P). OBJECTIVES: Provide EQ-5D, MSIS-8D and MSIS-8D-P utility values from a large UK MS cohort and investigate their association with demographic/clinical characteristics...

Disability accrual is mainly driven by progression independent of relapse activity, which is present even in early stages of relapsing-remitting multiple sclerosis (RRMS) and sometimes overlooked. This multicenter, non-interventional study evaluated whether patient-reported outcomes measures (PROMs) could capture disability in 189 early-stage RRMS patients (mean age: 36.1 ± 9.4 years, 71.4% female, mean disease duration: 1.4 ± 0.8 years, median EDSS: 1.0). The 9-Hole Peg Test (9-HPT), NeuroQoL Upper Extremity (NeuroQoL-UE), Timed 25-Foot Walk (T25-FW), Multiple Sclerosis Walking Scale (MSWS-12), Symbol Digit Modalities Test (SDMT), and Perceived Deficits Questionnaire (PDQ-5) were used to assess hand function, gait, and cognition, respectively...

BACKGROUND: CombiRx was a randomized, double-blind, placebo-controlled phase 3 trial in treatment-naive relapsing-remitting multiple sclerosis (RRMS) patients randomized to intramuscular interferon beta-1a (IM IFN beta-1a), glatiramer acetate (GA), or both therapies. OBJECTIVE: This analysis investigated changes in serum neurofilament light-chain (sNfL) levels in response to treatment and assessed baseline sNfL as a predictor of relapse. METHODS: RRMS patients treated with IM IFN beta-1a 30 µg weekly + placebo (n = 159), GA 20 mg/mL daily + placebo (n = 172), or IM IFN beta-1a + GA (n = 344) were included...

INTRODUCTION: Mortality is an important feature of the natural history of multiple sclerosis (MS). We report the mortality of all individuals with MS in Iceland, identified in a nationwide population-based study. PATIENTS AND METHODS: The results are based on a prevalence cohort and an incidence cohort. The prevalence cohort consisted of all patients with MS (n = 526) living in Iceland on the 31 December 2007. The incidence cohort consisted of all residents of Iceland (n = 222) diagnosed with MS during 2002 to 2007...

BACKGROUND: Fatigue is associated with reduced quality of life and social participation, and poor employment outcomes. However, most studies examining fatigue are limited by small sample sizes or short follow-up periods. OBJECTIVE: To characterize the natural history of fatigue. METHODS: The North American Research Committee on Multiple Sclerosis Registry participants with ≥7 years of longitudinal data between 2004 and 2019 and a relapsing disease course were included...

BACKGROUND: There is limited knowledge about T cell responses in patients with multiple sclerosis (MS) after 3 doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine. OBJECTIVES: Assess the SARS-CoV-2 spike antibody and T cell responses in MS patients and healthy controls (HCs) after 2 doses (2-vax) and 3 doses (3-vax) of SARS-CoV-2 mRNA vaccination. METHODS: We studied seroconversion rates and T cell responses by flow cytometry in HC and MS patients on fingolimod or ocrelizumab...