Background: Radiologically isolated syndrome (RIS) is typified by multiple sclerosis (MS)-like lesions on imaging, without clinical MS symptoms. The prevalence of pediatric RIS is largely unknown. Objective: The objective of the study is to provide an estimated RIS prevalence in a population-based cohort of children. Methods: We used data from the Generation R study to identify the childhood RIS prevalence

Pediatric-onset multiple sclerosis (MS) affects 2%–10% of all individuals with MS and is known to be associated with greater magnetic resonance imaging (MRI) lesion burden,1 but a lengthier time to progression to irreversible disability than in the adult MS population.2 Importantly, numerous studies have highlighted high levels of depression and fatigue,3–5 and high rates of cognitive impairment in

Background: Newly approved, drug-modifying therapies are associated with still unknown adverse events, although clinical trials leading to approval have strict inclusion and exclusion criteria and analyse safety and efficacy. Objectives: The aim of this study was to analyse the eligibility of multiple sclerosis (MS) patients treated in routine care into the phase III clinical trial of the respective

There is little evidence on the role of diet in childhood/adolescence and multiple sclerosis (MS) in adulthood. The MS Sunshine Study recruited adults with recent-onset MS (n = 602) and matched controls (n = 653). Of these, 84% provided dietary recall for specific ages between childhood and young adulthood (6–10, 11–15 and 16–20 years). We used logistic regression to test associations between age-specific

Background: Human endogenous retrovirus (HERV) expression in multiple sclerosis (MS) brain lesions may contribute to chronic inflammation, but expression of genome-wide HERVs in different MS lesions is unknown. Objective: We examined the HERV expression landscape in different MS lesions compared to control brains. Methods: Transcripts from 71 MS brain samples and 25 control WM were obtained by next-generation

Background: The expanded disability status scale (EDSS) is the standard clinical outcome measure in primary progressive multiple sclerosis (PPMS), even though the timed 25-foot walk (T25FW), nine-hole peg test (NHPT) or combinations of these measures may be more useful. The paced auditory serial addition test (PASAT) is a widely used cognitive measure in MS, but little is known about change in PASAT

Background: Extracellular vesicles (EVs), a recently described mechanism of cell communication, are released from activated microglial cells and macrophages and are a candidate biomarker in diseases characterized by chronic inflammatory process such as multiple sclerosis (MS). Methods: We explored cerebrospinal fluid extracellular vesicle (CSF EV) of myeloid origin (MEVs), cytokine and chemokine levels

Background: Prognostic markers are needed to guide multiple sclerosis (MS) management in the context of large availability of disease-modifying drugs (DMDs). Objective: To investigate the role of cerebrospinal fluid (CSF) markers to inform long-term MS outcomes. Methods: Demographic features, IgM index, oligoclonal IgM bands (OCMB), lipid-specific OCMB, CSF neurofilament light chain protein levels

Background: A delayed onset of treatment effect, termed therapeutic lag, may influence the assessment of treatment response in some patient subgroups. Objectives: The objective of this study is to explore the associations of patient and disease characteristics with therapeutic lag on relapses and disability accumulation. Methods: Data from MSBase, a multinational multiple sclerosis (MS) registry, and

Objective: The objective of this study is to assess the association between vascular comorbidity burden with clinical and imaging features of disease burden in a large population of people with multiple sclerosis (MS). Methods: We included participants from the MS Partners Advancing Technology Health Solutions (MS PATHS) cohort. We evaluated if vascular comorbidities (diabetes, hypertension, and dyslipidemia)

Magnetic resonance imaging (MRI) has gained an essential role in state-of-the-art research and clinical practice for neuroimmunological conditions and especially multiple sclerosis (MS) by providing important information on focal inflammation with demyelination and structural alterations with atrophy and neurodegeneration.

Over the past 10 years, 7 Tesla (7 T) magnetic resonance imaging (MRI) has brought many advances in the in vivo exploration of the pathophysiological mechanisms of multiple sclerosis (MS). Thanks to increased signal-to-noise ratio and contrast-to-noise ratio, as well as increased spatial resolution (voxel size below 500 µm3), 7 T MRI provides access to precise anatomical details, not or barely visible

Background: Long-term effectiveness of treatment remains a key question in multiple sclerosis (MS) and the cumulative effects of past treatment have not been investigated so far. Objective: Explore the relationship between treatment exposure and disability risk in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: A total of 2285 adult patients from the French nationwide cohort were

Background: Severe residual visual loss (SRVL) is frequent in neuromyelitis optica spectrum disorders (NMOSD). Identifying higher-risk patients at onset is important to prevent disability accumulation. Objective: To determine predictors of SRVL in a large NMOSD cohort. Methods: Patient characteristics at last visual acuity (VA) evaluation were retrospectively collected. VA was scored 0: better than

Seven-tesla (7T) magnetic resonance imaging (MRI) has become an important tool to investigate noninvasively the cerebral pathology affecting patients with multiple sclerosis (MS). Indeed, the superior image resolution and contrast achieved at 7T has allowed researchers to study brain lesions in great detail and advance our understanding of the formation and extent of these lesions throughout the evolution

Background: We recently compared clinical outcomes in secondary progressive MS (SPMS) clinical trials and found an association of timed 25 foot walk (T25FW) worsening events and baseline disability scores. It is unclear whether disability worsening in clinical trials is comparable to that seen in clinical practice. Objective: The objective of this study is to compare disability worsening between the

Background: Outcome measures need to be valid and have good test–retest reliability and responsiveness. We compared the responsiveness of the RAND-12 and the Health Utilities Index—mark III (HUI3) in persons with multiple sclerosis (MS). Methods: In Spring 2018 and 2019, North American Research Committee on Multiple Sclerosis (NARCOMS) registry participants completed the HUI3, the RAND-12, and reported

Background: Previous studies suggest a 3- to-10-fold increased risk of multiple sclerosis (MS) in offspring of mothers with diabetes mellitus (DM). Objectives: To examine MS risk in offspring of diabetic mothers, overall and according to type of maternal DM, that is, pregestational DM or gestational DM, as well as to examine MS risk among offspring of diabetic fathers. Methods: The study cohort included

Autoimmunity to chitinase 3-like 1 (CHI3L1) has recently been reported in hepatic and bowel inflammatory conditions. Considering that CHI3L1 plays a role as prognostic biomarker in multiple sclerosis (MS), here we investigated CHI3L1 as potential autoantigenic target in the disease. We determined serum CHI3L1 autoantibodies by enzyme-linked immunosorbent assay (ELISA) in a cohort of 60 untreated MS

Van Geel F, Veldkamp R, Severijns D, Dalgas U, & Feys P. Day-to-day reliability, agreement and discriminative validity of measuring walking-related performance fatigability in persons with multiple sclerosis. Multiple Sclerosis Journal 2020; 26(13): 1785-1789. doi:10.1177/1352458519872465

Background: Sphingolipids are myelin components and inflammatory signaling intermediates. Sphingolipid metabolism may be altered in people with multiple sclerosis (PwMS), but existing studies are limited by small sample sizes. Objectives: To compare the levels of serum ceramides between PwMS and healthy controls (HCs) and to determine whether ceramide levels correlate with disability status, as well

Objective: To understand how longitudinal serum neurofilament light chain (sNfL) patterns can inform its use as a prognostic biomarker in multiple sclerosis (MS) and evaluate whether sNfL reflects MS disease activity and disease-modifying therapy usage. Methods: This was a post hoc analysis of longitudinal data and samples from the ADVANCE trial (NCT00906399) of patients with relapsing–remitting MS

Background: Prior studies have suggested that subclinical retinal abnormalities may be present in aquaporin-4 immunoglobulin G (AQP4-IgG) seropositive neuromyelitis optica spectrum disorder (NMOSD), in the absence of a clinical history of optic neuritis (ON). Objective: Our aim was to compare retinal layer thicknesses at the fovea and surrounding macula between AQP4-IgG+ NMOSD eyes without a history

Objectives: The objective of this study is to examine the burden of depressive symptoms across the adult age span in people with multiple sclerosis (MS) and test if the relationship between depressive symptoms and MS characteristics vary across age groups. Methods: In analyses of the MS Partners Advancing Technology and Health Solutions (MS PATHS) network of adults with MS, we compared the prevalence

Background: Regulatory CD4+ T cells (Tregs) exhibit functional alterations in patients with multiple sclerosis (MS). Transforming growth factor (TGF)-β is a key regulator of Treg development and function. Objective: The objective of this study is to determine whether the expression of functionally relevant TGF-β-regulated molecules is altered in Tregs from patients with MS. Methods: Expression of nine

Background: Only progressive multifocal leukoencephalopathy (PML) is currently described in the dimethyl fumarate (DMF) prescribing information. Objectives: To describe opportunistic infections (OIs), other than PML, reported in association with DMF. Methods: The FDA Adverse Event Reporting System (FAERS) and medical literature were searched. Results: We retrieved 34 cases of serious OIs with a causal

Background: Cognitive decline remains difficult to predict as structural brain damage cannot fully explain the extensive heterogeneity found between MS patients. Objective: To investigate whether functional brain network organization measured with magnetoencephalography (MEG) predicts cognitive decline in MS patients after 5 years and to explore its value beyond structural pathology. Methods: Resting-state

Background: To demonstrate an inflammatory process in the central nervous system, the presence of at least two immunoglobulin (Ig) bands in the cerebrospinal fluid (CSF) is required. So far, the presence of a single abnormal Ig band is considered as negative. Objective: The objective was to assess retrospectively the significance of a single CSF Ig band in clinical practice. Methods and results: Out

Background: The relationship between structural and functional deficits in multiple sclerosis (MS) is unclear. Objective: This study explored structure-function relationships during the 5 years following a clinically isolated syndrome and their role in cognitive performance. Methods: Thirty-two patients were enrolled after their first neurological episode suggestive of MS and followed for 5 years,

S. Pittock1, K. Fujihara2, J. Palace3, A. Berthele4, H.J. Kim5, C. Oreja-Guevara6, I. Nakashima7, M. Levy8, A. Pace9, M. Yountz9, L. Miller9, R. Armstrong10, D. WingerchUK11

C. Maguire, B. Caslin, S. Bazzi, E. Melamed, D. Wylie

M. Lohrberg1, A. Winkler1, J. Franz1, F. Van Der Meer1, A. Barrantes-Freer2, C. Stadelmann1

Aaen G..........................P1082, PS04.04

Background: Sex steroids could explain the course of multiple sclerosis (MS) in pregnancy. Objective: To compare the annualized relapse rate (ARR) 12 weeks post-partum in women treated with nomegestrol acetate (NOMAc) and 17-beta-estradiol (E2) versus placebo. Methods: POPARTMUS is a randomized, proof-of-concept trial in women with MS, receiving oral NOMAc 10 mg/day and transdermal estradiol 75 µg/week

Please be aware that it was the submitter’s responsibility to fill in all data correctly and completely. Any errors in spelling, grammar or scientific fact have been reproduced as typed by the author/submitter.

Please be aware that it was the submitter’s responsibility to fill in all data correctly and completely. Any errors in spelling, grammar or scientific fact have been reproduced as typed by the author/submitter.

Samantha Turner1, Jenny Freeman2

Background: The absence of reliable imaging or biological markers of phenotype transition in multiple sclerosis (MS) makes assignment of current phenotype status difficult. Objective: The authors sought to determine whether clinical information can be used to accurately assign current disease phenotypes. Methods: Data from the clinical visits of 14,387 MS patients in Sweden were collected. Classifying

A more objective classification of multiple sclerosis (MS) has long been the aim of our field, or such, wrote Charles Poser1 in March 1965: ‘[an aim of this study] was to establish a more objective system of scoring [and classification], based upon clinical signs and symptoms’. This ambition, however, has remained elusive half a century later.

Background:: While damage to the optic nerve following optic neuritis (ON) is readily quantifiable, the evaluation of prognosis for visual function and neuroaxonal loss in the acute ON is challenging. Objective:: The objective of this study is to investigate the value of multifocal visual evoked potential (mfVEP) in acute ON, diagnostically for acute ON and prognostically for visual outcome and subsequent

Background: Cognition is affected by relapses in persons with multiple sclerosis (PwMS), yet the Expanded Disability Status Scale (EDSS) does not readily detect cognitive changes. Objective: The objective of this study is to improve the detection of cognitive decline during relapses, by incorporating the Symbol Digit Modalities Test (SDMT) into the cerebral Functional System Score (CFSS) of the EDSS

Background: Moderate and vigorous physical activity is associated with improved outcomes in youth with multiple sclerosis (MS). Physical fitness may also influence disease and health outcomes in this population. Objectives: To determine if there were differences in physical fitness between youth with MS and healthy controls (HC). To examine relationships between physical fitness, physical activity

Background: In persons with multiple sclerosis (MS), the Expanded Disability Status Scale (EDSS) is the criterion standard for assessing disability, but its in-person nature constrains patient participation in research and clinical assessments. Objective: The aim of this study was to develop and validate a scalable, electronic, unsupervised patient-reported EDSS (ePR-EDSS) that would capture MS-related

Background Cognitive impairment is highly prevalent in multiple sclerosis (MS). Progressive aerobic exercise (PAE) represents a promising approach toward preservation or even improvement of cognitive performance in people with MS (pwMS). Objective To investigate the effects of PAE on the cognitive domains of information processing, learning and memory, and verbal fluency in pwMS. Methods This randomized

Background: Slow-burning inflammation is putatively associated with lesion expansion and leads to progressive loss of axons and disability worsening. Objective: To investigate the incidence and extent of chronic white matter lesion expansion in relapsing–remitting multiple sclerosis (RRMS) patients and to evaluate its relationship with biomarkers of disease progression. Methods: Pre- and post-gadolinium

Background: No uniform criteria for a sensitive identification of the transition from relapsing–remitting multiple sclerosis (MS) to secondary-progressive multiple sclerosis (SPMS) are available. Objective: To compare risk factors of SPMS using two definitions: one based on the neurologist judgment (ND) and an objective data-driven algorithm (DDA). Methods: Relapsing-onset MS patients (n = 19,318)

The CoronaVirus Disease 19 (COVID-19) pandemic is a threat of particular concern for people affected by chronic immune-mediated diseases, such as multiple sclerosis (MS), who are often treated with immunomodulatory and immunosuppressive drugs, which may increase the risk of infections in general. At the beginning of the COVID-19 pandemic, empirical guidelines on how to manage treatments for immune-mediated

Background: In multiple sclerosis, impact of treatment on disability progression can be confounded if treatment also reduces relapses. Objective: To distinguish siponimod’s direct effects on disability progression from those on relapses in the EXPAND phase 3 trial. Methods: Three estimands, one based on principal stratum and two on hypothetical scenarios (no relapses, or equal relapses in both treatment

Background: Persons with multiple sclerosis (MS) and depression symptoms report real-world cognitive difficulties that may be missed by laboratory cognitive tests. Objective: To examine the relationship of depressive symptoms to cognitive monotasking versus multitasking in early MS. Method: Persons with early MS (n = 185; ⩽5 years diagnosed) reported mood, completed monotasking and multitasking cognitive

Background: In multiple sclerosis (MS), up to 57% of white matter lesions are chronically active. These slowly expanding lesions (SELs) contribute to disability progression. Objective: The aim of this study is to compare fingolimod and natalizumab effects on progressive linearly enlarging lesions (i.e. SELs), a putative biomarker of smouldering inflammation. Methods: Relapsing-remitting MS patients

Tonsils are believed to be the initial site of the John Cunningham virus (JCV) infection. The long-term effect of childhood tonsillectomy on JCV status in multiple sclerosis (MS) patients has not been investigated. In this retrospective case–control study, we analyzed data of 144 JCV seropositive cases and 82 JCV seronegative controls from three outpatient MS clinics in the United States. Early tonsillectomy

Background: Neurogenic bowel dysfunctions (NBDs) in the form of both fecal incontinence (FI) and functional constipation (FC) are frequent in multiple sclerosis (MS) patients and significantly affect their quality of life. Therapeutic options are limited. Objective: To investigate effectiveness of percutaneous posterior tibial nerve stimulation (PTNS) in MS patients suffering from FI and FC. Methods:

Fatigue, depression, and pain affect the majority of multiple sclerosis (MS) patients, which causes a substantial burden to patients and society. The pathophysiology of these symptoms is not entirely clear, and current treatments are only partially effective. Clinically, these symptoms share signs of anhedonia, such as reduced motivation and a lack of positive affect. In the brain, they are associated

Background: Propensity score (PS) analyses are increasingly used in multiple sclerosis (MS) research, largely owing to the greater availability of large observational cohorts and registry databases. Objective: To evaluate the use and quality of reporting of PS methods in the recent MS literature. Methods: We searched the PubMed database for articles published between January 2013 and July 2019. We

As the second decade of the 21st century draws to a close, we can take stock and potentially congratulate ourselves on the remarkable progress in the treatment and care of multiple sclerosis (MS). Improvements in the diagnosis of MS, proliferation of treatment options for relapsing forms of MS, and some, albeit modestly useful, treatments for the progressive forms of the disease, alongside a robust

Background: High-quality epidemiologic data worldwide are needed to improve our understanding of disease risk, support health policy to meet the diverse needs of people with multiple sclerosis (MS) and support advocacy efforts. Objectives: The Atlas of MS is an open-source global compendium of data regarding the epidemiology of MS and the availability of resources for people with MS reported at country

Studies using cotinine levels to define smokers have generally failed to detect an association between smoking and multiple sclerosis (MS). Using a Swedish population-based case-control study, we show that associations in relation to MS risk and progression differ considerably depending on how smoking is measured. The risk of conversion into secondary progressive disease was increased among smokers

Background: Clinical measures in multiple sclerosis (MS) face limitations that may be overcome by utilising smartphone keyboard interactions acquired continuously and remotely during regular typing. Objective: The aim of this study was to determine the reliability and validity of keystroke dynamics to assess clinical aspects of MS. Methods: In total, 102 MS patients and 24 controls were included in

Background: Progressive multifocal leukoencephalopathy (PML) can in rare cases occur in natalizumab-treated patients with high serum anti-JCPyV antibodies, hypothetically due to excessive blockade of immune cell migration. Objective: Immune cell recruitment to the central nervous system (CNS) was assessed in relapsing-remitting multiple sclerosis (RRMS) patients stratified by low versus high anti-JCPyV