An MRI assessment of mechanisms underlying lesion growth and shrinkage in multiple sclerosis.

Objective: To assess the pathological mechanisms contributing to white matter (WM) lesion expansion or contraction and remyelination in multiple sclerosis (MS).

Methods: We assessed 1,613 lesions in 49 people with relapsing-remitting MS in the CCMR-One bexarotene trial (EudraCT 2014-003145-99). We measured lesion orientation relative to WM tracts, surface-in gradients and veins.

Explaining cognitive function in multiple sclerosis through networks of grey and white matter features: a joint independent component analysis.

Cognitive impairment (CI) in multiple sclerosis (MS) is only partially explained by whole-brain volume measures, but independent component analysis (ICA) can extract regional patterns of damage in grey matter (GM) or white matter (WM) that have proven more closely associated with CI. Pathology in GM and WM occurs in parallel, and so patterns can span both. This study assessed whether joint-ICA of GM and WM features better explained cognitive function compared to single-tissue ICA.

Evaluating multiple sclerosis severity loci 30 years after a clinically isolated syndrome.

The first genome-wide significant multiple sclerosis severity locus, rs10191329, has been pathologically linked to cortical lesion load and brain atrophy. However, observational cohorts such as MSBase have not replicated associations with disability outcomes, instead finding other loci. We evaluated rs10191329 and MSBase loci in a unique cohort of 53 people followed for 30 years after a clinically isolated syndrome, with deep clinical phenotyping and MRI measures of inflammation and neurodegeneration.

Treatment effect modifiers of immunotherapies for relapsing-remitting multiple sclerosis-A systematic review and meta-analysis.

Background: This meta-analysis aimed to assess the treatment effects of immunotherapies in subgroups of adults with clinically isolated syndrome or relapsing forms of multiple sclerosis (MS) and the effect of potential treatment effect modifiers (TEMs).

Methods: Phase 2 and 3 RCTs with a placebo comparator were analyzed. Risk of bias was assessed.

The influence of MOGAD on diagnosis of multiple sclerosis using MRI.

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an immune-mediated demyelinating disease that is challenging to differentiate from multiple sclerosis (MS), as the clinical phenotypes overlap, and people with MOGAD can fulfil the current MRI-based diagnostic criteria for MS. In addition, the MOG antibody assays that are an essential component of MOGAD diagnosis are not standardized. Accurate diagnosis of MOGAD is crucial because the treatments and long-term prognosis differ from those for MS.

The evolving contribution of MRI measures towards the prediction of secondary progressive multiple sclerosis.

Background: In multiple sclerosis (MS), both lesion accrual and brain atrophy predict clinical outcomes. However, it is unclear whether these prognostic features are equally relevant throughout the course of MS. Among 103 participants recruited following a clinically isolated syndrome (CIS) and followed up over 30 years, we explored (1) whether white matter lesions were prognostically more relevant earlier and brain atrophy later in the disease course towards development of secondary progressive (SP) disease; (2) if so, when the balance in prognostic contribution shifts and (3) whether optimised prognostic models predicting SP disease should include different features dependent on disease duration.

Qualitative user experience evaluation of the MS trust's online treatment decision aid tool's accommodation of planning pregnancy.

Background: Decision-making about treatment when planning a pregnancy (family planning) is complex for women living with multiple sclerosis (MS). Decision tools can help this process, in 2016 MS Trust launched their online digital treatment decision tool to support people with MS.

Objectives: To evaluate user-experience of this tool by exploring women's opinions about its content, interface, and usefulness in the context of family planning; and to synthesize recommendations to improve the tool.

An update on the role of magnetic resonance imaging in predicting and monitoring multiple sclerosis progression.

Introduction: While magnetic resonance imaging (MRI) is established in diagnosing and monitoring disease activity in multiple sclerosis (MS), its utility in predicting and monitoring disease progression is less clear.

Areas Covered: The authors consider changing concepts in the phenotypic classification of MS, including progression independent of relapses; pathological processes underpinning progression; advances in MRI measures to assess them; how well MRI features explain and predict clinical outcomes, including models that assess disease effects on neural networks, and the potential role for machine learning.

Expert Opinion: Relapsing-remitting and progressive MS have evolved from being viewed as mutually exclusive to having considerable overlap.

Treatment reduces the incidence of newly appearing multiple sclerosis lesions evolving into chronic active, slowly expanding lesions: A retrospective analysis.

Background And Purpose: Newly appearing lesions in multiple sclerosis (MS) may evolve into chronically active, slowly expanding lesions (SELs), leading to sustained disability progression. The aim of this study was to evaluate the incidence of newly appearing lesions developing into SELs, and their correlation to clinical evolution and treatment.

Methods: A retrospective analysis of a fingolimod trial in primary progressive MS (PPMS; INFORMS, NCT00731692) was undertaken.

Networks of microstructural damage predict disability in multiple sclerosis.

Background: Network-based measures are emerging MRI markers in multiple sclerosis (MS). We aimed to identify networks of white (WM) and grey matter (GM) damage that predict disability progression and cognitive worsening using data-driven methods.

Methods: We analysed data from 1836 participants with different MS phenotypes (843 in a discovery cohort and 842 in a replication cohort).

The relation of sarcopenia and disability in multiple sclerosis.

Background: The relation of sarcopenia and disability in MS is unknown.

Objective: To investigate the relation of temporal muscle thickness (TMT) and disability.

Methods: A cohort of 132 people who presented with a clinically isolated syndrome (CIS) suggestive of MS at a mean age of 30.

Relationship between paramagnetic rim lesions and slowly expanding lesions in multiple sclerosis.

Background: Magnetic resonance imaging (MRI) markers for chronic active lesions in MS include slowly expanding lesions (SELs) and paramagnetic rim lesions (PRLs).

Objectives: To identify the relationship between SELs and PRLs in MS, and their association with disability.

Methods: 61 people with MS (pwMS) followed retrospectively with MRI including baseline susceptibility-weighted imaging, and longitudinal T1 and T2-weighted scans.

Remyelination varies between and within lesions in multiple sclerosis following bexarotene.

Objective: In multiple sclerosis chronic demyelination is associated with axonal loss, and ultimately contributes to irreversible progressive disability. Enhancing remyelination may slow, or even reverse, disability. We recently trialled bexarotene versus placebo in 49 people with multiple sclerosis.

Immunotherapy for people with clinically isolated syndrome or relapsing-remitting multiple sclerosis: treatment response by demographic, clinical, and biomarker subgroups (PROMISE)-a systematic review protocol.

Background: Multiple sclerosis (MS) is an inflammatory and degenerative disease of the central nervous system with an increasing worldwide prevalence. Since 1993, more than 15 disease-modifying immunotherapies (DMTs) have been licenced and have shown moderate efficacy in clinical trials. Based on the heterogeneity of the disease and the partial effectiveness of therapies, a personalised medicine approach would be valuable taking individual prognosis and suitability of a chosen therapy into account to gain the best possible treatment effect.

Slowly expanding lesions relate to persisting black-holes and clinical outcomes in relapse-onset multiple sclerosis.

Background: Slowly expanding lesions (SELs) are MRI markers of chronic active lesions in multiple sclerosis (MS). T1-hypointense black holes, and reductions in magnetization transfer ratio (MTR) are pathologically correlated with myelin and axonal loss. While all associated with progressive MS, the relationship between these lesion's metrics and clinical outcomes in relapse-onset MS has not been widely investigated.

Remyelination in humans due to a retinoid-X receptor agonist is age-dependent.

Remyelination efficiency declines with advancing age in animal models, but this has been harder to demonstrate in people with multiple sclerosis. We show that bexarotene, a putatively remyelinating retinoid-X receptor agonist, shortened the visual evoked potential latency in patients with chronic optic neuropathy aged under 42 years only (with the effect diminishing by 0.45 ms per year of age); and increased the magnetization transfer ratio of deep gray matter lesions in those under 43 years only.