Diffusivity anisotropy signature of the slowly expanding lesions predicts progression independent of relapse activity in multiple sclerosis.

Background: Slowly expanding lesions (SELs) in multiple sclerosis (MS) are markers of chronic active lesions and seem to trigger disability. This study aimed to analyse spatial features of SELs through diffusion MRI and their clinical impact on progression independent of relapse activity (PIRA).

Methods: An observational study of MS subjects prospectively followed since 2011; inclusion required at least three longitudinal T1/T2-weighted and diffusion-weighted MRIs.

Executive Dysfunction and Disability in SPMS: Predictive Value of the Frontal Assessment Battery in the UCLH MS-STAT2 Cohort.

Introduction: Cognitive impairment is common in secondary progressive multiple sclerosis (SPMS), with executive dysfunction disproportionately so. The frontal assessment battery (FAB) is a bedside test assessing executive function. This study explores the distribution of FAB scores in a large SPMS cohort and their associations with disability.

Optical coherence tomography in secondary progressive multiple sclerosis: cross-sectional and longitudinal exploratory analysis from the MS-SMART randomised controlled trial.

Background: Optical coherence tomography (OCT) inner retinal metrics reflect neurodegeneration in multiple sclerosis (MS). We explored OCT measures as biomarkers of disease severity in secondary progressive MS (SPMS).

Methods: We investigated people with SPMS from the Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial OCT substudy, analysing brain MRIs, clinical assessments and OCT at baseline and 96 weeks.

Vascular risk factors are associated with grey matter atrophy in secondary progressive multiple sclerosis.

Background: Comorbidities including vascular risk factors can be associated with whole and regional brain atrophy in multiple sclerosis (MS). This has been examined in mixed MS cohorts in prospective or observational studies; however, the association between vascular comorbidities (VCM) in secondary progressive MS (SPMS) and brain atrophy has been less well studied. The aim was to investigate the cross-sectional and longitudinal association between VCM, comorbidity burden and brain atrophy in SPMS.

The use of 7T MRI in multiple sclerosis: review and consensus statement from the North American Imaging in Multiple Sclerosis Cooperative.

The use of ultra-high-field 7-Tesla (7T) MRI in multiple sclerosis (MS) research has grown significantly over the past two decades. With recent regulatory approvals of 7T scanners for clinical use in 2017 and 2020, the use of this technology for routine care is poised to continue to increase in the coming years. In this context, the North American Imaging in MS Cooperative (NAIMS) convened a workshop in February 2023 to review the previous and current use of 7T technology for MS research and potential future research and clinical applications.

Investigating the relationship between thalamic iron concentration and disease severity in secondary progressive multiple sclerosis using quantitative susceptibility mapping: Cross-sectional analysis from the MS-STAT2 randomised controlled trial.

Background: Deep grey matter pathology is a key driver of disability worsening in people with multiple sclerosis. Quantitative susceptibility mapping (QSM) is an advanced magnetic resonance imaging (MRI) technique which quantifies local magnetic susceptibility from variations in phase produced by changes in the local magnetic field. In the deep grey matter, susceptibility has previously been validated against tissue iron concentration.

Evaluating the effectiveness of simvastatin in slowing the progression of disability in secondary progressive multiple sclerosis (MS-STAT2): protocol for a multicentre, randomised controlled, double-blind, phase 3 clinical trial in the UK.

Introduction: There remains a high unmet need for disease-modifying therapies that can impact disability progression in secondary progressive multiple sclerosis (SPMS). Following positive results of the phase 2 MS-STAT study, the MS-STAT2 phase 3 trial will evaluate the efficacy and cost-effectiveness of repurposed high-dose simvastatin in slowing the progression of disability in SPMS.

Methods And Analysis: MS-STAT2 will be a multicentre, randomised, placebo-controlled, double-blind trial of participants aged between 25 and 65 (inclusive) who have SPMS with an Expanded Disability Status Scale (EDSS) score of 4.

Brain reserve and physical disability in secondary progressive multiple sclerosis.

Background: The brain reserve hypothesis posits that larger maximal lifetime brain growth (MLBG) may confer protection against physical disability in multiple sclerosis (MS). Larger MLBG as a proxy for brain reserve, has been associated with reduced progression of physical disability in patients with early MS; however, it is unknown whether this association remains once in the secondary progressive phase of MS (SPMS). Our aim was to assess whether larger MLBG is associated with decreased physical disability progression in SPMS.

Retinal Damage and Visual Network Reconfiguration Defines Visual Function Recovery in Optic Neuritis.

Background And Objectives: Recovery of vision after acute optic neuritis (AON) is critical to improving the quality of life of people with demyelinating diseases. The objective of the study was to prospectively assess the changes in visual acuity, retinal layer thickness, and cortical visual network in patients with AON to identify the predictors of permanent visual disability.

Methods: We studied a prospective cohort of 88 consecutive patients with AON with 6-month follow-up using high and low-contrast (2.

What contributes to disability in progressive MS? A brain and cervical cord-matched quantitative MRI study.

Background: We assessed the ability of a brain-and-cord-matched quantitative magnetic resonance imaging (qMRI) protocol to differentiate patients with progressive multiple sclerosis (PMS) from controls, in terms of normal-appearing (NA) tissue abnormalities, and explain disability.

Methods: A total of 27 patients and 16 controls were assessed on the Expanded Disability Status Scale (EDSS), 25-foot timed walk (TWT), 9-hole peg (9HPT) and symbol digit modalities (SDMT) tests. All underwent 3T brain and (C2-C3) cord structural imaging and qMRI (relaxometry, quantitative magnetisation transfer, multi-shell diffusion-weighted imaging), using a fast brain-and-cord-matched protocol with brain-and-cord-unified imaging readouts.

Predictive value of retinal atrophy for cognitive decline across disease duration in multiple sclerosis.

Background: We investigated the association between changes in retinal thickness and cognition in people with MS (PwMS), exploring the predictive value of optical coherence tomography (OCT) markers of neuroaxonal damage for global cognitive decline at different periods of disease.

Method: We quantified the peripapillary retinal nerve fibre (pRFNL) and ganglion cell-inner plexiform (GCIPL) layers thicknesses of 207 PwMS and performed neuropsychological evaluations. The cohort was divided based on disease duration (≤5 years or >5 years).

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.

Longitudinal Metabolite Changes in Progressive Multiple Sclerosis: A Study of 3 Potential Neuroprotective Treatments.

Background: H-magnetic resonance spectroscopy (H-MRS) may provide a direct index for the testing of medicines for neuroprotection and drug mechanisms in multiple sclerosis (MS) through measures of total N-acetyl-aspartate (tNAA), total creatine (tCr), myo-inositol (mIns), total-choline (tCho), and glutamate + glutamine (Glx). Neurometabolites may be associated with clinical disability with evidence that baseline neuroaxonal integrity is associated with upper limb function and processing speed in secondary progressive MS (SPMS).

Purpose: To assess the effect on neurometabolites from three candidate drugs after 96-weeks as seen by H-MRS and their association with clinical disability in SPMS.

Diffusion-based structural connectivity patterns of multiple sclerosis phenotypes.

Background: We aimed to describe the severity of the changes in brain diffusion-based connectivity as multiple sclerosis (MS) progresses and the microstructural characteristics of these networks that are associated with distinct MS phenotypes.

Methods: Clinical information and brain MRIs were collected from 221 healthy individuals and 823 people with MS at 8 MAGNIMS centres. The patients were divided into four clinical phenotypes: clinically isolated syndrome, relapsing-remitting, secondary progressive and primary progressive.

Cardiovascular risk factors in secondary progressive multiple sclerosis: A cross-sectional analysis from the MS-STAT2 randomized controlled trial.

Background And Purpose: There is increasing evidence that cardiovascular risk (CVR) contributes to disability progression in multiple sclerosis (MS). CVR is particularly prevalent in secondary progressive MS (SPMS) and can be quantified through validated composite CVR scores. The aim was to examine the cross-sectional relationships between excess modifiable CVR, whole and regional brain atrophy on magnetic resonance imaging, and disability in patients with SPMS.

Feasibility of in vivo multi-parametric quantitative magnetic resonance imaging of the healthy sciatic nerve with a unified signal readout protocol.

Magnetic resonance neurography (MRN) has been used successfully over the years to investigate the peripheral nervous system (PNS) because it allows early detection and precise localisation of neural tissue damage. However, studies demonstrating the feasibility of combining MRN with multi-parametric quantitative magnetic resonance imaging (qMRI) methods, which provide more specific information related to nerve tissue composition and microstructural organisation, can be invaluable. The translation of emerging qMRI methods previously validated in the central nervous system to the PNS offers real potential to characterise in patients in vivo the underlying pathophysiological mechanisms involved in a plethora of conditions of the PNS.

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.

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.

Association of Slowly Expanding Lesions on MRI With Disability in People With Secondary Progressive Multiple Sclerosis.

Background And Objective: To explore the relationship between slowly expanding lesions (SELs) on MRI and disability in secondary progressive multiple sclerosis (SPMS).

Methods: We retrospectively studied 345 patients with SPMS enrolled in the MS-SMART trial. They underwent brain MRI at baseline and at 24 and 96 weeks.

Spatial patterns of brain lesions assessed through covariance estimations of lesional voxels in multiple Sclerosis: The SPACE-MS technique.

Predicting disability in progressive multiple sclerosis (MS) is extremely challenging. Although there is some evidence that the spatial distribution of white matter (WM) lesions may play a role in disability accumulation, the lack of well-established quantitative metrics that characterise these aspects of MS pathology makes it difficult to assess their relevance for clinical progression. This study introduces a novel approach, called SPACE-MS, to quantitatively characterise spatial distributional features of brain MS lesions, so that these can be assessed as predictors of disability accumulation.

In vivo imaging of chronic active lesions in multiple sclerosis.

New clinical activity in multiple sclerosis (MS) is often accompanied by acute inflammation which subsides. However, there is growing evidence that a substantial proportion of lesions remain active well beyond the acute phase. Chronic active lesions are most frequently found in progressive MS and are characterised by a border of inflammation associated with iron-enriched cells, leading to ongoing tissue injury.

Reduced neurite density in the brain and cervical spinal cord in relapsing-remitting multiple sclerosis: A NODDI study.

Background: Multiple sclerosis (MS) affects both brain and spinal cord. However, studies of the neuraxis with advanced magnetic resonance imaging (MRI) are rare because of long acquisition times. We investigated neurodegeneration in MS brain and cervical spinal cord using neurite orientation dispersion and density imaging (NODDI).

Erratum: Author Correction: High-dimensional detection of imaging response to treatment in multiple sclerosis.

[This corrects the article DOI: 10.1038/s41746-019-0127-8.].

High-dimensional detection of imaging response to treatment in multiple sclerosis.

Changes on brain imaging may precede clinical manifestations or disclose disease progression opaque to conventional clinical measures. Where, as in multiple sclerosis, the pathological process has a complex anatomical distribution, such changes are not easily detected by low-dimensional models in common use. This hinders our ability to detect treatment effects, both in the management of individual patients and in interventional trials.

LncRNAs expression profile in peripheral blood mononuclear cells from multiple sclerosis patients.

LncRNA PCR arrays containing 90 common LncRNAs were used to screen lncRNA expression levels in PBMC from a discovery population of patients with MS. Data from discovery and replications cohorts showed a generalized dysregulation of lncRNA levels in MS patients compared with controls. MALAT1, MEG9, NRON, ANRIL, TUG1, XIST, SOX2OT, GOMAFU, HULC, BACE-1AS were significantly downregulated in MS patients in comparison with controls.