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).

Longitudinal analysis of new multiple sclerosis lesions with magnetization transfer and diffusion tensor imaging.

Objective: The potential of magnetization transfer imaging (MTI) and diffusion tensor imaging (DTI) for the detection and evolution of new multiple sclerosis (MS) lesions was analyzed.

Methods: Nineteen patients with MS obtained conventional MRI, MTI, and DTI examinations bimonthly for 12 months and again after 24 months at 1.5 T MRI.

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.

A comparative assessment of myelin-sensitive measures in multiple sclerosis patients and healthy subjects.

Introduction: Multiple Sclerosis (MS) is a common neurological disease primarily characterized by myelin damage in lesions and in normal - appearing white and gray matter (NAWM, NAGM). Several quantitative MRI (qMRI) methods are sensitive to myelin characteristics by measuring specific tissue biophysical properties. However, there are currently few studies assessing the relative reproducibility and sensitivity of qMRI measures to MS pathology in vivo in patients.

A New Advanced MRI Biomarker for Remyelinated Lesions in Multiple Sclerosis.

Objectives: Neuropathological studies have shown that multiple sclerosis (MS) lesions are heterogeneous in terms of myelin/axon damage and repair as well as iron content. However, it remains a challenge to identify specific chronic lesion types, especially remyelinated lesions, in vivo in patients with MS.

Methods: We performed 3 studies: (1) a cross-sectional study in a prospective cohort of 115 patients with MS and 76 healthy controls, who underwent 3 T magnetic resonance imaging (MRI) for quantitative susceptibility mapping (QSM), myelin water fraction (MWF), and neurite density index (NDI) maps.

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.

Myelin and axon pathology in multiple sclerosis assessed by myelin water and multi-shell diffusion imaging.

Damage to the myelin sheath and the neuroaxonal unit is a cardinal feature of multiple sclerosis; however, a detailed characterization of the interaction between myelin and axon damage in vivo remains challenging. We applied myelin water and multi-shell diffusion imaging to quantify the relative damage to myelin and axons (i) among different lesion types; (ii) in normal-appearing tissue; and (iii) across multiple sclerosis clinical subtypes and healthy controls. We also assessed the relation of focal myelin/axon damage with disability and serum neurofilament light chain as a global biological measure of neuroaxonal damage.

Long-term safety and efficacy of daclizumab beta in relapsing-remitting multiple sclerosis: 6-year results from the SELECTED open-label extension study.

Objective: SELECTED, an open-label extension study, evaluated daclizumab beta treatment for up to 6 years in participants with relapsing multiple sclerosis who completed the randomized SELECT/SELECTION studies. We report final results of SELECTED.

Methods: Eligible participants who completed 1-2 years of daclizumab beta treatment in SELECT/SELECTION received daclizumab beta 150 mg subcutaneously every 4 weeks for up to 6 years in SELECTED.

White matter lesion location correlates with disability in relapsing multiple sclerosis.

Background: Lesion location is a prognostic factor of disease progression and disability accrual.

Objective: To investigate lesion formation in 11 brain regions, assess correlation between lesion location and physical and cognitive disability measures and investigate treatment effects by region.

Methods: In 2355 relapsing-remitting multiple sclerosis patients from the FREEDOMS and FREEDOMS II studies, we extracted T2-weighted lesion number, volume and density for each brain region; we investigated the (Spearman) correlation in lesion formation between brain regions, studied association between location and disability (at baseline and change over 2 years) using linear/logistic regression and assessed the regional effects of fingolimod versus placebo in negative binomial models.

Accurate, rapid and reliable, fully automated MRI brainstem segmentation for application in multiple sclerosis and neurodegenerative diseases.

Neurodegenerative disorders, such as Alzheimer's disease (AD) and progressive forms of multiple sclerosis (MS), can affect the brainstem and are associated with atrophy that can be visualized by MRI. Anatomically accurate, large-scale assessments of brainstem atrophy are challenging due to lack of automated, accurate segmentation methods. We present a novel method for brainstem volumetry using a fully-automated segmentation approach based on multi-dimensional gated recurrent units (MD-GRU), a deep learning based semantic segmentation approach employing a convolutional adaptation of gated recurrent units.

Association of brain volume loss and long-term disability outcomes in patients with multiple sclerosis treated with teriflunomide.

Background: Teriflunomide 14 mg significantly reduced brain volume loss (BVL) and confirmed disability worsening (CDW) compared with placebo in the TEMSO core study.

Objective: To investigate the relationship between BVL from Baseline to Year 2 in the TEMSO core study and long-term CDW (Year 7) in the TEMSO long-term extension (NCT00803049).

Methods: Structural Image Evaluation using Normalization of Atrophy determined BVL.

Automated Detection and Segmentation of Multiple Sclerosis Lesions Using Ultra-High-Field MP2RAGE.

Objectives: The aim of this study was to develop a new automated segmentation method of white matter (WM) and cortical multiple sclerosis (MS) lesions visible on magnetization-prepared 2 inversion-contrast rapid gradient echo (MP2RAGE) images acquired at 7 T MRI.

Materials And Methods: The proposed prototype (MSLAST [Multiple Sclerosis Lesion Analysis at Seven Tesla]) takes as input a single image contrast derived from the 7T MP2RAGE prototype sequence and is based on partial volume estimation and topological constraints. First, MSLAST performs a skull-strip of MP2RAGE images and computes tissue concentration maps for WM, gray matter (GM), and cerebrospinal fluid (CSF) using a partial volume model of tissues within each voxel.

Clinical associations of T2-weighted lesion load and lesion location in small vessel disease: Insights from a large prospective cohort study.

Background: Subcortical T2-weighted (T2w) lesions are very common in older adults and have been associated with dementia. However, little is known about the strategic lesion distribution and how lesion patterns relate to vascular risk factors and cognitive impairment.

Aim: The aim of this study was to analyze the association between T2w lesion load and location, vascular risk factors, and cognitive impairment in a large cohort of older adults.

A comparison of brain magnetic resonance imaging lesions in multiple sclerosis by race with reference to disability progression.

Background: We compared the magnetic resonance imaging (MRI) features between Japanese and Caucasian patients with multiple sclerosis (MS), and identified the relationships between MRI features and disability.

Methods: From the baseline data of phase II fingolimod trials, 95 Japanese and 246 Caucasian relapsing-remitting MS patients were enrolled. The number, volume, and distribution of brain MRI lesions were evaluated using T2-weighted (T2W) images.

MRI-based prediction of conversion from clinically isolated syndrome to clinically definite multiple sclerosis using SVM and lesion geometry.

Neuroanatomical pattern classification using support vector machines (SVMs) has shown promising results in classifying Multiple Sclerosis (MS) patients based on individual structural magnetic resonance images (MRI). To determine whether pattern classification using SVMs facilitates predicting conversion to clinically definite multiple sclerosis (CDMS) from clinically isolated syndrome (CIS). We used baseline MRI data from 364 patients with CIS, randomised to interferon beta-1b or placebo.

Clinical Correlations of Brain Lesion Location in Multiple Sclerosis: Voxel-Based Analysis of a Large Clinical Trial Dataset.

There is a limited correlation between white matter (WM) lesion load as determined by magnetic resonance imaging and disability in multiple sclerosis (MS). The reasons for this so-called clinico-radiological paradox are diverse and may, at least partly, relate to the fact that not just the overall lesion burden, but also the exact anatomical location of lesions predict the severity and type of disability. We aimed at studying the relationship between lesion distribution and disability using a voxel-based lesion probability mapping approach in a very large dataset of MS patients.

Fingolimod effect on gray matter, thalamus, and white matter in patients with multiple sclerosis.

Objective: To study the effect of fingolimod on deep gray matter (dGM), thalamus, cortical GM (cGM), white matter (WM), and ventricular volume (VV) in patients with relapsing-remitting multiple sclerosis (RRMS).

Methods: Data were pooled from 2 phase III studies. A total of 2,064 of 2,355 (88%) contributed to the analysis: fingolimod 0.

A comparison of multiple sclerosis disease activity after discontinuation of fingolimod and placebo.

Background: Cases of higher-than-expected disease activity have been reported following fingolimod discontinuation.

Objective: The objective of this paper is to assess the risk of substantially higher-than-expected disease activity post-study drug discontinuation (SDD) at the individual patient level using data from the Phase III, placebo-controlled FREEDOMS and FREEDOMS II trials.

Methods: Baseline gadolinium-enhancing T1-lesion volumes were used to statistically model the expected level of MRI disease activity post-SDD.

Teriflunomide slows BVL in relapsing MS: A reanalysis of the TEMSO MRI data set using SIENA.

Objective: To assess, using structural image evaluation using normalization of atrophy (SIENA), the effect of teriflunomide, a once-daily oral immunomodulator, on brain volume loss (BVL) in patients with relapsing forms of MS enrolled in the phase 3 TEMSO study.

Methods: TEMSO MR scans were analyzed (study personnel masked to treatment allocation) using SIENA to assess brain volume changes between baseline and years 1 and 2 in patients treated with placebo or teriflunomide. Treatment group comparisons were made via rank analysis of covariance.

Sodium intake and multiple sclerosis activity and progression in BENEFIT.

Objective: To assess whether a high-salt diet, as measured by urinary sodium concentration, is associated with faster conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS) and MS activity and disability.

Methods: BENEFIT was a randomized clinical trial comparing early versus delayed interferon beta-1b treatment in 465 patients with a CIS. Each patient provided a median of 14 (interquartile range = 13-16) spot urine samples throughout the 5-year follow-up.

Tracking the Evolution of Cerebral Gadolinium-Enhancing Lesions to Persistent T1 Black Holes in Multiple Sclerosis: Validation of a Semiautomated Pipeline.

Background: Some gadolinium-enhancing multiple sclerosis (MS) lesions remain T1-hypointense over months ("persistent black holes, BHs") and represent areas of pronounced tissue loss. A reduced conversion of enhancing lesions to persistent BHs could suggest a favorable effect of a medication on tissue repair. However, the individual tracking of enhancing lesions can be very time-consuming in large clinical trials.

Introduction to Magnetic Resonance Imaging for Neurologists.

Purpose Of Review: In neuroradiology, highly sophisticated methods such as MRI are implemented to investigate different entities of the central nervous system and to acquire miscellaneous images where tissues display varying degrees of characteristic signal intensity or brightness. Compared to x-ray, CT, and ultrasound, MRI produces clearer images of tissues, body fluids, and fat. The basics of MRI may be unknown to neurologists; this article introduces MRI physics, techniques, and interpretation guidelines.

Striatal functional connectivity changes following specific balance training in elderly people: MRI results of a randomized controlled pilot study.

Background: Practice-induced effects of specific balance training on brain structure and activity in elderly people are largely unknown.

Aim: In the present study, we investigated morphological and functional brain changes following slacking training (balancing over nylon ribbons) in a group of elderly people.

Methods: Twenty-eight healthy volunteers were recruited and randomly assigned to the intervention (mean age: 62.

Safety and efficacy of daclizumab in relapsing-remitting multiple sclerosis: 3-year results from the SELECTED open-label extension study.

Background: Daclizumab is a humanized monoclonal antibody against CD25 that modulates interleukin 2 signaling. The SELECT TRILOGY of clinical studies (SELECT/SELECTION/SELECTED) evaluated the safety and efficacy of daclizumab in patients with relapsing-remitting multiple sclerosis (RRMS). We report the long-term safety and efficacy of daclizumab 150 mg subcutaneous every 4 weeks in patients with RRMS in the SELECTED open-label extension study.

Defining brain volume cutoffs to identify clinically relevant atrophy in RRMS.

Objective: To define values of normalized brain volume (NBV) that can be categorized as low, medium, or high, according to baseline characteristics of relapsing-remitting multiple sclerosis (RRMS) patients.

Methods: Expected NBV (eNBV) was calculated for each patient based on age, disease duration, sex, baseline Expanded Disability Status Scale (EDSS), and T2-lesion volume, entering these variables into a multiple regression model run on 2342 RRMS patients (pooled FREEDOMS/FREEDOMS-II population). According to the difference between their observed NBV and their eNBV, patients were classified as having low NBV, medium NBV, or high NBV.