Analysis and visualization of the effect of multiple sclerosis on biological brain age.

Introduction: The rate of neurodegeneration in multiple sclerosis (MS) is an important biomarker for disease progression but can be challenging to quantify. The brain age gap, which quantifies the difference between a patient's chronological and their estimated biological brain age, might be a valuable biomarker of neurodegeneration in patients with MS. Thus, the aim of this study was to investigate the value of an image-based prediction of the brain age gap using a deep learning model and compare brain age gap values between healthy individuals and patients with MS.

The Canadian Prospective Cohort Study to understand progression in multiple sclerosis: baseline characteristics.

Background: Disease progression is observed across the spectrum of people with multiple sclerosis (MS) and identification of effective treatment strategies to halt progression remains one of the greatest unmet clinical needs.

Objectives: The Canadian Prospective Cohort Study to Understand Progression in MS (CanProCo) was designed to evaluate a wide range of factors associated with the onset and rate of clinical disease progression in MS and to describe the interplay between these factors.

Design: A prospective cohort study.

Feasibility study to assess lesion repair in relapsing-remitting multiple sclerosis: A randomized controlled pilot clinical trial of domperidone add-on treatment.

Background: Identification of therapies to promote repair in multiple sclerosis is challenged by the lack of an accepted trial model and associated outcome measures. The goal of this study was to determine the feasibility of a new trial model that enrolls disease modifying therapy (DMT)-treated relapsing-remitting multiple sclerosis (RRMS) participants who have enhancing lesions on clinically indicated brain MRI, and to explore estimates of lesion repair using MRI.

Methods: This was a single site randomized controlled clinical trial.

Distinct characteristics and severity of brain magnetic resonance imaging lesions in women and men with multiple sclerosis assessed using verified texture analysis measures.

Background And Goal: characterization of brain lesion types in multiple sclerosis (MS) has been an ongoing challenge. Based on verified texture analysis measures from clinical magnetic resonance imaging (MRI), this study aimed to develop a method to identify two extremes of brain MS lesions that were approximately severely demyelinated (sDEM) and highly remyelinated (hREM), and compare them in terms of common clinical variables.

Method: Texture analysis used an optimized gray-level co-occurrence matrix (GLCM) method based on FLAIR MRI from 200 relapsing-remitting MS participants.

Patient-reported outcomes of neurologic and neuropsychiatric symptoms in mild COVID-19: a prospective cohort study.

Background: Various neurologic manifestations have been reported in patients with COVID-19, mostly in retrospective studies of patients admitted to hospital, but there are few data on patients with mild COVID-19. We examined the frequency and persistence of neurologic/neuropsychiatric symptoms in patients with mild COVID-19 in a 1-year prospective cohort study, as well as assessment of use of health care services and patient-reported outcomes.

Methods: Participants in the Alberta HOPE COVID-19 trial (hydroxychloroquine v.

Accounting for uncertainty in training data to improve machine learning performance in predicting new disease activity in early multiple sclerosis.

Introduction: Machine learning (ML) has great potential for using health data to predict clinical outcomes in individual patients. Missing data are a common challenge in training ML algorithms, such as when subjects withdraw from a clinical study, leaving some samples with missing outcome labels. In this study, we have compared three ML models to determine whether accounting for label uncertainty can improve a model's predictions.

Simple parameters from complete blood count predict lymphopenia, adverse effects and efficacy in people with MS treated with dimethyl fumarate.

Background: Dimethyl fumarate (DMF) is a first-line oral therapy for relapsing-remitting multiple sclerosis (RRMS). This retrospective study aims to determine the utility of routine complete blood counts (CBC) in predicting lymphopenia, adverse effects and efficacy in a real-world clinical setting.

Methods: The Calgary Multiple Sclerosis (MS) Clinic manages over 1800 people with MS on disease-modifying therapies (DMT).

Good multiple sclerosis (MS) care and how to get there in Canada: Perspectives of Canadian healthcare providers working with persons with MS.

Objective: The literature that has examined healthcare access and needs of the multiple sclerosis (MS) population is limited. Currently, no research has engaged healthcare providers delivering services to this population to examine their perspectives on the provision of MS care in Canada. We aimed to summarize what good MS care should look like according to Canadian healthcare providers working with people with MS, and to identify the supports and resources required, within their care setting, to enable this standard of care.

Expression of risk genes linked to vitamin D receptor super-enhancer regions and their association with phenotype severity in multiple sclerosis.

Multiple sclerosis (MS) is a chronic debilitating neurological condition with a wide range of phenotype variability. A complex interplay of genetic and environmental factors contributes to disease onset and progression in MS patients. Vitamin D deficiency is a known susceptibility factor for MS, however the underlying mechanism of vitamin D-gene interactions in MS etiology is still poorly understood.

Advanced diffusion MRI and image texture analysis detect widespread brain structural differences between relapsing-remitting and secondary progressive multiple sclerosis.

Introduction: Disease development in multiple sclerosis (MS) causes dramatic structural changes, but the exact changing patterns are unclear. Our objective is to investigate the differences in brain structure locally and spatially between relapsing-remitting MS (RRMS) and its advanced form, secondary progressive MS (SPMS), through advanced analysis of diffusion magnetic resonance imaging (MRI) and image texture.

Methods: A total of 20 patients with RRMS and nine patients with SPMS from two datasets underwent 3T anatomical and diffusion tensor imaging (DTI).

The Canadian prospective cohort study to understand progression in multiple sclerosis (CanProCo): rationale, aims, and study design.

Background: Neurological disability progression occurs across the spectrum of people living with multiple sclerosis (MS). Although there are a handful of disease-modifying treatments approved for use in progressive phenotypes of MS, there are no treatments that substantially modify the course of clinical progression in MS. Characterizing the determinants of clinical progression can inform the development of novel therapeutic agents and treatment approaches that target progression in MS, which is one of the greatest unmet needs in clinical practice.

Hydroxychloroquine for Primary Progressive Multiple Sclerosis.

Objective: Primary progressive multiple sclerosis (PPMS) does not respond well to immunomodulatory or immunosuppressive treatment. Chronic activation of microglia has been implicated in the pathophysiology of PPMS. The antimalarial drug hydroxychloroquine (HCQ) reduces the activity of human microglia and has neuroprotective effects in vitro.

Cannabinoids and bladder symptoms in multiple sclerosis.

Background: Research on the health benefits of cannabis has been limited because use remains restricted or illegal in most countries. Medical cannabis has been legal in Canada since 2001 and recreational use became legal in October 2018. While there are data that support a biological mechanism by which cannabinoids can impact various other symptoms of MS, the evidence of effectiveness of cannabis as a treatment for bladder symptoms remains unsettled.

Nonlesional diffusely abnormal appearing white matter in clinically isolated syndrome: Prevalence, association with clinical and MRI features, and risk for conversion to multiple sclerosis.

Background And Purpose: While diffusely abnormal white matter (DAWM) is a nonlesional MRI abnormality identified in ∼25% of patients with multiple sclerosis (MS), it has yet to be investigated in patients at an earlier disease stage, namely clinically isolated syndrome (CIS). The goals of this study were to (1) determine the prevalence of DAWM in patients with a CIS suggestive of MS, (2) evaluate the association between DAWM and demographic, clinical, and MRI features, and (3) evaluate the prognostic significance of DAWM on conversion from CIS to MS.

Methods: One hundred and forty-two CIS participants were categorized into DAWM and non-DAWM groups at baseline and followed for up to 24 months or until MS diagnosis.

Repurposing Domperidone in Secondary Progressive Multiple Sclerosis: A Simon 2-Stage Phase 2 Futility Trial.

Objective: To assess whether treatment with the generic drug domperidone can reduce the progression of disability in secondary progressive multiple sclerosis (SPMS), we conducted a phase 2 futility trial following the Simon 2-stage design.

Methods: We enrolled patients in an open-label, Simon 2-stage, single-center, phase 2, single-arm futility trial at the Calgary Multiple Sclerosis Clinic if they met the following criteria: age of 18 to 60 years, SPMS, screening Expanded Disability Status Scale score of 4.0 to 6.

Multiple Sclerosis Clinic Utilization is Associated with Fewer Emergency Department Visits.

Objective: Alberta is a Canadian province with a high prevalence of multiple sclerosis (MS). In this ecological study, we examined group differences in health care utilization among persons with MS (pwMS) living within different regions of the province.

Methods: pwMS were identified from provincial administrative databases spanning 2002-2011.

Advanced Analysis of Diffusion Tensor Imaging Along With Machine Learning Provides New Sensitive Measures of Tissue Pathology and Intra-Lesion Activity in Multiple Sclerosis.

Tissue pathology in multiple sclerosis (MS) is highly complex, requiring multi-dimensional analysis. In this study, our goal was to test the feasibility of obtaining high angular resolution diffusion imaging (HARDI) metrics through single-shell modeling of diffusion tensor imaging (DTI) data, and investigate how advanced measures from single-shell HARDI and DTI tractography perform relative to classical DTI metrics in assessing MS pathology. We examined 52 relapsing-remitting MS patients who had 3T anatomical brain MRI and DTI.

Multimodal peripheral fluid biomarker analysis in clinically isolated syndrome and early multiple sclerosis.

Background: Increasing evidence suggests that various inflammatory, immunological and metabolic pathways are altered in the clinically isolated syndrome (CIS) of multiple sclerosis (MS). Moreover, recent diagnostic criteria have made possible the very early diagnosis of MS. We evaluated multiple fluid biomarkers in people with early MS and CIS.

Multiple sclerosis-related fatigue: the role of impaired corticospinal responses and heightened exercise fatigability.

It is unclear whether motor fatigability and perceived fatigue share a common pathophysiology in people with multiple sclerosis (PwMS). This cross-sectional investigation explored the relationship between the mechanisms of motor fatigability from cycling and fatigue severity in PwMS. Thirteen highly fatigued (HF) and thirteen nonfatigued (LF) PwMS and thirteen healthy controls (CON) completed a step test until volitional exhaustion on an innovative cycle ergometer.

Long noncoding RNAs associated with phenotypic severity in multiple sclerosis.

Introduction: Multiple sclerosis (MS) is a disease that causes progressive neurological disability. Treatments are available that are protective against MS relapses and it is thought that reduction of early neuroinflammation may improve long term prognosis. At present there is no biomarker that can predict which patients may have a more severe disease course, and potentially benefit from more aggressive therapy.

Biomarkers of intestinal barrier function in multiple sclerosis are associated with disease activity.

Background: Recent evidence suggests a role for the gut-brain axis in the pathophysiology of multiple sclerosis (MS).

Materials And Methods: We studied biomarkers of intestinal permeability in 126 people with MS (57 relapsing-remitting multiple sclerosis (RRMS) and 69 progressive MS) and in a group of healthy controls for comparison. Serum/plasma concentrations of zonulin (a regulator of enterocyte tight junctions), tight junction proteins (ZO-1 and occludin), intestinal fatty acid binding protein (IFABP)/ileal bile acid binding protein (IBABP), D-lactate, and lipopolysaccharide (LPS) binding protein were measured.

Clinically Isolated Syndrome and Early Relapsing Multiple Sclerosis.

Purpose Of Review: This article reviews management of clinically isolated syndrome and early relapsing-remitting multiple sclerosis (MS). It provides a general approach to patient management and determination of prognosis, reviews first-line disease-modifying therapies, and provides an approach to treatment selection.

Recent Findings: Revision of the MS diagnostic criteria allows an earlier MS diagnosis, which reduces diagnostic uncertainty and often allows additional treatment options.

Focus on the gut-brain axis: Multiple sclerosis, the intestinal barrier and the microbiome.

The brain-gut axis serves as the bidirectional connection between the gut microbiome, the intestinal barrier and the immune system that might be relevant for the pathophysiology of inflammatory demyelinating diseases. People with multiple sclerosis have been shown to have an altered microbiome, increased intestinal permeability and changes in bile acid metabolism. Experimental evidence suggests that these changes can lead to profound alterations of peripheral and central nervous system immune regulation.