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Progressive multiple sclerosis

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https://www.readbyqxmd.com/read/28549714/the-enigmatic-role-of-viruses-in-multiple-sclerosis-molecular-mimicry-or-disturbed-immune-surveillance
#1
REVIEW
Jens Geginat, Moira Paroni, Massimiliano Pagani, Daniela Galimberti, Raffaele De Francesco, Elio Scarpini, Sergio Abrignani
Multiple sclerosis (MS) is a T cell driven autoimmune disease of the central nervous system (CNS). Despite its association with Epstein-Barr Virus (EBV), how viral infections promote MS remains unclear. However, there is increasing evidence that the CNS is continuously surveyed by virus-specific T cells, which protect against reactivating neurotropic viruses. Here, we discuss how viral infections could lead to the breakdown of self-tolerance in genetically predisposed individuals, and how the reactivations of viruses in the CNS could induce the recruitment of both autoaggressive and virus-specific T cell subsets, causing relapses and progressive disability...
May 23, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28548004/reduced-cellularity-of-bone-marrow-in-multiple-sclerosis-with-decreased-msc-expansion-potential-and-premature-ageing-in-vitro
#2
Juliana Redondo, Pamela Sarkar, Kevin Kemp, Paul F Virgo, Joya Pawade, Aimie Norton, David C Emery, Martin G Guttridge, David I Marks, Alastair Wilkins, Neil J Scolding, Claire M Rice
BACKGROUND: Autologous bone-marrow-derived cells are currently employed in clinical studies of cell-based therapy in multiple sclerosis (MS) although the bone marrow microenvironment and marrow-derived cells isolated from patients with MS have not been extensively characterised. OBJECTIVES: To examine the bone marrow microenvironment and assess the proliferative potential of multipotent mesenchymal stromal cells (MSCs) in progressive MS. METHODS: Comparative phenotypic analysis of bone marrow and marrow-derived MSCs isolated from patients with progressive MS and control subjects was undertaken...
May 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28545479/endoplasmic-reticulum-stress-and-inflammation-in-the-central-nervous-system
#3
REVIEW
Neil T Sprenkle, Savannah G Sims, Cristina L Sánchez, Gordon P Meares
Persistent endoplasmic reticulum (ER) stress is thought to drive the pathology of many chronic disorders due to its potential to elicit aberrant inflammatory signaling and facilitate cell death. In neurodegenerative diseases, the accumulation of misfolded proteins and concomitant induction of ER stress in neurons contributes to neuronal dysfunction. In addition, ER stress responses induced in the surrounding neuroglia may promote disease progression by coordinating damaging inflammatory responses, which help fuel a neurotoxic milieu...
May 25, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28543098/brain-endothelial-cell-expression-of-sparcl-1-is-specific-to-chronic-multiple-sclerosis-lesions-and-is-regulated-by-inflammatory-mediators-in-vitro
#4
C Bridel, M J A Koel-Simmelink, L Peferoen, C Derada Troletti, S Durieux, R Gorter, E Nutma, P Gami, E Iacobeus, L Brundin, J Kuhle, H Vrenken, J Killestein, S R Piersma, T V Pham, H E De Vries, S Amor, C R Jimenez, C E Teunissen
AIMS: Cell matrix modulating protein SPARCL-1 is highly expressed by astrocytes during CNS development and following acute CNS damage. Applying NanoLC-MS/MS to CSF of RRMS and SPMS patients, we identified SPARCL-1 as differentially expressed between these two stages of MS, suggesting a potential as CSF biomarker to differentiate RRMS from SPMS and a role in MS pathogenesis. METHODS: This study examines the potential of SPARCL-1 as CSF biomarker discriminating RRMS from SPMS in 3 independent cohorts (n=249), analyses its expression pattern in MS lesions (n= 26), and studies its regulation in cultured human brain microvasculature endothelial cells (BEC) after exposure to MS-relevant inflammatory mediators...
May 24, 2017: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/28542724/viruses-and-endogenous-retroviruses-in-multiple-sclerosis-from-correlation-to-causation
#5
REVIEW
A-F A Mentis, E Dardiotis, N Grigoriadis, E Petinaki, G M Hadjigeorgiou
Multiple sclerosis is an immune-mediated disease with an environmental component. According to a long-standing but unproven hypothesis dating to initial descriptions of multiple sclerosis (MS) at the end of the 19th century, viruses are either directly or indirectly implicated in MS pathogenesis. Whether viruses in MS are principally causal or simply contributory remains to be proven, but many viruses or viral elements-predominantly Epstein-Barr virus, human endogenous retroviruses (HERVs) and human herpesvirus 6 (HHV-6) but also less common viruses such as Saffold and measles viruses-are associated with MS...
May 23, 2017: Acta Neurologica Scandinavica
https://www.readbyqxmd.com/read/28541408/loss-of-homeostatic-microglia-and-patterns-of-their-activation-in-active-multiple-sclerosis
#6
Tobias Zrzavy, Simon Hametner, Isabella Wimmer, Oleg Butovsky, Howard L Weiner, Hans Lassmann
Microglia and macrophages accumulate at the sites of active demyelination and neurodegeneration in the multiple sclerosis brain and are thought to play a central role in the disease process. We used recently described markers to characterize the origin and functional states of microglia/macrophages in acute, relapsing and progressive multiple sclerosis. We found microglia activation in normal white matter of controls and that the degree of activation increased with age. This microglia activation was more pronounced in the normal-appearing white matter of patients in comparison to controls and increased with disease duration...
May 24, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28540179/evaluating-the-effect-of-multiple-sclerosis-lesions-on-automatic-brain-structure-segmentation
#7
Sandra González-Villà, Sergi Valverde, Mariano Cabezas, Deborah Pareto, Joan C Vilanova, Lluís Ramió-Torrentà, Àlex Rovira, Arnau Oliver, Xavier Lladó
In recent years, many automatic brain structure segmentation methods have been proposed. However, these methods are commonly tested with non-lesioned brains and the effect of lesions on their performance has not been evaluated. Here, we analyze the effect of multiple sclerosis (MS) lesions on three well-known automatic brain structure segmentation methods, namely, FreeSurfer, FIRST and multi-atlas fused by majority voting, which use learning-based, deformable and atlas-based strategies, respectively. To perform a quantitative analysis, 100 synthetic images of MS patients with a total of 2174 lesions are simulated on two public databases with available brain structure ground truth information (IBSR18 and MICCAI'12)...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28537110/three-year-clinical-outcomes-of-relapsing-multiple-sclerosis-patients-treated-with-dimethyl-fumarate-in-a-united-states-community-health-center
#8
Kyle Smoot, Kateri J Spinelli, Tamela Stuchiner, Lindsay Lucas, Chiayi Chen, Lois Grote, Elizabeth Baraban, Kiren Kresa-Reahl, Stanley Cohan
BACKGROUND: Following approval of dimethyl fumarate (DMF), we established a registry of relapsing multiple sclerosis (RMS) patients taking DMF at our community MS center. OBJECTIVE: To track DMF patients' tolerability, disease progression, and lymphopenia. METHODS: Patients prescribed DMF for RMS from March 2013 to March 2016 were prospectively enrolled ( N = 412). Baseline data, clinical relapses, magnetic resonance imaging (MRI) activity, discontinuation, and lymphocyte counts were captured through chart review...
May 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28536997/plxna3-variant-rs5945430-is-associated-with-severe-clinical-course-in-male-multiple-sclerosis-patients
#9
Moaz Qureshi, Mohamed Hatem, Raed Alroughani, Sindhu P Jacob, Rabeah Abbas Al-Temaimi
Multiple sclerosis (MS) exhibits sex bias in disease clinical course as male MS patients develop severe, progressive clinical course with accumulating disability. So far, no factors have been found associating with this sex bias in MS severity. We set out to determine the genetic factor contributing to MS male-specific progressive disease. This is an MS cross-sectional study involving 213 Kuwaiti MS patients recruited at Dasman Diabetes Institute. Exome sequencing was performed on 18 females and 8 male MS patients' genomic DNA...
May 23, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28536996/models-for-studying-myelination-demyelination-and-remyelination
#10
REVIEW
I Osorio-Querejeta, M Sáenz-Cuesta, M Muñoz-Culla, D Otaegui
One of the most widely studied demyelinating diseases is multiple sclerosis, which is characterised by the appearance of demyelinating plaques, followed by myelin regeneration. Nevertheless, with disease progression, remyelination tends to fail, increasing the characteristic neurodegeneration of the disease. It is essential to understand the mechanisms that operate in the processes of myelination, demyelination and remyelination to develop treatments that promote the production of new myelin, thereby protecting the central nervous system...
May 23, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28536921/progressive-multifocal-leukoencephalopathy-in-patients-treated-with-fumaric-acid-esters-a-review-of-19-cases
#11
Robbert-Jan Gieselbach, Annemarie H Muller-Hansma, Martijn T Wijburg, Marjolein S de Bruin-Weller, Bob W van Oosten, Dennis J Nieuwkamp, Frank E Coenjaerts, Mike P Wattjes, Jean-Luc Murk
Progressive multifocal leukoencephalopathy (PML) is a rare and potentially fatal condition caused by a brain infection with JC polyomavirus (JCV). PML develops almost exclusively in immunocompromised patients and has recently been associated with use of fumaric acid esters (FAEs), or fumarates. We reviewed the literature and the Dutch and European pharmacovigilance databases in order to identify all available FAE-associated PML cases and distinguish possible common features among these patients. A total of 19 PML cases associated with FAE use were identified...
May 23, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28534643/bicams-in-the-argentine-population-relationship-with-clinical-and-sociodemographic-variables
#12
Sandra Vanotti, A Smerbeck, María B Eizaguirre, Maria L Saladino, Ralph R H Benedict, Fernando J Caceres
The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) was developed to provide valid assessment of cognitive impairment in multiple sclerosis (MS). The relationship between clinical and social variables and cognitive disorders has been extensively studied, but primarily in developed countries with a focus on other cognitive measures or batteries. The objectives of this study were to analyze the relationship between the BICAMS data and key clinical and sociodemographic variables in the Argentine MS population...
May 23, 2017: Applied Neuropsychology. Adult
https://www.readbyqxmd.com/read/28530523/cost-effectiveness-of-peginterferon-beta-1a-and-alemtuzumab-in-relapsing-remitting-multiple-sclerosis
#13
Ankur A Dashputre, Khalid M Kamal, Gauri Pawar
BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, affecting 2.5 million people globally and 400,000 people in the United States. While no cure exists for MS, the goal is to manage the disease using disease-modifying therapies (DMTs), which have been shown to slow disease progression and prevent relapses. Relapsing-remitting MS (RRMS) is the most common form of MS at the time of diagnosis. Peginterferon beta-1a (PEG) and alemtuzumab (ALT) were recently approved and have demonstrated good clinical outcomes, including reduced relapse rates in clinical trials...
June 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28529497/efficacy-and-safety-of-fingolimod-in-daily-practice-experience-of-an-academic-ms-french-center
#14
Thomas Roux, Elisabeth Maillart, Jean-Sébastien Vidal, Sophie Tezenas du Montcel, Catherine Lubetzki, Caroline Papeix
INTRODUCTION: Fingolimod (Fg), a sphingosine 1-phosphate receptor modulator, decreases the annual relapse rate (ARR) in relapsing-remitting multiple sclerosis (RRMS). The aim of this study was to assess the efficacy and safety of Fg in daily practice in patients with RRMS, previously treated with natalizumab (Nz) or not, and systematically followed during at least 1 year. METHODS: Data were collected from the patient files. Primary endpoint was the comparison between the ARR the year before Fg onset and after 1 and 2 years of Fg treatment...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28524746/a-contemporary-profile-of-primary-progressive-multiple-sclerosis-participants-from-the-narcoms-registry
#15
Amber Salter, Nina P Thomas, Tuula Tyry, Gary R Cutter, Ruth Ann Marrie
BACKGROUND: Primary progressive multiple sclerosis (PPMS) represents 10%-15% of all multiple sclerosis (MS) diagnoses. Information regarding socio-demographic and clinical characteristics of persons with PPMS is limited. OBJECTIVE: To characterize persons with PPMS in the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry. METHODS: We compared demographic and health-related characteristics of NARCOMS Registry participants reporting PPMS in the spring 2015 update survey with those reporting relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS), with characteristics of published PPMS cohorts...
May 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28523586/ocrelizumab-first-global-approval
#16
James E Frampton
Ocrelizumab (Ocrevus™) is a humanised anti-CD20 monoclonal antibody that has been developed by Genentech, Inc. (a subsidiary of Roche) for the treatment of multiple sclerosis (MS). The drug is designed to deplete B cells, which play an important role in the pathogenesis of MS. In March 2017, ocrelizumab was approved in the USA for the treatment of patients with relapsing or primary progressive forms of MS; currently, it is awaiting approval in the EU for the same indications. This article summarizes the milestones in the development of ocrelizumab leading to its first global approval for the treatment of MS...
June 2017: Drugs
https://www.readbyqxmd.com/read/28522962/alterations-in-cd200-cd200r1-system-during-eae-already-manifest-at-presymptomatic-stages
#17
Tony Valente, Joan Serratosa, Unai Perpiñá, Josep Saura, Carme Solà
In the brain of patients with multiple sclerosis, activated microglia/macrophages appear in active lesions and in normal appearing white matter. However, whether they play a beneficial or a detrimental role in the development of the pathology remains a controversial issue. The production of pro-inflammatory molecules by chronically activated microglial cells is suggested to contribute to the progression of neurodegenerative processes in neurological disease. In the healthy brain, neurons control glial activation through several inhibitory mechanisms, such as the CD200-CD200R1 interaction...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28521647/a-qualitative-investigation-of-lay-perspectives-of-diagnosis-and-self-management-strategies-employed-by-people-with-progressive-multiple-sclerosis
#18
Julia Frost, Jane Grose, Nicky Britten
This article explores how people with progressive multiple sclerosis give meaning to their experiences. It builds upon the self-management literature, which has captured the tension between the desire for retaining normalcy and the increasing burden of self-management associated with chronic disease progression. This repeat interview study is empirically grounded in 28 interviews with 14 people with progressive multiple sclerosis. We identified gender differences in diagnosis-seeking which impacted subsequent sense-making...
May 2017: Health (London)
https://www.readbyqxmd.com/read/28521618/markers-of-oxidative-nitrative-damage-of-plasma-proteins-correlated-with-edss-and-bdi-scores-in-patients-with-secondary-progressive-multiple-sclerosis
#19
Agnieszka Morel, Michał Bijak, Marta Niwald, Elżbieta Miller, Joanna Saluk
Objectives The objective of the present study was to evaluate oxidative/nitrative stress in the plasma of 50 patients suffering from the secondary progressive course of multiple sclerosis (MS), and to verify its correlation with physical and mental disability as assessed by the Expanded Disability Status Scale (EDSS), and the Beck Depression Inventory (BDI). Methods Oxidative and nitrative damage to proteins was determined by the level of carbonyl groups and 3-nitrotyrosine using ELISA test. Based on the reaction with Ellman's reagent, we estimated the concentration of oxidized thiol groups...
May 19, 2017: Redox Report: Communications in Free Radical Research
https://www.readbyqxmd.com/read/28521040/cortical-remyelination-is-heterogeneous-in-multiple-sclerosis
#20
Eva M M Strijbis, Evert-Jan Kooi, Paul van der Valk, Jeroen J G Geurts
Cortical lesions (CLs) are an important component of multiple sclerosis (MS) pathology; they correlate better with physical disability and cognitive impairment than white matter lesions (WMLs). Because remyelination can be extensive in CLs, we quantified remyelination in gray matter (GM) and white matter (WM), addressing oligodendrocyte (OGD) maturation state and clinical relevance of remyelination. Brain tissue samples from 21 chronic MS patients were immunohistochemically stained for myelin proteolipid protein, Olig2, which is strongly expressed in OGD precursor cells (OPCs), but weakly expressed in mature OGDs and other OGD markers...
May 1, 2017: Journal of Neuropathology and Experimental Neurology
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