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      An update on immunopathogenesis, diagnosis, and treatment of multiple sclerosis

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          Abstract

          Background

          Multiple sclerosis is an acquired demyelinating disease of the central nervous system. It is the second most common cause of disability in adults in United States after head trauma.

          Discussion

          The etiology of MS is probably multifactorial, related to genetic, environmental, and several other factors. The pathogenesis is not fully understood but is believed to involve T-cell-mediated inflammation directed against myelin and other related proteins with a possible role for B cells. The McDonald criteria have been proposed and revised over the years to guide the diagnosis of MS and are based on clinical presentation and magnetic resonance imaging (MRI) of the brain and spinal cord to establish dissemination in time and space. The treatment of MS includes disease modification with immunomodulator drugs and symptom management to address the specific symptoms such as fatigue, spasticity, and pain.

          Conclusion

          An update on etiology, pathogenesis, diagnosis, and immunomodulatory treatment of MS is presented.

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          Most cited references76

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          The relation between inflammation and neurodegeneration in multiple sclerosis brains

          Some recent studies suggest that in progressive multiple sclerosis, neurodegeneration may occur independently from inflammation. The aim of our study was to analyse the interdependence of inflammation, neurodegeneration and disease progression in various multiple sclerosis stages in relation to lesional activity and clinical course, with a particular focus on progressive multiple sclerosis. The study is based on detailed quantification of different inflammatory cells in relation to axonal injury in 67 multiple sclerosis autopsies from different disease stages and 28 controls without neurological disease or brain lesions. We found that pronounced inflammation in the brain is not only present in acute and relapsing multiple sclerosis but also in the secondary and primary progressive disease. T- and B-cell infiltrates correlated with the activity of demyelinating lesions, while plasma cell infiltrates were most pronounced in patients with secondary progressive multiple sclerosis (SPMS) and primary progressive multiple sclerosis (PPMS) and even persisted, when T- and B-cell infiltrates declined to levels seen in age matched controls. A highly significant association between inflammation and axonal injury was seen in the global multiple sclerosis population as well as in progressive multiple sclerosis alone. In older patients (median 76 years) with long-disease duration (median 372 months), inflammatory infiltrates declined to levels similar to those found in age-matched controls and the extent of axonal injury, too, was comparable with that in age-matched controls. Ongoing neurodegeneration in these patients, which exceeded the extent found in normal controls, could be attributed to confounding pathologies such as Alzheimer's or vascular disease. Our study suggests a close association between inflammation and neurodegeneration in all lesions and disease stages of multiple sclerosis. It further indicates that the disease processes of multiple sclerosis may die out in aged patients with long-standing disease.
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            Multiple sclerosis--the plaque and its pathogenesis.

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              Risk alleles for multiple sclerosis identified by a genomewide study.

              Multiple sclerosis has a clinically significant heritable component. We conducted a genomewide association study to identify alleles associated with the risk of multiple sclerosis. We used DNA microarray technology to identify common DNA sequence variants in 931 family trios (consisting of an affected child and both parents) and tested them for association. For replication, we genotyped another 609 family trios, 2322 case subjects, and 789 control subjects and used genotyping data from two external control data sets. A joint analysis of data from 12,360 subjects was performed to estimate the overall significance and effect size of associations between alleles and the risk of multiple sclerosis. A transmission disequilibrium test of 334,923 single-nucleotide polymorphisms (SNPs) in 931 family trios revealed 49 SNPs having an association with multiple sclerosis (P<1x10(-4)); of these SNPs, 38 were selected for the second-stage analysis. A comparison between the 931 case subjects from the family trios and 2431 control subjects identified an additional nonoverlapping 32 SNPs (P<0.001). An additional 40 SNPs with less stringent P values (<0.01) were also selected, for a total of 110 SNPs for the second-stage analysis. Of these SNPs, two within the interleukin-2 receptor alpha gene (IL2RA) were strongly associated with multiple sclerosis (P=2.96x10(-8)), as were a nonsynonymous SNP in the interleukin-7 receptor alpha gene (IL7RA) (P=2.94x10(-7)) and multiple SNPs in the HLA-DRA locus (P=8.94x10(-81)). Alleles of IL2RA and IL7RA and those in the HLA locus are identified as heritable risk factors for multiple sclerosis. Copyright 2007 Massachusetts Medical Society.
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                Author and article information

                Journal
                Brain Behav
                Brain Behav
                brb3
                Brain and Behavior
                John Wiley & Sons, Ltd (Chichester, UK )
                2162-3279
                2162-3279
                September 2015
                03 August 2015
                : 5
                : 9
                : e00362
                Affiliations
                [1 ]Department of Neurology, University of Massachusetts Medical School Worcester, Massachusetts, 01655
                [2 ]Department of Pathology, University of Massachusetts Medical School Worcester, Massachusetts, 01655
                Author notes
                Correspondence Neeta Garg, Department of Neurology, University of Massachusetts Medical School, 55 Lake Ave North, Worcester, MA 01655. Tel: +508 334 2527; Fax: +774 442 9122; E-mail: Neeta.Garg@ 123456umassmemorial.org and, Thomas W. Smith, Department of Pathology, University of Massachusetts Medical School, 55 Lake Ave North, Worcester, MA 01655. Tel: +508 856 2331; Fax: +508-793-6110; E-mail: Thomas.Smith@ 123456umassmemorial.org

                Funding Information No funding information provided.

                Article
                10.1002/brb3.362
                4589809
                26445701
                34c44279-1271-4b74-8516-5dce96d5af79
                © 2015 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 09 January 2015
                : 13 April 2015
                : 04 May 2015
                Categories
                Original Research

                Neurosciences
                demyelination,diagnosis,etiology,immunomodulator,multiple sclerosis,pathogenesis,treatment
                Neurosciences
                demyelination, diagnosis, etiology, immunomodulator, multiple sclerosis, pathogenesis, treatment

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