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      Osteopontin levels are associated with late-time lower regional brain volumes in multiple sclerosis

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          Abstract

          Osteopontin (OPN) is a proinflammatory marker produced by systemic immune and central nervous system (CNS) resident cells. We examined, if the level of OPN in the cerebrospinal fluid (CSF) and blood is associated with late-time regional brain volumes and white matter (WM) lesion load in MS. Concentrations of OPN in blood and CSF were related to MRI findings 10.1 ± 2.0 years later in 46 patients with MS. OPN concentration was measured by ELISA, while regional brain volumes and lesion load was assessed by magnetic resonance imaging (MRI) using 3D MPRAGE sequence and automated MR volumetry. OPN measured in the CSF was associated with several regional brain volumes and WM lesion load measured 10.1 ± 2.0 years later. CSF OPN concentration correlated with long-term enlargement of lateral- and inferior lateral ventricles and the elevation of gross CSF volume, in conjunction with the reduction of several cortical/subcortical gray matter and WM volumes. Serum OPN showed no long-term association with regional brain volumes. OPN measured from the CSF but not from the serum was associated with lower regional brain volumes measured a decade later, indicating the primary role of inflammation within the CNS in developing long-term brain related alterations.

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          Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria

          The 2010 McDonald criteria for the diagnosis of multiple sclerosis are widely used in research and clinical practice. Scientific advances in the past 7 years suggest that they might no longer provide the most up-to-date guidance for clinicians and researchers. The International Panel on Diagnosis of Multiple Sclerosis reviewed the 2010 McDonald criteria and recommended revisions. The 2017 McDonald criteria continue to apply primarily to patients experiencing a typical clinically isolated syndrome, define what is needed to fulfil dissemination in time and space of lesions in the CNS, and stress the need for no better explanation for the presentation. The following changes were made: in patients with a typical clinically isolated syndrome and clinical or MRI demonstration of dissemination in space, the presence of CSF-specific oligoclonal bands allows a diagnosis of multiple sclerosis; symptomatic lesions can be used to demonstrate dissemination in space or time in patients with supratentorial, infratentorial, or spinal cord syndrome; and cortical lesions can be used to demonstrate dissemination in space. Research to further refine the criteria should focus on optic nerve involvement, validation in diverse populations, and incorporation of advanced imaging, neurophysiological, and body fluid markers.
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            Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain.

            We present a technique for automatically assigning a neuroanatomical label to each voxel in an MRI volume based on probabilistic information automatically estimated from a manually labeled training set. In contrast to existing segmentation procedures that only label a small number of tissue classes, the current method assigns one of 37 labels to each voxel, including left and right caudate, putamen, pallidum, thalamus, lateral ventricles, hippocampus, and amygdala. The classification technique employs a registration procedure that is robust to anatomical variability, including the ventricular enlargement typically associated with neurological diseases and aging. The technique is shown to be comparable in accuracy to manual labeling, and of sufficient sensitivity to robustly detect changes in the volume of noncortical structures that presage the onset of probable Alzheimer's disease.
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              Defining the clinical course of multiple sclerosis

              Accurate clinical course descriptions (phenotypes) of multiple sclerosis (MS) are important for communication, prognostication, design and recruitment of clinical trials, and treatment decision-making. Standardized descriptions published in 1996 based on a survey of international MS experts provided purely clinical phenotypes based on data and consensus at that time, but imaging and biological correlates were lacking. Increased understanding of MS and its pathology, coupled with general concern that the original descriptors may not adequately reflect more recently identified clinical aspects of the disease, prompted a re-examination of MS disease phenotypes by the International Advisory Committee on Clinical Trials of MS. While imaging and biological markers that might provide objective criteria for separating clinical phenotypes are lacking, we propose refined descriptors that include consideration of disease activity (based on clinical relapse rate and imaging findings) and disease progression. Strategies for future research to better define phenotypes are also outlined.
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                Author and article information

                Contributors
                gergo.orsi@gmail.com
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                8 December 2021
                8 December 2021
                2021
                : 11
                : 23604
                Affiliations
                [1 ]GRID grid.9679.1, ISNI 0000 0001 0663 9479, MTA-PTE Clinical Neuroscience MR Research Group, , Eötvös Loránd Research Network (ELKH), ; Ret str. 2, 7623 Pecs, Hungary
                [2 ]GRID grid.9679.1, ISNI 0000 0001 0663 9479, Department of Neurology, Medical School, , University of Pecs, ; Pecs, Hungary
                [3 ]GRID grid.9679.1, ISNI 0000 0001 0663 9479, Department of Immunology and Biotechnology, Medical School, , University of Pecs, ; Pecs, Hungary
                [4 ]GRID grid.7143.1, ISNI 0000 0004 0512 5013, Department of Neurology, , Odense University Hospital, ; Odense, Denmark
                [5 ]GRID grid.10825.3e, ISNI 0000 0001 0728 0170, Department of Clinical Research, , University of Southern Denmark, ; Odense, Denmark
                Article
                3173
                10.1038/s41598-021-03173-3
                8654976
                34880402
                53d160d8-1934-4022-b1f0-3fa7eed9f8e7
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 11 May 2021
                : 22 November 2021
                Funding
                Funded by: “The role of neuro-inflammation in neurodegeneration: from molecules to clinics”, the Institutional Excellence Program for the Higher Education II within the framework of the 5th thematic program
                Award ID: EFOP-3.6.2-16-2017-00008
                Award Recipient :
                Funded by: Thematic Excellence Programme by the National Research, Development and Innovation Fund of Hungary
                Award ID: 2020-4.1.1-TKP2020
                Award Recipient :
                Funded by: Hungarian Brain Research Program
                Award ID: 2017-1.2.1-NKP-2017-00002
                Award Recipient :
                Funded by: University of Pécs Medical School Research Fund
                Award ID: KA-2017-06
                Award Recipient :
                Funded by: Odense University Hospital and Rigshospital joint grant
                Categories
                Article
                Custom metadata
                © The Author(s) 2021

                Uncategorized
                neurology,neurological disorders
                Uncategorized
                neurology, neurological disorders

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