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      Impact of the McDonald Criteria 2017 on Early Diagnosis of Relapsing-Remitting Multiple Sclerosis

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          Abstract

          Multiple sclerosis is a chronic immune mediated demyelinating disease leading to neurological disabilities that need to be diagnosed and treated early. Guidelines on multiple sclerosis diagnosis and monitoring experienced comprehensive changes over the last decades. The first McDonald criteria published in 2001 emphasized the importance of MR imaging but also recognized the role of cerebrospinal fluid diagnostics. The demonstration of an intrathecal immunoglobulin G synthesis is a well-established additional component and has a long tradition in the diagnosis of relapsing-remitting multiple sclerosis. However, the role of cerebrospinal fluid for diagnostic purposes was rather diminished in each revision of the McDonald criteria. In the latest revision of the McDonald criteria of 2017, the detection of an intrathecal immunoglobulin G synthesis as oligoclonal bands experienced a revival. Patients with the first clinical event suggesting multiple sclerosis who fulfill the criteria for dissemination in space can be diagnosed with relapsing-remitting multiple sclerosis when oligoclonal bands in cerebrospinal fluid are detected. The diagnostic sensitivity of these novel criteria with a focus on dissemination in time and oligoclonal bands as a substitute for dissemination in time was published in different cohorts in the last year and is of special interest in this review. Recently published data show that by applying the 2017 McDonald criteria, multiple sclerosis can be diagnosed more frequently at the time of first clinical event as compared to the 2010 McDonald criteria. The main effect was due to the implementation of oligoclonal bands as a substitute for dissemination in time. However, careful differential diagnosis is essential in patients with atypical clinical manifestations to avoid misdiagnoses.

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          Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions.

          Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system that causes motor, sensory, and cognitive deficits. The present study characterized demyelinated lesions in the cerebral cortex of MS patients. One hundred twelve cortical lesions were identified in 110 tissue blocks from 50 MS patients. Three patterns of cortical demyelination were identified: Type I lesions were contiguous with subcortical white matter lesions; Type II lesions were small, confined to the cortex, and often perivascular; Type III lesions extended from the pial surface to cortical layer 3 or 4. Inflammation and neuronal pathology were studied in tissue from 8 and 7 patients, respectively. Compared to white matter lesions, cortical lesions contained 13 times fewer CD3-positive lymphocytes (195 vs 2,596/mm3 of tissue) and 6 times fewer CD68-positive microglia/macrophages (11,948 vs 67,956/mm3 of tissue). Transected neurites (both axons and dendrites) occurred at a density of 4,119/mm3 in active cortical lesions, 1,107/mm3 in chronic active cortical lesions, 25/mm3 in chronic inactive cortical lesions, 8/mm3 in myelinated MS cortex, and 1/mm3 in control cortex. In active and chronic active cortical lesions, activated microglia closely apposed and ensheathed apical dendrites, neurites, and neuronal perikarya. In addition, apoptotic neurons were increased significantly in demyelinated cortex compared to myelinated cortex. These data support the hypothesis that demyelination, axonal transection, dendritic transection, and apoptotic loss of neurons in the cerebral cortex contribute to neurological dysfunction in MS patients.
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            Clinically isolated syndromes.

            Clinically isolated syndrome (CIS) is a term that describes a first clinical episode with features suggestive of multiple sclerosis (MS). It usually occurs in young adults and affects optic nerves, the brainstem, or the spinal cord. Although patients usually recover from their presenting episode, CIS is often the first manifestation of MS. The most notable risk factors for MS are clinically silent MRI lesions and CSF oligoclonal bands; weak or uncertain risk factors include vitamin D deficiency, Epstein-Barr virus infection, smoking, HLA genes, and miscellaneous immunological abnormalities. Diagnostic investigations including MRI aim to exclude alternative causes and to define the risk for MS. MRI findings incorporated into diagnostic criteria in the past decade enable MS to be diagnosed at or soon after CIS presentation. The course of MS after CIS is variable: after 15-20 years, a third of patients have a benign course with minimal or no disability and a half will have developed secondary progressive MS with increasing disability. Prediction of the long-term course at disease onset is unreliable. Disease-modifying treatments delay the development from CIS to MS. Their use in CIS is limited by uncertain long-term clinical prognosis and treatment benefits and adverse effects, although they have the potential to prevent or delay future tissue damage, including demyelination and axonal loss. Targets for future therapeutic progress are to achieve safe and effective long-term immunomodulation with neuroprotection and repair. Copyright © 2012 Elsevier Ltd. All rights reserved.
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              Cerebrospinal fluid in the diagnosis of multiple sclerosis: a consensus report.

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                Author and article information

                Contributors
                Journal
                Front Neurol
                Front Neurol
                Front. Neurol.
                Frontiers in Neurology
                Frontiers Media S.A.
                1664-2295
                15 March 2019
                2019
                : 10
                : 188
                Affiliations
                [1] 1Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School , Hannover, Germany
                [2] 2Department of Diagnostic and Interventional Neuroradiology, Hannover Medical School , Hannover, Germany
                Author notes

                Edited by: Tobias Ruck, University of Münster, Germany

                Reviewed by: Mario Habek, University of Zagreb, Croatia; Massimiliano Di Filippo, University of Perugia, Italy

                *Correspondence: Thomas Skripuletz skripuletz.thomas@ 123456mh-hannover.de

                This article was submitted to Multiple Sclerosis and Neuroimmunology, a section of the journal Frontiers in Neurology

                Article
                10.3389/fneur.2019.00188
                6428717
                30930829
                af4c68ae-6d73-4a25-9a2d-1ad310aef33b
                Copyright © 2019 Schwenkenbecher, Wurster, Konen, Gingele, Sühs, Wattjes, Stangel and Skripuletz.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 03 January 2019
                : 14 February 2019
                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 61, Pages: 8, Words: 6346
                Categories
                Neurology
                Mini Review

                Neurology
                multiple sclerosis,clinically isolated syndrome,mcdonald criteria,mri,oligoclonal bands,cerebrospinal fluid

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