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      Assessment of lesions on magnetic resonance imaging in multiple sclerosis: practical guidelines

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          Abstract

          MRI has improved the diagnostic work-up of multiple sclerosis, but inappropriate image interpretation has contributed to misdiagnosis. Filippi et al. provide a practical guide to the proper recognition of multiple sclerosis lesions, including a thorough description and illustration of typical MRI features, as well as a discussion of red flags suggestive of alternative diagnoses.

          Abstract

          MRI has improved the diagnostic work-up of multiple sclerosis, but inappropriate image interpretation and application of MRI diagnostic criteria contribute to misdiagnosis. Some diseases, now recognized as conditions distinct from multiple sclerosis, may satisfy the MRI criteria for multiple sclerosis (e.g. neuromyelitis optica spectrum disorders, Susac syndrome), thus making the diagnosis of multiple sclerosis more challenging, especially if biomarker testing (such as serum anti-AQP4 antibodies) is not informative. Improvements in MRI technology contribute and promise to better define the typical features of multiple sclerosis lesions (e.g. juxtacortical and periventricular location, cortical involvement). Greater understanding of some key aspects of multiple sclerosis pathobiology has allowed the identification of characteristics more specific to multiple sclerosis (e.g. central vein sign, subpial demyelination and lesional rims), which are not included in the current multiple sclerosis diagnostic criteria. In this review, we provide the clinicians and researchers with a practical guide to enhance the proper recognition of multiple sclerosis lesions, including a thorough definition and illustration of typical MRI features, as well as a discussion of red flags suggestive of alternative diagnoses. We also discuss the possible place of emerging qualitative features of lesions which may become important in the near future.

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          Most cited references88

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          Clinical and pathological insights into the dynamic nature of the white matter multiple sclerosis plaque.

          An extensive analysis of white matter plaques in a large sample of multiple sclerosis (MS) autopsies provides insights into the dynamic nature of MS pathology.
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            Subpial demyelination in the cerebral cortex of multiple sclerosis patients.

            The extent and pattern of demyelination in the cerebral cortex was determined in 78 tissue blocks from the brains of 20 multiple sclerosis (MS) patients and 28 tissue blocks from 7 patients without neurological disease. Tissue blocks from 4 predetermined areas (cingulate gyrus, frontal, parietal, and temporal lobe) were studied, irrespective of macroscopically evident MS plaques. All tissue blocks contained cerebral cortex and periventricular and/or subcortical white matter. One hundred and nine demyelinating lesions were detected in the cerebral cortex, of which 92 (84.4%) were purely intracortical and 17 (15.6%) were lesions extending through both white and gray matter areas. In 5 of the 20 MS brains, subpial demyelination was extensive in the 4 widely spaced cortical areas studied, thus considered to represent a general cortical subpial demyelination. The percentage of demyelinated area was significantly higher in the cerebral cortex (mean 26.5%, median 14.1%) than in white matter (mean 6.5%, median 0%) (p = 0.001). Both gray and white matter demyelination was more prominent in the cingulate gyrus than in the other areas examined (p < 0.05). These results indicate that the cerebral cortex is likely to be a predilection site for MS lesions and identify general cortical subpial demyelination as a distinct pattern occurring in a significant subpopulation of MS patients.
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              Progressive multiple sclerosis patients show substantial lesion activity that correlates with clinical disease severity and sex: a retrospective autopsy cohort analysis

              Multiple sclerosis (MS) is a highly heterogeneous disease with large inter-individual differences in disease course. MS lesion pathology shows considerable heterogeneity in localization, cellular content and degree of demyelination between patients. In this study, we investigated pathological correlates of disease course in MS using the autopsy cohort of the Netherlands Brain Bank (NBB), containing 182 MS brain donors. Using a standardized autopsy procedure including systematic dissection from standard locations, 3188 tissue blocks containing 7562 MS lesions were dissected. Unbiased measurements of lesion load were made using the tissue from standard locations. Lesion demyelinating and innate inflammatory activity were visualized by immunohistochemistry for proteolipid protein and human leukocyte antigen. Lesions were classified into active, mixed active/inactive (also known as chronic active), inactive or remyelinated, while microglia/macrophage morphology was classified as ramified, amoeboid or foamy. The severity score was calculated from the time from first symptoms to EDSS-6. Lesion type prevalence and microglia/macrophage morphology were analyzed in relation to clinical course, disease severity, lesion load and sex, and in relation to each other. This analysis shows for the first time that (1) in progressive MS, with a mean disease duration of 28.6 ± 13.3 years (mean ± SD), there is substantial inflammatory lesion activity at time to death. 57% of all lesions were either active or mixed active/inactive and 78% of all patients had a mixed active/inactive lesion present; (2) patients that had a more severe disease course show a higher proportion of mixed active/inactive lesions (p = 6e−06) and a higher lesion load (p = 2e−04) at the time of death, (3) patients with a progressive disease course show a higher lesion load (p = 0.001), and a lower proportion of remyelinated lesions (p = 0.03) compared to patients with a relapsing disease course, (4) males have a higher incidence of cortical grey matter lesions (p = 0.027) and a higher proportion of mixed active/inactive lesions compared to females across the whole cohort (p = 0.007). We confirm that there is a higher proportion of mixed active/inactive lesions (p = 0.006) in progressive MS compared to relapsing disease. Identification of mixed active/inactive lesions on MRI is necessary to determine whether they can be used as a prognostic tool in living MS patients. Electronic supplementary material The online version of this article (10.1007/s00401-018-1818-y) contains supplementary material, which is available to authorized users.
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                Author and article information

                Journal
                Brain
                Brain
                brainj
                Brain
                Oxford University Press
                0006-8950
                1460-2156
                July 2019
                17 June 2019
                17 June 2019
                : 142
                : 7
                : 1858-1875
                Affiliations
                [1 ]Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy
                [2 ]Neurology Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy
                [3 ]Vita-Salute San Raffaele University, Milan, Italy
                [4 ]Division of Neurology, Children’s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA
                [5 ]Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands
                [6 ]Institutes of Neurology and Healthcare Engineering, University College London, London, UK
                [7 ]Queen Square MS Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, UK
                [8 ]National Institute for Health Research University College London Hospitals Biomedical Research Center, National Institute for Health Research, London, UK
                [9 ]Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy
                [10 ]Department of Anatomy and Neurosciences, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
                [11 ]NeuroCure Clinical Research Center and Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine and Charité -Universitätsmedizin Berlin, Berlin, Germany
                [12 ]Translational Neuroradiology Section, Division of Neuroimmunology and Neurovirology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
                [13 ]MS/MRI Research Group, Djavad Mowafaghian Centre for Brain Health, Division of Neurology, University of British Columbia, Vancouver, British Columbia, Canada
                [14 ]Faculty of Medicine, Division of Neurology, University of British Columbia, Vancouver, British Columbia, Canada
                [15 ]Department of Neuroradiology, Hannover Medical School, Hannover, Germany
                [16 ]Division of Neuroradiology and Neurophysics, UCL Institute of Neurology, London, UK
                [17 ]Lysholm Department of Neuroradiology, London, UK
                [18 ]Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany
                [19 ]Sorbonne University, AP-HP Pitié-Salpétriére Hospital, Department of Neurology, 75013 Paris, France
                [20 ]Department of Neurology, Mayo Clinic, Rochester, MN, USA
                Author notes
                Correspondence to: Prof. Massimo Filippi Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy E-mail: filippi.massimo@ 123456hsr.it
                Author information
                http://orcid.org/0000-0002-5485-0479
                http://orcid.org/0000-0002-7826-0019
                http://orcid.org/0000-0003-2358-4320
                Article
                awz144
                10.1093/brain/awz144
                6598631
                31209474
                5114ee90-a07f-4c14-8c74-c2d97eca4d1f
                © The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 20 March 2019
                : 29 April 2019
                : 1 May 2019
                Page count
                Pages: 18
                Funding
                Funded by: National Institute for Health Research University College London Hospitals Biomedical Research Centre
                Categories
                Review Article

                Neurosciences
                multiple sclerosis,magnetic resonance imaging,lesions,diagnostic criteria,guidelines
                Neurosciences
                multiple sclerosis, magnetic resonance imaging, lesions, diagnostic criteria, guidelines

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