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      Advances in brain imaging in multiple sclerosis

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          Abstract

          Brain imaging is increasingly used to support clinicians in diagnosing multiple sclerosis (MS) and monitoring its progression. However, the role of magnetic resonance imaging (MRI) in MS goes far beyond its clinical application. Indeed, advanced imaging techniques have helped to detect different components of MS pathogenesis in vivo, which is now considered a heterogeneous process characterized by widespread damage of the central nervous system, rather than multifocal demyelination of white matter. Recently, MRI biomarkers more sensitive to disease activity than clinical disability outcome measures, have been used to monitor response to anti-inflammatory agents in patients with relapsing–remitting MS. Similarly, MRI markers of neurodegeneration exhibit the potential as primary and secondary outcomes in clinical trials for progressive phenotypes. This review will summarize recent advances in brain neuroimaging in MS from the research setting to clinical applications.

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          Most cited references87

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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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            Cortical demyelination and diffuse white matter injury in multiple sclerosis.

            Focal demyelinated plaques in white matter, which are the hallmark of multiple sclerosis pathology, only partially explain the patient's clinical deficits. We thus analysed global brain pathology in multiple sclerosis, focusing on the normal-appearing white matter (NAWM) and the cortex. Autopsy tissue from 52 multiple sclerosis patients (acute, relapsing-remitting, primary and secondary progressive multiple sclerosis) and from 30 controls was analysed using quantitative morphological techniques. New and active focal inflammatory demyelinating lesions in the white matter were mainly present in patients with acute and relapsing multiple sclerosis, while diffuse injury of the NAWM and cortical demyelination were characteristic hallmarks of primary and secondary progressive multiple sclerosis. Cortical demyelination and injury of the NAWM, reflected by diffuse axonal injury with profound microglia activation, occurred on the background of a global inflammatory response in the whole brain and meninges. There was only a marginal correlation between focal lesion load in the white matter and diffuse white matter injury, or cortical pathology, respectively. Our data suggest that multiple sclerosis starts as a focal inflammatory disease of the CNS, which gives rise to circumscribed demyelinated plaques in the white matter. With chronicity, diffuse inflammation accumulates throughout the whole brain, and is associated with slowly progressive axonal injury in the NAWM and cortical demyelination.
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              Regulation of innate immune responses in the brain.

              Microglial cells are the main innate immune cells of the complex cellular structure of the brain. These cells respond quickly to pathogens and injury, accumulate in regions of degeneration and produce a wide variety of pro-inflammatory molecules. These observations have resulted in active debate regarding the exact role of microglial cells in the brain and whether they have beneficial or detrimental functions. Careful targeting of these cells could have therapeutic benefits for several types of trauma and disease specific to the central nervous system. This Review discusses the molecular details underlying the innate immune response in the brain during infection, injury and disease.
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                Author and article information

                Contributors
                Journal
                Ther Adv Neurol Disord
                Ther Adv Neurol Disord
                TAN
                sptan
                Therapeutic Advances in Neurological Disorders
                SAGE Publications (Sage UK: London, England )
                1756-2856
                1756-2864
                27 June 2019
                2019
                : 12
                : 1756286419859722
                Affiliations
                [1-1756286419859722]Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London (UCL), London, UK
                [2-1756286419859722]Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Institute of Neurology, Russell Square, London WC1B 5EH, UK
                [3-1756286419859722]Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London (UCL), London, UK
                [4-1756286419859722]National Institute for Health Research, UCL Hospitals, Biomedical Research Centre, London, UK
                [5-1756286419859722]Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London (UCL), London, UK
                Author notes
                [†]

                both authors have equally contributed to this paper

                Author information
                https://orcid.org/0000-0001-7485-1367
                Article
                10.1177_1756286419859722
                10.1177/1756286419859722
                6598314
                31275430
                3e61add2-2880-4da3-a8c8-db08d45e1381
                © The Author(s), 2019

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 7 January 2019
                : 21 May 2019
                Categories
                Advances in Neuroimaging
                Review
                Custom metadata
                January-December 2019

                brain,diagnosis,magnetic resonance imaging,multiple sclerosis,pathogenesis,progression

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