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      Advanced neuroimaging in neuropsychiatric systemic lupus erythematosus

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          Purpose of review

          Neuropsychiatric lupus (NPSLE) comprises a disparate collection of syndromes affecting the central and peripheral nervous systems. Progress in the attribution of neuropsychiatric syndromes to SLE-related mechanisms and development of targeted treatment strategies has been impeded by a lack of objective imaging biomarkers that reflect specific neuropsychiatric syndromes and/or pathologic mechanisms. The present review addresses recent publications of neuroimaging techniques in NPSLE.

          Recent findings

          Imaging studies grouping all NPSLE syndromes together are unable to differentiate between NPSLE and non-NPSLE. In contrast, diffusion tensor imaging, FDG-PET, resting, and functional MRI techniques in patients with stable non-NPSLE demonstrate abnormal network structural and functional connectivity and regional brain activity in multiple cortical areas involving the limbic system, hippocampus, frontal, parietal, and temporal lobes. Some of these changes associate with impaired cognitive performance or mood disturbance, autoantibodies or inflammatory proteins. Longitudinal data suggest progression over time. DCE-MRI demonstrates increased Blood–brain barrier permeability.

          Summary

          Study design issues related to patient selection (non-NPSLE vs. NPSLE syndromes, SLE disease activity, medications) are critical for biomarker development. Regional and network structural and functional changes identified with advanced brain imaging techniques in patients with non-NPSLE may be further developed as biomarkers for cognitive and mood disorders attributable to SLE-related mechanisms.

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          Most cited references45

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          Association of cerebrospinal fluid anti-NR2 glutamate receptor antibodies with diffuse neuropsychiatric systemic lupus erythematosus.

          To explore the association of antibodies directed against N-methyl-D-aspartate receptor subunit NR2 (anti-NR2) in cerebrospinal fluid (CSF) with neuropsychiatric manifestations in systemic lupus erythematosus (NPSLE). Paired serum and CSF specimens were obtained from 56 patients with NPSLE (38 with diffuse psychiatric/neuropsychological syndromes [diffuse NPSLE] and 18 with neurologic syndromes or peripheral neuropathy [focal NPSLE]) and from 20 control patients with noninflammatory neurologic diseases. IgG anti-NR2 antibodies were measured by enzyme-linked immunosorbent assay using synthetic peptide containing the extracellular ligand-binding domain of NR2. The binding of affinity-purified anti-NR2 to human neuroblastoma cell line SK-N-MC was examined by flow cytometry. Purified anti-NR2 bound to the surface of SK-N-MC cells. Levels of anti-NR2 antibodies in CSF were significantly elevated in patients with diffuse NPSLE compared with levels in control patients or those with focal NPSLE, whereas there were no significant differences in serum anti-NR2 levels among the 3 groups. In 31 of the 38 patients with diffuse NPSLE (81.6%) and 8 of the 18 patients with focal NPSLE (44.4%), CSF anti-NR2 levels were more than 3 SD above the mean level in the control patients (P=0.0120 by chi-square test). These results indicate that anti-NR2 is a constituent of antineuronal antibodies and, more importantly, that anti-NR2 antibodies in CSF, but not in serum, are associated with diffuse NPSLE.
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            Brain histopathology in patients with systemic lupus erythematosus: identification of lesions associated with clinical neuropsychiatric lupus syndromes and the role of complement

            Neuropsychiatric (NP) involvement is a poorly understood manifestation of SLE. We studied post-mortem histopathology in relation to clinical NPSLE syndromes and complement deposition in brains of NPSLE and SLE patients and controls. Furthermore, we investigated the correlation between cerebral post-mortem histopathology and ex vivo 7 T MRI findings in SLE and NPSLE.
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              IL-6, IL-8, IP-10, MCP-1 and G-CSF are significantly increased in cerebrospinal fluid but not in sera of patients with central neuropsychiatric lupus erythematosus.

              To determine whether the intrathecal concentrations of cytokines/chemokines are associated with, or influenced by, serum concentrations in patients with central neuropsychiatric systemic lupus erythematosus (NPSLE), and to ascertain whether the increased production of cytokines/chemokines intrathecally relative to serum levels is associated with the presence of central NPSLE.
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                Author and article information

                Journal
                Curr Opin Neurol
                Curr. Opin. Neurol
                CONEU
                Current Opinion in Neurology
                Lippincott Williams & Wilkins
                1350-7540
                1473-6551
                June 2020
                28 April 2020
                : 33
                : 3
                : 353-361
                Affiliations
                [a ]Center for Autoimmune, Musculoskeletal and Hematopoietic Diseases
                [b ]Susan and Leonard Feinstein Center for Neurosciences, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, New York, USA
                Author notes
                Correspondence to Meggan Mackay, MD, Feinstein Institutes for Medical Research, 350 Community Drive, Manhasset, NY 11030, USA. Tel: +1 516 562 3838; fax: +516 562 2537; e-mail: mmackay@ 123456northwell.edu
                Article
                WCO330317 00016
                10.1097/WCO.0000000000000822
                7259387
                32349105
                03187f47-3f4a-4864-b65b-c1cc345cc100
                Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0

                History
                Categories
                CNS INFLAMMATORY DISORDERS OUTSIDE MULTIPLE SCLEROSIS: Edited by Bruce T. Volpe
                Custom metadata
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                biomarkers,cognitive dysfunction,neuroimaging,neuropsychiatric lupus

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