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      Longitudinal changes in cerebral white matter microstructure in newly diagnosed systemic lupus erythematosus patients

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          Abstract

          Objectives

          To evaluate longitudinal variations in diffusion tensor imaging (DTI) metrics of different white matter (WM) tracts of newly diagnosed SLE patients, and to assess whether DTI changes relate to changes in clinical characteristics over time.

          Methods

          A total of 17 newly diagnosed SLE patients (19–55 years) were assessed within 24 months from diagnosis with brain MRI (1.5 T Philips Achieva) at baseline, and after at least 12 months. Fractional anisotropy, mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity values were calculated in several normal-appearing WM tracts. Longitudinal variations in DTI metrics were analysed by repeated measures analysis of variance. DTI changes were separately assessed for 21 WM tracts. Associations between longitudinal alterations of DTI metrics and clinical variables (SLEDAI-2K, complement levels, glucocorticoid dosage) were evaluated using adjusted Spearman correlation analysis.

          Results

          Mean MD and RD values from the normal-appearing WM significantly increased over time ( P = 0.019 and P = 0.021, respectively). A significant increase in RD ( P = 0.005) and MD ( P = 0.012) was found in the left posterior limb of the internal capsule; RD significantly increased in the left retro-lenticular part of the internal capsule ( P = 0.013), and fractional anisotropy significantly decreased in the left corticospinal tract ( P = 0.029). No significant correlation was found between the longitudinal change in DTI metrics and the change in clinical measures.

          Conclusion

          Increase in diffusivity, reflecting a compromised WM tissue microstructure, starts in initial phases of the SLE disease course, even in the absence of overt neuropsychiatric (NP) symptoms. These results indicate the importance of monitoring NP involvement in SLE, even shortly after diagnosis.

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          Most cited references42

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          Updating the American college of rheumatology revised criteria for the classification of systemic lupus erythematosus

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            Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus.

            The Systemic Lupus International Collaborating Clinics (SLICC) group revised and validated the American College of Rheumatology (ACR) systemic lupus erythematosus (SLE) classification criteria in order to improve clinical relevance, meet stringent methodology requirements, and incorporate new knowledge regarding the immunology of SLE. The classification criteria were derived from a set of 702 expert-rated patient scenarios. Recursive partitioning was used to derive an initial rule that was simplified and refined based on SLICC physician consensus. The SLICC group validated the classification criteria in a new validation sample of 690 new expert-rated patient scenarios. Seventeen criteria were identified. In the derivation set, the SLICC classification criteria resulted in fewer misclassifications compared with the current ACR classification criteria (49 versus 70; P = 0.0082) and had greater sensitivity (94% versus 86%; P < 0.0001) and equal specificity (92% versus 93%; P = 0.39). In the validation set, the SLICC classification criteria resulted in fewer misclassifications compared with the current ACR classification criteria (62 versus 74; P = 0.24) and had greater sensitivity (97% versus 83%; P < 0.0001) but lower specificity (84% versus 96%; P < 0.0001). The new SLICC classification criteria performed well in a large set of patient scenarios rated by experts. According to the SLICC rule for the classification of SLE, the patient must satisfy at least 4 criteria, including at least one clinical criterion and one immunologic criterion OR the patient must have biopsy-proven lupus nephritis in the presence of antinuclear antibodies or anti-double-stranded DNA antibodies. Copyright © 2012 by the American College of Rheumatology.
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              Systemic lupus erythematosus disease activity index 2000.

              To describe the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), a modification of SLEDAI to reflect persistent, active disease in those descriptors that had previously only considered new or recurrent occurrences, and to validate SLEDAI-2K against the original SLEDAI as a predictor for mortality and as a measure of global disease activity in the clinic. All visits in our cohort of 960 patients were used to correlate SLEDAI-2K against the original SLEDAI, and the whole cohort was used to validate SLEDAI-2K as a predictor of mortality. A subgroup of 212 patients with SLE followed at the Lupus Clinic who had 5 regular visits, 3-6 months apart, in 1991-93 was also included. An uninvolved clinician evaluated each patient record and assigned a clinical activity level. The SLEDAI score was calculated from the database according to both the original and modified definitions. SLEDAI-2K correlated highly (r = 0.97) with SLEDAI. Both methods for SLEDAI scoring predicted mortality equally (p = 0.0001), and described similarly the range of disease activity as recognized by the clinician. SLEDAI-2K, which allows for persistent activity in rash, mucous membranes, alopecia, and proteinuria, is suitable for use in clinical trials and studies of prognosis in SLE.
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                Author and article information

                Journal
                Rheumatology (Oxford)
                Rheumatology (Oxford)
                brheum
                Rheumatology (Oxford, England)
                Oxford University Press
                1462-0324
                1462-0332
                June 2021
                30 November 2020
                30 November 2020
                : 60
                : 6
                : 2678-2687
                Affiliations
                [1 ] Rheumatology Unit, Department of Medical Sciences, University of Ferrara and Azienda Ospedaliero-Universitaria S. Anna , Cona (Ferrara), Italy
                [2 ] Department of Radiology, Leiden University Medical Center , Leiden, the Netherlands
                [3 ] Neuroradiology Unit, Department of Radiology, Azienda Ospedaliero-Universitaria Sant’Anna , Cona (Ferrara), Italy
                [4 ] Department of Biomedical Data Sciences, Leiden University Medical Center , Leiden, the Netherlands
                [5 ] Neurological Clinic, University Hospital San Paolo , Milan, Italy
                [6 ] Department of Rheumatology, Leiden University Medical Center , Leiden, the Netherlands
                [7 ] Neuroradiology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence , Florence, Italy
                Author notes

                Ettore Silvagni and Francesca Inglese contributed equally to this study.

                Correspondence to: Ece Ercan, C. J. Gorter Center for High Field MRI, Department of Radiology, C3Q, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, the Netherlands. E-mail: A.E.Ercan@ 123456lumc.nl
                Author information
                https://orcid.org/0000-0001-7654-8222
                https://orcid.org/0000-0002-8187-2075
                Article
                keaa677
                10.1093/rheumatology/keaa677
                8213425
                33507240
                be62686d-aef0-439b-8f4a-14a1aadfeded
                © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.

                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
                : 26 June 2020
                : 10 September 2020
                Page count
                Pages: 10
                Funding
                Funded by: Dutch Research Council, DOI 10.13039/501100003246;
                Award ID: #16862
                Categories
                Clinical Science
                AcademicSubjects/MED00360

                Rheumatology
                systemic lupus erythematosus,longitudinal mri,diffusion tensor imaging
                Rheumatology
                systemic lupus erythematosus, longitudinal mri, diffusion tensor imaging

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