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May 2020; 7 (3) ArticleOpen Access

Covarying patterns of white matter lesions and cortical atrophy predict progression in early MS

View ORCID ProfileMuthuraman Muthuraman, Vinzenz Fleischer, Julia Kroth, Dumitru Ciolac, Angela Radetz, Nabin Koirala, Gabriel Gonzalez-Escamilla, Heinz Wiendl, Sven G. Meuth, Frauke Zipp, Sergiu Groppa
First published February 5, 2020, DOI: https://doi.org/10.1212/NXI.0000000000000681
Muthuraman Muthuraman
From the Department of Neurology (M.M., V.F., J.K., D.C., A.R., N.K., G.G.-E., F.Z., S.G.), Focus Program Translational Neuroscience (FTN), Research Center for Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz; and Department of Neurology with Institute of Translational Neurology (H.W., S.G.M.), University of Munster, Germany.
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  • ORCID record for Muthuraman Muthuraman
Vinzenz Fleischer
From the Department of Neurology (M.M., V.F., J.K., D.C., A.R., N.K., G.G.-E., F.Z., S.G.), Focus Program Translational Neuroscience (FTN), Research Center for Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz; and Department of Neurology with Institute of Translational Neurology (H.W., S.G.M.), University of Munster, Germany.
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Julia Kroth
From the Department of Neurology (M.M., V.F., J.K., D.C., A.R., N.K., G.G.-E., F.Z., S.G.), Focus Program Translational Neuroscience (FTN), Research Center for Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz; and Department of Neurology with Institute of Translational Neurology (H.W., S.G.M.), University of Munster, Germany.
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Dumitru Ciolac
From the Department of Neurology (M.M., V.F., J.K., D.C., A.R., N.K., G.G.-E., F.Z., S.G.), Focus Program Translational Neuroscience (FTN), Research Center for Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz; and Department of Neurology with Institute of Translational Neurology (H.W., S.G.M.), University of Munster, Germany.
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Angela Radetz
From the Department of Neurology (M.M., V.F., J.K., D.C., A.R., N.K., G.G.-E., F.Z., S.G.), Focus Program Translational Neuroscience (FTN), Research Center for Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz; and Department of Neurology with Institute of Translational Neurology (H.W., S.G.M.), University of Munster, Germany.
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Nabin Koirala
From the Department of Neurology (M.M., V.F., J.K., D.C., A.R., N.K., G.G.-E., F.Z., S.G.), Focus Program Translational Neuroscience (FTN), Research Center for Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz; and Department of Neurology with Institute of Translational Neurology (H.W., S.G.M.), University of Munster, Germany.
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Gabriel Gonzalez-Escamilla
From the Department of Neurology (M.M., V.F., J.K., D.C., A.R., N.K., G.G.-E., F.Z., S.G.), Focus Program Translational Neuroscience (FTN), Research Center for Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz; and Department of Neurology with Institute of Translational Neurology (H.W., S.G.M.), University of Munster, Germany.
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Heinz Wiendl
From the Department of Neurology (M.M., V.F., J.K., D.C., A.R., N.K., G.G.-E., F.Z., S.G.), Focus Program Translational Neuroscience (FTN), Research Center for Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz; and Department of Neurology with Institute of Translational Neurology (H.W., S.G.M.), University of Munster, Germany.
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Sven G. Meuth
From the Department of Neurology (M.M., V.F., J.K., D.C., A.R., N.K., G.G.-E., F.Z., S.G.), Focus Program Translational Neuroscience (FTN), Research Center for Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz; and Department of Neurology with Institute of Translational Neurology (H.W., S.G.M.), University of Munster, Germany.
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Frauke Zipp
From the Department of Neurology (M.M., V.F., J.K., D.C., A.R., N.K., G.G.-E., F.Z., S.G.), Focus Program Translational Neuroscience (FTN), Research Center for Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz; and Department of Neurology with Institute of Translational Neurology (H.W., S.G.M.), University of Munster, Germany.
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Sergiu Groppa
From the Department of Neurology (M.M., V.F., J.K., D.C., A.R., N.K., G.G.-E., F.Z., S.G.), Focus Program Translational Neuroscience (FTN), Research Center for Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz; and Department of Neurology with Institute of Translational Neurology (H.W., S.G.M.), University of Munster, Germany.
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Citation
Covarying patterns of white matter lesions and cortical atrophy predict progression in early MS
Muthuraman Muthuraman, Vinzenz Fleischer, Julia Kroth, Dumitru Ciolac, Angela Radetz, Nabin Koirala, Gabriel Gonzalez-Escamilla, Heinz Wiendl, Sven G. Meuth, Frauke Zipp, Sergiu Groppa
Neurol Neuroimmunol Neuroinflamm May 2020, 7 (3) e681; DOI: 10.1212/NXI.0000000000000681

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    Figure 1 Data analysis flowchart

    (A) WM lesion volumes derived from structural MRI data sets (T1W, T2W FLAIR) and (B) cortical atrophy rates (FreeSurfer processing) from the same patients were used as inputs for the pattern identification analysis. The weights were assigned based on the correlation between these 2 parameters. Parallel ICA was performed, and distinct covarying lesion patterns of cortical atrophy and WM lesions were identified. For each lesion pattern, the component loads of each patient related to cortical atrophy (brown line) and WM lesion volume (green line) were correlated. FLAIR = fluid-attenuated inversion recovery; ICA = independent component analysis; T1W = T1‐weighted; T2W = T2‐weighted; WM = white matter.

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    Figure 2 Three significant covarying patterns of regional cortical atrophy and the corresponding WM lesion volume

    (A) Cerebellar lesion pattern, (B) bihemispheric lesion pattern, and (C) left-lateralized lesion pattern. WM = white matter.

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    Figure 3 Comparison of ROC curves showing the accuracy of covarying lesion patterns in predicting disability progression

    The shadowed areas represent the 95% CIs. In the legend, the AUC and the 95% CIs are presented. The cerebellar pattern shows the best accuracy in predicting disability progression over time in comparison to the bihemispheric and left-lateralized patterns (*p < 0.05). AUC = area under the curve.

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    Figure 4 Map of the cerebellar lesion distribution

    Here, each particular voxel shows how this region contributes to the prediction analysis for disease progression in the study cohort (A) and in the replication cohort (B). Color bar indicates the component load of the cerebellar pattern. (C) shows the Buckner 7-network cerebellar nuclei atlas, and (D) represents the corresponding cortical connectivity map. ICA = independent component analysis.

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