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Long-term dynamics of multiple sclerosis iron rim lesions

  • Author Footnotes
    ± Joint first authors
    Claudia E. Weber
    Footnotes
    ± Joint first authors
    Affiliations
    Department of Neurology, Medical Faculty Mannheim and Mannheim Center of Translational Neurosciences (MCTN), Heidelberg University, Theodor-Kutzer-Ufer 1 – 3, 68167 Mannheim, Germany
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  • Author Footnotes
    ± Joint first authors
    Matthias Wittayer
    Footnotes
    ± Joint first authors
    Affiliations
    Department of Neurology, Medical Faculty Mannheim and Mannheim Center of Translational Neurosciences (MCTN), Heidelberg University, Theodor-Kutzer-Ufer 1 – 3, 68167 Mannheim, Germany
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  • Matthias Kraemer
    Affiliations
    VGMorph GmbH, Waterloostr. 32, 45472 Mülheim an der Ruhr, Germany

    Neurocentrum, Am Ziegelkamp 1f, 41515 Grevenbroich, Germany
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  • Andreas Dabringhaus
    Affiliations
    VGMorph GmbH, Waterloostr. 32, 45472 Mülheim an der Ruhr, Germany
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  • Kathrin Bail
    Affiliations
    Department of Neurology, Medical Faculty Mannheim and Mannheim Center of Translational Neurosciences (MCTN), Heidelberg University, Theodor-Kutzer-Ufer 1 – 3, 68167 Mannheim, Germany
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  • Michael Platten
    Affiliations
    Department of Neurology, Medical Faculty Mannheim and Mannheim Center of Translational Neurosciences (MCTN), Heidelberg University, Theodor-Kutzer-Ufer 1 – 3, 68167 Mannheim, Germany

    Institute for Innate Immunoscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
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  • Lucas Schirmer
    Affiliations
    Department of Neurology, Medical Faculty Mannheim and Mannheim Center of Translational Neurosciences (MCTN), Heidelberg University, Theodor-Kutzer-Ufer 1 – 3, 68167 Mannheim, Germany

    Institute for Innate Immunoscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

    Interdisciplinary Center for Neurosciences, Heidelberg University, Heidelberg, Germany
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  • Author Footnotes
    # Joint senior authors
    Achim Gass
    Footnotes
    # Joint senior authors
    Affiliations
    Department of Neurology, Medical Faculty Mannheim and Mannheim Center of Translational Neurosciences (MCTN), Heidelberg University, Theodor-Kutzer-Ufer 1 – 3, 68167 Mannheim, Germany
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  • Author Footnotes
    # Joint senior authors
    Philipp Eisele
    Correspondence
    Corresponding author at: Department of Neurology, Medical Faculty Mannheim and Mannheim Center of Translational Neurosciences (MCTN), Heidelberg University, Theodor-Kutzer-Ufer 1 – 3, 68167 Mannheim, Germany.
    Footnotes
    # Joint senior authors
    Affiliations
    Department of Neurology, Medical Faculty Mannheim and Mannheim Center of Translational Neurosciences (MCTN), Heidelberg University, Theodor-Kutzer-Ufer 1 – 3, 68167 Mannheim, Germany
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Published:October 18, 2021DOI:https://doi.org/10.1016/j.msard.2021.103340

      Highlights

      • We investigated long-term follow-up of multiple sclerosis (MS) iron rim lesions (IRLs).
      • During follow-up, persistent IRLs significantly enlarged, whereas non-IRLs showed a tendency to shrink.
      • During follow-up, apparent diffusion coefficient values significantly increased in persistent IRLs.
      • IRLs are associated with sustained tissue damage.

      Abstract

      Background

      Several studies have pointed out that seemingly chronic multiple sclerosis (MS) lesions may also be in inflammatory states. In pathological studies, up to 40% of chronic MS lesions are characterized as “chronic active” or “smoldering” lesions that are characterized by a rim of iron-laden proinflammatory macrophages/microglial cells at the lesion edge with low-grade continuous myelin breakdown. In vivo, these lesions can be visualized as “iron rim lesions” (IRLs) on susceptibility-weighted imaging (SWI). The aim of this study was to investigate the long-term dynamics of IRLs in vivo for a more detailed evolution of dynamic lesion volume changes occurring over time.

      Methods

      We retrospectively identified patients with MS who were followed for at least 36 months (up to 72 months) and underwent at least an annual MRI on the same 3 Tsystem. Using Voxel-Guided Morphometry (VGM) we investigated regional volume changes within lesions and correlated these findings with SWI for the presence of a characteristic hypointense lesion rim. To estimate tissue damage, apparent diffusion coefficient (ADC) values for every lesion at baseline and follow-up MRIs were determined.

      Results

      Forty-three patients were included in the study. Overall, we identified 302 supratentorial non-confluent MS lesions (52 persistent IRLs, nine transient IRLs, 228 non-IRLs and 13 acute contrast-enhancing lesions). During follow-up, persistent IRLs significantly enlarged, whereas non-IRLs showed a tendency to shrink. At baseline MRI, ADC values were significantly higher in persistent IRLs (1.23 × 10−3 mm/s2) compared to non-IRLs (1.01 × 10−3 mm/s2; p < 0.001), but not compared to transient IRLs (1.06 × 10−3 mm/s2; p = 0.15) and contrast-enhancing lesions (1.15 × 10−3 mm/s2; p = 1.0). During follow-up, ADC values significantly increased more often in persistent IRLs compared to all other lesion types (p < 0.0001).

      Conclusions

      Our long-term data demonstrate that persistent IRLs enlarge during disease duration, whereas non-IRLs show a tendency to shrink. Furthermore, IRLs are associated with sustained tissue damage, supporting the notion that IRLs could represent a new imaging biomarker in MS.

      Keywords

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