Long-term dynamics of multiple sclerosis iron rim lesions

Claudia E Weber; Matthias Wittayer; Matthias Kraemer; Andreas Dabringhaus; Kathrin Bail; Michael Platten; Lucas Schirmer; Achim Gass; Philipp Eisele

doi:10.1016/j.msard.2021.103340

Long-term dynamics of multiple sclerosis iron rim lesions

Mult Scler Relat Disord. 2022 Jan:57:103340. doi: 10.1016/j.msard.2021.103340. Epub 2021 Oct 18.

Authors

Claudia E Weber¹, Matthias Wittayer², Matthias Kraemer³, Andreas Dabringhaus⁴, Kathrin Bail⁵, Michael Platten⁶, Lucas Schirmer⁷, Achim Gass⁸, Philipp Eisele⁹

Affiliations

¹ Department of Neurology, Medical Faculty Mannheim and Mannheim Center of Translational Neurosciences (MCTN), Heidelberg University, Theodor-Kutzer-Ufer 1 - 3, 68167 Mannheim, Germany. Electronic address: claudia.weber@umm.de.
² Department of Neurology, Medical Faculty Mannheim and Mannheim Center of Translational Neurosciences (MCTN), Heidelberg University, Theodor-Kutzer-Ufer 1 - 3, 68167 Mannheim, Germany. Electronic address: matthias.wittayer@umm.de.
³ VGMorph GmbH, Waterloostr. 32, 45472 Mülheim an der Ruhr, Germany; Neurocentrum, Am Ziegelkamp 1f, 41515 Grevenbroich, Germany. Electronic address: matthias.kraemer@vgmorph.com.
⁴ VGMorph GmbH, Waterloostr. 32, 45472 Mülheim an der Ruhr, Germany. Electronic address: andreas.dabringhaus@vgmorph.com.
⁵ Department of Neurology, Medical Faculty Mannheim and Mannheim Center of Translational Neurosciences (MCTN), Heidelberg University, Theodor-Kutzer-Ufer 1 - 3, 68167 Mannheim, Germany. Electronic address: kathrin.bail@umm.de.
⁶ 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. Electronic address: michael.platten@umm.de.
⁷ 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. Electronic address: lucas.schirmer@medma.uni-heidelberg.de.
⁸ Department of Neurology, Medical Faculty Mannheim and Mannheim Center of Translational Neurosciences (MCTN), Heidelberg University, Theodor-Kutzer-Ufer 1 - 3, 68167 Mannheim, Germany. Electronic address: achim.gass@medma.uni-heidelberg.de.
⁹ Department of Neurology, Medical Faculty Mannheim and Mannheim Center of Translational Neurosciences (MCTN), Heidelberg University, Theodor-Kutzer-Ufer 1 - 3, 68167 Mannheim, Germany. Electronic address: philipp.eisele@medma.uni-heidelberg.de.

PMID: 35158450
DOI: 10.1016/j.msard.2021.103340

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: Chronic active lesions; Iron rim lesions; MRI; Multiple sclerosis; SWI.

MeSH terms

Brain / diagnostic imaging
Humans
Iron
Magnetic Resonance Imaging
Multiple Sclerosis* / diagnostic imaging
Retrospective Studies

Substances

Iron