Long-term dynamics of multiple sclerosis iron rim lesions

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

doi:10.1016/j.msard.2021.103340

Cited by 30 publications

(28 citation statements)

References 40 publications

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“…Previous studies demonstrated that IRLs are associated with higher disease severity and ongoing tissue destruction 2–7 . Consistent with these findings, in our study, MS patients with at least one brain IRL on MRI also had higher disability scores (EDSS, pyramidal functional system), emphasizing IRLs as a novel imaging marker of disease severity.…”

Section: Discussionsupporting

confidence: 91%

“…In line with previous studies, 12,13,32,33 T1/T2w values of brain lesions were significantly lower compared to the NAWM, emphasizing that the T1/T2w ratio represents a sensitive (semi)quantitative marker of microstructural tissue damage in MS patients. Of note, T1/T2w values of brain IRLs were significantly lower compared to non-IRLs, supporting the findings of previous quantitative MRI 1,3 and histopathological studies 1,2 that IRLs are associated with a pronounced tissue matrix damage.…”

Section: Discussionsupporting

confidence: 86%

“…In multiple sclerosis (MS), in vivo demonstration of chronic active lesions as paramagnetic or iron rim lesions (IRLs) on iron‐sensitive (ultra)high field MRI sequences has been suggested as a novel imaging marker of a chronic “smoldering” inflammation including ongoing myelin degradation and axonal degeneration, 1,2 associated with higher neurological disability and disease severity 2–7 …”

Section: Introductionmentioning

confidence: 99%

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Multiple sclerosis iron rim lesions are linked to impaired cervical spinal cord integrity using the T1/T2‐weighted ratio

Wenzel

Wittayer

Weber

et al. 2022

Journal of Neuroimaging

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Background and Purpose In multiple sclerosis (MS), iron rim lesions (IRLs) are characterized by pronounced tissue matrix damage. The T1/T2‐weighted (T1/T2w) ratio represents a postprocessing MRI approach to investigate tissue integrity, but studies investigating spinal cord pathology are missing until now. The aim of this study was to characterize tissue integrity using the T1/T2w ratio in lesions and the normal‐appearing white and gray matter (NAWM, NAGM) in the spinal cord and brain in MS patients with and without brain IRLs. Methods Forty MS patients (20 patients with at least one brain IRL and 20 age‐ and sex‐matched patients without IRLs) were included. Normalized cross‐sectional area (nCSA) of the upper cervical cord was calculated in addition to T1/T2w values and standard brain and spinal cord MRI parameters. Results Patients with IRLs had higher disability scores, a smaller nCSA, and a higher cervical T2 lesion volume. T1/T2w values of brain IRLs were significantly lower compared to non‐IRLs (p < .001). Furthermore, T1/T2w values of lesions were significantly lower compared to the NAGM and NAWM, both in the brain and the spinal cord (p < .05 for all comparisons). T1/T2w values of the NAGM and NAWM in the brain and spinal cord did not statistically differ between the IRL group and the non‐IRL group. Conclusion IRLs constitute an imaging marker of disease severity. T1/T2w ratio maps represent an interesting technique to capture diffuse tissue properties. Calculation of T1/T2w ratio maps of the spinal cord might provide additional insights into the pathophysiological processes of MS.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

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Multiple sclerosis iron rim lesions are linked to impaired cervical spinal cord integrity using the T1/T2‐weighted ratio

Wenzel

Wittayer

Weber

et al. 2022

Journal of Neuroimaging

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“…In this study, T1/T2 ratios decreased in all IRLs, a finding that is in line with previous studies that used other quantitative MRI approaches to detect progressive tissue matrix damage in IRLs in vivo. 3,8 Of note, this decrease was significantly higher at the second FU in patients without DMT compared to MS patients starting DMT suggesting that DMTs have a beneficial, but delayed effect on evolving tissue damage in IRLs. Our results are supported by a study that demonstrated dimethyl fumarate–induced reduced susceptibility in IRLs, indicating a decreased activation state in microglial cells.…”

Section: Discussionmentioning

confidence: 94%

Impact of disease-modifying therapies on evolving tissue damage in iron rim multiple sclerosis lesions

et al. 2022

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We investigated the impact of disease-modifying therapies (DMTs) on the evolving tissue damage in iron rim multiple sclerosis lesions using a novel post-processing magnetic resonance imaging (MRI) approach, the T1/T2 ratio. In this study, on baseline and 1-year follow-up, T1/T2 ratios of iron rim lesions (IRLs) in patients starting DMT (dimethyl fumarate, fingolimod, ocrelizumab) did not statistically differ compared to patients without DMT. At the second follow-up, T1/T2 ratios were significantly lower in IRLs in patients without DMT ( p = 0.002), suggesting that DMTs have a beneficial delayed effect on lesion evolution and tissue matrix damage in IRLs.

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“…Therefore, one of our inclusion criteria contained a follow-up MRI including SWI after at least 3 months. In addition, more recent studies showed that in a small percentage of IRLs the rim even wanes and finally disappears during long-term follow-up [ 39 , 40 ]. Future studies including more CELs and longer follow-up observation time points are recommended.…”

Section: Discussionmentioning

confidence: 99%

MRI predictors for the conversion from contrast-enhancing to iron rim multiple sclerosis lesions

et al. 2022

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Background In multiple sclerosis (MS), iron rim lesions (IRLs) are characterized by progressive tissue matrix damage. Therefore, early identification could represent an interesting target for therapeutic intervention to minimize evolving tissue damage. The aim of this study was to identify magnetic resonance imaging (MRI) parameters predicting the conversion from contrast-enhancing to IRLs. Methods We retrospective identified MS patients scanned on the same 3 T MRI system presenting at least one supratentorial contrast-enhancing lesion (CEL) and a second MRI including susceptibility-weighted images after at least 3 months. On baseline MRI, pattern of contrast-enhancement was categorized as “nodular” or “ring-like”, apparent diffusion coefficient (ADC) maps were assessed for the presence of a peripheral hypointense rim. Lesion localization, quantitative volumes (ADC, lesion volume) and the presence of a central vein were assessed. Results Eighty-nine acute contrast-enhancing lesions in 54 MS patients were included. On follow-up, 16/89 (18%) initially CELs converted into IRLs. CELs that converted into IRLs were larger and demonstrated significantly more often a ring-like contrast-enhancement pattern and a peripheral hypointense rim on ADC maps. Logistic regression model including the covariables pattern of contrast-enhancement and presence of a hypointense rim on ADC maps showed the best predictive performance (area under the curve = 0.932). Discussion The combination of a ring-like contrast-enhancement pattern and a peripheral hypointense rim on ADC maps has the ability to predict the evolution from acute to IRLs. This could be of prognostic value and become a target for early therapeutic intervention to minimize the associated tissue damage.

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Long-term dynamics of multiple sclerosis iron rim lesions

Cited by 30 publications

References 40 publications

Multiple sclerosis iron rim lesions are linked to impaired cervical spinal cord integrity using the T1/T2‐weighted ratio

Multiple sclerosis iron rim lesions are linked to impaired cervical spinal cord integrity using the T1/T2‐weighted ratio

Impact of disease-modifying therapies on evolving tissue damage in iron rim multiple sclerosis lesions

MRI predictors for the conversion from contrast-enhancing to iron rim multiple sclerosis lesions

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