Certain MS Lesions Linked to Worse Disability, but Location Not a Factor

The presence of iron rim lesions (IRLs), which are regions of chronic nervous system damage with ongoing inflammation, visible on MRI scans, is linked with more substantial disability in people with multiple sclerosis (MS), according to a new study.

However, the connection between these lesions and worse disability does not seem to be explained by the location of the areas of damage. The researchers proposed that the connection may lie in a link between IRLs and nerve cell degeneration, but stressed a need for further research on these associations.

“IRLs are associated with higher disability scores. However, our results suggest that a higher disability is not explained by the sheer topography [location] of IRLs,” the team wrote.

The study, “Spatial distribution of multiple sclerosis iron rim lesions and their impact on disability,” was published in Multiple Sclerosis and Related Disorders.

In MS, damage to the brain and spinal cord — which comprise the central nervous system — is visible on MRI scans as lesions.

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Iron rim lesions linked to worse MS

Iron rim lesions, called IRLs and also referred to as paramagnetic rim lesions or “smoldering” lesions, are a particular kind of brain lesion. They have a characteristic “rim” caused by the presence of iron-laden inflammatory immune cells. An emerging body of evidence suggests that IRLs are linked to more severe MS.

However, the clinical relevance of these lesions — meaning their impact on a patient’s medical treatment — is still being explored.

Now, scientists in Germany set out to evaluate if the specific distribution of these lesions in the brain determined their impact on disability status. To find out, the team analyzed data from 134 MS patients. Half had at least one IRL visible on MRI scans — with an average of 2.18 IRLs per patient — and the other 67 were sex- and age-matched patients without such lesions.

These two groups were generally similar in terms of MS type, patterns of MS treatment, disease duration, and relapse activity.

However, patients with IRLs reported more severe disability, measured with the Expanded Disability Status Scale, and also had significantly larger lesion volume and lower brain volume.

“We demonstrated that MS patients with IRLs had higher [disability] scores compared to age- and sex-matched patients without IRLs, confirming the results of previous studies that IRLs are associated with higher disability,” the researchers wrote.

The scientists then conducted a battery of analyses looking at the specific locations of the IRLs and other lesion types within the brain. These results generally did not show significant differences between IRLs and other lesions.

“We found no significant differences between patients with versus patients without IRLs in terms of lesion distribution. Furthermore, in our IRL group, we observed no brain regions that were significantly more often affected by IRLs compared to non-IRLs,” the team wrote.

Further analyses showed no clear association between the locations of iron rim lesions and disability outcomes. The findings also indicated that IRLs generally had less impact on brain networks than other types of lesions.

The results did show a “significantly higher network disruption per volume in patients without IRLs compared to patients with IRLs.” Additionally, in the group with iron rim lesions, “IRLs caused a significantly less network disruption per volume compared to non-IRLs,” the researchers wrote — noting these outcomes were “contrary to our initial expectations.”

“These findings accordingly prompt the question how IRLs are eventually associated with disability,” the team added.

One possible explanation, according to the scientists, is the link between IRLs and reduced brain volume, which was identified in this study and has also been reported previously. Since reduced brain volume is typically a result of the death of nerve cells in the brain (neurodegeneration), these results imply a connection between more IRLs and more neurodegeneration, which could ultimately result in worse disability outcomes.

“One could hypothesize that neurodegenerative mechanisms have a crucial impact on disability,” the researchers wrote.

The team stressed a need for further research, noting that this analysis is limited by a relatively small sample size, with images taken at only one point in time, and focusing only on the brain and not the spinal cord.