Paramagnetic rim lesions linked to MS disability progression
2 University of Buffalo studies examine brain lesions over time
A specific type of brain lesion called a paramagnetic rim lesion, or PRL, is associated with worse disability over time in people with multiple sclerosis (MS), but available disease-modifying therapies (DMT) can lower the chances of the appearance of these lesions, according to two studies published by scientists at the University at Buffalo.
Looking at PRLs themselves may not be practical for measuring the effectiveness of new MS treatments in clinical trials, as several hundred patients would have to be enrolled to detect mild reductions in those lesions, the researchers said. Still, they said, PRLs may be examined alongside other disease biomarkers to better establish a person’s prognosis in the clinic.
“Our group is among the first to study the factors that influence how PRLs evolve over time, and the first to study how this evolution is related to multiple sclerosis disease progression,” Robert Zivadinov, MD, PhD, senior author on both papers and professor of neurology at Buffalo, said in a university news story.
MS is marked by inflammation that causes damage to the brain and spinal cord. This is visible on imaging scans as lesions, which are spots where brain tissue has become scarred and damaged.
Recent advances in imaging technology have led to the identification of PRLs, regions of chronic inflammation defined by a rim of inflammatory cells around a central core of pronounced nerve cell damage. Emerging data suggest that PRLs may be useful markers for diagnosing MS, but the relevance of these lesions in terms of disability progression isn’t fully understood.
PRLs and disease progression
“We were motivated to study [PRLs] because existing multiple sclerosis imaging markers, such as overall … lesion volume, poorly predict future MS disease progression,” Zivadinov said. “However, much is still unknown regarding the long-term evolution of PRLs and their relationship with disease progression.”
One of the studies, “Associations Between Paramagnetic Rim Lesion Evolution and Clinical and Radiologic Disease Progression in Persons With Multiple Sclerosis,” was published in Neurology. The researchers looked at the association between PRLs and rates of disability progression in 160 MS patients.
Results showed that the disappearance of PRLs was associated with lower rates of disability worsening, including a form of disability progression that occurs in the absence of relapses. Conversely, patients who developed new PRLs were more likely to experience disability progression without relapse activity.
“Overall, our findings show that resolution of existing PRLs and lack of new PRLs are associated with improved clinical outcomes,” the researchers concluded. The findings imply that treatments to reduce the appearance of PRLs or to resolve existing ones might help people with MS stave off disability worsening.
PRL evolution over time
The other study, “Determinants of long-term paramagnetic rim lesion evolution in people with multiple sclerosis,” was published in the Annals of Clinical and Translational Neurology. In this study, the researchers wanted to examine how PRLs change over time and how the appearance and disappearance of PRLs is influenced by DMTs.
Results showed that MS patients who are younger or are current smokers tend to have more PRLs, and also that it’s common for these lesions to appear or disappear over years of follow-up. The researchers noted that PRLs that remained present for many years were more likely to lead to permanent brain tissue loss.
“This indicates that PRL disappearance may be associated with preservation of underlying [brain] tissue integrity, potentially from cessation of local chronic inflammation,” they said.
Findings also suggested that the appearance of new PRLs is less likely when patients are treated with DMTs. Both high-efficacy and low-to-moderate efficacy DMTs significantly reduced the appearance of new PRLs compared with no treatment, but neither type of treatment was effective at resolving existing PRLs.
“Given these data, use of currently available DMTs may be the best available tool to prevent PRL formation,” they wrote.
Theoretically, this could mean that stopping the appearance of new PRLs could be a useful marker for trials that are testing new DMTs. However, based on available data, the researchers calculated that a clinical trial would need at least 430 patients followed for at least a year to get statistically meaningful results for a hypothetical treatment that can reduce the occurrence of new PRLs by 50%. A less potent DMT would need even more participants followed for longer to yield meaningful results.
“Based on our findings, the utility of PRL disappearance or new PRL appearance as outcome measures in clinical trials is to some extent limited,” said Jack Reeves, a doctoral student at Buffalo and study co-author. “A clinical trial with significantly more participants will be needed in order to more precisely determine how moderate efficacy drugs affect PRLs.”
The researchers stressed that much about PRLs is still unknown, and further work will be needed to understand these lesions in greater detail.
“These papers looked at how PRLs evolve over long time periods, five to 10 years, but it would be valuable to look at PRL evolution at more regular intervals, such as annually, to better understand the exact trajectory of how PRLs evolve in serial imaging studies,” Zivadinov said.
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