Key Takeaways:
- Patients with multiple sclerosis (MS) who develop areas of brain inflammation called paramagnetic rim lesions (PRLs) become disabled more rapidly
- Reducing or preventing PRLs could significantly slow MS progression
- Prescribing high-efficacy disease-modifying therapies (DMTs) to patients with MS earlier may prevent PRLs and slow the progression of the disease
- Assessing PRLs should be included in the workup of patients with MS
- Future research should focus on developing new DMTs that directly act on existing PRLs
Newswise — ORLANDO, Fla., Sept. 16, 2024 – Starting patients with multiple sclerosis (MS) on aggressive treatment earlier may help prevent the development of paramagnetic rim lesions (PRL), areas of chronic brain inflammation that are linked to faster decline due to the disease, suggests new research presented at the 149th Annual Meeting of the American Neurological Association (ANA).
People with MS who have PRLs tend to have greater brain atrophy and disability. Treatment for MS includes low-, moderate- or high-efficacy disease-modifying therapies (DMTs), such as monoclonal antibodies, immunomodulators and immunosuppressants. While high-efficacy DMTs have more side effects, previous research suggests they may help prevent PRLs from forming (unlike low- or moderate-efficacy DMTs), potentially outweighing the downsides. No currently available DMT has been shown to reduce existing PRLs.
“Checking PRL levels is not currently a standard part of an MS diagnosis and workup, but our findings suggest that it should be,” said Jack Reeves, Ph.D., lead author and M.D./Ph.D. candidate at Jacobs School of Medicine and Biomedical Engineering at the State University of New York at Buffalo. “Based on our preliminary findings, starting patients on high-efficacy DMTs rather than low- or moderate-efficacy DMTs may lead to better clinical outcomes by preventing PRLs from occurring and should be the gold standard for patients with higher disease activity, meaning they have more brain lesions and more relapses.”
People with MS sometimes develop acute lesions in the brain, which can, in turn, develop into PRLs. PRLs are a type of chronic active lesion made up of microglia – the housekeeping cells of the brain – that are inflamed. PRLs that develop and remain over an extended period are considered persistent. About half of people with MS have PRLs, and about one in five have four or more PRLs, said Reeves.
High-efficacy DMTs reduce inflammation by suppressing the immune system. Serious side effects of high-efficacy DMTs include infections, infusion reactions and raising the risk of cancer or heart problems. However, the research suggests treating patients who have MS with high-efficacy DMTs soon after diagnosis may outweigh the risk by preventing acute lesions from forming and developing into PRLs, aligning with the goal of inhibiting inflammation as early and aggressively as possible, he said.
Researchers used 3T magnetic resonance imaging (MRI) to assess the existence of persistent PRLs in 155 patients at the beginning of the study and again five years later. The findings were compared to the patients’ confirmed disability progression (CDP) and progression of independent relapse activity (PIRA) scores, which are measurements of MS progression and decline. Researchers determined that preventing new PRLs would result in a 7.5% reduction in PIRA-related decline over five years. They also determined that patients with a higher number of persistent PRLs had faster MS progression. They estimated that treatments that target persistent PRLs could reduce 5-year PIRA prevalence by 29% and 5-year CDP prevalence by 19%.
MS is a chronic disease of the central nervous system that has no cure and affects everyone differently. As MS progresses, patients may have weak muscles, vision problems, spasms, pain, trouble walking, and cognitive changes, such as problems with memory and problem-solving. Nearly 1 million Americans live with MS, according to the National Multiple Sclerosis Society.
“PRLs are a potentially useful tool for helping decide the best DMT to use, but are just one piece of the puzzle and should be interpreted in context by an experienced neurologist who specializes in MS,” said Reeves. “Future research should focus on developing new DMTs that directly act on existing PRLs.”
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*** ANA 2024 news releases may contain updated data that does not match what is reported in the abstract.
About the American Neurological Association (ANA)
From advances in stroke and dementia to movement disorders and epilepsy, the American Neurological Association has been the vanguard of research since 1875 as the premier professional society of academic neurologists and neuroscientists devoted to understanding and treating diseases of the nervous system. Its monthly Annals of Neurology is among the world’s most prestigious medical journals, and the ANA’s Annals of Clinical and Translational Neurology is an online-only, open access journal providing rapid dissemination of high-quality, peer-reviewed research related to all areas of neurology. The acclaimed ANA Annual Meeting draws faculty and trainees from the top academic departments across the U.S. and abroad for groundbreaking research, networking, and career development. For more information, visit www.myana.org or @TheNewANA1.
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