Paramagnetic Rim Lesions Predicts Future Cognitive Decline in Multiple Sclerosis

A new cohort study presented at the 2024 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, February 29 to March 2, in West Palm Beach, Florida, showed that the presence of paramagnetic rim lesions (PRLs), a subset of chronic active lesions (CF), at baseline, is associated with lower cognitive function in patients with multiple sclerosis (MS) after 4 years of follow-up. These findings reveal the impact of PRLs on subsequent cognitive function and suggest they may be an imaging marker to identify patients with MS who are at risk for cognitive decline.¹

The study comprised of 88 patients who had a mean age of 41.76 (±9.97) years, median Expanded Disability Status Scale (EDSS) scores of 1.00 (IQR 0.00, 2.00) and disease duration of 10.71 (±7) years. Of these patients, 36 (40.9%) had at least 1 PRL at baseline. Although investigators observed no statistically significant difference in baseline Symbol Digit Modalities Test (SDMT) scores between patients with at least 1 PRL and patients without (P = 0.453), SDMT at year 4 was lower for patients with at least one PRL (mean, 54.56 [SD, 11.59]) in comparison with those without PRLs (mean, 59.98 [SD, 12.89]; P = 0.046).

Presented by lead author Theodore H. Schwartz, MD, professor of neurological surgery at Weill Cornell Medicine, the cohort included patients with clinically isolated syndrome (n = 5, 5.7%), relapsing-remitting MS (n = 81, 92%), and secondary progressive MS (n = 5, 3.3%). Participants underwent a baseline MRI of quantitative susceptibility mapping (QSM) to recognize PRLs, FAST-T2 for myelin water fraction, and structural imaging to obtain thalamic volume and cortical thickness. Investigators utilized the Brief International Cognitive Assessment for Multiple Sclerosis to assess CF and included SDMT, California Verbal Learning Test (CVLT), and Brief Visuospatial Memory Test (BVMT) assessments at baseline and at 4 years.

Top Clinical Takeaways

Paramagnetic rim lesions (PRLs) at baseline in MS are associated with lower cognitive function after 4 years, suggesting their potential as predictive markers.
Although no significant difference was observed in baseline cognitive scores, patients with at least 1 PRL at baseline showed lower Symbol Digit Modalities Test scores at year 4.
The study indicates the need for future research to confirm the utility of quantitative susceptibility mapping in tailoring treatments for enhancing cognitive functions in MS.

Authors assessed the relationship between baseline imaging features and CF at year 4 with univariate linear models. In addition, researchers performed multiple linear models with all possible iterations, such as variables including all baseline imaging and baseline CF, and final models were determined based on significant variables only.

In a linear model, investigators observed that SDMT scores at year 4 were associated with the interaction between baseline SDMT and the presence of PRLs (β = -0.3368; P = 0.0434). After controlling for baseline BVMT, author observed lower BVMT at year 4 in patients with at least 1 PRL at baseline (β = -2.5390; P = 0.0292) in a separate linear model. Notably, researchers reported no relationship between PRLs and CVLT at year 4 among the participants with MS. Authors noted that future research is required to confirm if using QSM to identify PRLs can assist with tailoring treatments to enhance the processing speed and other cognitive functions in MS.¹

In a previous study presented at the 2022 ACTRIMS Forum findings demonstrated that patients referred for a new evaluation for clinical or radiological suspicion of MS may benefit from the diagnostic capabilities of PRL.² In the analysis, 95 patients who had clinical or radiological suspicion of MS underwent phase imaging that included high-resolution echo-planar-imaging scans, as well as 3D T2-FLAIR images, which were acquired at 3T. Three independent raters were blinded during the initial evaluation, followed up by group consensus with an expert rater. Presented by author Brian Renner, MD, a research associate in the Neuroimaging Program in the Department of Neurology at Cedars-Sina, PRLs were defined by a complete or partial hypointense rim surrounding an isointense core on phase colocalizing with a hyperintense T2-FLAIR lesion.

Of the entire cohort, 46% (n = 44) met the 2017 McDonald criteria and 39% (n = 37) were given an alternative diagnosis to MS. The remaining 14 patients were considered at risk of developing MS, with diagnoses of clinically isolated syndrome (CIS) or radiologically isolating syndrome (RIS). In total, 41 of the 95 patients had at least 1 PRL recorded, whereas in the remaining 53, no PRL was observed. For those who were diagnosed with MS, a total of 122 PRLs were recorded, with 35 of the 44 (79.5%) individuals showing at least 1 PRL. In comparison, for those who did not meet an MS diagnosis, only 6 of the 51 (11.7%) individuals had 1 or more PRLs.