The Presence of a Paramagnetic Phase Rim is Linked to Lesion Age in Multiple Sclerosis

Background and Objectives

In relapsing-remitting multiple sclerosis (RRMS), smouldering inflammation at the rims of chronic active lesions has emerged as a crucial contributor to disease progression. Paramagnetic rim lesions (PRLs), has been proposed as the most pathologically validated marker for chronic active lesions. However, the strength of the association between PRLs and clinical or radiological measures of disease progression remains unclear, and the relationship between PRL presence and lesion-specific characteristics, such as lesion size and age, is not well understood. The objective of this study is to investigate the effect of PRL presence on clinical and radiological markers of disease progression, and its association with lesion characteristics such as size and age.

Methods

60 RRMS patients, each with at least five years of previous structural MRI data were investigated using SWAN protocols. Lesions exceeding a volume of 100 mm³ were included in analysis.

Results

PRLs were present in 48% of patients, comprising 13% (80 out of 607) of the total lesion count. Patients with PRLs were significantly younger than those without (p<0.001). Furthermore, PRLs were significantly larger (p<0.0001) and exhibited more severe structural damage compared to non-PRLs (p<0.0001). These characteristics were consistent both within and between patients. PRL count and volume were significantly correlated with radiological measures of disease progression, including central and total brain atrophy (p<0.001 and <0.05 for PRL count and volume, respectively).

Crucially, our results showed that all 32 lesions appearing within five years preceding SWAN imaging displayed a paramagnetic rim. This finding was validated in two independent international cohorts, reinforcing the link between PRLs and lesion age. Moreover, the proportion of rim-positive lesions decreased as lesion age increased. In a sub-set of patients with longitudinal susceptibility data the paramagnetic rim tended to diminish or disappear over time.

Conclusion

Our findings indicate that the presence of a paramagnetic rim in MS lesions is a characteristic feature of all newly formed lesions that exceed a specific size threshold, and that this rim gradually diminishes as lesions age. As such, this study enhances the understanding of lesion formation and may also have significant implications for using PRLs as a biomarker of lesion activity.