Pathophysiological and clinical implications of PRL heterogeneity in multiple sclerosis
(2025) Belgian MS Researcher Day 2025 — Location: Leuven, Belgium
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- Introduction Recent studies suggest substantial heterogeneity in paramagnetic rim lesion (PRL)-associated tissue damage which, compared to classical PRL assessment, improves the association with MS clinical outcomes. However, it remains unclear how tissue damage evolves in PRL and how this correlates with ongoing neuroaxonal damage and potential treatment effect. Aim To investigate the development of PRL-associated tissue damage using serial 3T MRI, matched serum neurofilament (sNfL), and clinical data. Material and Methods In 139 subjects (92 relapsing, 47 progressive MS; 45 male), PRL status was assessed on 3D EPI-phase, and mean lesion T1 was obtained from MP2RAGE-derived T1 maps. Lesion age was determined by the time of gadolinium enhancement. As previously described in Stölting et al. 2024, lesions were classified as short-T1 (<1572ms) and long-T1 (≥1572ms). Finally, longitudinal (~ 4 years) lesion T1 changes were analysed in a subset of patients before and after anti-CD20 antibody treatments (18/31, treated/untreated). Results A total of 2727 lesions were analysed (504 PRL). Lesion age assessment was available for 129 lesions (58 PRL), showing that long-T1 PRL were older than short-T1 PRL (2.1±0.1 vs 1.5±0.2y; p<0.001), whereas no differences in non-PRL were found (age long-T1 vs short-T1: 1.7y±0.3 vs 1.3±0.2y; p=0.2). After correction for EDSS, T2 lesion load, treatment status, and relapse activity, the volume of short-T1 PRL positively correlated with higher sNfL z-scores (p=0.008), while the volume of long-T1 PRL did not (p=0.1). When adjusted for normalised brain volume, treatment status and relapse activity, higher EDSS was associated with higher volume of long-T1 PRL (p<0.001) but not with the volume of short-T1 PRL (p=0.2). Preliminary pre-post treatment analyses showed different T1 behaviour in untreated vs treated PRL (with decreasing T1 values in treated PRL; p=0.003). PRL heterogeneity analysis showed that these changes were likely driven by short-T1 PRL (p=0.004) but not long-T1 PRL (p=0.4) Discussion Less destructive, likely younger short-T1 PRL are characterized by increasing tissue damage and axonal degeneration, while more destructive long-T1 PRL better correlate with established clinical disability. Our preliminary pre-post anti-CD20 analyses suggests that timely treatment of less destructive PRL might forestall future disability accrual in MS.
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Stölting, A., Vanden Bulcke, C., Borrelli, S., Deltombe, M., Bayart, J.-L., Bugli, C., Perdaens, O., Guisset, F., Van Pesch, V., María I. Gaitán, Martina Absinta, Daniel S. Reich, & Maggi, P. (2025). Pathophysiological and clinical implications of PRL heterogeneity in multiple sclerosis. Belgian MS Researcher Day 2025, Leuven, Belgium. https://hdl.handle.net/2078.5/247606