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Background: White matter lesions (WMLs) on brain magnetic resonance imaging (MRI) in multiple sclerosis (MS) may contribute to misdiagnosis. In chronic active lesions, peripheral iron-laden macrophages appear as paramagnetic rim lesions (PRLs). Objective: To evaluate the sensitivity and specificity of PRLs in differentiating MS from mimics using clinical 3T MRI scanners. Method: This retrospective international study reviewed MRI scans of patients with MS (n = 254), MS mimics (n = 91) and older healthy controls (n = 217). WMLs, detected using fluid-attenuated inversion recovery MRI, were analysed with phase-sensitive imaging. Sensitivity and specificity were assessed for PRLs. Results: At least one PRL was found in 22.9% of MS and 26.1% of clinically isolated syndrome (CIS) patients. Only one PRL was found elsewhere. The identification of ⩾1 PRL was the optimal cut-off and had high specificity (99.7%, confidence interval (CI) = 98.20%–99.99%) when distinguishing MS and CIS from mimics and healthy controls, but lower sensitivity (24.0%, CI = 18.9%–36.6%). All patients with a PRL showing a central vein sign (CVS) in the same lesion (n = 54) had MS or CIS, giving a specificity of 100% (CI = 98.8%–100.0%) but equally low sensitivity (21.3%, CI = 16.4%–26.81%) Conclusion: PRLs may reduce diagnostic uncertainty in MS by being a highly specific imaging diagnostic biomarker, especially when used in conjunction with the CVS.

Supplemental material, sj-docx-1-msj-10.1177_13524585221118677 for Paramagnetic rims are a promising diagnostic imaging biomarker in multiple sclerosis by Isobel Meaton, Amjad Altokhis, Christopher Martin Allen, Margareta A Clarke, Tim Sinnecker, Dominik Meier, Christian Enzinger, Massimiliano Calabrese, Nicola De Stefano, Alain Pitiot, Antonio Giorgio, Menno M Schoonheim, Friedemann Paul, Mikolaj A Pawlak, Reinhold Schmidt, Cristina Granziera, Ludwig Kappos, Xavier Montalban, Àlex Rovira, Jens Wuerfel and Nikos Evangelou in Multiple Sclerosis Journal