Paramagnetic rims are a promising diagnostic imaging biomarker in multiple sclerosis

Abstract

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.

Susceptibility-based imaging aids accurate distinction of pediatric-onset MS from myelin oligodendrocyte glycoprotein antibody-associated disease

“…PRLs are considered highly specific for MS and are present across all MS phenotypes. 18,24,25 The presence of PRLs has also been reported in 77% of 13 POMS subjects in a recent study, a similar rate compared to our observation. 28 Our results confirm these findings suggesting that chronic inflammation is present from the early phases of MS, even in young subjects.…”

Present and future of the diagnostic work-up of multiple sclerosis: the imaging perspective

“…A higher prevalence and/or number of PRLs have been found to be quite specific and clinically relevant for MS. They have been described in patients with radiologically isolated syndrome (RIS) (12% of all WM lesions, with 61% of RIS patients having ≥ 1 PRLs) [ 39 ] and CIS (19.9% of all WM lesions) [ 40 ], but not in MS-mimics [ 40 – 42 ], including NMOSD, Susac syndrome, and small-vessel disease.…”

“…In a large cohort of subjects with CIS/MS ( n = 254), MS mimickers ( n = 91) and old healthy controls ( n = 271), the identification of ≥ 1 PRLs was the optimal cut-off to distinguish CIS/MS patients from MS mimickers and old healthy controls (specificity = 99.7%, sensitivity = 24.0%, AUC = 0.71, 95% confidence interval [CI] = 0.64–0.78). Of note, the fulfilment of ≥ 1 PRLs or ≥ 4 lesions with CVS improved specificity (90.6%), sensitivity (57.9%) and AUC (0.83, 95% CI = 0.79–0.87) [ 42 ].…”

Relationship between paramagnetic rim lesions and slowly expanding lesions in multiple sclerosis

“…10 However, limited MRI sensitivity in detecting intracellular iron 8 may suggest an underestimation of the true number of such lesions. PRLs are specific for MS 11 and having four PRLs is associated with greater motor and cognitive disability at an earlier age, 12 but it remains uncertain if they preferentially accumulate in progressive MS. 13,14 Chronic lesion activity can also be detected with slowly expanding lesions (SELs) using deformationbased volumetric MRI. As with PRLs, SELs are seen in all MS phenotypes, 15,16 appear more numerous with progressive (primary and secondary) progressive compared with relapsing-remitting MS, 15 and have been associated with neurological and cognitive disability.…”

“… 10 However, limited MRI sensitivity in detecting intracellular iron 8 may suggest an underestimation of the true number of such lesions. PRLs are specific for MS 11 and having four PRLs is associated with greater motor and cognitive disability at an earlier age, 12 but it remains uncertain if they preferentially accumulate in progressive MS. 13 , 14 …”