Paramagnetic rim lesions are highly specific for multiple sclerosis in real-world data

Abstract

Paramagnetic rim lesions (PRLs) are an emerging biomarker for multiple sclerosis representing chronic, low-grade intraparenchymal brain inflammation. In addition to associating with greater disease severity, PRLs may be diagnostically supportive. Our aim in this study was to determine PRL specificity and sensitivity for discriminating multiple sclerosis from its diagnostic mimics using real-world clinical diagnostic and imaging data. This is a retrospective, cross-sectional analysis of a longitudinal cohort of patients with prospectively collected observational data. Patients were included if they underwent clinical evaluation in our academic neuroimmunology centre and had an available MRI scan from the same clinical 3-T magnet that included a T2*-weighted sequence with susceptibility post-processing (Susceptibility Weighted ANgiography protocol, General Electric). Susceptibility imaging-derived filtered phase maps and corresponding T2-fluid attenuated inversion recovery images were manually reviewed to determine PRLs. PRLs were categorized as 'definite', 'probable' or 'possible' based on modified, recent consensus criteria. We hypothesized that PRLs would convey a high specificity to discriminate multiple sclerosis from its MRI mimics. Five hundred seventy-four patients were evaluated in total: 473 with multiple sclerosis, 53 with non-inflammatory neurological disease and 48 with other inflammatory neurological disease. Identification of 'definite' or 'probable' PRL provided a specificity of 98% to discriminate multiple sclerosis from non-inflammatory neurological disease and other inflammatory neurological disease; sensitivity was 36%. Interrater agreement was almost perfect for definite/probable identification at a subject level. PRLs convey high specificity for multiple sclerosis and can aid in the diagnostic evaluation. Modest sensitivity limits their use as single diagnostic indicators. Including lesions with lower confidence ('possible') rapidly erodes specificity and should be interpreted with caution given the potential harms associated with misdiagnosis.

Keywords: diagnosis; mimics; multiple sclerosis; paramagnetic rim lesion; specificity.

Graphical Abstract

Figure 1

Examples of PRL ratings of different confidence categories in relapsing-remitting multiple sclerosis. Axial, fluid attenuated inversion recovery images (left) are coregistered to high-pass filtered phase susceptibility images (‘susceptibility weighted angiography’, General Electric; right) in four different examples demonstrating ratings of (A) ‘definite’, (B) and (C) ‘probable’ and (D) ‘possible’ PRLs. Small white arrows identify some of the many features that often reduce rater confidence in assessment.

Figure 2

Probable PRLs in non-multiple sclerosis. PRLs were rated as ‘probable’ in two patients from the cohort, diagnosed with (A) small vessel disease (NIND) and (B) neurolupus (OIND). Axial, fluid attenuated inversion recovery images are on the left and high-pass filtered phase susceptibility images are on the right. White arrows point to an edge of the probable PRL.

Figure 3

Examples of rater disagreement at different confidence levels for PRL ratings. Frequent sources of disagreement occurred due to faint signal, paramagnetic heterogeneity within the lesion or lesion border, as well as the potential for venous structures to mimic the PRL edge. Diagnoses are relapsing multiple sclerosis (A, B, D) and clinically isolated syndrome (C).

Figure 4

Examples of vascular and heterogeneity ‘flags’ in PRL evaluation that could lead to false positives. (A) An enlarged central vein that could readily be mistaken for a paramagnetic rim in a patient with relapsing multiple sclerosis; an inlay (dotted box) depicts the coregistered edges of the fluid attenuated inversion recovery lesion, which depict an important misalignment. Because the ependymal surface of the ventricle is also paramagnetic, periventricular lesions could be graded with caution. Example (B) shows a faint, thickened and incomplete paramagnetic signal proximate to the edges of a fluid attenuated inversion recovery hyperintense lesion in a patient with non-inflammatory neurological disease (vascular risk factors, hyperhomocysteinemia and history of moderate traumatic brain injuries); additional ‘flags’ include dense vascularity traversing the edges. Neither rater identified this as a possible PRL.