Frequency and Diagnostic Implications of Paramagnetic Rim Lesions in People Presenting for Diagnosis to a Multiple Sclerosis Clinic

Abstract

Background and objectives: Paramagnetic rim lesions (PRLs) are a well-established imaging biomarker of chronic active multiple sclerosis (MS) lesions. PRLs have been shown to be highly specific for MS (∼90% specificity), and their prevalence has been estimated to be approximately 50% in patients with clinically established diagnoses of MS. In this study, we evaluated the frequency and diagnostic value of PRLs in patients at first clinical presentation.

Methods: Adults age 18-64 years presenting with clinical symptoms or radiologic suspicion of demyelinating disease referred to academic specialty MS centers without a definitive diagnosis were prospectively enrolled in a multicenter, cross-sectional, observational study. Phase images from high-resolution 3D echo-planar imaging were acquired on 3-tesla brain MRI and evaluated for PRLs by 3 independent raters, blinded to diagnosis, with adjudication from a fourth expert rater. Diagnostic performance of PRLs for a diagnosis of MS using the 2017 McDonald criteria as gold standard was evaluated using diagnostic thresholds based on the presence of at least 1 PRL (≥1 PRL) or at least 2 PRLs (≥2 PRLs).

Results: Seventy-eight participants were analyzed (mean age, years [range]: 45.0 [18-64] female sex n = 55 [71%]); a total of 124 PRLs were counted in 36 (46%) of the 78 participants (median: 3 PRLs; range: 1-9 PRLs). Thirty-two (89%) of the 36 PRL-positive participants fulfilled 2017 McDonald criteria, and the remaining 4 (11%) had an alternate diagnosis. The presence of ≥1 PRL had a sensitivity of 0.86 (95% CI 0.71-0.95) and a specificity of 0.90 (95% CI 0.77-0.97). For ≥2 PRLs, specificity increased to 0.95 (95% CI 0.83-0.99), whereas sensitivity decreased to 0.59 (95% CI 0.42-0.75). For participants with MS, shorter duration from initial symptom onset was associated with higher probability of having PRLs, with the odds of being PRL positive (≥1 PRL) increasing by 28% for every 1 year decrease from symptom onset (odds ratio 1.28 per year, 95% CI 1.03-1.59, p = 0.03).

Discussion: PRLs are highly prevalent early in patients with MS at the time of first clinical presentation and can differentiate MS from mimics with high accuracy.

Figure 1. Representative Example of a Paramagnetic Rim Lesion

Red arrows point to the same lesion shown on 4 different contrast images: phase-EPI, T2*-EPI, T2-FLAIR, and T1-GRE post-Gd. The lesion is focal and hyperintense on T2-FLAIR, nonenhancing on T1-GRE post-Gd, and has a hypointense rim on both phase-EPI and T2*-EPI phase-EPI = T2*-weighted echo-planar imaging (phase reconstruction), T2*-EPI = T2*-weighted echo-planar imaging (magnitude reconstruction), T2-FLAIR = T2-weighted fluid-attenuated inversion recovery, T1-GRE post-gd = T1-weighted gradient-recalled echo after injection of gadolinium contrast agent.

Figure 2. Flowchart Summary of Participant Stratification in the Primary Analysis

CIS = clinically isolated syndrome; DMT = disease-modifying therapy; MS = multiple sclerosis; Gd = gadolinium-based contrast agent; RIS = radiologically isolated syndrome.

Figure 3. Distribution of PRL Across all the Participants Included in the Primary Analysis (n = 78)

MC2017 = McDonald 2017 Criteria; PRL = paramagnetic rim lesion.

Figure 4. ROC Curve for the Presence of PRL (≥1 PRL) Relative to MS Diagnosis With 2017 McDonald Criteria

The area under the ROC curve is 0.88 (95% CI 0.81–0.96). PRL = paramagnetic rim lesion; ROC = receiver operating characteristic.