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

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. 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). 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). 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.