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September 10, 2025

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

BRBrian RennerCedars-Sinai Medical Center EVElizabeth VerterCedars-Sinai Medical Center MAMartina AbsintaHumanitas University

Key Points

The presence of ≥1 paramagnetic rim lesion shows a sensitivity of 0.86 and specificity of 0.90 for diagnosing multiple sclerosis.
Of 78 participants with suspected demyelinating disease, 46% displayed paramagnetic rim lesions, helping distinguish MS cases.
Shorter durations from initial symptom onset correlate with higher likelihood of observing paramagnetic rim lesions in multiple sclerosis patients.
Diagnostic performance was assessed using the 2017 McDonald criteria, confirming the relevance of paramagnetic rim lesions in clinical evaluations.

Abstract

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.

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