Abstract
BACKGROUND: Paramagnetic rim lesions (PRL) are an emerging biomarker for multiple sclerosis (MS). In addition to associating with greater disease severity, PRL may be diagnostically supportive. OBJECTIVE: Our aim was to determine PRL specificity and sensitivity for discriminating MS from its diagnostic mimics using real-world clinical diagnostic and imaging data. METHODS: This is a retrospective, cross-sectional analysis of a longitudinal cohort of patients with prospectively collected observational data. Patients were included if they underwent neuroimmunological evaluation in our academic MS center, and had an available MRI scan from the same clinical 3T magnet that included a T2*-weighted sequence with susceptibility postprocessing (SWAN protocol, GE). SWAN-derived filtered phase maps and corresponding T2-FLAIR images were manually reviewed to determine PRL. PRL were categorized as "definite," "probable," or "possible" based on modified, recent consensus criteria. We hypothesized that PRL would convey a high specificity to discriminate MS from its MRI mimics. RESULTS: 580 patients were evaluated in total: 473 with MS, 57 with non-inflammatory neurological disease (NIND), and 50 with other inflammatory neurological disease (OIND). Identification of "definite" or "probable" PRL provided a specificity of 98% to discriminate MS from NIND and OIND; sensitivity was 36%. Interrater agreement was almost perfect for definite/probable identification at a subject level. CONCLUSIONS: PRL convey high specificity for MS and can aid in the diagnostic evaluation. Modest sensitivity limits their use as single diagnostic indicators. Including lesions with lower confidence ("possible" PRL) rapidly erodes specificity and should be interpreted with caution given the potential harms associated with misdiagnosis.