This episode explores new evidence showing that paramagnetic rim lesions (PRLs) are highly prevalent early in multiple sclerosis (MS) and can differentiate MS from mimics with striking accuracy. Dr. Daniel Ontaneda, Cleveland Clinic Lerner College of Medicine, Cleveland, OH, and Dr. Pascal Sati, Cedars-Sinai Medical Center,  Los Angeles, CA, discuss how PRLs, paired with optimized susceptibility-based MRI, are reshaping diagnostic confidence and informing the latest revisions to the McDonald criteria.