Which imaging feature best distinguishes PML from multiple sclerosis on MRI?

• A. Lesions that are typically ring-enhancing with edema.
• B. Non-enhancing lesions with little mass effect.
• C. Lesions limited to the spinal cord.
• D. Calcified plaques in periventricular white matter.

Answer: (B)

The distinguishing clue on MRI is the enhancement and mass effect of the lesions. In PML, the demyelinating lesions typically do not enhance after gadolinium and show little to no edema or mass effect, reflecting the primarily destructive but noninflammatory nature of JC virus–induced damage. In contrast, multiple sclerosis lesions often reflect inflammatory activity; during relapses they may enhance with gadolinium as the blood–brain barrier is disrupted, and they can be associated with mild mass effect depending on size. Therefore, non-enhancing lesions with little mass effect are most characteristic of PML and help separate it from MS.