A 25-year-old woman with known multiple sclerosis on natalizumab for 30 months tests JC virus antibody positive with an index of 3.2. She develops rapidly progressive cognitive decline, aphasia, and a new large white matter lesion on MRI (T2-hyperintense, no enhancement). Which complication is most likely?

• A MS relapse requiring high-dose methylprednisolone
• B CNS lymphoma complicating immunosuppression
• C Natalizumab-associated cerebral vasculitis
• D Progressive multifocal leukoencephalopathy (PML) ✓

Explanation

Progressive multifocal leukoencephalopathy (PML), caused by JC virus reactivation, is a recognised complication of natalizumab therapy, particularly after >24 months and with a JC antibody index >0.9 (high risk >1.5). This patient has all three risk factors: >24 months of treatment, JC-positive serology with high index, and no prior immunosuppressant use (which is the highest risk category). MRI shows non-enhancing T2/FLAIR white matter lesions without mass effect, distinct from MS plaques.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.