A 40-year-old HIV-positive patient (CD4 count 50/µL) develops subacute encephalopathy. MRI shows non-enhancing, confluent white matter signal changes bilaterally. CSF PCR is positive for JC virus. What is the pathological basis of the white matter changes?

• A JC virus infects CD4+ T cells in white matter, causing focal demyelination via cytotoxic T-cell attack
• B JC virus infects astrocytes causing reactive gliosis and periventricular calcifications
• C JC virus induces inflammatory demyelination resembling MS via molecular mimicry of myelin basic protein
• D JC virus infects oligodendrocytes, causing lytic infection, demyelination, and loss of myelin-producing cells ✓

Explanation

Progressive multifocal leukoencephalopathy (PML) is caused by JC virus (a polyomavirus) reactivation in immunocompromised patients. JC virus specifically infects oligodendrocytes, the myelin-producing cells of the CNS, causing productive lytic infection. Destruction of oligodendrocytes leads to widespread, multifocal demyelination of the white matter. Histologically, enlarged oligodendrocyte nuclei with viral inclusions, bizarre giant astrocytes, and foamy macrophages are seen. The absence of enhancement reflects the lack of inflammatory response in severe immunosuppression.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.