A 48-year-old HIV-positive man with CD4 count below 50 cells/microlitre presents with progressive cognitive decline over two months. MRI shows bilateral, asymmetric, confluent T2/FLAIR hyperintense lesions in the parieto-occipital subcortical white matter involving U-fibres, with no mass effect, no enhancement, and no diffusion restriction. The most likely diagnosis is:

• A HIV encephalitis
• B Progressive multifocal leukoencephalopathy ✓
• C Primary CNS lymphoma
• D Cerebral toxoplasmosis

Explanation

Progressive multifocal leukoencephalopathy, caused by JC virus reactivation in severe immunosuppression, produces asymmetric demyelinating white matter lesions that involve subcortical U-fibres and characteristically show no enhancement, no mass effect, and no diffusion restriction because the blood-brain barrier remains intact. HIV encephalitis is symmetric and spares the U-fibres, while lymphoma and toxoplasmosis enhance, which excludes them despite the similar patient profile.

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

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Written and medically reviewed by the StethoPrep medical team.