Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the CNS caused by the reactivation of the JC virus. It occurs mainly in patients with severe immunosuppression (e.g., AIDS) and clinical manifestations include focal neurological deficits, seizures, and vision changes. The diagnosis is usually made based on typical imaging findings, but brain biopsy is the gold standard for diagnosis. Treatment is primarily supportive, and in patients with HIV, ART should be started immediately.
See also “HIV-associated conditions.”
- Mainly in patients with severe immunosuppression (e.g., patients with lymphoma/leukemia, patients that received organ transplantation)
- In patients with HIV 
Epidemiological data refers to the US, unless otherwise specified.
Reactivation of a past subclinical infection with JC virus is triggered (e.g., by immunosuppression) → oligodendrocyte infection → viral DNA mutation → aggressive replication within brain tissue → demyelination, destruction of infected oligodendrocytes 
Symptoms due to PML are insidious in onset and can progress over several weeks. 
- A presumptive diagnosis of PML can be made based on the clinical presentation (e.g., progressive onset of focal neurological deficits) and neuroimaging findings.
- Confirmatory testing with CSF analysis (or rarely, brain biopsy) can be considered as needed; for example
Neuroimaging findings 
- MRI brain without and with gadolinium contrast (preferred)
- CT brain with contrast 
- if HIV status is unknown.
- CD4 count: for patients with HIV: typically < 200 
- CSF analysis
Brain biopsy and histology 
- Indications: Consider when there is incongruence between clinical findings, imaging, and/or CSF.
- Findings: The classic triad consists of
- Treatment is mainly supportive (e.g., treatment of seizures).
- Patients with HIV
- Monitor for IRIS, which may cause a paradoxical worsening of PML.
PML typically progresses rapidly and is associated with high mortality.