27th June 2023

Progressive multifocal leukoencephalopathy (PML)

PML is a CNS disease caused by JC virus. JC virus is a small ubiquitous DNA virus. PML is extremely rare in immunocompetent individuals; ~80% of cases are associated with HIV. Most patients with HIV have a CD4 count of <200 cells/μL, however, over 10% of cases have a greater CD4 count. JC virus transforms in PML to cause lysis of oligodendrocytes, causing demyelination. Presenting features include:

• Seizures
• Focal neurological deficits
• Gait disturbance
• Speech disturbance
• Ataxia
• Aphasia
• Visual changes

Imaging can aid diagnosis. CT shows hypodense lesions in the white matter, while MRI is more sensitive to white matter changes. There are often multifocal lesions. CSF is useful to exclude other diagnoses, and JC virus PCR can be conducted on CSF samples. Restoration of immunity with HAART in the treatment of PML may result in immune reconstitution inflammatory syndrome (IRIS). The newly reconstituted immune system targets oligodendritic cells, causing inflammatory demyelination. The most effective treatment for PML is immune reconstitution with antiretroviral therapy. In cases of IRIS, steroids are given alongside antiretroviral medications to control inflammation.