pml

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of the central nervous system caused by reactivation of the JC virus in people with compromised immune function. The JC virus is common and remains latent in kidneys and lymphoid tissue, usually harmless unless immunity declines.

Most cases occur in individuals with severe immunosuppression, including HIV/AIDS, cancers, organ transplantation, or treatment with immunomodulatory therapies such as natalizumab or rituximab.

Pathology shows multifocal demyelinating lesions in the cerebral white matter due to infection and destruction of oligodendrocytes; lesions commonly involve subcortical white matter and may affect parietal-occipital regions, with possible frontal, callosal, brainstem, or cerebellar involvement.

Clinically, PML presents with subacute, progressive focal deficits over weeks to months, such as weakness, ataxia, visual disturbance, language impairment, sensory loss, or cognitive change.

Diagnosis relies on MRI and CSF testing. MRI typically shows multifocal, asymmetric T2-hyperintense white matter lesions without mass effect; JC virus DNA in CSF by PCR supports the diagnosis. Brain biopsy is reserved for uncertain cases.

Treatment centers on restoring immune function; there is no proven antiviral therapy. In HIV, antiretroviral therapy is essential; in other settings, reducing or stopping immunosuppression may allow recovery. Management of IRIS and supportive rehabilitation are important.

Prognosis is variable and generally guarded; outcomes range from stabilization to deterioration, with better survival after immune reconstitution in some contexts.