Progressive multifocal leukoencephalopathy
Progressive multifocal leukoencephalopathy is an opportunistic demyelinating brain infection caused by reactivation of JC virus in significantly immunosuppressed patients, most often with AIDS or on natalizumab, rituximab, or other immunomodulators. Diagnosis rests on MRI white matter lesions plus CSF JC virus PCR; there is no antiviral treatment, so management is restoring immune function.
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What this article covers
- Overview
Definition: progressive multifocal leukoencephalopathy (PML) is a subacute to progressive demyelinating disease of the central nervous system (CNS) caused by reactivation of JC (John Cunningham)…
- Epidemiology
Classic association with AIDS: historically the most common setting, occurring predominantly with CD4 counts below 200 cells/mcL; incidence fell after effective antiretroviral therapy (ART) became…
- Risk factors
Advanced HIV/AIDS with CD4 count under 200 cells/mcL is the classic and most common risk factor worldwide.
- Pathophysiology
JC virus establishes lifelong latency in the kidneys, bone marrow, and lymphoid tissue after childhood or early adult infection, seroprevalence in adults is high, and the virus is asymptomatic in nearly everyone who carries it.
- Clinical features
Progressive, usually painless, subacute neurologic decline over weeks to a few months is the typical tempo, though rapid progression to dementia or coma over a few weeks can occur.
- Differential diagnosis
HIV-associated dementia/encephalopathy: diffuse cognitive decline with diffuse atrophy and symmetric white matter change on MRI, lacking the discrete asymmetric multifocal lesions of PML.
- Diagnosis
Diagnosis is established by the combination of a compatible MRI pattern in an appropriately immunosuppressed host, confirmed by detection of JC virus DNA in the CSF; when CSF polymerase chain…
- Management
First action: identify and address the cause of immunosuppression, since no drug directly targets JC virus; the entire treatment strategy is restoring functional cell-mediated immunity.
- Complications
Permanent focal neurologic deficits (hemiparesis, visual field loss, cognitive impairment) even with successful immune reconstitution, reflecting irreversible demyelination and tissue loss in affected regions.
- Prognosis
Historically poor without immune recovery, with most untreated or unreversed cases progressing to death within a few months of diagnosis.
- Prevention
Effective, sustained antiretroviral therapy in HIV-positive patients, maintaining the CD4 count above 200 cells/mcL, is the single most effective preventive measure against HIV-associated PML.
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