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Progressive multifocal leukoencephalopathy

Last updated: September 17, 2021

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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.”

A demyelinating disease of the central nervous system caused by the JC virus

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 [2]

Symptoms due to PML are insidious in onset and can progress over several weeks. [1]

Approach

Neuroimaging findings [1][3]

Laboratory studies [3]

Brain biopsy and histology [3]

Brain biopsy and histology is the gold standard test for CML but is not routinely performed as it is associated with a significant risk of complications.

  • Treatment is mainly supportive (e.g., treatment of seizures).
  • Patients with HIV
    • Start ART immediately.
    • For those already taking ART, optimize regimes to improve immune status.
  • Monitor for IRIS, which may cause a paradoxical worsening of PML.

References: [1]

PML typically progresses rapidly and is associated with high mortality.

  1. Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-opportunistic-infection/introduction?view=full. Updated: August 18, 2020. Accessed: December 18, 2020.
  2. Berger JR, Aksamit AJ, Clifford DB, et al. PML diagnostic criteria: Consensus statement from the AAN Neuroinfectious Disease Section. Neurology. 2013; 80 (15): p.1430-1438. doi: 10.1212/wnl.0b013e31828c2fa1 . | Open in Read by QxMD
  3. Smith AB, Smirniotopoulos JG, Rushing EJ. Central Nervous System Infections Associated with Human Immunodeficiency Virus Infection: Radiologic-Pathologic Correlation. RadioGraphics. 2008; 28 (7): p.2033-2058. doi: 10.1148/rg.287085135 . | Open in Read by QxMD
  4. Anand P, Hotan GC, Vogel A, Venna N, Mateen FJ. Progressive multifocal leukoencephalopathy. Neurol Neuroimmunol Neuroinflamm. 2019; 6 (6): p.e618. doi: 10.1212/nxi.0000000000000618 . | Open in Read by QxMD
  5. White MK, Khalili K. Pathogenesis of Progressive Multifocal Leukoencephalopathy—Revisited. J Infect Dis. 2011; 203 (5): p.578-586. doi: 10.1093/infdis/jiq097 . | Open in Read by QxMD