CME information and disclosures![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
To see contributor disclosures related to this article, hover over this reference: [1]
Physicians may earn CME/MOC credit by reading information in this article to address a clinical question, and then completing a brief evaluation, in which they will identify their question and report the impact of any information learned on their clinical practice.
AMBOSS designates this Internet point-of-care activity for a maximum of 0.5 AMA PRA Category 1 Credit(s)™. Physicians should claim only credit commensurate with the extent of their participation in the activity.
For answers to questions about AMBOSS CME, including how to redeem CME/MOC credit, see “Tips and Links” at the bottom of this article.
Summary![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
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.”
Definition![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
A demyelinating disease of the central nervous system caused by the JC virus
Epidemiology![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
- Mainly in patients with severe immunosuppression (e.g., patients with lymphoma/leukemia, patients that received organ transplantation)
- In patients with HIV [2]
Epidemiological data refers to the US, unless otherwise specified.
Etiology![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
-
Reactivation of JC virus in the setting of immunosuppression due to: [2]
- HIV infection (AIDS-defining opportunistic infection)
- Hematological and solid cancers
- Inflammatory diseases
- Treatment with immunosuppressants or immunomodulators: e.g., natalizumab, rituximab
Pathophysiology![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
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 [3]
Clinical features![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
Symptoms due to PML are insidious in onset and can progress over several weeks. [2]
- Focal neurologic deficits: e.g., hemiplegia, aphasia, ataxia
- Seizures
- Impaired attention
- Vision alterations, most commonly hemianopsia
- Isolated encephalopathy, dementia, altered mental state, and behavioral changes are uncommon but may occur alongside focal neurological deficits.
Diagnostics![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
Approach
- 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
- Inconclusive neuroimaging findings and/or atypical clinical features
- Before initiating ART in patients with PML as the initial manifestation of HIV infection
- For prognostication
Neuroimaging findings [2][4]
-
MRI brain without and with gadolinium contrast (preferred)
- Multifocal, bilateral, asymmetric white matter lesions (hypointense on T1, hyperintense on T2) without mass effect
- Frontal, parietal and occipital lobes are mostly commonly involved.
- Lesions may exhibit faint contrast enhancement
-
CT brain with contrast [5]
- Focal, asymmetric hypodense white matter lesions without mass effect
- Contrast enhancement in the periventricular and subcortical white matter seen in rare cases
Laboratory studies [4]
- Screen for HIV if HIV status is unknown.
- CD4 count: for patients with HIV: typically < 200 [4]
- CSF analysis
Brain biopsy and histology [4]
Brain biopsy and histology is the gold standard test for PML but is not routinely performed as it is associated with a significant risk of complications.
- Indications: Consider when there is incongruence between clinical findings, imaging, and/or CSF.
-
Findings: The classic triad consists of
- Demyelination of axons
- Enlarged oligodendrocyte nuclei with intranuclear inclusions
- Bizarre astrocytes
Treatment![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
Prognosis![toggle arrow icon](https://manus-media.amboss.com/icons/chevron_up.svg)
PML typically progresses rapidly and is associated with high mortality.
- Patients without HIV: Median survival is 3 months. [6]
- Patients with HIV: One-year survival is ≥ 50% (with antiretroviral therapy). [6]