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Progressive multifocal leukoencephalopathy
Background
Overview
Definition
PML is a rare opportunistic infection of the CNS, caused by the reactivation of the ubiquitous John Cunningham virus in immunocompromised conditions.
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Pathophysiology
The John Cunningham virus predominantly infects oligodendrocytes in the brain, leading to their destruction. This lytic infection causes progressive demyelination, resulting in multiple lesions in the white matter of the brain.
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Epidemiology
The seroprevalence of of John Cunningham virus is estimated at 40-70% in adults. The incidence of PML in patients with HIV has declined since the introduction of antiretroviral therapy, dropping from 14.8 cases per 1,000 patients in 1996 to 0.8 cases per 1,000 patients in 2011.
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Risk factors
PML is associated with a variety of immunosuppressive therapies and conditions, including HIV, hematologic malignancies, organ transplantation, and the use of immunomodulatory therapies such as natalizumab, rituximab, and other monoclonal antibodies and anti-TNF therapy.
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Disease course
PML starts with a subacute onset of focal neurological deficits prgressing over weeks to months. Common symptoms and signs include motor weakness, cognitive deficits, dysarthria, aphasia, ataxia, behavioral and personality changes, and sensory deficits. Involvement of the optic nerve or spinal cord is rare.
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Prognosis and risk of recurrence
The prognosis of PML is generally poor, with a 3-month mortality rate of 20-50%. Many patients experience significant neurological deficits after treatments.
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Guidelines
Key sources
The following summarized guidelines for the evaluation and management of progressive multifocal leukoencephalopathy are prepared by our editorial team based on guidelines from the U.S. Department of Health and Human Services (DHHS 2025), the British Society for Rheumatology (BSR 2019), the American Academy of Neurology (AAN 2018), the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS/EAN 2018), and ...
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Screening and diagnosis
Medical management
Direct antiviral therapy: as per DHHS 2025 guidelines, recognize that there is no effective direct-acting antiviral therapy for the prevention or treatment of JC virus infection or PML.
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Antiretroviral therapy
Corticosteroids
Therapies with no evidence for benefit