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Progressive multifocal leukoencephalopathy is a slow virus infection that usually occurs in patients with impaired cell-mediated immunity. It produces subacute and progressive CNS demyelination, multifocal neurologic deficits, and death, usually within a year. Diagnosis is with contrast-enhanced CT or MRI plus CSF PCR. Treatment is supportive.

Progressive multifocal leukoencephalopathy (PML) is probably caused by reactivation of the JC virus, a ubiquitous human papovavirus that is typically acquired during childhood and remains latent in the kidneys and possibly other sites (eg, mononuclear cells, CNS). The reactivated virus has a tropism for oligodendrocytes. Most patients have depressed cell-mediated immunity due to AIDS (the most common risk factor), reticuloendothelial system disorders (eg, leukemia, lymphoma), or other conditions (eg, Wiskott-Aldrich syndrome, organ transplantation). The risk in AIDS increases with increasing HIV viral load; prevalence of PML has decreased because of widespread use of more effective antiretrovirals.

Symptoms and Signs

Clumsiness may be the 1st symptom. Hemiparesis is the most common finding. Aphasia, dysarthria, and hemianopia are also common. Multifocal cortical damage produces cognitive impairment in ²⁄₃ of patients. Sensory, cerebellar, and brain stem deficits may be present. Occasionally, transverse myelitis develops. Headaches and convulsive seizures are rare and occur most often in patients with AIDS. Gradual, relentless progression culminates in death, usually 1 to 9 mo after symptoms begin.

Diagnosis and Treatment

PML is suspected in patients with unexplained progressive brain dysfunction, particularly in those with depressed cell-mediated immunity. Contrast-enhanced MRI or CT is done and may strongly suggest PML, showing single or multiple white matter lesions. MRI shows hyperintense T-2–weighted images. A contrast agent enhances, usually faintly and peripherally, 5 to 15% of lesions. CT usually shows low-density, nonenhancing lesions. CSF is analyzed for JC viral antigen using PCR; a positive result with compatible neuroimaging findings is nearly pathognomonic. Routine CSF analysis is usually normal. Serologic tests are not helpful. Stereotaxic biopsy can provide a definitive diagnosis but is rarely warranted.

Treatment is supportive. Cidofovir Some Trade Names
VISTIDE
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and other antivirals are under study but do not appear to provide much benefit. Patients with AIDS may improve as antivirals reduce the HIV viral load.

Last full review/revision November 2005

Content last modified November 2005