A progressive disorder due to infection with the JC virus, a human polyoma virus; characterized pathologically by multifocal areas of demyelination of varying size distributed throughout the CNS but sparing the spinal cord and optic nerves. In addition, there are characteristic cytologic alterations in both astrocytes and oligodendrocytes. Pts often present with visual deficits (45%), typically a homonymous hemianopia, and mental impairment (38%) (dementia, confusion, personality change), weakness, and ataxia. Seizures occur in ~20% of patients. Almost all pts have an underlying immune disorder or are receiving immunosuppressive therapy. More than 80% of currently diagnosed PML cases occur in pts with AIDS; it has been estimated that up to 5% of AIDS pts will develop PML. Immunosuppressant drugs such as natalizumab have also been associated with PML.
MRI reveals multifocal asymmetric, coalescing white matter lesions located periventricularly, in the centrum semiovale, in the parietal-occipital region, and in the cerebellum. These lesions have increased T2 and decreased T1 signal, are generally nonenhancing (rarely they may show ring enhancement), and are not associated with edema or mass effect. CT scans, which are less sensitive than MRI for the diagnosis of PML, often show hypodense nonenhancing white matter lesions.
The CSF is typically normal, although mild elevation in protein and/or IgG may be found. Pleocytosis occurs in <25% of cases, is predominantly mononuclear, and rarely exceeds 25 cells/µL. PCR amplification of JC virus DNA from CSF has become an important diagnostic tool. A positive CSF PCR for JC virus DNA in association with typical MRI lesions in the appropriate clinical setting is diagnostic of PML. Pts with negative CSF PCR studies may require brain biopsy for definitive diagnosis as sensitivity of this test is variable; JC virus antigen and nucleic acid can be detected by immunocytochemistry, in situ hybridization, or PCR amplification on tissue. Detection of JC virus antigen or genomic material should be considered diagnostic of PML only if accompanied by characteristic pathologic changes, since both antigen and genomic material have been found in the brains of normal pts. Serologic studies are of no utility for diagnosis given high basal seroprevalence level, but are extremely useful for risk stratification in pts contemplating therapy with certain immunomodulatory drugs such as natalizumab.
Treatment: Progressive Multifocal Leukoencephalopathy
Ps suspected of having PML who are receiving immunomodulatory antibodies should have therapy halted and circulating antibodies cleared by plasma exchange; discontinuation of therapy may lead to transient clinical and radiologic worsening, termed immune reconstitution inflammatory syndrome (IRIS). |
For a more detailed discussion, see Roos KL, Tyler KL: Meningitis, Encephalitis, Brain Abscess, and Empyema, Chap. 164, p. 883, in HPIM-19; and HPIM-19 chapters covering specific organisms or infections. |
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