Progressive multifocal leukoencephalopathy (PML)
What are the typical clinical features, diagnostic findings, and treatment for progressive multifocal leukoencephalopathy (PML)?
PML is an opportunistic infection of the CNS due to invasion of oligodendrocytes by the JC virus leading to demyelination.
The JC virus latently infects over half the population but does not cause disease unless a person is immunocompromised due to HIV, lymphoreticular malignancy, or immunosuppressive drugs, most significantly natalizumab for the treatment of multiple sclerosis.
Patients will present with deficits in the corticospinal tracts, gait abnormalities, memory or behavioral disturbance, or cortical sensory loss due to demyelination immediately below the cortex.
What are the diagnostic findings of progressive multifocal leukoencephalopathy
MRI shows T2 hyperintensity at the gray-white matter junction with little to no enhancement or mass effect. Lesions are common in the cerebrum but may be seen in the brain stem or cerebellum.
Basic studies of CSF such as cell counts and chemistries are typically nonspecific, and diagnosis is made by imaging in conjunction with JC virus, PCR, or biopsy if PCR is negative.
How is progressive multifocal leukoencephalopathy treated?
Prognosis remains poor. The disease may carry as high as a 50% mortality rate when due to HIV, with little recovery of deficits among survivors.
Management centers around immune reconstitution with cases due to AIDS optimized on ART and those due to natalizumab potentially undergoing plasma exchange to speed clearance of the medication.
Cases not due to AIDS may benefit from cytosine arabinoside. Immune reconstitution inflammatory syndrome (IRIS) may complicate the condition in those previously on natalizumab who have stopped treatment and AIDS patients newly on ART.
PML IRIS may result in fulminant clinical deterioration and MRI findings of contrast enhancement and mass effect.
Corticosteroids may be administered to reduce inflammation although the benefit is not clear.
Kranick SM, Nath A: Neurologic complications of HIV-1 infection and its treatment in the era of antiretroviral therapy. Continuum 18(6):1319-1337, 2012.