Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by the reactivation of a ubiquitous polyomavirus JC (JCV). PML was for many years a rare disease occurring only in patients with underlying severe impaired immunity.

Over the past three decades, the incidence of PML has significantly increased related to the AIDS (acquired immunodeficiency syndrome) pandemic and, more recently, to the growing use of immunosuppressive drugs. The clinical presentation of PML is variable with neurological symptoms corresponding to affected cerebral areas. Usually, the clinical outcome of patients with PML is poor with an inexorable progression to death within 6 months of symptom onset. Although PML usually requires a brain biopsy or autopsy for confirmation, radiological imaging and a demonstration of JCV-DNA in the CSF (cerebrospinal fluid) provide supportive evidence for the diagnosis. Although there is no proven effective therapy for PML, patients with HIV (human immunodeficiency virus)-related PML may benefit significantly from HAART (highly active antiretroviral therapy).

An independent adjudication committee (IAC) determined that patients whose evaluation fulfilled all three of the following criteria would receive a diagnosis of confirmed PML: progressive clinical disease, MRI findings typical of PML, and detectable JC virus DNA in the cerebrospinal fluid.

Progressive clinical course of disease "clinical vigilance"

• Cognitive impairments
• Motor dysfunctions
• Visual deficits

Neuroradiologic evidence from MRI or CT

• Subcortical white matter lesions
• Non-contrast enhancing

Laboratory detection of JCV DNA or protein in CSF

• PCR analysis of CSF
• In situ DNA hybridization in brain tissue
• In situ immunocytochemistry in brain tissue

References:

1. Yousry TA, Major EO, Ryschkewitsch C, Fahle G, Fischer S, Hou J, Curfman B, Miszkiel K, Mueller-Lenke N, Sanchez E, Barkhof F, Radue EW, Jäger HR, Clifford DB. Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy. N Engl J Med. 2006 Mar 2;354(9):924-33. [Medline]
2. Weber T. Progressive multifocal leukoencephalopathy. Neurol Clin. 2008 Aug;26(3):833-54 [Medline]

Created: Jan 20, 2010