Progressive Multifocal Leukoencephalopathy

Introduction

Progressive multifocal leukoencephalopathy (PML) is an opportunistic subacute demyelinating infection of the central nervous system (CNS) first described in 1958. The causative agent is the polyomavirus JC that has tropism for oligodendrocytes. Asymptomatic primary infection occurs in childhood, with the virus remaining latent in the kidneys and lymphoid tissue. With profound cellular immunosuppression, the virus reactivates and spreads to the CNS.

Presenting symptoms from most to least common include limb weakness, cognitive deficits, speech and visual difficulties, ataxia, seizures, and headache. The preferred diagnostic method is cerebral spinal fluid polymerase chain reaction (CSF PCR) for detection of JC virus DNA. However, since the introduction of highly active antiretroviral therapy (HAART), more PML patients are now negative for JC virus DNA in their CSF. Stereotactic brain biopsy remains the reference standard for diagnosis.

PML occurs almost exclusively in immunosuppressed patients, including those with AIDS (79%), hematologic malignancies (13%), organ transplants (5%), and autoimmune diseases on immunosuppressive therapy (3%). PML has rarely been reported in patients with occult immunosuppression such as hepatic cirrhosis and renal failure. Both the incidence and mortality of PML has decreased since the introduction of HAART. Although there is no specific treatment for PML, restoration of the host adaptive immune response has been shown to prolong survival.