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.

Progressive Multifocal Leukoencephalopathy Imaging Evolution

Optimal management of PML depends on timely and accurate diagnosis that requires an understanding of the disease’s temporal evolution. Fortunately, the combination of characteristic imaging features and appropriate laboratory tests can be used to confidently diagnose PML.

PML can be conceptually organized into early and late stages ( Table 12.1 ). Early PML begins as single or multifocal round or oval white matter lesions (WMLs). The lesions are asymmetric in distribution and most commonly are located in the parietal and occipital lobes, as well as the corpus callosum ( Fig. 12.1 ). Involvement of the arcuate or U-fibers forms a sharp or scalloped border between the lesions and the cortex. There is no significant mass effect or enhancement, and the lesions typically spare the periventricular white matter. Restricted diffusion may rarely be seen in very small acute lesions and more commonly along the advancing edge of larger lesions corresponding to areas of active infection and subsequent demyelination ( Fig. 12.2 ). In late PML with disease progression, the lesions become larger and more confluent and atrophy can be seen. The lesions tend to follow white matter tracts.

TABLE 12.1

Progressive Multifocal Leukoencephalopathy (PML) Temporal Evolution

	Early PML	Late PML
Lesion Size	Small	Large
Lesion Number	Single to a few	Multiple
Atrophy	None	Mild
Mass Effect	None	None
Enhancement	None	None to minimal
Distribution	Asymmetric, separate lesions	Asymmetric, more confluent