Elsevier

Clinical Radiology

Volume 65, Issue 6, June 2010, Pages 431-439
Clinical Radiology

Review
Imaging manifestations of progressive multifocal leukoencephalopathy

https://doi.org/10.1016/j.crad.2010.03.001Get rights and content

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease caused by reactivation of JC virus in immunosuppressed patients. The diagnosis is usually suggested on imaging and confirmed by cerebrospinal fluid polymerase chain reaction (PCR) for JC virus DNA. In this article, we review the imaging manifestations of PML on computed tomography (CT), magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI), MR spectroscopy, single photon-emission computed tomography (SPECT) and positron-emission tomography (PET), and outline the role of imaging in follow-up and prognostication.

Introduction

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease caused by the reactivation of JC virus in immunocompromised patients. The name JC virus was derived from the initials of the patient from whose brain the virus was first isolated.1

Histopathologically, PML is characterized by extensive and progressive demyelination with notable absence of significant inflammatory response. The affected oligodendrocytes are enlarged and contain prominent intranuclear inclusion bodies.

With improved survival of immunocompromised patients and increased use of immunomodulatory medications for autoimmune/inflammatory diseases, radiologists are now more likely to encounter PML in routine clinical practice. The diagnosis is frequently considered for the first time based on imaging findings. Novel, more effective therapies for acquired immunodeficiency syndrome (AIDS) and PML have not only improved survival but have also altered the expected imaging features in PML. Newer imaging modes like diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI), and magnetization transfer technique are being used to assess treated PML patients. In this article, we present a review of PML focusing on the radiological aspects of the disease.

Section snippets

Epidemiology

PML was originally described in patients with chronic diseases associated with compromised immune response, such as lymphoma, leukaemia, sarcoidosis, tuberculosis, and in patients with renal transplants during immunosuppressive therapy.2, 3, 4 A surge in PML occurred in the 1980s with the AIDS pandemic.5 PML has also been described in patients with many rheumatic and autoimmune diseases.6, 7 Immunosuppressive drugs related to development of PML include corticosteroids, chemotherapeutic agents,

Clinical features and diagnosis

Clinical symptoms and signs of PML are nonspecific. PML can be the initial AIDS-defining illness in up to 25% cases.21 Limb weakness, cognitive deficits, speech and visual difficulties, ataxia, seizures, and headache are the reported presenting symptoms, from most to least common.

Stereotactic brain biopsy is the reference standard for diagnosis, but it is not the preferred method due to its invasive nature. Cerebrospinal fluid polymerase chain reaction (CSF-PCR) for JC virus DNA is the method

CT

CT abnormalities in PML were first described in 1977. On CT, low-density lesions of central and convolutional white matter with scalloped borders are typically seen (Fig. 1). Lesions demonstrate no mass effect or contrast enhancement. With disease progression, PML lesions may show enlargement on CT, however, the temporal evolution of CT findings often lags behind the rate of clinical progression.30, 31 CT is less sensitive than magnetic resonance imaging (MRI) in the initial stages of PML.

MRI

The

Summary

The diagnosis of PML should be considered in any patient with immunosuppression who has multifocal white matter lesions with absence of mass effect and no or minimal contrast enhancement. Knowledge of typical and atypical imaging features of PML can be helpful in differential diagnosis from other infections and tumours that are also common in these patient populations. DWI, MR spectroscopy, and magnetization transfer have a complementary role to conventional MRI in terms of lesion

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      MRI lesions appear hypointense on T1w images and hyperintense on T2w and FLAIR images, with borders less defined toward the WM [7,15–19]. DWI characteristics are phase-specific: the advancing edge of the newer lesions shows diffusion restriction on DWI due to oligodendrocytes swelling and a low ADC, but progressively DWI signal decreases, ADC value increases, and Diffusion Tensor Imaging (DTI) shows an increased diffusivity with decreased anisotropy [16,20–22]. PML lesions classically do not exhibit mass effect, nor contrast enhancement, although punctate and/or rim-like contrast enhancement has been described both in HIV-positive and HIV-negative PML patients [17–19,23].

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