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  • Review Article
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Progressive multifocal leukoencephalopathy and other forms of JC virus disease

Nature Reviews Neurology volume 6, pages 667–679 (2010)Cite this article

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Abstract

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the brain caused by the JC virus (JCV). PML usually occurs via reactivation of JCV when an immune system becomes compromised. A diagnosis of PML is normally made on the basis of distinguishing neurological features at presentation, characteristic brain MRI changes and the presence of JCV DNA in cerebrospinal fluid. PML has a 3 month mortality rate of 20–50%, so prompt intervention is essential. Currently, reconstitution of the immune system affords the best prognosis for this condition. When PML is first suspected, and where possible, immunosuppressant or immunomodulatory therapy should be suspended or reduced. If PML is associated with a protein therapy that has a long half-life the use of plasma exchange to accelerate the removal of the drug from the circulation may aid the restoration of immune system function. Rapid improvements in immune function, however, might lead to transient worsening of the disease. In this Review, we critically appraise the controversies surrounding JCV infection, and provide practical management guidelines for PML.

Key Points

  • Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the brain caused by the JC virus (JCV), and is predominantly associated with HIV infection and immunomodulatory therapies

  • A diagnosis of PML is based on neurological signs at presentation, an MRI scan that is consistent with PML, and the presence of JCV DNA in cerebrospinal fluid

  • When possible, a suspicion of PML should prompt suspension or reduction of immunosuppressant therapy, and the patient should have a thorough neurological assessment by a physician with neurological experience

  • Reconstitution of the immune system is associated with the best PML prognosis

  • Patients who have received immune system reconstitution therapy should be carefully monitored, as they can develop immune reconstitution inflammatory syndrome (IRIS)

  • When IRIS is suspected to be the cause of neurological deterioration, corticosteroid treatment should be considered

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Figure 1: Proposed disease course of PML.
Figure 2: FLAIR images showing progression of progressive multifocal leukoencephalopathy immune reconstitution inflammatory syndrome.

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Acknowledgements

N. W. S. Davies receives funding from the Peel Medical Trust. Laurie Barclay, freelance writer and reviewer, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the MedscapeCME-accredited continuing medical education activity associated with this article.

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Authors and Affiliations

  1. Department of Neurology and St Vincent's Center for Applied Medical Research, St Vincent's Hospital and University of New South Wales, Victoria Street, Sydney, 2010, NSW, Australia

    Bruce J. Brew & Nicholas W. S. Davies

  2. Department of Infectious Diseases, San Raffaele Scientific Institute, via Stamira d'Ancona 20, Milan, 20132, Italy

    Paola Cinque

  3. Departments of Neurology and Medicine, Washington University, 660 South Euclid, Campus Box 8111, St Louis, 63110, MO, USA

    David B. Clifford

  4. Department of Neurology, Johns Hopkins University, Pathology Building Room 509, 600 North Wolfe Street, Baltimore, 21287, MD, USA

    Avindra Nath

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  1. Bruce J. Brew
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Contributions

B. J. Brew, N. W. S. Davies and A. Nath researched the data for the article, provided substantial contributions to discussions of the content, and contributed to writing the article and to review and editing of the manuscript before submission. D. B. Clifford researched the data for the article and provided substantial contributions to discussions of the content, and contributed to review and editing of the manuscript before submission. P. Cinque researched the data for the article and provided substantial contributions to discussions of the content.

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Correspondence to Bruce J. Brew.

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Competing interests

B. J. Brew has received honoraria from Biogen Idec, GlaxoSmithKline for consulting. He has also received research funding from GlaxoSmithKline and NeurogesX. P. Cinque has received honoraria from Biogen Idec, GlaxoSmithKline for lectures. She has also received research funding from Biogen Idec. D. B. Clifford has received honoraria from Biogen Idec, Elan, Genentech, Genzyme, GlaxoSmithKline, Millennium Pharmaceuticals, Novartis, Roche, Schering-Plough for consulting. He has also received research funding from Bavarian Nordic, Centocor Ortho Biotech, NeurogesX, Novartis, Pfizer, Savient Pharmaceuticals, Schering-Plough and Tibotec. A. Nath has received honoraria from Biogen Idec for consulting. N. W. S. Davies declares no competing interests.

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Brew, B., Davies, N., Cinque, P. et al. Progressive multifocal leukoencephalopathy and other forms of JC virus disease. Nat Rev Neurol 6, 667–679 (2010). https://doi.org/10.1038/nrneurol.2010.164

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