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Progressive Multifocal Leukoencephalopathy (PML)

Last Updated: October 1, 2018

Open Table of Contents: Progressive Multifocal Leukoencephalopathy (PML)

Figure 1: This AIDS patients initial imaging demonstrates a linear, T1 hypointense (top row left), FLAIR hyperintense (top row right) region within the subcortical white matter of the left dorsolateral frontal lobe with associated volume loss. There was minimal associated peripheral reduced diffusivity (second row left) and no significant contrast enhancement (second row right). Little was known about the patient when they presented to the ER and given their recent onset symptoms, a diagnosis of subacute infarction was made.

Followup examinations over the next several months demonstrated significant interval increase in T1 hypointense (third row left), FLAIR hyperintense (third row right) signal abnormality within the subcortical white matter extending to the lateral ventricle. The degree of adjacent reduced diffusivity continued to increase in size. The post-contrast images were without abnormal enhancement (bottom row left). The continued increase in size and degree of signal abnormality on multiple followup examinations raised concern of a glioma. Ultimately, the lesion was resected and demonstrated findings compatible with PML.


  • Opportunistic infection caused by JC polyomavirus


  • Hematogenous spread of JC virus or reactivation of latent brain lesion
  • Progressive demyelinating disorder that results from JC virus infection of the myelin-producing oligodendrocytes

Clinical Features

  • Symptoms
    • AMS, progressive neurological symptoms, headache, lethargy
  • Demographics

    • Associated with immune suppression
      • AIDS, post organ transplant, on chemotherapy or biologics (most commonly natalizumab, a common treatment for refractory multiple sclerosis)
  • Prognosis

    • 30-50% mortality rate in the first few months


  • General
    • Asymmetric, multifocal, demyelinating plaques involving the subcortical and deep white matter
    • Mass effect is unusual
    • Enhancement may be associated with improved survival rates
    • Evaluate pattern of enhancement. If increasing, this is suggestive of immune reconstitution syndrome.
  • Modality specific

    • CT
      • Asymmetric focal zone(s) of low attenuation that involve the periventricular and subcortical white matter
    • MR

      • T1WI
        • Hypointense
      • T2WI/FLAIR

        • Hyperintense
        • Involves the juxtacortical white matter
      • DWI

        • May demonstrate peripheral diffusion restriction in acute setting
      • Contrast

        • Faint peripheral enhancement may be present
      • MRS

        • Decreased NAA, increased lactate, choline and lipids
  • Imaging Recommendations

    • Standard protocol MR (including DWI) with intravenous contrast
  • Mimic

    • The appearance may be very similar to an infiltrative glioma and often has a similar time course and growth pattern. Striking T1 hypointensity and juxtacortical (without cortical) involvement often helps to distinguish.

For more information, please see the corresponding chapter in Radiopaedia, and the Progressive Multifocal Leukoencephalopathy chapter within the Cerebral Infectious Diseases sub-volume in the Neurosurgical Atlas.

Contributor: Sean Dodson, MD

DOI: https://doi.org/10.18791/nsatlas.v1.03.02.22


Donovan MJ, et al. Progressive Multifocal Leukoencephalopathy in AIDS: Are There Any MR Findings Useful to Patient Management and Predictive of Patient Survival. AJNR. 1999; 20:1896-1906.

Honce JM, et al. Neuroimaging of Natalizumab Complications in Multiple Sclerosis: PML and Other Associated Entities. Multiple Sclerosis International. 2015. http://dx.doi.org/10.1155/2015/809252

Rabelo NN, et al. Differential Diagnosis between Neoplastic and Non-Neoplastic Brain Lesions in Radiology. Arq Bras Neurocir. 2016. Doi: 10.1055/s-0035-1570362.

Smith AB, et al. Central Nervous System Infections Associated with Human Immunodeficiency Virus Infection; Radiologic-Pathologic Correlation. Radiographics. 2008; 28(7):2033-58.

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