Table 1

Clinical and MRI features that may be considered in the differential diagnosis of MS and PML

FeatureMultiple sclerosisProgressive multifocal leukoencephalopathy
Clinical features
  • Over hours to days

  • Normally stabilises

  • Resolves spontaneously even without therapy

  • Over weeks

  • Progressive

 Clinical presentation
  • Diplopia

  • Paresthesia

  • Paraparesis

  • Optic neuritis

  • Myelopathy

  • Aphasia

  • Behavioural and neuropsychological alteration

  • Retrochiasmal visual deficits

  • Hemiparesis

  • Seizures

MRI features
 Aspect and location of new lesionsFocal, generally periventricular in location. Lesions occur in all areas of the brain particularly the corpus callosum and spinal cordDiffuse. Generally large >3 cm lesions in a unifocal, multifocal or widespread distribution. Subcortical location rather than periventricular. Affecting U fibres and extending into the gyrus. Cortical GM involvement in 50% of cases. Posterior fossa less frequent site. Spinal cord presentation rare
 BordersSharp edges; mostly round or flame shaped (especially periventricular lesions), confluent with other lesions; U-fibres may be involvedIrregular in shape. Ill-defined border toward the white matter, sharp border toward the cortical grey matter
 Mode of extensionInitially focal, lesions enlarge within days or weeks and later decrease in size within monthsLesion volume increases continuously, and sometimes rapidly to contiguous (multifocal) and non-contiguous regions (widespread) confined to white matter tracts, sparing the cortex
 Mass effectLarge acute lesions may have mass effectNo mass effect even in large lesions apart from when inflammatory response is present
 On T2-weighted sequenceHomogeneous hyperintensityDiffuse hyperintensity, little irregular signal intensity within the lesions, can have a punctate microcystic appearance. Small punctate T2 lesions may be seen in proximity to the lesion
 On T1-weighted sequenceAcute lesions: hypointense (due to oedema) or isointense. Increasing signal intensity over time in 80%; decreasing signal intensity (axonal loss) in about 20%Slightly hypointense at onset, with signal intensity decreasing over time in the affected area; no reversion to isointense signal intensity
 On FLAIR sequenceHyperintense, sharply delineatedFLAIR is the preferred sequence for PML diagnosis, because of the subcortical location
 Contrast enhancementAcute lesions: homogeneous nodular or ring enhancement, with sharp edges eventual resolution over 1–2 months. Chronic lesions: no enhancementLess than half of the cases to date have shown some enhancement at the time of presentation often with a patchy or punctate appearance. Rim enhancement at leading edge can be seen in larger lesions
 Diffusion-weighted imagingAcute lesions hyperintense. Chronic lesions isointense. Conforms to shape of lesions on FLAIR and T2WAcute PML lesions are hyperintense but not specific for PML. Helpful to detect new PML lesions within confluent areas of chronic WM disease. ADC maps not helpful
 AtrophyFocal atrophy possible, due to focal white-matter degeneration; no progressionNo focal atrophy initially, but can be seen in late stages of PML progression
  • It should be noted that none of the MRI features are pathognomonic of MS or PML. Adapted from Physician information and management guidelines for multiple sclerosis patients on Tysabri therapy, Biogen, V.14, 22 May 2015 (permission obtained).

  • ADC, Apparent diffusion coefficient; FLAIR, fluid-attenuated inversion recovery; GM, grey matter; MS, multiple sclerosis; PML, progressive multifocal leukoencephalopathy; T2W, T2 weighted; WM, white matter.