Table 1

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

Feature	Multiple sclerosis	Progressive multifocal leukoencephalopathy
Clinical features
Onset	Acute	Subacute
Evolution	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 lesions	Focal, generally periventricular in location. Lesions occur in all areas of the brain particularly the corpus callosum and spinal cord	Diffuse. 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
Borders	Sharp edges; mostly round or flame shaped (especially periventricular lesions), confluent with other lesions; U-fibres may be involved	Irregular in shape. Ill-defined border toward the white matter, sharp border toward the cortical grey matter
Mode of extension	Initially focal, lesions enlarge within days or weeks and later decrease in size within months	Lesion volume increases continuously, and sometimes rapidly to contiguous (multifocal) and non-contiguous regions (widespread) confined to white matter tracts, sparing the cortex
Mass effect	Large acute lesions may have mass effect	No mass effect even in large lesions apart from when inflammatory response is present
On T2-weighted sequence	Homogeneous hyperintensity	Diffuse 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 sequence	Acute 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 sequence	Hyperintense, sharply delineated	FLAIR is the preferred sequence for PML diagnosis, because of the subcortical location
Contrast enhancement	Acute lesions: homogeneous nodular or ring enhancement, with sharp edges eventual resolution over 1–2 months. Chronic lesions: no enhancement	Less 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 imaging	Acute lesions hyperintense. Chronic lesions isointense. Conforms to shape of lesions on FLAIR and T2W	Acute 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
Atrophy	Focal atrophy possible, due to focal white-matter degeneration; no progression	No 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.