Table 1

Basic MRI features of infectious and non-infectious adverse events during multiple sclerosis (MS) therapies

	Location	Shape/appearance	MRI sequences
JCV
PML	Juxtacortical WM, infiltrating adjacent GM Extending in deep WM Can start in cortical or deep GM Infratentorial in 10%	Unifocal or multifocal, later diffuse/confluent Spreading via WM tracts Punctate lesions with perivascular distribution Microcystic appearance on T2 Later: development of PML-IRIS: patchy/punctuate contrast enhancement lesion border and swelling	T2/FLAIR hyperintense T1 isointense or hypointense (especially later as demyelinisation progresses) Contrast enhancement in 30%
GCN	Cerebellum Sometimes concomitant PML lesions (infratentorial and/or supratentorial)	Cerebellar atrophy Sometimes ‘hot cross bun sign’	T1 and T2 shows atrophy T2 and FLAIR show ‘hot cross bun sign’ T2 and FLAIR show PML lesions
Herpesviruses
HSE	Temporal lobe(s)/insular in 80% Extratemporal in 55%: brainstem, cerebellum, cortical or a combination	Starting in cortex, spreading along limbic pathways Later spreading parietal, occipital, brainstem	T2/FLAIR hyperintense and T1 hypointense
VZV	Meninges Cortex/parenchyma Spinal cord Large and small intracranial vessels or a combination of the above	Meningitis Cortical/parenchymal lesions (encephalitis) Myelitis Irregularities and dilation (vasculopathy) of large vessels, and ischaemic lesions	Meningeal contrast enhancement T2/FLAIR hyperintense cortex/parenchyma MRA vasculopathy, DWI/ADC map ischemia
Cryptococcus	Meninges Parenchymal gelatinous pseudocysts Parenchymal cryptococcomas in mesencephalon and basal ganglia	Meningitis in 69% Dilated perivascular spaces Hydrocephalus Gelatinous pseudocysts: ‘soap bubble’ appearance Single or multiple round cryptococcoma masses	Meningeal contrast enhancement Cryptococcomas and pseudocysts T2 and FLAIR hyperintense and T1 hypointense Cryptococcomas homogeneous or ring enhancement
Listeriosis	Brainststem, cerebellum and/or thalamus	Subcortical abscesses in the thalamus, pons and medulla Cerebritis	T2/FLAIR hyperintense T1 hypointense or isointense DWI hyperintense ADC map hypointense Ring enhancement and/or cranial nerve enhancement
Nocardiosis	Brain parenchyma Meninges	Parenchymal brain abscess (often multiple) Meningitis	T1 with rim enhancement Diffusion restriction (including low ADC) Meningeal contrast enhancement
RCVS	Infarcts and haemorrhage typically in watershed areas Infarcts usually bilateral and symmetrical Oedema in posterior regions	Cerebral infarction (39%) Convexity SAH (34%) Lobar haemorrhage (20%) Oedema resembling PRES	Fitting ischaemia, SAH or lobar haemorrhage ‘String of beads’ on vascular imaging; bilateral narrowing of all intracerebral arteries
PRES	Bilateral parieto-occipital region in 70% Also frequently superior frontal sulcus or watershed pattern	Vasogenic oedema	T2/FLAIR hyperintense ADC hyperintense Contrast enhancement in 20%
PCNSL	Cerebral hemispheres (38%) Basal ganglia and thalamus (16%) Corpus callosum (14%)	Mostly a single lesion (65%) Often near CSF Moderate perifocal oedema	Often contrast enhancement T2/FLAIR often isointense but shows perifocal oedema
TDL	Mostly supratentorial in frontal and parietal lobes	Large lesions Mass effect (45%) Oedema (77%)	T2/FLAIR hyperintense T2 hypodense ring surrounding lesion Almost always contrast enhancement (eg, open-ring enhancement)

Cerebrovascular events (in patients treated with alemtuzumab) are not included in this table due to the diversity of reported events in patients treated with alemtuzumab, which on its own are radiologically similar to those seen in patients with a primarily cardiovascular cause for the event.
ADC, apparent diffusion coefficient; CSF, cerebral spinal fluid; DWI, diffusion weighted imaging; FLAIR, fluid attenuation inversion recovery; GCN, granule cell neuronopathy; GM, grey matter; IRIS, immune reconstitution inflammatory syndrome; JCV, JC virus; MRA, magnetic resonance angiography; PCNSL, primary central nervous system lymphoma; PML, progressive multifocal leukoencephalopathy; PRES, posterior reversible encephalopathy syndrome; RCVS, reversible cerebral vasoconstriction syndrome; SAH, subarachnoidal haemorrhage; TDL, tumefactive demyelinating lesion; WM, white matter.