Black holes

Black holes are defined as areas with unequivocal hypointensity compared with normal-appearing WM and GM matter on T1-weighted images obtained with spin-echo sequences at 1.5 T and have a corresponding T2-hyperintense WM lesion. Black holes are classified as acute or chronic (persistent or permanent). Whereas acute black holes reflect transient edema and inflammation, chronic black hole are those T1-hypointesities persisting ≥6 months after their first appearance on MRI and are characterized, pathologically, by severe demyelination and axonal loss.126,127

Diffuse spinal cord abnormalities

Abnormal areas of subtle increases of signal intensity on PD-weighted or STIR images, between that of focal lesions and normal-appearing spinal cord, lacking well-demarcated borders from adjacent normal-appearing cord.128

Slowly expanding lesions

Pathologically, slowly expanding (also known as chronic active or smoldering) lesions represent up to 57% of chronic lesions (although credible estimates are in the range of 25%). They are often characterized by a ‘rim’ of iron-laden activated microglia/macrophages, although not in all lesions,98 and signs of peripheral slow but ongoing demyelination and axonal loss around an inactive core without substantial BBB damage, thus reflecting a compartmentalized pathological process.79,81,94 Slowly expanding lesions have been investigated in vivo in lesions that progressively increase in size and show a paramagnetic rim on susceptibility-based MRI,85,94–96 corresponding, pathologically, to peripheral iron-laden microglia, or by evaluating the gradual expansion on conventional T1- and T2-weighted sequences of lesions showing a progressive decline of T1-hypointensity.97,100

Dirty-appearing white matter

DAWM (or diffusely abnormal WM) is defined as area with ill-defined borders and with signal intensity on T2- and/or PD-weighted MRI between that of focal WM lesions and the surrounding normal-appearing WM and isointense to the signal of the nearby cortical GM.62–64 Typically, DAWM is noted in the periventricular regions especially parieto-occipital or in the centrum semiovale. Pathologically, DAWM is characterized by inflammatory infiltrates, BBB disruption, demyelination, gliosis and axonal loss, which are less severe compared to focal WM lesions.129

Abbreviations: BBB=blood-brain barrier; DAWM=dirty-appearing white matter; GM=gray matter; MRI=magnetic resonance imaging; PD=proton density; STIR=short tau inversion recovery.