Increasing role of imaging in differentiating MS from non-MS and defining indeterminate borderline cases

Multiple sclerosis (MS) is a heterogenous condition with differences between patients regarding disease presentation, imaging features, disease activity, prognosis and treatment responses. Following the discovery of new biomarkers, the concept of MS has evolved, with syndromes previously considered to be its variants now recognised as separate entities, including aquaporin-4 (AQP4)-antibody (Ab) neuromyelits optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein (MOG)-Ab disease (MOGAD). In line with their distinct pathology, the newly emerging conditions have imaging characteristics which are dissimilar to typical MS. Progress in reclassifying such demyelinating CNS conditions has highlighted the challenge in meaningful categorisation of atypical presentations at the borders of MS, such as antibody-negative neuromyelitis optica-like syndromes, tumefactive demyelinating lesions, or Balo's concentric sclerosis. In this review, we discuss the increasing role of imaging in distinguishing MS from non-MS CNS inflammatory/demyelinating conditions and defining undetermined borderline cases. This progress relies both on better characterisation of imaging features of these conditions on conventional imaging in terms of their appearance and location, as well as on the implementation of novel image acquisition and/or post-processing techniques allowing for more in-depth lesion assessment, including the presence of a central vein sign or paramagnetic rim.