The Spectrum of Atypical Inflammatory Demyelinating Syndromes of the Central Nervous System

The atypical demyelinating syndromes are a group of conditions, characterized pathologically by demyelination, that form part of the differential diagnosis of multiple sclerosis (MS), but differ from it due to variations in clinical presentation, MRI appearance, pathology, or response to treatment. The potential for some of these syndromes to overlap with conventional MS means that diagnostic uncertainties are common, and therapeutic decision-making focuses on whether to commence MS disease-modifying therapies (DMTs) or other immunosuppression. In this chapter, the spectrum of atypical demyelinating diseases is reviewed. We discuss the difficulties in diagnosing and distinguishing between conditions such as acute disseminated encephalomyelitis (ADEM), tumefactive demyelination, Baló’s concentric sclerosis, Marburg’s multiple sclerosis, and Schilder’s diffuse myelinoclastic sclerosis and contrast these conditions with conventional MS, neuromyelitis spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein-associated disease (MOGAD). Advances in magnetic resonance imaging (MRI) and immunobiology may prove useful in our future understanding of these conditions.