Diagnostic Approach to Presumptive Demyelinating Solitary CNS Lesions

OBJECTIVE: This article focuses on diagnostic approaches to solitary lesions in the central nervous system with a presumed demyelinating etiology. LATEST DEVELOPMENTS: A greater understanding of the broad spectrum of presentations of multiple sclerosis overlap conditions, aquaporin-4 neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has combined with improvements in MRI to better define the characteristics of solitary demyelinating lesions, leading to more accurate diagnosis. ESSENTIAL POINTS: Diagnosing a single demyelinating lesion in the supratentorial brain, brainstem, or spinal cord requires careful consideration of clinical, radiologic, and laboratory data. A key approach is to establish whether a solitary lesion may be part of a presentation seen in multiple sclerosis or other conditions that overlap with multiple sclerosis, such as tumefactive demyelination or solitary sclerosis, or whether it could be due to NMOSD or MOGAD. This article presents clues to the diagnosis of a presumed solitary demyelinating lesion and draws attention to important nondemyelinating conditions that can form the differential diagnosis at each of these sites in the central nervous system.