Multiple sclerosis mimics that you do not want to miss in the context of 2024 McDonald criteria

Multiple Sclerosis (MS) is a highly heterogenic disorder, including radiologically isolated syndrome (RIS) with no clinical symptomatology, clinically isolated syndrome (CIS), typical relapsing-remitting or progressive course, aggressive, and even tumefactive cases. The latest version of the diagnostic McDonald criteria (2024) enables MS diagnosis as early as in RIS if specific conditions are fulfilled. New magnetic resonance imaging (MRI) biomarkers, namely central vein sign (CVS) and paramagnetic rim lesions (PRLs), have been included in the criteria to prevent false positive diagnoses. However, CVS and PRLs are not definitive MS biomarkers, lacking complete specificity (because CVS may occur, albeit less frequently, in lesions associated with small vessel disease or Behçet's disease) or sensitivity (because only half of MS patients will have at least one PRL per scan). Early diagnosis prompts early disease-modifying treatment (DMT). Therefore, now more than ever, clinicians should focus on careful exclusion of other pathologies that may mimic MS, to ascertain appropriate treatment. This review focuses on a selection of non-infectious MS mimics that must be considered when applying the 2024 McDonald criteria to patients with MRI or clinical findings suggestive of MS. Differentiating characteristics are updated and discussed in the context of MRI biomarkers and, as with diseases with optic nerve involvement, in the context of the newly added fifth typical MS topography (optic nerve).