Recognition and management of acute relapse of multiple sclerosis, neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody-associated disease.

Autoimmune diseases of the central nervous system include multiple sclerosis (MS) and an ever-expanding spectrum of related disorders, such as neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Despite differences in targeted neuroantigens and immune effector mechanisms, these disorders share a common clinical pattern: acute neurological episodes, typically termed attacks at the onset, and relapses during the disease course. Timely recognition of an acute attack or relapse is challenging, not only because of discrepancies between patient-reported and physician-affirmed neurological symptoms, but also due to other confounding factors, such as comorbidities, treatment-related side effects, and transient symptom fluctuations unrelated to underlying disease. Once an attack/relapse is recognized, prompt initiation of treatment is essential, as responsiveness to treatment at the acute stage largely determines the long-term neurological outcomes. In this review, we focus on MS, NMOSD and MOGAD, and discuss the clinical patterns of acute attacks and relapses, including the clinical and para-clinical modalities that are critical for timely recognition and diagnosis. We present the available evidence regarding treatment selection and responsiveness for three categories of therapy: intravenous methylprednisolone (IVMP), intravenous immunoglobulin (IVIG), and plasma exchange/immunoadsorption (PLEX/IA). Notably, we update ongoing clinical trials that incorporate fast-acting, targeted biologic complement inhibitors and neonatal Fc receptor (FcRn) antagonists. We discuss potential drivers of relapses and emerging mechanism-guided interventions for acute management. Finally, we call for international collaborative efforts in this important yet under-investigated area to establish clear criteria for relapse, with the ultimate goal of developing more effective therapies.