Recognizing and Differentiating Area Postrema Syndrome Across NMOSD, MOGAD, and GFAP Astrocytopathy

Area postrema syndrome (APS)—intractable nausea, vomiting, and/or hiccups persisting ≤48 h—is a recognized presenting feature of neuromyelitis optica spectrum disorder (NMOSD) and, less commonly, of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and glial fibrillary acidic protein (GFAP)-astrocytopathy. APS is still frequently misattributed to primary gastrointestinal disease, delaying immunotherapy by weeks to months. For years its pathophysiology was inferred largely from lesion topography rather than demonstrated at the level of neuronal signaling. A study presented at the 2025 American Neurological Association annual meeting, and subsequently posted as a preprint, proposes a mechanistic account: elevated glucagon-like peptide-1 (GLP-1) and its receptor (GLP-1R) correlate with APS presence and severity in AQP4-IgG-positive NMOSD, and receptor blockade normalizes neuronal hyperexcitability in animal models. This finding comes from a single center and has not yet completed independent replication or full peer review; throughout this review we treat it as hypothesis-generating rather than established. Using that hypothesis as an organizing frame, this narrative review summarizes the anatomical and clinical basis of APS; expands the biological and clinical comparison of APS across NMOSD, MOGAD, and GFAP-astrocytopathy, including the mechanistic reasons the three disorders diverge; and characterizes the diagnostic pathway that routes patients through gastroenterology before neurology. It closes with the clinical implications, and the explicit limitations, of a putatively hormone-modulated area postrema circuit.