Post-COVID-19 Area Postrema Syndrome With SARS-CoV-2 in CSF: A Dual-Case Report and Review of the Literature

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune astrocytopathy characterized by inflammatory demyelinating lesions in the central nervous system. Area postrema syndrome (APS), marked by intractable nausea, vomiting, and hiccups, is a recognized but less common initial manifestation. Post-infectious autoimmunity triggered by SARS-CoV-2 has been increasingly associated with NMOSD pathogenesis; however, the clinical significance of direct viral neuroinvasion and its relationship to divergent patient outcomes remains poorly understood.

We report two female patients who developed isolated APS shortly after COVID-19 infection. Both patients underwent comprehensive neurological evaluation, including brain and spinal magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis with metagenomic next-generation sequencing (mNGS), and serological testing for aquaporin-4 immunoglobulin G (AQP4-IgG), myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG), and glial fibrillary acidic protein immunoglobulin G (GFAP-IgG) using cell-based assays. Clinical outcomes were compared in the context of antibody serostatus and treatment strategies. A review of the relevant literature on post-COVID NMOSD was also performed.

Both patients presented with intractable vomiting and hiccups following SARS-CoV-2 infection, and MRI demonstrated isolated T2/FLAIR hyperintense lesions in the dorsal medulla consistent with area postrema involvement. SARS-CoV-2 RNA sequences were detected in the CSF of both patients via mNGS, suggesting direct viral neuroinvasion or blood-brain barrier compromise. Despite similar initial presentations, their outcomes diverged dramatically. Patient 1 was AQP4-IgG negative, responded well to immunotherapy with intravenous immunoglobulin and corticosteroids followed by mycophenolate mofetil maintenance, and remained relapse-free at 12-month follow-up with significant lesion regression on MRI. Patient 2 was AQP4-IgG positive in both serum and CSF, and despite acute treatment, experienced a fatal relapse 6 months later with longitudinally extensive transverse myelitis while on low-dose prednisone monotherapy.

Isolated APS may represent an important yet under-recognized manifestation of post-COVID-19 autoimmune neuroinflammation. Detection of SARS-CoV-2 in CSF supports a role for direct viral neuroinvasion as a localized inflammatory stimulus. AQP4-IgG serostatus serves as a critical prognostic determinant: seronegativity is associated with a benign, monophasic course, whereas seropositivity mandates prompt initiation of potent immunosuppressive therapy to prevent devastating relapses. Clinicians should maintain a high index of suspicion for NMOSD in patients with unexplained persistent vomiting following COVID-19, and perform urgent neuroimaging and antibody testing for early risk stratification.