Shared mechanisms in neuromyelitis optica spectrum disorder and spaceflight-associated neuro-ocular syndrome: Insights into central nervous system fluid dynamics, glymphatic function, and astrocyte dysregulation

Abstract

Spaceflight-Associated Neuro-ocular Syndrome (SANS) and Neuromyelitis Optica Spectrum Disorder (NMOSD) represent distinct neurological challenges with intriguing parallels in their disruption of central nervous system (CNS) fluid dynamics and the clinical neuro-ophthalmic manifestations. SANS, affecting astronauts during prolonged spaceflight, is characterized by optic disc edema, globe flattening, and vision changes resulting from microgravity-induced cephalad fluid shifts. NMOSD, an autoimmune astrocytopathy, is driven by aquaporin-4 (AQP4) autoantibodies that compromise astrocytic water regulation and blood-brain barrier integrity. This review explores the shared pathophysiological processes of SANS and NMOSD, focusing on AQP4 dysregulation, cerebrospinal fluid dynamics, and neuroinflammatory mechanisms. We examine advanced imaging techniques, biomarkers, and molecular pathways relevant to both conditions, highlighting how insights from NMOSD research might inform our understanding of SANS. The role of the glymphatic system and its potential impairment in both disorders is discussed as a novel perspective on CNS waste clearance. By identifying parallels between SANS and NMOSD, we aim to provide a framework for translating findings between space medicine and terrestrial neuroimmunology. This comparative analysis may drive innovative therapeutic approaches for conditions involving CNS fluid dysregulation, ultimately advancing both astronaut health and patient care for NMOSD and related disorders.