Neuromyelitis optica brain lesions localized at sites of high aquaporin 4 expression

Background: Neuromyelitis optica (NMO)-IgG is a specific autoantibody marker for NMO. It binds selectively to aquaporin 4 (AQP4), which is highly concentrated in astrocytic foot processes at the blood-brain barrier and is not restricted to optic nerve and spinal cord. Although it is conventionally believed that the brain is spared, brain imaging abnormalities are not uncommon in patients with NMO. Objective: To investigate the location of brain lesions that are distinctive for NMO with respect to the localization of AQP4 in mammalian brain. Design: Observational, retrospective case series. Setting: Clinical serologic cohort of patients tested for NMO-IgG for whom brain MRI images were available. Patients: We identified 120 patients seropositive for NMO-IgG for whom brain magnetic resonance images were available. Main Outcome Measure: Magnetic resonance imaging abnormalities. Results: In 8 patients we observed recurring and distinctive magnetic resonance imaging abnormalities in the hypothalamic and periventricular areas that corresponded to brain regions of high AQP4 expression. Conclusion: The distribution of NMO-characteristic brain lesions corresponds to sites of high AQP4 expression.