Reflections from a NMOSD case with serum AQP4-Ab negativity but CSF positivity: narrative review of how to interpret AQP4-Ab test results

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease of the central nervous system. The differential diagnosis of NMOSD in clinical practice is often challenging despite the phenotypical and serological characteristics of the disease. The discovery of anti-aquaporin-4 antibody (AQP4-Ab) enabled clinicians to diagnose NMOSD relatively earlier and more easily, as the AQP4-Ab can mediate the pathogenesis of NMOSD. Testing for AQP4-Ab in the serum of patients can play a crucial role in the diagnosis of NMOSD. Three-quarters of patients with NMOSD have serum immunoglobulin-G (IgG) autoantibodies to the AQP4 channel. Nevertheless, the test results for AQP4-Ab can be affected by several factors, such as assay methods, clinical stages, the types of treatment, sample status, and pre-test error, among others. In patients with seronegative NMOSD, it would be better to test serum and CSF AQP4-Ab together to improve the positive rate, especially when NMOSD is highly suspected. This article aims to update readers on the recent developments in AQP4-Ab testing and how to interpret the results of the AQP4-Ab test.