AQP4 and neuromyelitis optica: Whilst NMO was initially defined by the occurrence of longitudinally extensive transverse myelitis (LETM) and optic neuritis, the development of more specific assays, particularly cell-based assays (CBAs) with transfected HEK-293 cells expressing AQP4 (4), led to the realization that the spectrum of disorders associated with AQP4-IgG was broader than previously thought, encompassing limited forms of the disease (e.g., isolated optic neuritis or isolated myelitis), and also brain and brainstem involvement (previously regarded as an exclusion criteria for NMO).