The phenotypic spectrum of the idio-pathic inflammatory demyelinating disorders of the central nervous system (CNS) suggests that neuromyelitis optica (NMO), which includes Devic’s disease, is a distinct clinical entity separate from classic or conventional multiple sclerosis. 1 NMO is also phenotypically similar to the opticospinal form of multiple sclerosis (OSMS) that occurs commonly in Asian populations with multiple sclerosis. 2 NMO and OSMS, by definition, involve the optic nerves and spinal cord. They tend to be severe diseases, typically causing complete transverse myelitis associated with longitudinally extensive lesions, as seen on magnetic resonance imaging (MRI), which may evolve to form a syrinx. An MRI of the brain is typically normal. NMO is often associated with a mild cerebrospinal fluid (CSF) pleocytosis, which is often polymorphonuclear in nature. Locally synthesised oligoclonal immunoglobulin G (IgG) bands are typically absent in NMO. 1 Pathologically, NMO is characterised by necrosis, eosinophilic and neutrophilic infiltrates, vascular proliferation, and hyalinisation and complement activation in a perivascular ‘‘rosette’’pattern. 1 3 These clinical and pathological features are uncommon in patients with multiple sclerosis. 3 In 2004, the Mayo Clinic group, by using indirect immunofluorescence, reported a characteristic autoantibody staining pattern of CNS tissues with serum from cases with NMO; IgG was shown to outline CNS microvessels of the pia, subpia and Virchow–Robin spaces and co-localised with laminin. 4 They aptly named this autoantibody NMO-IgG. 4 The sensitivity and specificity of the NMO-IgG staining pattern in distinguishing cases of NMO and OSMS from related neurological disorders, including cases of conventional multiple slcerosis, were 73%(95% confidence interval (CI) 60 to 86) and 91%(95% CI 79 to 100) for NMO, and 58%(95% CI 30 to 86) and 100%(95% CI 66 to 100) for OSMS. More recently, they have shown that NMO-IgG binds selectively to aquaporin (AQP) 4, 5 the predominant CNS water channel. AQPs are a family of membraneinserted water channel proteins providing a pathway for osmotically driven water transport through cell membranes. They have a vital role in the reabsorption of water from the renal tubular fluid. 6 A failure to insert AQP molecules into renal tubular membranes causes nephrogenic diabetes insipidus. 6 In the CNS, AQP1 is restricted to the apical domain of the epithelial cells of the choroid plexus. AQP4 is expressed on astrocytic foot processes and ependymocytes. AQP9 is localised in tanycytes (hypothalamic bipolar cells bridging the CSF and the hypothalamic portal capillaries) and astrocytic processes. 7 Messenger RNA expression of AQP3, AQP5 and AQP8 has also been reported to occur in cultured astrocytes. 7 AQPs in the CNS have a role in osmoreception, potassium siphoning and CSF formation, and are strongly implicated in the pathogenesis of cerebral oedema. 7

Involvement of the brain has been considered to be an exclusion criterion for the diagnosis of NMO. 8 Abnormalities on MRI scans of the brain have, however, been described in patients with NMO9–11: they are usually non-specific, but hypothalamic and periventricular lesions may be more specific for NMO. 9 11 AQP4 expression is not restricted to the optic nerve and spinal cord: the hypothalamic and periventricular distribution of AQP4 seems to correspond with distribution of lesions as evident on the MRI of patients with NMO-IgG. 12