Neuromyelitis optica (NMO) is a demyelinating disease of the central nervous system that preferentially affects the optic nerves and spinal cord. NMO-IgG/anti-aquaporin 4 antibody (AQP4-Ab) is considered as a specific diagnostic marker for NMO. A previous study using animal models passively transferred with AQP4-Ab has partially proven that NMO-IgG/AQP4-Ab has an effector function in the pathogenesis of NMO, exemplifying the diagnostic significance of this antibody. Further, this marker can be used to differentiate the limited forms of NMO, such as recurrent myelitis or optic neuritis or NMO with isolated cerebral/brainstem lesions during the early course of the disease, from other diseases with a different etiology. NMO spectrum disorders (NMOSD) comprise these clinically heterogeneous conditions, all of which are positive for AQP4-Ab. However, few patients show clinical characteristic features of NMO, without AQP4-Ab positivity. We should be careful to introduce interferon beta for the prevention of relapse to these seronegative but suspicious for NMO patients. A few NMOSD patients have also been diagnosed with systemic lupus erythematosus (SLE) or Sjogren syndrome (SjS). However, there have been no reported cases of patients with SLE/SjS who do not exhibit any neurological symptoms and AQP4-Ab-positivity, and it is likely that these 2 autoimmune diseases incidentally overlap. NMO might follow myasthenia gravis (MG), after thymectomy for the treatment of MG. Taken together,as in the case of other systemic autoimmune diseases,an antibody-mediated pathomechanism of NMO is suggested.