In this chapter, two autoimmune disorders against astrocytes are reviewed: neuromyelitis optica (NMO), recently renamed NMO spectrum disorders (NMOSD) which frequently associates with antibodies against AQP4; and a meningoencephalitis without specific clinical or brain MRI features, which occurs in association with antibodies against glial fibrillary acidic protein (GFAP) that are mainly detected in CSF. NMOSD should be considered a syndrome rather than a disease because it associates with different antibodies and pathogenic mechanisms. In epidemiological studies, 73% of patients with NMOSD have aquaporin 4 (AQP4) antibodies whereas 12% harbour myelin oligodendrocyte glycoprotein (MOG) antibodies and 15% are seronegative. The diagnosis of NMOSD is based on clinical and laboratory criteria that require the presence of one or two core clinical syndromes, depending on the positivity of AQP4 antibodies. Relapses in NMOSD are common and several treatments with monoclonal antibodies have shown efficacy, including the following targets: the C5 complement protein (eculizumab), the interleukin 6 receptor (satralizumab), and the CD19 B cell receptor (inebilizumab). The pathogenic role of AQP4 antibodies is supported by the neuropathological findings in patients with NMOSD, and by in-vitro studies and passive transfer of antibodies to experimental animals.

This chapter focuses on the MOG-antibody-associated disease as a distinct neurological disorder that includes several demyelinating syndromes, and it follows a monophasic or more frequently a relapsing–remitting course. In children, MOG antibody-associated disease usually presents as acute disseminated encephalomyelitis (ADEM), ADEM variants, or encephalitis that may present with seizures and isolated or predominant cortical hyperintense lesions in FLAIR MRI studies (FLAMES). In teenagers and adults the common clinical presentation is optic neuritis, myelitis, or brainstem syndromes. Some of the patients fulfil criteria of neuromyelitis optica spectrum disorders (NMOSD). Persistence of MOG antibodies is common in patients with relapses. The optimal treatment to prevent relapses has not been established. ADEM is the most frequent autoimmune encephalitis in children. The syndrome was characterized before the description of MOG antibodies and associates with distinct clinical and neuroimaging features. Brain MRI shows multiple hyperintense T2 lesions similar to those seen in anti-GABAaR encephalitis. As occur with NMOSD, ADEM is probably caused by different pathogenic mechanisms as MOG antibodies are only found in ~60% of patients. Besides MOG antibody-associated disease there are two other antibody-associated neurological syndromes that target oligodendrocytes as part of an immune attack: anti-NMDAR encephalitis and paraneoplastic encephalomyelitis with CRMP5 antibodies.