MRI image of a patient with transverse myelitis, one of the diagnostic criteria for NMOSD. NMOSD is diagnosed using consensus clinical criteria, which have undergone multiple revisions, most recently in 2015. Diagnostic criteria are more relaxed for seropositive AQP4–IgG cases than they are for seronegative AQP4-IgG ones. If AQP4-IgG is detected, then 1 core clinical criterion, along with the ruling out of alternative diagnoses, is sufficient for NMOSD diagnosis. If AQP4-IgG is undetected, or its status is unknown, 2 core clinical criteria, each with supportive MRI findings, along with the ruling out of alternative diagnoses, are needed for an NMOSD diagnosis. + NMOSD diagnostic criteria Core criteria Additional MRI findings for absent/unknown AQP4-IgG<unk> neuritis Either 1) brain MRI showing normal findings or only nonspecific white matter lesions, or 2)<unk> nerve MRI showing T2-hyperintesity, or T1 enhancing lesion, greater than 1/2<unk> nerve length or involving<unk> chiasm Acute myelitis intramedullary lesion > 3 contiguous segments, or spinal atrophy ≥ 3 contiguous segments Area Postrema Syndrome (prolonged episodes of hiccuping or vomiting/nausea) dorsal medulla/area postrema lesions Acute brainstem syndrome periependymal brainstem lesions Symptomatic narcolepsy/acute diencephalic clinical syndrome with an MRI showing diencephalon lesion(s) None additional Symptomatic cerebral syndrome with NMOSD-typical brain lesion(s) None additional Rarely, it has been reported that some courses of anti-NMDAR are consistent with NMO. Preliminary reports suggest that other autoantibodies may play a role in rare cases of NMO. NMOSD with MOG-IgG is considered a manifestation of anti-MOG associated encephalomyelitis.<unk>  constituents After the development of the NMO-IgG test, the<unk>  of<unk> s comprising NMO was expanded. The<unk>  is now believed to consist of: * Standard NMO, according to the diagnostic criteria described above * Limited forms of NMO, such as single or recurrent events of longitudinally extensive myelitis, and bilateral simultaneous or recurrent<unk> neuritis * Asian<unk> spinal multiple sclerosis (OSMS), or AQP4+ OSMS. This variant can present brain lesions like MS does, but it should not be confused with an AQP4-negative form of inflammatory demyelinating diseases of the central nervous system<unk> , sometimes called<unk> spinal MS * Longitudinally extensive myelitis or<unk> neuritis associated with systemic autoimmune disease *<unk> neuritis or myelitis associated with lesions in specific brain areas such as the hypothalamus, periventricular nucleus, and brainstem * NMO-IgG negative NMO: AQP4 antibody-seronegative NMO poses a diagnostic challenge. Some cases could be related to anti-myelin oligodendrocyte glycoprotein (MOG) autoantibodies. Differential diagnosis AQP4-Ab-negative NMO presents problems for differential diagnosis. The behavior of the oligoclonal bands can help to establish a more accurate diagnosis. Oligoclonal bands in NMO are rare and they tend to disappear after attacks, while in MS they are nearly always present and persistent. It is important to notice for differential diagnosis that, though uncommon, it is possible to have longitudinal lesions in MS. Another problem for diagnosis is that AQP4-ab in MOG-ab levels can be too low to be detected. Some additional biomarkers have been proposed. NMO differs from MS in that it usually has more severe sequelae after an acute episode than standard MS, which infrequently presents as transverse myelitis, and oligoclonal bands in the CSF, as well as white matter lesions on brain MRIs being uncommon in NMO, but occurring in over 90% of MS patients. Recently, the presence of AQP4 has been found to distinguish standard MS from NMO; but as MS is a heterogeneous condition, and some MS cases are reported to be Kir4.1 channelopathies (autoimmunity against the potassium channels), it is still possible to consider NMO as part of the MS<unk> . Besides, some NMO-AQP4(−) variants are not astrocytopathic, but demyelinating. Tumefactive demyelinating lesions in NMO are not usual, but they have been reported to appear in several cases mistakenly treated with interferon beta. Also, an overlap with Sjögren syndrome has been reported. Evolution of diagnostic criteria Since the discovery of the AQP4 autoantibody, it has been found that it appears also in patients with NMO-like symptoms that do not fulfill the clinical requirements to be diagnosed with NMO (recurrent and simultaneous<unk> nerve and spinal cord inflammation). The term<unk> s (NMOSD) has been designed to allow incorporation of cases associated with non-AQP4 biomarkers. Therefore, it includes all the clinical variants due to anti-AQP4, plus other non-related but clinically similar syndromes such as anti-MOG associated encephalomyelitis. Some cases with MOG+ and AQP4+ antibodies have been found. These variants are expected to respond to the same treatments as standard NMO. Some authors propose to use the name "autoimmune aquaporin-4 channelopathy" for these diseases, while others prefer a more generic term "AQP4-astrocytopathy", which also includes deficiencies of AQP4 with a non-autoimmune origin.
Neuromyelitis optica spectrum disorder
Alexander disease
Corneal-cerebellar syndrome
Leber's hereditary optic neuropathy
Subacute myelo-optic neuropathy
Canavan disease
Grinker myelinopathy
Toxic and nutritional optic neuropathy