{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T23:34:30Z","timestamp":1791934470885,"version":"4.3.4"},"reference-count":142,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,6,10]],"date-time":"2015-06-10T00:00:00Z","timestamp":1433894400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["RO1 NS065829-01"],"award-info":[{"award-number":["RO1 NS065829-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:p>\n                    The discovery of AQP4\u2010IgG (a pathogenic antibody that targets the astrocytic water channel aquaporin\u20104), as the first sensitive and specific biomarker for any inflammatory central nervous system demyelinating disease (IDD), has shifted emphasis from the oligodendrocyte and myelin to the astrocyte as a central immunopathogenic player. Neuromyelitis optica (NMO) spectrum disorders (SDs) represent an evolving spectrum of IDDs extending beyond the optic nerves and spinal cord to include the brain (especially in children) and, rarely, muscle. NMOSD typical brain lesions are located in areas that highly express the target antigen, AQP4, including the circumventricular organs (accounting for intractable nausea and vomiting) and the diencephalon (accounting for sleep disorders, endocrinopathies, and syndrome of inappropriate antidiuresis). Magnetic resonance imaging brain abnormalities fulfill Barkoff criteria for multiple sclerosis in up to 10% of patients. As the spectrum broadens, the importance of highly specific assays that detect pathogenic AQP4\u2010IgG targeting extracellular epitopes of AQP4 cannot be overemphasized. The rapid evolution of our understanding of the immunobiology of AQP4 autoimmunity necessitates continuing revision of NMOSD diagnostic criteria. Here, we describe scientific advances that have occurred since the discovery of NMO\u2010IgG in 2004 and review novel targeted immunotherapies. We also suggest that NMOSDs should now be considered under the umbrella term\n                    <jats:italic>autoimmune aquaporin\u20104 channelopathy<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1111\/nyas.12794","type":"journal-article","created":{"date-parts":[[2015,6,19]],"date-time":"2015-06-19T10:07:52Z","timestamp":1434708472000},"page":"20-39","source":"Crossref","is-referenced-by-count":198,"title":["Neuromyelitis optica and the evolving spectrum of autoimmune aquaporin\u20104 channelopathies: a decade later"],"prefix":"10.1111","volume":"1366","author":[{"given":"Sean J.","family":"Pittock","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine\/Pathology  Rochester Minnesota"},{"name":"Department of Neurology, Mayo Clinic College of Medicine  Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia F.","family":"Lucchinetti","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic College of Medicine  Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,6,10]]},"reference":[{"key":"e_1_2_17_2_1","unstructured":"Devic E.1895.My\u00e9lite aigu\u00eb dorso\u2010lombaire avec n\u00e9vrite optique \u2010 Autopsie. Congr\u00e8s Fran\u00e7ais de Med\u00e9cine.434\u2013439."},{"key":"e_1_2_17_3_1","unstructured":"Gault F.1894.De la neuromy\u00e9lite optique aigu\u00eb. Th\u00e8se: Facult\u00e9 de M\u00e9decine et de Pharmacie. Lyon: Rey."},{"key":"e_1_2_17_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-10-8"},{"key":"e_1_2_17_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458511411758"},{"key":"e_1_2_17_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-011-6355-8"},{"key":"e_1_2_17_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2011.09.025"},{"key":"e_1_2_17_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.53.5.1107"},{"key":"e_1_2_17_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)17551-X"},{"key":"e_1_2_17_10_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050304"},{"key":"e_1_2_17_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(07)70216-8"},{"key":"e_1_2_17_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/cen3.12103"},{"key":"e_1_2_17_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20770"},{"key":"e_1_2_17_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2010.07.011"},{"key":"e_1_2_17_15_1","first-page":"612","article-title":"Anti\u2010aquaporin\u20104 IgG in patients presenting with unilateral optic neuritis: a cohort study","volume":"3","author":"Etemadifar M.","year":"2012","journal-title":"Int. J. Prev. Med"},{"key":"e_1_2_17_16_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-01-00171.1997"},{"key":"e_1_2_17_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.20.11981"},{"key":"e_1_2_17_18_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000284600.80782.d5"},{"key":"e_1_2_17_19_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000216139.44259.74"},{"key":"e_1_2_17_20_1","doi-asserted-by":"publisher","DOI":"10.7224\/1537-2073.2012-048"},{"key":"e_1_2_17_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(03)00308-9"},{"key":"e_1_2_17_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh624"},{"key":"e_1_2_17_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-009-0009-0"},{"key":"e_1_2_17_24_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182190f74"},{"key":"e_1_2_17_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2011.03529.x"},{"key":"e_1_2_17_26_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2012.314"},{"key":"e_1_2_17_27_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2012.249"},{"key":"e_1_2_17_28_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-1019131"},{"key":"e_1_2_17_29_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000049912.02954.2C"},{"key":"e_1_2_17_30_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182a6cb5c"},{"key":"e_1_2_17_31_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.5055"},{"key":"e_1_2_17_32_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2011.127"},{"key":"e_1_2_17_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2007.08.004"},{"key":"e_1_2_17_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2006.06.060"},{"key":"e_1_2_17_35_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181af78b8"},{"key":"e_1_2_17_36_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000345042.53843.d5"},{"key":"e_1_2_17_37_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2008.166207"},{"key":"e_1_2_17_38_1","first-page":"163","article-title":"Preferential spinal central gray matter involvement in neuromyelitis optica","volume":"255","author":"Nakamura M.","year":"2008","journal-title":"An MRI study. J. Neurol."},{"key":"e_1_2_17_39_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2014.2137"},{"key":"e_1_2_17_40_1","first-page":"153","article-title":"Asymptomatic myelitis in neuromyelitis optica and autoimmune aquaporin\u20104 channelopathy","volume":"86","author":"Flanagan E.P.","year":"2014","journal-title":"Neurol. Clin. Pract"},{"key":"e_1_2_17_41_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2012.112"},{"key":"e_1_2_17_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2014.129"},{"key":"e_1_2_17_43_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318229e694"},{"key":"e_1_2_17_44_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458514522103"},{"key":"e_1_2_17_45_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0071500"},{"key":"e_1_2_17_46_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.63.3.390"},{"key":"e_1_2_17_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.12058"},{"key":"e_1_2_17_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2011.03565.x"},{"key":"e_1_2_17_49_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.63.7.964"},{"key":"e_1_2_17_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21753"},{"key":"e_1_2_17_51_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182887957"},{"key":"e_1_2_17_52_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000343001.36493.ae"},{"key":"e_1_2_17_53_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000183151.19351.82"},{"key":"e_1_2_17_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22121"},{"key":"e_1_2_17_55_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182343377"},{"key":"e_1_2_17_56_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2014.775"},{"key":"e_1_2_17_57_1","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.51.7898"},{"key":"e_1_2_17_58_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181fac76b"},{"key":"e_1_2_17_59_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181dd445b"},{"key":"e_1_2_17_60_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2012.03880.x"},{"key":"e_1_2_17_61_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182698d39"},{"key":"e_1_2_17_62_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws098"},{"key":"e_1_2_17_63_1","first-page":"288","article-title":"In\u2010vivo identification of a novel retinal pathology in neuromyelitis optica","volume":"18","author":"Sotirchos E.S.","year":"2012","journal-title":"Mult. Scler. J."},{"key":"e_1_2_17_64_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000326601.93739.79"},{"key":"e_1_2_17_65_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000314832.24682.c6"},{"key":"e_1_2_17_66_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1301483"},{"key":"e_1_2_17_67_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318250d812"},{"key":"e_1_2_17_68_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31824c466f"},{"key":"e_1_2_17_69_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318248dec1"},{"key":"e_1_2_17_70_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000011"},{"key":"e_1_2_17_71_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.3890"},{"key":"e_1_2_17_72_1","doi-asserted-by":"publisher","DOI":"10.3109\/08916934.2014.883501"},{"key":"e_1_2_17_73_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12883-014-0162-7"},{"key":"e_1_2_17_74_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2007.17"},{"key":"e_1_2_17_75_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.21197"},{"key":"e_1_2_17_76_1","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1179\/2045772312Y.0000000018","article-title":"Long extensive transverse myelitis associated with aquaporin\u20104 antibody and breast cancer: favorable response to cancer treatment","volume":"35","author":"Armagan H.","journal-title":"J. Spinal Cord. Med"},{"key":"e_1_2_17_77_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-009-0112-0"},{"key":"e_1_2_17_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2013.07.003"},{"key":"e_1_2_17_79_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.65.5.629"},{"key":"e_1_2_17_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hemonc.2014.06.001"},{"key":"e_1_2_17_81_1","doi-asserted-by":"publisher","DOI":"10.3109\/00207454.2013.854208"},{"key":"e_1_2_17_82_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-009-5274-4"},{"key":"e_1_2_17_83_1","doi-asserted-by":"publisher","DOI":"10.3109\/00207450903428970"},{"key":"e_1_2_17_84_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.1246"},{"key":"e_1_2_17_85_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.668"},{"key":"e_1_2_17_86_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2008.150698"},{"key":"e_1_2_17_87_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023489"},{"key":"e_1_2_17_88_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181e2414b"},{"key":"e_1_2_17_89_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02680"},{"key":"e_1_2_17_90_1","doi-asserted-by":"publisher","DOI":"10.1038\/72256"},{"key":"e_1_2_17_91_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-1723fje"},{"key":"e_1_2_17_92_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4226"},{"key":"e_1_2_17_93_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458515571446"},{"key":"e_1_2_17_94_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi990941s"},{"key":"e_1_2_17_95_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.26.13052"},{"key":"e_1_2_17_96_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.39.22907"},{"key":"e_1_2_17_97_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.20.10908"},{"key":"e_1_2_17_98_1","first-page":"239","article-title":"Orthogonal arrays of intramembranous particles: a review with special reference to astrocytes","volume":"36","author":"Wolburg H.","year":"1995","journal-title":"J. Hirnforsch"},{"key":"e_1_2_17_99_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-386043-9.00001-3"},{"key":"e_1_2_17_100_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2235843100"},{"key":"e_1_2_17_101_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20855"},{"key":"e_1_2_17_102_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2012.07.008"},{"key":"e_1_2_17_103_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000289761.64862.ce"},{"key":"e_1_2_17_104_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1109980108"},{"key":"e_1_2_17_105_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20081241"},{"key":"e_1_2_17_106_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq177"},{"key":"e_1_2_17_107_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2006.09.008"},{"key":"e_1_2_17_108_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22341"},{"key":"e_1_2_17_109_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(00)00067-8"},{"key":"e_1_2_17_110_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22635"},{"key":"e_1_2_17_111_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awf151"},{"key":"e_1_2_17_112_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0061835"},{"key":"e_1_2_17_113_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22686"},{"key":"e_1_2_17_114_1","doi-asserted-by":"publisher","DOI":"10.1177\/10454411950060020301"},{"key":"e_1_2_17_115_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awm047"},{"key":"e_1_2_17_116_1","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12099"},{"key":"e_1_2_17_117_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awp309"},{"key":"e_1_2_17_118_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2011.03.007"},{"key":"e_1_2_17_119_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21802"},{"key":"e_1_2_17_120_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21837"},{"key":"e_1_2_17_121_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.06.085"},{"key":"e_1_2_17_122_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2010.02.157"},{"key":"e_1_2_17_123_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl371"},{"key":"e_1_2_17_124_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318214332c"},{"key":"e_1_2_17_125_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001126"},{"key":"e_1_2_17_126_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.53.8.1705"},{"key":"e_1_2_17_127_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000106946.08741.41"},{"key":"e_1_2_17_128_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318200d80c"},{"key":"e_1_2_17_129_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2014.141"},{"key":"e_1_2_17_130_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70076-0"},{"key":"e_1_2_17_131_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1017385108"},{"key":"e_1_2_17_132_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000317"},{"key":"e_1_2_17_133_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2009.184"},{"key":"e_1_2_17_134_1","doi-asserted-by":"publisher","DOI":"10.4161\/mabs.21338"},{"key":"e_1_2_17_135_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22657"},{"key":"e_1_2_17_136_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70253-2"},{"key":"e_1_2_17_137_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70310-1"},{"key":"e_1_2_17_138_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-8-184"},{"key":"e_1_2_17_139_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31826aac4e"},{"key":"e_1_2_17_140_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000101"},{"key":"e_1_2_17_141_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.5857"},{"key":"e_1_2_17_142_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000062"},{"key":"e_1_2_17_143_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2012.06.002"}],"container-title":["Annals of the New York Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fnyas.12794","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nyas.12794","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T04:29:09Z","timestamp":1694492949000},"score":1,"resource":{"primary":{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/10.1111\/nyas.12794"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,10]]},"references-count":142,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,2]]}},"alternative-id":["10.1111\/nyas.12794"],"URL":"https:\/\/doi.org\/10.1111\/nyas.12794","archive":["Portico"],"relation":{},"ISSN":["0077-8923","1749-6632"],"issn-type":[{"value":"0077-8923","type":"print"},{"value":"1749-6632","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,6,10]]}}}