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Because spinal white matter pathology in NMO is not well characterized, we aimed to clarify spinal white matter pathology of LESCLs in NMO.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed 50 spinal cord lesions from eleven autopsied NMO\/NMO spectrum disorder (NMOSD) cases. We also evaluated LESCLs with three or fewer spinal cord attacks by 3\u2010tesla MRI in 15 AQP4 antibody\u2010positive NMO\/NMOSD patients and in 15 AQP4 antibody\u2010negative multiple sclerosis (MS) patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Pathological analysis revealed seven cases of AQP4 loss and four predominantly demyelinating cases. Forty\u2010four lesions from AQP4 loss cases involved significantly more frequently posterior columns (PC) and lateral columns (LC) than anterior columns (AC) (59.1%, 63.6%, and 34.1%, respectively). The posterior horn (PH), central portion (CP), and anterior horn (AH) were similarly affected (38.6%, 36.4% and 31.8%, respectively). Isolated perivascular inflammatory lesions with selective loss of astrocyte endfoot proteins, AQP4 and connexin 43, were present only in white matter and were more frequent in PC and LC than in AC (22.7%, 29.5% and 2.3%, <jats:italic>P<\/jats:italic><jats:sup>corr<\/jats:sup>\u2009=\u20090.020, and <jats:italic>P<\/jats:italic><jats:sup>corr<\/jats:sup>\u2009=\u20090.004, respectively). MRI indicated LESCLs more frequently affected PC and LC than AC in anti\u2010AQP4 antibody\u2010seropositive NMO\/NMOSD (86.7%, 60.0% and 20.0%, <jats:italic>P<\/jats:italic><jats:sup>corr<\/jats:sup>\u2009=\u20090.005, and <jats:italic>P<\/jats:italic><jats:sup>corr<\/jats:sup>\u2009=\u20090.043, respectively) and AQP4 antibody\u2010seronegative MS patients (86.7%, 73.3% and 33.3%, <jats:italic>P<\/jats:italic><jats:sup>corr<\/jats:sup>\u2009=\u20090.063, and <jats:italic>P<\/jats:italic><jats:sup>corr<\/jats:sup>\u2009=\u20090.043, respectively). PH, CP and AH were involved in 93.3%, 86.7% and 73.3% of seropositive patients, respectively, and in 53.3%, 60.0% and 40.0% of seronegative patients, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>NMO frequently and extensively affects spinal white matter in addition to central gray matter, especially in PC and LC, where isolated perivascular lesions with astrocyte endfoot protein loss may emerge. Spinal white matter involvement may also appear in early NMO, similar to cerebral white matter lesions.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bpa.12386","type":"journal-article","created":{"date-parts":[[2016,4,15]],"date-time":"2016-04-15T15:35:20Z","timestamp":1460734520000},"page":"249-265","source":"Crossref","is-referenced-by-count":33,"title":["Early and extensive spinal white matter involvement in neuromyelitis optica"],"prefix":"10.1111","volume":"27","author":[{"given":"Shotaro","family":"Hayashida","sequence":"first","affiliation":[{"name":"Departments of Neurology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuhisa","family":"Masaki","sequence":"additional","affiliation":[{"name":"Departments of Neurology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomomi","family":"Yonekawa","sequence":"additional","affiliation":[{"name":"Departments of Neurology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi 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