title: Early and extensive spinal white matter involvement in neuromyelitis optica.
abstract: Studies of longitudinally extensive spinal cord lesions (LESCLs) in neuromyelitis optica (NMO) have focused on gray matter, where the relevant antigen, aquaporin-4 (AQP4), is abundant. Because spinal white matter pathology in NMO is not well characterized, we aimed to clarify spinal white matter pathology of LESCLs in NMO.
  
  
  
  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-tesla MRI in 15 AQP4 antibody-positive NMO/NMOSD patients and in 15 AQP4 antibody-negative multiple sclerosis (MS) patients.
  
  
  
  Pathological analysis revealed seven cases of AQP4 loss and four predominantly demyelinating cases. Forty-four 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%, Pcorr= 0.020, and Pcorr= 0.004, respectively). MRI indicated LESCLs more frequently affected PC and LC than AC in anti-AQP4 antibody-seropositive NMO/NMOSD (86.7%, 60.0% and 20.0%, Pcorr= 0.005, and Pcorr= 0.043, respectively) and AQP4 antibody-seronegative MS patients (86.7%, 73.3% and 33.3%, Pcorr= 0.063, and Pcorr= 0.043, 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.
  
  
  
  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.
authors.affiliation: Departments of Neurology.
authors.forename: Shotaro
authors.initials: S
authors.lastname: Hayashida
authors.affiliation: Departments of Neurology.
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Masaki
authors.affiliation: Departments of Neurology.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Yonekawa
authors.affiliation: Neuropathology.
authors.forename: Satoshi O
authors.initials: SO
authors.lastname: Suzuki
authors.affiliation: Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Hiwatashi
authors.affiliation: Departments of Neurology.
authors.forename: Takuya
authors.initials: T
authors.lastname: Matsushita
authors.affiliation: Departments of Neurology.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Departments of Neurology.
authors.forename: Ryo
authors.initials: R
authors.lastname: Yamasaki
authors.affiliation: Department of Neurology, Tenri Hospital, Tenri, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Suenaga
authors.affiliation: Neuropathology.
authors.forename: Toru
authors.identifier: 0000-0001-7826-870X
authors.initials: T
authors.lastname: Iwaki
authors.affiliation: Neurological Therapeutics, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Murai
authors.affiliation: Departments of Neurology.
authors.forename: Jun-Ichi
authors.initials: JI
authors.lastname: Kira
mesh_terms: D000328:Adult; D000368:Aged; D051401:Aquaporin 4 / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D018450:Disease Progression; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009471:Neuromyelitis Optica / Q000000981:diagnostic imaging* / Q000276:immunology / Q000473:pathology*; D013116:Spinal Cord / Q000000981:diagnostic imaging* / Q000473:pathology*; D013997:Time Factors; D066127:White Matter / Q000000981:diagnostic imaging* / Q000473:pathology*
chemical_list: C496030:AQP4 protein, human; D051401:Aquaporin 4; D001323:Autoantibodies
keywords: isolated perivascular lesion; longitudinally extensive spinal cord lesion (LESCL); multiple sclerosis; neuromyelitis optica; white matter