TY - JOUR
T1 - Early and extensive spinal white matter involvement in neuromyelitis optica
AU - Hayashida, Shotaro
AU - Masaki, Katsuhisa
AU - Yonekawa, Tomomi
AU - Suzuki, Satoshi O.
AU - Hiwatashi, Akio
AU - Matsushita, Takuya
AU - Watanabe, Mitsuru
AU - Yamasaki, Ryo
AU - Suenaga, Toshihiko
AU - Iwaki, Toru
AU - Murai, Hiroyuki
AU - Kira, Jun Ichi
N1 - Funding Information:
This study was supported in part by a Health and Labour Sciences Research Grant on Intractable Diseases (H26-Nanchitou (Nan)-Ippan-074) from the Ministry of Health, Labour, and Welfare, Japan, by a Grant-in-Aid for Scientific Research B (No. 25293204), a Grant-in Aid for Scientific Research C (No. 26461295) and a “Glial Assembly” Grant-in Aid for Scientific Research on Innovative Areas (No. 25117012) from the Ministry of Education, Culture, Sports, Science and Technology, Japan. We thank Ms. Sachiko Koyama and Mr. Takaaki Kanemaru from the Department of Neuropathology and Morphology Core Unit, Kyushu University, for excellent technical assistance, and Mr. Junji Kishimoto from the Center for Clinical and Translational Research, Kyushu University, for support with statistical analyses.
Publisher Copyright:
© 2016 International Society of Neuropathology
PY - 2017/5
Y1 - 2017/5
N2 - Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.
AB - Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.
UR - http://www.scopus.com/inward/record.url?scp=85017519470&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85017519470&partnerID=8YFLogxK
U2 - 10.1111/bpa.12386
DO - 10.1111/bpa.12386
M3 - Article
C2 - 27082714
AN - SCOPUS:85017519470
SN - 1015-6305
VL - 27
SP - 249
EP - 265
JO - Brain Pathology
JF - Brain Pathology
IS - 3
ER -