Pathologic and immunologic profiles of a limited form of neuromyelitis optica with myelitis.
BACKGROUND
Neuromyelitis optica (NMO) is a demyelinating syndrome characterized by myelitis and optic neuritis. Detection of anti-NMO immunoglobulin G antibody that binds to aquaporin-4 (AQP4) water channels allows the diagnosis of a limited form of NMO in the early stage with myelitis, but not optic neuritis. However, the detailed clinicopathologic features and long-term course of this limited form remain elusive.


METHODS
We investigated 8 patients with the limited form of NMO with myelitis in comparison with 9 patients with the definite form.


RESULTS
All patients with limited and definite form showed uniform relapsing-remitting courses, with no secondary progressive courses. Pathologic findings of biopsy specimens from the limited form were identical to those of autopsy from the definite form, demonstrating extremely active demyelination of plaques, extensive loss of AQP4 immunoreactivity in plaques, and diffuse infiltration by macrophages containing myelin basic proteins with thickened hyalinized blood vessels. Moreover, the definite form at the nadir of relapses displayed significantly higher amounts of the inflammatory cytokines interleukin (IL)-1beta and IL-6 in CSF than the limited form and multiple sclerosis.


CONCLUSIONS
This consistency of pathologic findings and uniformity of courses indicates that aquaporin 4-specific autoantibodies as the initiator of the neuromyelitis optica (NMO) lesion consistently play an important common role in the pathogenicity through the entire course, consisting of both limited and definite forms, and NMO continuously displays homogeneity of pathogenic effector immune mechanisms through terminal stages, whereas multiple sclerosis should be recognized as the heterogeneous 2-stage disease that could switch from inflammatory to degenerative phase. This report is a significant description comparing the pathologic and immunologic data of limited NMO with those of definite NMO.
Yanagawa
K
K
Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan.
Kawachi
I
I
Toyoshima
Y
Y
Yokoseki
A
A
Arakawa
M
M
Hasegawa
A
A
Ito
T
T
Kojima
N
N
Koike
R
R
Tanaka
K
K
Kosaka
T
T
Tan
C-F
CF
Kakita
A
A
Okamoto
K
K
Tsujita
M
M
Sakimura
K
K
Takahashi
H
H
Nishizawa
M
M
D000328:Adult; D051401:Aquaporin 4 / Q000276:immunology / Q000378:metabolism; D001323:Autoantibodies / Q000378:metabolism; D001808:Blood Vessels / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009187:Myelitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D009471:Neuromyelitis Optica / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D012008:Recurrence; D012189:Retrospective Studies; D013116:Spinal Cord / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
C496030:AQP4 protein, human; D051401:Aquaporin 4; D001323:Autoantibodies; D004676:Myelin Basic Protein