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 Volume 73, Number 20, November 17, 2009
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NEUROLOGY 2009;73:1628-1637
© 2009 American Academy of Neurology

Pathologic and immunologic profiles of a limited form of neuromyelitis optica with myelitis

K. Yanagawa, MD, I. Kawachi, MD, PhD, Y. Toyoshima, MD, PhD, A. Yokoseki, MD, M. Arakawa, MD, A. Hasegawa, MD, PhD, T. Ito, MD, PhD, N. Kojima, MD, R. Koike, MD, PhD, K. Tanaka, MD, PhD, T. Kosaka, MD, C. -F. Tan, MD, PhD, A. Kakita, MD, PhD, K. Okamoto, MD, PhD, M. Tsujita, PhD, K. Sakimura, PhD, H. Takahashi, MD, PhD and M. Nishizawa, MD, PhD

From the Department of Neurology (K.Y., I.K., A.Y., M.A., M.N.), Department of Pathology (Y.T., T.K., C.-F.T., A.K., H.T.), Center for Integrated Human Brain Science (M.T.), Department of Cellular and Neurobiology (K.S.), Department of Neurosurgery (K.O.), Brain Research Institute, and Department of Orthopedic Surgery (T.I.), Niigata University; Department of Neurology (N.K.), Kobari Hospital; Department of Neurology (A.H., R.K.), Nishi-Niigata Chuo National Hospital, Niigata; and Department of Neurology (K.T.), Kanazawa Medical University, Kanazawa, Japan.

Address correspondence and reprint requests to Masatoyo Nishizawa, MD, PhD, Department of Neurology, Brain Research Institute, Niigata University, 757 Asahimachi 1, Chuo-ku, Niigata 950-0088, Japan nishi{at}bri.niigata-u.ac.jp

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.

Result: 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)-1β and IL-6 in CSF than the limited form and multiple sclerosis.

Conclusion: 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.

Abbreviations: AQP4 = aquaporin 4; definite NMO = definite form of neuromyelitis optica; EDSS = Extended Disability Status Scale; GFAP = glial fibrillary acidic protein; HIMP = high-dose IV methylprednisolone; IFN = interferon; Ig = immunoglobulin; IL = interleukin; IP = interferon-inducible protein; LEM = longitudinally extensive myelitis; limited NMO (MY) = limited form of neuromyelitis optica with myelitis; limited NMO (ON) = limited form of neuromyelitis optica with optic neuritis; MBP = myelin basic protein; MIG = monokine induced by interferon {gamma}; MCP = monocyte chemoattractant protein; MS = multiple sclerosis; NMO = neuromyelitis optica; NMO-IgG = neuromyelitis optica immunoglobulin G; OSMS = optic-spinal multiple sclerosis; RANTES = regulated on activation, normal T-cell expressed, and secreted; TNF = tumor necrosis factor.

Supplemental data at www.neurology.org

*These authors contributed equally to this work.

Supported by a Grant-in-Aid for Scientific Research (C) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (20590991, I.K.), a Grant for the Promotion of Niigata University Research Projects (I.K.), and Research Grants for research on intractable diseases (Neuroimmunological Disease Research Committee) from Ministry of Health, Labor and Welfare of Japan (M.N.).

Disclosure: The authors report no disclosures.

Received March 24, 2009. Accepted in final form July 17, 2009.