Advertisement

Neuromyelitis optica and astrocytic damage in its pathogenesis

Published:March 14, 2011DOI:https://doi.org/10.1016/j.jns.2011.02.018

      Abstract

      Neuromyelitis optica (NMO) is characterized by severe optic neuritis and longitudinally extended, transverse myelitis. There have been long controversial whether NMO is a variant of multiple sclerosis (MS) or a different disease. However, since the discovery of an NMO-specific autoantibody to aquaporin 4 (AQP4), a dominant water channel in the central nervous system densely expressed on foot processes of astrocytes, the clinical distinction between NMO and MS has become clear, and now AQP4 antibody status is critically important for neurologists in deciding on treatment strategy. Moreover, pathological studies demonstrated an extensive loss of immunoreactivities to AQP4 and glial fibrillary acidic protein (GFAP) with relative preservation of the staining of myelin basic protein in acute NMO lesions, which is not seen in MS. In fact, the GFAP levels in the cerebrospinal fluid during acute exacerbation of NMO are remarkably elevated, while the values in MS are not different from those in controls. In addition, recent experimental studies conducted in vitro and in vivo have shown that AQP4 antibody is pathogenic. These findings strongly suggest that AQP4 antibody has diagnostic, therapeutic and pathogenetic implications, and that severe astrocytic damage mediated by AQP4 antibody distinguishes NMO from MS.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of the Neurological Sciences
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Mandler R.N.
        • Davis L.E.
        • Jeffery D.R.
        • Kornfeld M.
        Devic's neuromyelitis optica: a clinicopathological study of 8 patients.
        Ann Neurol. 1993; 34: 162-168
        • O'Riordan J.I.
        • Gallagher H.L.
        • Thompson A.J.
        • Howard R.S.
        • Kingsley D.P.
        • Thompson E.J.
        • et al.
        Clinical, CSF, and MRI findings in Devic's neuromyelitis optica.
        J Neurol Neurosurg Psychiatry. 1996; 60: 382-387
        • Wingerchuk D.M.
        • Hogancamp W.F.
        • O'Brien P.C.
        • Weinshenker B.G.
        The clinical course of neuromyelitis optica (Devic's syndrome).
        Neurology. 1999; 53: 1107-1114
        • Wingerchuk D.M.
        • Lennon V.A.
        • Lucchinetti C.F.
        • Pittock S.J.
        • Weinshenker B.G.
        The spectrum of neuromyelitis optica.
        Lancet Neurol. 2007; 6: 805-815
        • Lennon V.A.
        • Wingerchuk D.M.
        • Kryzer T.J.
        • Pittock S.J.
        • Lucchinetti C.F.
        • Fujihara K.
        • et al.
        A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis.
        Lancet. 2004; 364: 2106-2112
        • Weinshenker B.G.
        • Wingerchuk D.M.
        • Nakashima I.
        • Fujihara K.
        • Lennon V.A.
        OSMS is NMO, but not MS: proven clinically and pathologically.
        Lancet Neurol. 2006; 5: 110-111
        • Lennon V.A.
        • Kryzer T.J.
        • Pittock S.J.
        • Verkman A.S.
        • Hinson S.R.
        IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel.
        J Exp Med. 2005; 202: 473-477
        • Devic E.
        Myélite aiguë compliquée de névrite optique.
        Bull Med (Paris). 1894; 8: 1033-1034
        • Gault F.
        De la neuromyélite optique aiguë.
        Lyon. 1894;
        • Kira J.
        Multiple sclerosis in the Japanese population.
        Lancet Neurol. 2003; 2: 117-127
        • Pittock S.J.
        • Lennon V.A.
        • de Seze J.
        • Vermersch P.
        • Homburger H.A.
        • Wingerchuk D.M.
        • et al.
        Neuromyelitis optica and non organ-specific autoimmunity.
        Arch Neurol. 2008; 65: 78-83
        • McKeon A.
        • Lennon V.A.
        • Jacob A.
        • Matiello M.
        • Lucchinetti C.F.
        • Kale N.
        • et al.
        Coexistence of myasthenia gravis and serological markers of neurological autoimmunity in neuromyelitis optica.
        Muscle Nerve. 2009; 39: 87-90
        • Takahashi T.
        • Fujihara K.
        • Nakashima I.
        • Misu T.
        • Miyazawa I.
        • Nakamura M.
        • et al.
        Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO: a study on antibody titer.
        Brain. 2007; 130: 1235-1243
        • Waters P.
        • Vincent A.
        Detection of anti-aquaporin-4 antibodies in neuromyelitis optica: current status of the assays.
        Int MS J. 2008; 15: 99-105
        • Jarius S.
        • Aboul-Enein F.
        • Waters P.
        • Kuenz B.
        • Hauser A.
        • Berger T.
        • et al.
        Antibody to aquaporin-4 in the long-term course of neuromyelitis optica.
        Brain. 2008; 131: 3072-3080
        • Weinshenker B.G.
        • Wingerchuk D.M.
        • Vukusic S.
        • Linbo L.
        • Pittock S.J.
        • Lucchinetti C.F.
        • et al.
        Neuromyelitis optica IgG predicts relapse after longitudinally extensive transverse myelitis.
        Ann Neurol. 2006; 59: 566-569
        • Miyazawa I.
        • Fujihara K.
        • Itoyama Y.
        Neuromyelitis optica(Devic disease) and optic-spinal form multiple sclerosis.
        No To Shinkei (Brain and Nerve). 2001; 53: 901-910
        • Wingerchuk D.M.
        • Pittock S.J.
        • Lucchinetti C.F.
        • Lennon V.A.
        • Weinshenker B.G.
        A secondary progressive clinical course is uncommon in neuromyelitis optica.
        Neurology. 2007; 68: 603-605
        • de Seze J.
        • Blanc F.
        • Jeanjean L.
        • Zéphir H.
        • Labauge P.
        • Bouyon M.
        • et al.
        Optical coherence tomography in neuromyelitis optica.
        Arch Neurol. 2008; 65: 920-923
        • Nakamura M.
        • Miyazawa I.
        • Fujihara K.
        • Nakashima I.
        • Misu T.
        • Watanabe S.
        • et al.
        Preferential spinal central gray matter involvement in neuromyelitis optica: an MRI study.
        J Neurol. 2008; 255: 163-170
        • Pittock S.J.
        • Lennon V.A.
        • Krecke K.
        • Wingerchuk D.M.
        • Lucchinetti C.F.
        • Weinshenker B.G.
        Brain abnormalities in neuromyelitis optica.
        Arch Neurol. 2006; 63: 390-396
        • Nakashima I.
        • Fujihara K.
        • Miyazawa I.
        • Misu T.
        • Narikawa K.
        • Nakamura M.
        • et al.
        Clinical and MRI features of Japanese patients with multiple sclerosis positive for NMO-IgG.
        J Neurol Neurosurg Psychiatry. 2006; 77: 1073-1075
        • Pittock S.J.
        • Weinshenker B.G.
        • Lucchinetti C.F.
        • Wingerchuk D.M.
        • Corboy J.R.
        • Lennon V.A.
        Neuromyelitis optica brain lesions localized at sites of high aquaporin 4 expression.
        Arch Neurol. 2006; 63: 964-968
        • Misu T.
        • Fujihara K.
        • Nakashima I.
        • Sato S.
        • Itoyama Y.
        Intractable hiccup and nausea with periaqueductal lesions in neuromyelitis optica.
        Neurology. 2005; 65: 1479-1482
        • Takahashi T.
        • Miyazawa I.
        • Misu T.
        • Takano R.
        • Nakashima I.
        • Fujihara K.
        • et al.
        Intractable hiccup and nausea in neuromyelitis optica with anti-aquaporin-4 antibody: a herald of acute exacerbations.
        J Neurol Neurosurg Psychiatry. 2008; 79: 1075-1078
        • Nakamura M.
        • Misu T.
        • Fujihara K.
        • Miyazawa I.
        • Nakashima I.
        • Takahashi T.
        • et al.
        Occurrence of acute large and edematous callosal lesions in neuromyelitis optica.
        Mult Scler. 2009; 15: 695-700
        • Baba T.
        • Nakashima I.
        • Kanbayashi T.
        • Konno M.
        • Takahashi T.
        • Fujihara K.
        • et al.
        Narcolepsy as an initial manifestation of neuromyelitis optica with anti-aquaporin-4 antibody.
        J Neurol. 2009; 256: 287-288
        • Wingerchuk D.M.
        • Lennon V.A.
        • Pittock S.J.
        • Lucchinetti C.F.
        • Weinshenker B.G.
        Revised diagnostic criteria for neuromyelitis optica.
        Neurology. 2006; 66: 1485-1489
        • Nakamura M.
        • Nakashima I.
        • Sato S.
        • Miyazawa I.
        • Fujihara K.
        • Itoyama Y.
        Clinical and laboratory features of neuromyelitis optica with oligoclonal IgG bands.
        Mult Scler. 2007; 13: 332-335
        • Keegan M.
        • Pineda A.A.
        • McClelland R.L.
        • Darby C.H.
        • Rodriguez M.
        • Weinshenker B.G.
        Plasma exchange for severe attacks of CNS demyelination: predictors of response.
        Neurology. 2002; 58: 143-146
        • Watanabe S.
        • Nakashima I.
        • Misu T.
        • Miyazawa I.
        • Shiga Y.
        • Fujihara K.
        • et al.
        Therapeutic efficacy of plasma exchange in NMO-IgG-positive patients with neuromyelitis optica.
        Mult Scler. 2007; 13: 128-132
        • Hosokawa S.
        • Oyamaguchi A.
        • Yoshida O.
        Successful immunoadsorption with membrane plasmapheresis for multiple sclerosis.
        ASAIO Trans. 1989; 35: 576-577
        • Papeix C.
        • Vidal J.S.
        • de Seze J.
        • Pierrot-Deseilligny C.
        • Tourbah A.
        • Stankoff B.
        • et al.
        Immunosuppressive therapy is more effective than interferon in neuromyelitis optica.
        Mult Scler. 2007; 13: 256-259
        • Matsuoka T.
        • Matsushita T.
        • Kawano Y.
        • Osoegawa M.
        • Ochi H.
        • Ishizu T.
        • et al.
        Heterogeneity of aquaporin-4 autoimmunity and spinal cord lesions in multiple sclerosis in Japanese.
        Brain. 2007; 130: 1206-1223
        • Tanaka M.
        • Tanaka K.
        • Komori M.
        Interferon-beta(1b) treatment in neuromyelitis optica.
        Eur Neurol. 2009; 62: 167-170
        • Shimizu Y.
        • Yokoyama K.
        • Misu T.
        • Takahashi T.
        • Fujihara K.
        • Kikuchi S.
        • et al.
        Development of extensive brain lesions following interferon beta therapy in relapsing neuromyelitis optica and longitudinally extensive myelitis.
        J Neurol. 2008; 255: 305-307
        • Watanabe S.
        • Misu T.
        • Miyazawa I.
        • Nakashima I.
        • Shiga Y.
        • Fujihara K.
        • et al.
        Low-dose corticosteroids reduce relapses in neuromyelitis optica: a retrospective analysis.
        Mult Scler. 2007; 13: 968-974
        • Mandler R.N.
        • Ahmed W.
        • Dencoff J.E.
        Devic's neuromyelitis optica: a prospective study of seven patients treated with prednisone and azathioprine.
        Neurology. 1998; 51: 1219-1220
        • Jacob A.
        • Matiello M.
        • Weinshenker B.G.
        • Wingerchuk D.M.
        • Lucchinetti C.
        • Shuster E.
        • et al.
        Treatment of neuromyelitis optica with mycophenolate mofetil: retrospective analysis of 24 patients.
        Arch Neurol. 2009; 66: 1128-1133
        • Weinstock-Guttman B.
        • Ramanathan M.
        • Lincoff N.
        • Napoli S.Q.
        • Sharma J.
        • Feichter J.
        • et al.
        Study of mitoxantrone for the treatment of recurrent neuromyelitis optica (Devic disease).
        Arch Neurol. 2006; 63: 957-963
        • Jacob A.
        • Weinshenker B.G.
        • Violich I.
        • McLinskey N.
        • Krupp L.
        • Fox R.J.
        • et al.
        Treatment of neuromyelitis optica with rituximab: retrospective analysis of 25 patients.
        Arch Neurol. 2008; 65: 1443-1448
        • Miyamoto K.
        • Kusunoki S.
        Intermittent plasmapheresis prevents recurrence in neuromyelitis optica.
        Ther Apher Dial. 2009; 13: 505-508
        • Lucchinetti C.F.
        • Mandler R.N.
        • McGavern D.
        • Bruck W.
        • Gleich G.
        • Ransohoff R.M.
        • et al.
        A role for humoral mechanisms in the pathogenesis of Devic's neuromyelitis optica.
        Brain. 2002; 125: 1450-1461
        • Misu T.
        • Fujihara K.
        • Nakamura M.
        • Murakami K.
        • Endo M.
        • Konno H.
        • et al.
        Loss of aquaporin-4 in active perivascular lesions in neuromyelitis optica: a case report.
        Tohoku J Exp Med. 2006; 209: 269-275
        • Roemer S.F.
        • Parisi J.E.
        • Lennon V.A.
        • Benarroch E.E.
        • Lassmann H.
        • Bruck W.
        • et al.
        Pattern-specific loss of aquaporin-4 immunoreactivity distinguishes neuromyelitis optica from multiple sclerosis.
        Brain. 2007; 130: 1194-1205
        • Misu T.
        • Fujihara K.
        • Kakita A.
        • Konno H.
        • Nakamura M.
        • Watanabe S.
        • et al.
        Loss of aquaporin-4 in lesions of neuromyelitis optica: distinction from multiple sclerosis.
        Brain. 2007; 130: 1224-1234
        • Misu T.
        • Takano R.
        • Fujihara K.
        • Takahashi T.
        • Sato S.
        • Itoyama Y.
        Marked Increase of CSF GFAP in neuromyelitis optica — an astrocytic damage marker.
        J Neurol Neurosurg Psychiatry. 2009; 80: 575-577
        • Hinson S.R.
        • Pittock S.J.
        • Lucchinetti C.F.
        • Roemer S.F.
        • Fryer J.P.
        • Kryzer T.J.
        • et al.
        Pathogenic potential of IgG binding to water channel extracellular domain in neuromyelitis optica.
        Neurology. 2007; 69: 2221-2231
        • Vincent T.
        • Saikali P.
        • Cayrol R.
        • Roth A.D.
        • Bar-Or A.
        • Prat A.
        • et al.
        Functional consequences of neuromyelitis optica-IgG astrocyte interactions on blood–brain barrier permeability and granulocyte recruitment.
        J Immunol. 2008; 181: 5730-5737
        • Kinoshita M.
        • Nakatsuji Y.
        • Moriya M.
        • Okuno T.
        • Kumanogoh A.
        • Nakano M.
        • et al.
        Astrocytic necrosis is induced by anti-aquaporin-4 antibody-positive serum.
        NeuroReport. 2009; 20: 508-512
        • Kinoshita M.
        • Nakatsuji Y.
        • Kimura T.
        • Moriya M.
        • Takata K.
        • Okuno T.
        • et al.
        Neuromyelitis optica: passive transfer to rats by human immunoglobulin.
        Biochem Biophys Res Commun. 2009; 386: 623-627
        • Bennett J.L.
        • Lam C.
        • Kalluri S.R.
        • Saikali P.
        • Bautista K.
        • Dupree C.
        • et al.
        Intrathecal pathogenic anti-aquaporin-4 antibodies in early neuromyelitis optica.
        Ann Neurol. 2009; 66: 617-629
        • Bradl M.
        • Misu T.
        • Takahashi T.
        • Watanabe M.
        • Mader S.
        • Reindl M.
        • et al.
        Neuromyelitis optica: pathogenicity of patient immunoglobulin in vivo.
        Ann Neurol. 2009; 66: 630-643
        • Saadoun S.
        • Waters P.
        • Bell B.A.
        • Vincent A.
        • Verkman A.S.
        • Papadopoulos M.C.
        Intra-cerebral injection of neuromyelitis optica immunoglobulin G and human complement produces neuromyelitis optica lesions in mice.
        Brain. 2010; 133: 349-361
        • Kinoshita M.
        • Nakatsuji Y.
        • Kimura T.
        • Moriya M.
        • Takata K.
        • Okuno T.
        • et al.
        Anti-aquaporin-4 antibody induces astrocytic cytotoxicity in the absence of CNS antigen-specific T cells.
        Biochem Biophys Res Commun. 2010; 394: 205-210
        • Nishiyama S.
        • Ito T.
        • Misu T.
        • Takahashi T.
        • Kikuchi A.
        • Suzuki N.
        • et al.
        A case of NMO seropositive for aquaporin-4-antibody over 10 years before the onset.
        Neurology. 2009; 72: 1960-1961
        • Sato D.
        • Fujihara K.
        NMO without typical opticospinal phenotype.
        Mult Scler. 2010; 16: 1154-1155