Devic’s neuromyelitis optica (DNMO) is a demyelinating and inflammatory disease of the central nervous system (CNS) essentially restricted to the spinal cord and the optic nerves. It is a rare disorder with a prevalence estimated at less than 1/100,000 in Western countries. Since the first description by Eugène Devic in 1894, the relationship between DNMO and multiple sclerosis (MS) has been controversial. Recent clinical, epidemiological, pathological and immunological data demonstrate that MS and DNMO are distinct entities. This distinction between DNMO and MS is crucial, as prognosis and treatment are indeed different. DNMO is now considered to be an autoimmune, antibody-mediated disease especially since the identification of a specific serum autoantibody, named NMO-IgG and directed against the main water channel of the CNS, aquaporin-4 (AQP4). The assessment of AQP4 antibodies (Abs) has initially been proposed to differentiate DNMO and MS. It has also enlarged the clinical spectrum of DNMO and proved to be helpful in predicting relapses and conversion to DNMO after a first episode of longitudinally extensive transverse myelitis or isolated optic neuritis. Lastly, the discovery of the pathogenic role of AQP4 Abs in DNMO leads to a better understanding of detailed DNMO immunopathology and the elaboration of relevant novel treatment strategies specific to DNMO. In this review, we summarize the present and future therapeutic implications generated by the discovery of the various pathogenic mechanisms of AQP4 Abs in DNMO pathophysiology.
Amiry-Moghaddam, M., Otsuka, T., Hurn, P.D., Traystman, R.J., Haug, F.M., Froehner, S.C. et al. (2003) An alpha-syntrophin-dependent pool of AQP4 in astroglial end-feet confers bidirectional water flow between blood: brain . Proc Natl Acad Sci U S A100: 2106-2111.
2.
Bakker, J. and Metz, L. ( 2004) Devic’s neuromyelitis optica treated with intravenous gamma globulin (IVIG). Can J Neurol Sci31: 265-267.
3.
Basso, A.S., Frenkel, D., Quintana, F.J., Costa-Pinto, F.A., Petrovic-Stojkovic, S., Puckett, L. et al. (2008) Reversal of axonal loss and disability in a mouse model of progressive multiple sclerosis. J Clin Invest118: 1532-1543.
4.
Bennett, J.L., Lam, C., Kalluri, S.R., Saikali, P., Bautista, K., Dupree, C. et al. (2009) Intrathecal pathogenic anti-aquaporin-4 antibodies in early neuromyelitis optica. Ann Neurol66: 617-629.
5.
Binder, D.K., Oshio, K., Ma, T., Verkman, A.S. and Manley, G.T. ( 2004) Increased seizure threshold in mice lacking aquaporin-4 water channels. Neuroreport15: 259-262.
6.
Bradl, M., Misu, T., Takahashi, T., Watanabe, M., Mader, S., Reindl, M. et al. (2009) Neuromyelitis optica: Pathogenicity of patient immunoglobulin in vivo. Ann Neurol66: 630-643.
7.
Bonnan, M., Valentino, R., Olindo, S., Mehdaoui, H., Smadja, D. and Cabre, P.(2009) Plasma exchange in severe spinal attacks associated with neuromyelitis optica spectrum disorder. Mult Scler4: 487-492.
8.
Capobianco, M., Malucchi, S., di Sapio, A., Gilli, F., Sala, A., Bottero, R. et al. (2007) Variable responses to rituximab treatment in neuromyelitis optica (Devic’s disease). Neurol Sci28: 209-211.
9.
Cassinotto, C., Joux, J., Chausson, N., Smadja, D. and Cabre, P. ( 2008) Failure of rituximab in relapsing neuromyelitis optica: case report with two-year prospective follow-up. Rev Neurol (Paris) 164: 394-397.
10.
Carlander, B., Vincent, T., Le Floch, A., Pageot, N., Camu, W. and Dauvilliers, Y. ( 2008) Hypocretinergic dysfunction in neuromyelitis optica with coma-like episodes. J Neurol Neurosurg Psychiatry79: 333-334.
11.
Collongues, N., Marignier, R., Zéphir, H., Papeix, C., Blanc, F., Ritleng, C. et al. (2010) Neuromyelitis optica in France: a multicenter study of 125 patients. Neurology74: 736-742.
12.
Cragg, M.S. and Glennie, M.J. ( 2004) Antibody specificity controls in vivo effector mechanisms of anti-CD20 reagents. Blood103: 2738-2743.
13.
Cree, B.A., Lamb, S., Morgan, K., Chen, A., Waubant, E. and Genain, C. ( 2005) An open label study of the effects of rituximab in neuromyelitis optica. Neurology64: 1270-1272.
14.
Dalakas, M.C. ( 2008) B cells as therapeutic targets in autoimmune neurological disorders. Nat Clin Pract Neurol4: 557-567.
15.
Diamond, B., Huerta, P.T., Mina-Osorio, P., Kowal, C. and Volpe, B.T.(2009) Losing your nerves? Maybe it’s the antibodies. Nat Rev Immunol9: 449-456.
16.
De Sèze, J., Arndt, C., Jeanjean, L., Zephir, H., Blanc, F., Labauge, P. et al. (2008) Relapsing inflammatory optic neuritis: is it neuromyelitis optica? Neurology70: 2075-2076.
17.
Devic, E. ( 1894) Myelite subaiguë compliquée de névrite optique. Bull Med8: 1033-1034.
18.
Dörner, T. ( 2006) Crossroads of B cell activation in autoimmunity: rationale of targeting B cells. J Rheumatol Suppl77: 3-11.
19.
Fazio, R., Malosio, M.L., Lampasona, V., De Feo, D., Privitera, D., Marnetto, F. et al. (2009) Antiacquaporin 4 antibodies detection by different techniques in neuromyelitis optica patients. Mult Scler10: 1153-1163.
20.
Franchimont, D. ( 2004) Overview of the actions of glucocorticoids on the immune response: a good model to characterize new pathways of immunosuppression for new treatment strategies. Ann N Y Acad Sci1024: 124-137.
21.
Gault, F. ( 1895) De la neuromyélite optique aiguë. Thèse n°891, Faculté de Médecine et de Pharmacie de Lyon.
22.
Genovese, M.C., Kaine, J.L., Lowenstein, M.B., Del Giudice, J., Baldassare, A., Schechtman, J. et al. for ACTION Study Group ( 2008) Ocrelizumab, a humanized anti-CD20 monoclonal antibody, in the treatment of patients with rheumatoid arthritis: a phase I/II randomized, blinded, placebo-controlled, dose-ranging study. Arthritis Rheum58: 2652-2656.
23.
Halstead, S.K., Zitman, F.M., Humphreys, P.D., Greenshields, K., Verschuuren, J.J., Jacobs, B.C. et al. (2008) Eculizumab prevents anti-ganglioside antibody-mediated neuropathy in a murine model. Brain131: 1197-1208.
24.
Hinson, S.R., Pittock, S.J., Lucchinetti, C.F., Roemer, S.F., Fryer, J.P., Kryzer, T.J. et al. (2007) Pathogenic potential of IgG binding to water channel extracellular domain in neuromyelitis optica. Neurology69: 2221-2231.
25.
Hinson, S.R., Roemer, S.F., Lucchinetti, C.F., Fryer, J.P., Kryzer, T.J., Chamberlain, J.L. et al. (2008) Aquaporin-4-binding autoantibodies in patients with neuromyelitis optica impair glutamate transport by down-regulating EAAT2 . J Exp Med205: 2473-2481.
26.
Jacob, A., Weinshenker, B.G., Violich, I., McLinskey, N., Krupp, L., Fox, R.J. et al. (2008) Treatment of neuromyelitis optica with rituximab: retrospective analysis of 25 patients. Arch Neurol65: 1443-1448.
27.
Jarius, S., Aboul-Enein, F., Waters, P., Kuenz, B., Hauser, A., Berger, T. et al. (2008) Antibody to aquaporin-4 in the long-term course of neuromyelitis optica. Brain131: 3072-3080.
28.
Jarius, S., Franciotta, D., Bergamaschi, R., Wright, H., Littleton, E., Palace, J. et al. (2007) NMO-IgG in the diagnosis of neuromyelitis optica . Neurology68: 1076-1077.
29.
Karadottir, R., Cavelier, P., Bergersen, L.H. and Attwell, D. ( 2005) NMDA receptors are expressed in oligodendrocytes and activated in ischaemia. Nature438: 1162-1166.
30.
Keegan, M., Pineda, A.A., McClelland, R.L., Darby, C.H., Rodriguez, M. and Weinshenker, B.G. ( 2002) Plasma exchange for severe attacks of CNS demyelination: predictors of response. Neurology58: 143-146.
31.
Kinoshita, M., Nakatsuji, Y., Moriya, M., Okuno, T., Kumanogoh, A., Nakano, M. et al. (2009) Astrocytic necrosis is induced by anti-aquaporin-4 antibody-positive serum. Neuroreport20: 508-512.
32.
Krumbholz, M., Faber, H., Steinmeyer, F., Hoffmann, L.A., Kümpfel, T., Pellkofer, H. et al. (2008) Interferon-beta increases BAFF levels in multiple sclerosis: implications for B cell autoimmunity. Brain131: 1455-1463.
33.
Lalive, P.H., Menge, T., Barman, I., Cree, B.A. and Genain, C.P. ( 2006) Identification of new serum autoantibodies in neuromyelitis optica using protein microarrays. Neurology67: 176-177.
34.
Lennon, V.A., Kryzer, T.J., Pittock, S.J., Verkman, A.S. and Hinson, S.R. ( 2005) IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med202: 473-7.
35.
Lennon, V.A., Wingerchuk, D.M., Kryzer, T.J., Pittock, S.J., Lucchinetti, C.F., Fujihara, K. et al. (2004) A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet364: 2106-2112.
36.
Lu, M., Lee, M.D., Smith, B.L., Jung, J.S., Agre, P., Verdijk, M.A. et al. (1996) The human AQP4 gene: definition of the locus encoding two water channel polypeptides in brain. Proc Natl Acad Sci U S A93: 10908-10912.
37.
Lucchinetti, C.F., Mandler, R.N., McGavern, D., Bruck, W., Gleich, G., Ransohoff, R.M. et al. (2002) A role for humoral mechanisms in the pathogenesis of Devic’s neuromyelitis optica. Brain125: 1450-1461.
38.
Mackay, F., Silveira, P.A. and Brink, R. ( 2007) B cells and the BAFF/APRIL axis: fast-forward on autoimmunity and signaling. Curr Opin Immunol19: 327-336.
39.
Mandler, R.N., Ahmed, W. and Dencoff, J.E. ( 1998) Devic’s neuromyelitis optica: a prospective study of seven patients treated with prednisone and azathioprine. Neurology51: 1219-1220.
40.
Marignier, R., De Seze, J., Vukusic, S., Durand-Dubief, F., Zephir, H. and Vermersch, P. ( 2007) Clinical, MRI and laboratory findings in a cohort of French Devic’s Neuromyelitis Optica: comparison between NMO-IgG seropositive and seronegative patients. In: Program and Abstracts of the 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), Prague, Czech Republic, 2007.
41.
Marignier, R., De Seze, J., Vukusic, S., Durand-Dubief, F., Zephir, H., Vermersch, P. et al. (2008) NMO-IgG and Devic’s neuromyelitis optica: a French experience. Mult Scler14: 440-445.
42.
Marignier, R., Nicolle, A., Watrin, C., Touret, M., Cavagna, S., Varrin-Doyer, M. et al. (2010) Neuromyelitis Optica-IgG induces oligodendrocyte injury through astrocyte alteration. Brain (in press).
43.
Matiello, M., Lennon, V.A., Jacob, A., Pittock, S.J., Lucchinetti, C.F., Wingerchuk, D.M. et al. (2008) NMO-IgG predicts the outcome of recurrent optic neuritis. Neurology70: 2197-2200.
44.
Matute, C. ( 2006) Oligodendrocyte NMDA receptors: a novel therapeutic target . Trends Mol Med12: 289-292.
45.
Matute, C., Sanchez-Gomez, M.V., Martinez-Millan, L. and Miledi, R. ( 1997) Glutamate receptor-mediated toxicity in optic nerve oligodendrocytes . Proc Natl Acad Sci U S A94: 8830-8835.
46.
McKeon, A., Fryer, J.P., Apiwattanakul, M., Lennon, V.A., Hinson, S.R., Kryzer, T.J. et al. (2009) Diagnosis of neuromyelitis spectrum disorders: comparative sensitivities and specificities of immunohistochemical and immunoprecipitation assays. Arch Neurol66: 1134-1138.
47.
Moreh, E., Gartsman, I., Karussis, D., Rund, D., Hiller, N. and Meiner, Z. ( 2008) Seronegative neuromyelitis optica: improvement following lymphocytapheresis treatment. Mult Scler14: 860-861.
48.
Misu, T., Fujihara, K., Kakita, A., Konno, H., Nakamura, M., Watanabe, S. et al. (2007) Loss of aquaporin 4 in lesions of neuromyelitis optica: distinction from multiple sclerosis. Brain130: 1224-1234.
49.
Nakashima, I., Takahashi, T., Cree, B., Kim, H.J., Suzuki, C., Genain, C., Vincent, T. et al. (2009) Anti-aquaporin 4 autoantibodies increase transiently after rituximab treatment in neuromyelitis optica: an association with B-cell activating factor. In: Program and Abstracts of the 25th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), Dusseldorf, Germany, 2009.
50.
Neely, J.D., Amiry-Moghaddam, M., Ottersen, O.P., Froehner, S.C., Agre, P. and Adams, M.E. ( 2001) Syntrophin-dependent expression and localization of Aquaporin-4 water channel protein. Proc Natl Acad Sci U S A98: 14108-14113.
51.
Nicchia, G.P., Mastrototaro, M., Rossi, A., Pisani, F., Tortorella, C., Ruggieri, M. et al. (2009) Aquaporin-4 orthogonal arrays of particles are the target for neuromyelitis optica autoantibodies. Glia57: 1363-1373.
52.
Nozaki, I., Hamaguchi, T., Komai, K. and Yamada, M. ( 2006) Fulminant Devic disease successfully treated by lymphocytapheresis . J Neurol Neurosurg Psychiatry77: 1094-1095.
53.
Okada, K., Matsushita, T., Kira, J. and Tsuji, S.(2010) B-cell activating factor of the TNF family is upregulated in neuromyelitis optica. Neurology74: 177-178.
54.
Okada, K., Tsuji, S. and Tanaka, K. ( 2007) Intermittent intravenous immunoglobulin successfully prevents relapses of neuromyelitis optica. Intern Med46: 1671-1672.
55.
O’Riordan, J.I., Gallagher, H.L., Thompson, A.J., Howard, R.S., Kingsley, D.P., Thompson, E.J. et al. (1996) Clinical, CSF, and MRI findings in Devic’s neuromyelitis optica. J Neurol Neurosurg Psychiatry60: 382-387.
56.
Papadopoulos, M.C., Manley, G.T., Krishna, S. and Verkman, A.S. ( 2004) Aquaporin-4 facilitates reabsorption of excess fluid in vasogenic brain edema. FASEB J18: 1291-1293.
57.
Papeix, C., Vidal, J.S., de Seze, J., Pierrot-Deseilligny, C., Tourbah, A., Stankoff, B. et al. (2007) Immunosuppressive therapy is more effective than interferon in neuromyelitis optica. Mult Scler13: 256-259.
58.
Parpura, V., Basarsky, T.A., Liu, F., Jeftinija, K., Jeftinija, S. and Haydon, P.G. ( 1994) Glutamate-mediated astrocyte-neuron signalling. Nature369: 744-747.
59.
Parpura, V. and Zorec, R. ( 2009) Gliotransmission: Exocytotic release from astrocytes. Brain Res Rev [Epub ahead of print].
60.
Petzold, A., Pittock, S., Lennon, V., Maggiore, C., Weinshenker, B.G. and Plant, G.T.(2010) Neuromyelitis optica-IgG (aquaporin-4) autoantibodies in immune mediated optic neuritis. J Neurol Neurosurg Psychiatry81: 109-111.
61.
Pittock, S.J., Lennon, V.A., de Seze, J., Vermersch, P., Homburger, H.A., Wingerchuk, D.M. et al. (2008) Neuromyelitis optica and non organ-specific autoimmunity . Arch Neurol65: 78-83.
62.
Pittock, S.J., Lennon, V.A., Krecke, K., Wingerchuk, D.M., Lucchinetti, C.F. and Weinshenker, B.G. ( 2006a) Brain abnormalities in neuromyelitis optica. Arch Neurol63: 390-396.
63.
Pittock, S.J., Weinshenker, B.G., Lucchinetti, C.F., Wingerchuk, D.M., Corboy, J.R. and Lennon, V.A. ( 2006b) Neuromyelitis optica brain lesions localized at sites of high aquaporin 4 expression. Arch Neurol63: 964-968.
64.
Preston, G.M., Carroll, T.P., Guggino, W.B. and Agre, P. ( 1992) Appearance of water channels in Xenopus oocytes expressing red cell CHIP28 protein. Science256: 385-387.
65.
Rash, J.E. ( 2009) Molecular disruptions of the panglial syncytium block potassium siphoning and axonal saltatory conduction: pertinence to neuromyelitis optica and other demyelinating diseases of the central nervous system. Neuroscience [Epub ahead of print].
66.
Roemer, S.F., Parisi, J.E., Lennon, V.A., Benarroch, E.E., Lassmann, H., Bruck, W. et al. (2007) Pattern-specific loss of aquaporin-4 immunoreactivity distinguishes neuromyelitis optica from multiple sclerosis. Brain130: 1194-1205.
67.
Rossi, A., Pisani, F., Nicchia, G.P., Svelto, M. and Frigeri, A.(2010) Evidences for a leaky scanning mechanism for the synthesis of the shorter M23 protein isoform of aquaporin-4: implication in orthogonal array formation and neuromyelitis optica antibody interaction. J Biol Chem285: 4562-4569.
68.
Rus, H., Cudrici, C., David, S. and Niculescu, F. ( 2006) The complement system in central nervous system diseases . Autoimmunity39: 395-402.
69.
Saadoun, S., Waters, P., Bell, B.A., Vincent, A., Verkman, A.S. and Papadopoulos, M.C.(2010) Intra-cerebral injection of neuromyelitis optica immunoglobulin G and human complement produces neuromyelitis optica lesions in mice. Brain133: 349-361.
70.
Sabater, L., Giralt, A., Boronat, A., Hankiewicz, K., Blanco, Y., Llufriu, S. et al. (2009) Cytotoxic effect of neuromyelitis optica antibody (NMO-IgG) to astrocytes: an in vitro study. J Neuroimmunol215: 31-35.
71.
Saini, H., Fernandez, G., Kerr, D. and Levy, M.(2010) Differential expression of aquaporin-4 isoforms localizes with neuromyelitis optica disease activity. J Neuroimmunol221: 68-72.
72.
Salter, M.G. and Fern, R. ( 2005) NMDA receptors are expressed in developing oligodendrocyte processes and mediate injury. Nature438: 1167-1171.
73.
Sato, S., Ono, N., Steeber, D.A., Pisetsky, D.S. and Tedder, T.F. ( 1996) CD19 regulates B lymphocyte signaling thresholds critical for the development of B-1 lineage cells and autoimmunity. J Immunol157: 4371-4378.
74.
Sellner, J., Boggild, M., Clanet, M., Hintzen, R.Q., Illes, Z., Montalban, X. et al. (2010) EFNS guidelines on diagnosis and management of neuromyelitis optica. Eur J Neurol [Epub ahead of print].
75.
Stashenko, P., Nadler, L.M., Hardy, R. and Schlossman, S.F. ( 1980) Characterization of a human B lymphocyte-specific antigen . J Immunol125: 1678-1685.
76.
Suzuki, H., Nishikawa, K., Hiroaki, Y. and Fujiyoshi, Y. ( 2008) Formation of aquaporin-4 arrays is inhibited by palmitoylation of N-terminal cysteine residues. Biochim Biophys Acta1778: 1181-1189.
77.
Takahashi, T., Fujihara, K., Nakashima, I., Misu, T., Miyazawa, I., Nakamura, M. et al. (2007) Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO: a study on antibody titre. Brain130: 1235-1243.
78.
Takahashi, T., Miyazawa, I., Misu, T., Takano, R., Nakashima, I., Fujihara, K. et al. (2008) Intractable hiccup and nausea in neuromyelitis optica with anti-aquaporin-4 antibody: a herald of acute exacerbations. J Neurol Neurosurg Psychiatry79: 1075-1078.
79.
Tedder, T.F., Poe, J.C. and Haas, K.M. ( 2005) CD22: a multifunctional receptor that regulates B lymphocyte survival and signal transduction. Adv Immunol88: 1-50.
80.
Verkman, A.S. ( 2005) More than just water channels: unexpected cellular roles of aquaporins. J Cell Sci118: 3225-3232.
81.
Verkman, A.S., Binder, D.K., Bloch, O., Auguste, K. and Papadopoulos, M.C. ( 2006) Three distinct roles of aquaporin-4 in brain function revealed by knockout mice. Biochim Biophys Acta1758: 1085-1093.
82.
Vincent, A. ( 2010) Autoimmune channelopathies: well-established and emerging immunotherapy-responsive diseases of the peripheral and central nervous systems . J Clin Immunol [Epub ahead of print].
83.
Vincent, T., Saikali, P., Cayrol, R., Roth, A.D., Bar-Or, A., Prat, A. et al. (2008) Functional consequences of neuromyelitis optica-IgG astrocyte interactions on blood-brain barrier permeability and granulocyte recruitment. J Immunol181: 5730-5737.
84.
Wallstrom, E., Diener, P., Ljungdahl, A., Khademi, M., Nilsson, C.G. and Olsson, T. ( 1996) Memantine abrogates neurological deficits, but not CNS inflammation, in Lewis rat experimental autoimmune encephalomyelitis. J Neurol Sci137: 89-96.
85.
Warabi, Y., Matsumoto, Y. and Hayashi, H. ( 2007) Interferon beta-1b exacerbates multiple sclerosis with severe optic nerve and spinal cord demyelination. J Neurol Sci252: 57-61.
86.
Warth, A. ( 2009) Prevention of orthogonal array of particles formation as a treatment approach for neuromyelitis optica. Med Hypotheses73: 361-362.
87.
Watanabe, S., Nakashima, I., Misu, T., Miyazawa, I., Shiga, Y., Fujihara, K. et al. (2007) Therapeutic efficacy of plasma exchange in NMO-IgG-positive patients with neuromyelitis optica. Mult Scler13: 128-132.
88.
Waters, P., Jarius, S., Littleton, E., Leite, M.I., Jacob, S., Gray, B. et al. (2008) Aquaporin-4 antibodies in neuromyelitis optica and longitudinally extensive transverse myelitis. Arch Neurol65: 913-919.
89.
Weinshenker, B.G., O’Brien, P.C., Petterson, T.M., Noseworthy, J.H., Lucchinetti, C.F., Dodick, D.W. et al. (1999) A randomized trial of plasma exchange in acute central nervous system inflammatory demyelinating disease. Ann Neurol46: 878-888.
90.
Weinshenker, B.G., Wingerchuk, D.M., Vukusic, S., Linbo, L., Pittock, S.J., Lucchinetti, C.F. et al. (2006) Neuromyelitis optica IgG predicts relapse after longitudinally extensive transverse myelitis. Ann Neurol59: 566-569.
91.
Weinstock-Guttman, B., Miller, C., Yeh, E., Stosic, M., Umhauer, M., Batra, N. et al. (2008) Neuromyelitis optica immunoglobulins as a marker of disease activity and response to therapy in patients with neuromyelitis optica. Mult Scler14: 1061-1067.
92.
Weinstock-Guttman, B., Ramanathan, M., Lincoff, N., Napoli, S.Q., Sharma, J., Feichter, J. et al. (2006) Study of mitoxantrone for the treatment of recurrent neuromyelitis optica (Devic disease). Arch Neurol63: 957-963.
93.
Wingerchuk, D.M., Hogancamp, W.F., O’Brien, P.C. and Weinshenker, B.G. ( 1999) The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology53: 1107-1114.
94.
Wingerchuk, D.M., Lennon, V.A., Lucchinetti, C.F., Pittock, S.J. and Weinshenker, B.G. ( 2007a) The spectrum of neuromyelitis optica. Lancet Neurol6: 805-815.
Wingerchuk, D.M., Pittock, S.J., Lucchinetti, C.F., Lennon, V.A. and Weinshenker, B.G. ( 2007b) A secondary progressive clinical course is uncommon in neuromyelitis optica. Neurology68: 603-605.
97.
Xu, G.Y., Liu, S., Hughes, M.G. and McAdoo, D.J. ( 2008) Glutamate-induced losses of oligodendrocytes and neurons and activation of caspase-3 in the rat spinal cord. Neuroscience153: 1034-1047.
98.
Yanagawa, K., Kawachi, I., Toyoshima, Y., Yokoseki, A., Arakawa, M., Hasegawa, A. et al. (2009) Pathologic and immunologic profiles of a limited form of neuromyelitis optica with myelitis. Neurology73: 1628-1637.
99.
Yang, B., Brown, D. and Verkman, A.S. ( 1996) The mercurial insensitive water channel (AQP-4) forms orthogonal arrays in stably transfected Chinese hamster ovary cells. J Biol Chem27: 4577-4580.
100.
Zeng, X.N., Sun, X.L., Gao, L., Fan, Y., Ding, J.H. and Hu, G. ( 2007) Aquaporin-4 deficiency down-regulates glutamate uptake and GLT-1 expression in astrocytes. Mol Cell Neurosci34: 34-39.
101.
Zisimopoulou, P., Lagoumintzis, G., Kostelidou, K., Bitzopoulou, K., Kordas, G., Trakas, N. et al. (2008) Towards antigen-specific apheresis of pathogenic autoantibodies as a further step in the treatment of myasthenia gravis by plasmapheresis. J Neuroimmunol201-202: 95-103.
102.
Zuliani, L., Lopez de Munain, A., Ruiz Martinez, J., Olascoaga, J., Graus, F. and Saiz, A. ( 2006) [NMO-IgG antibodies in neuromyelitis optica: a report of 2 cases]. Neurologia21: 314-317.
