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Published in: Current Neurology and Neuroscience Reports 9/2014

01-09-2014 | Demyelinating Disorders (DN Bourdette and V Yadav, Section Editors)

Neuromyelitis Optica Spectrum Disorders

Authors: Eoin P. Flanagan, Brian G. Weinshenker

Published in: Current Neurology and Neuroscience Reports | Issue 9/2014

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Abstract

Since the discovery of aquaporin 4-IgG, a sensitive and highly specific biomarker of neuromyelitis optica (NMO), a wide range of syndromes have been recognized as being associated with this condition. This observation has led to new proposed terminology for the entire disorder, NMO spectrum disorders (NMOSD). The discovery of a pathogenic autoantibody and its target antigen has also facilitated basic research into the immunopathogenesis of the disease. Key advances include establishment of passive transfer animal models demonstrating the pathogenic potential of the autoantibody and confirming an important role of complement suggested by immunopathology of NMO brain lesions and of B-cell subsets, plasmablasts in particular. These discoveries have led to phase 1 clinical trials of targeted immunotherapy with potential for improved efficacy and less toxicity than current empiric immunosuppressant medications used to treat NMOSD. Randomized clinical trials are beginning to assess the efficacy and safety of a variety of immunotherapies in NMOSD. Therapeutic options are likely to increase, and improved outcomes in NMOSD patients are anticipated.
Literature
1.
go back to reference Miyazawa I, Fujihara K, Itoyama Y. Eugene Devic (1858–1930). J Neurol. 2002;249(3):351–2.PubMed Miyazawa I, Fujihara K, Itoyama Y. Eugene Devic (1858–1930). J Neurol. 2002;249(3):351–2.PubMed
3.
go back to reference Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet. 2004;364(9451):2106–12. doi:10.1016/S0140-6736(04)17551-X.PubMed Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet. 2004;364(9451):2106–12. doi:10.​1016/​S0140-6736(04)17551-X.PubMed
8.
go back to reference Titulaer MJ, Hoftberger R, Iizuka T, Leypoldt F, McCracken L, Cellucci T, et al. Overlapping demyelinating syndromes and anti-N-methyl-D-aspartate receptor encephalitis. Ann Neurol. 2014;75(3):411–28. doi:10.1002/ana.24117.PubMed Titulaer MJ, Hoftberger R, Iizuka T, Leypoldt F, McCracken L, Cellucci T, et al. Overlapping demyelinating syndromes and anti-N-methyl-D-aspartate receptor encephalitis. Ann Neurol. 2014;75(3):411–28. doi:10.​1002/​ana.​24117.PubMed
10.
go back to reference Kitley J, Leite MI, Nakashima I, Waters P, McNeillis B, Brown R, et al. Prognostic factors and disease course in aquaporin-4 antibody-positive patients with neuromyelitis optica spectrum disorder from the United Kingdom and Japan. Brain. 2012;135(6):1834–49. doi:10.1093/brain/aws109.PubMed Kitley J, Leite MI, Nakashima I, Waters P, McNeillis B, Brown R, et al. Prognostic factors and disease course in aquaporin-4 antibody-positive patients with neuromyelitis optica spectrum disorder from the United Kingdom and Japan. Brain. 2012;135(6):1834–49. doi:10.​1093/​brain/​aws109.PubMed
11.
go back to reference Wingerchuk DM, Hogancamp WF, O'Brien PC, Weinshenker BG. The clinical course of neuromyelitis optica (Devic's syndrome). Neurology. 1999;53(5):1107–14.PubMed Wingerchuk DM, Hogancamp WF, O'Brien PC, Weinshenker BG. The clinical course of neuromyelitis optica (Devic's syndrome). Neurology. 1999;53(5):1107–14.PubMed
12.
14.
17.
go back to reference Apiwattanakul M, Popescu BF, Matiello M, Weinshenker BG, Lucchinetti CF, Lennon VA, et al. Intractable vomiting as the initial presentation of neuromyelitis optica. Ann Neurol. 2010;68(5):757–61. doi:10.1002/ana.22121.PubMed Apiwattanakul M, Popescu BF, Matiello M, Weinshenker BG, Lucchinetti CF, Lennon VA, et al. Intractable vomiting as the initial presentation of neuromyelitis optica. Ann Neurol. 2010;68(5):757–61. doi:10.​1002/​ana.​22121.PubMed
18.
go back to reference 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(2):287–8. doi:10.1007/s00415-009-0139-4.PubMed 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(2):287–8. doi:10.​1007/​s00415-009-0139-4.PubMed
19.
go back to reference Suzuki K, Nakamura T, Hashimoto K, Miyamoto M, Komagamine T, Nagashima T, et al. Hypothermia, hypotension, hypersomnia, and obesity associated with hypothalamic lesions in a patient positive for the anti-aquaporin 4 antibody: a case report and literature review. Arch Neurol. 2012;69(10):1355–9. doi:10.1001/archneurol.2012.300.PubMed Suzuki K, Nakamura T, Hashimoto K, Miyamoto M, Komagamine T, Nagashima T, et al. Hypothermia, hypotension, hypersomnia, and obesity associated with hypothalamic lesions in a patient positive for the anti-aquaporin 4 antibody: a case report and literature review. Arch Neurol. 2012;69(10):1355–9. doi:10.​1001/​archneurol.​2012.​300.PubMed
21.
go back to reference Viegas S, Weir A, Esiri M, Kuker W, Waters P, Leite MI, et al. Symptomatic, radiological and pathological involvement of the hypothalamus in neuromyelitis optica. J Neurol Neurosurg Psychiatry. 2009;80(6):679–82. doi:10.1136/jnnp.2008.157693.PubMed Viegas S, Weir A, Esiri M, Kuker W, Waters P, Leite MI, et al. Symptomatic, radiological and pathological involvement of the hypothalamus in neuromyelitis optica. J Neurol Neurosurg Psychiatry. 2009;80(6):679–82. doi:10.​1136/​jnnp.​2008.​157693.PubMed
23.
24.
go back to reference Jarius S, Lauda F, Wildemann B, Tumani H. Steroid-responsive hearing impairment in NMO-IgG/aquaporin-4-antibody-positive neuromyelitis optica. J Neurol. 2013;260(2):663–4. doi:10.1007/s00415-012-6755-4.PubMed Jarius S, Lauda F, Wildemann B, Tumani H. Steroid-responsive hearing impairment in NMO-IgG/aquaporin-4-antibody-positive neuromyelitis optica. J Neurol. 2013;260(2):663–4. doi:10.​1007/​s00415-012-6755-4.PubMed
31.
go back to reference Jarius S, Ruprecht K, Wildemann B, Kuempfel T, Ringelstein M, Geis C, et al. Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: a multicentre study of 175 patients. J Neuroinflammation. 2012;9:14. doi:10.1186/1742-2094-9-14.PubMedCentralPubMed Jarius S, Ruprecht K, Wildemann B, Kuempfel T, Ringelstein M, Geis C, et al. Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: a multicentre study of 175 patients. J Neuroinflammation. 2012;9:14. doi:10.​1186/​1742-2094-9-14.PubMedCentralPubMed
35.
go back to reference Asgari N, Skejoe HP, Lillevang ST, Steenstrup T, Stenager E, Kyvik KO. Modifications of longitudinally extensive transverse myelitis and brainstem lesions in the course of neuromyelitis optica (NMO): a population-based, descriptive study. BMC Neurol. 2013;13:33. doi:10.1186/1471-2377-13-33.PubMedCentralPubMed Asgari N, Skejoe HP, Lillevang ST, Steenstrup T, Stenager E, Kyvik KO. Modifications of longitudinally extensive transverse myelitis and brainstem lesions in the course of neuromyelitis optica (NMO): a population-based, descriptive study. BMC Neurol. 2013;13:33. doi:10.​1186/​1471-2377-13-33.PubMedCentralPubMed
36.
go back to reference Downer JJ, Leite MI, Carter R, Palace J, Kuker W, Quaghebeur G. Diagnosis of neuromyelitis optica (NMO) spectrum disorders: is MRI obsolete? Neuroradiology. 2012;54(4):279–85. doi:10.1007/s00234-011-0875-x.PubMed Downer JJ, Leite MI, Carter R, Palace J, Kuker W, Quaghebeur G. Diagnosis of neuromyelitis optica (NMO) spectrum disorders: is MRI obsolete? Neuroradiology. 2012;54(4):279–85. doi:10.​1007/​s00234-011-0875-x.PubMed
37.
go back to reference 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(2):163–70. doi:10.1007/s00415-008-0545-z.PubMed 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(2):163–70. doi:10.​1007/​s00415-008-0545-z.PubMed
38.•
go back to reference Flanagan EP, Weinshenker BG, Krecke KN, Lennon VA, Lucchinetti CF, McKeon A, et al. Short myelitis lesions in aquaporin-4-IgG-positive neuromyelitis optica spectrum. JAMA Neurol. 2014. This article reports that the initial myelitis episode in NMO/NMOSD is accompanied by a short lesion (fewer than three vertebral segments) in approximately 14% of cases, and when present this delays diagnosis/treatment. Certain clinical and radiological characteristics identified in this study may help select those with short myelitis lesions at highest risk of NMO/NMOSD. Therefore, short transverse myelitis lesions do not exclude AQP4-IgG testing nor NMOSD diagnosis. Flanagan EP, Weinshenker BG, Krecke KN, Lennon VA, Lucchinetti CF, McKeon A, et al. Short myelitis lesions in aquaporin-4-IgG-positive neuromyelitis optica spectrum. JAMA Neurol. 2014. This article reports that the initial myelitis episode in NMO/NMOSD is accompanied by a short lesion (fewer than three vertebral segments) in approximately 14% of cases, and when present this delays diagnosis/treatment. Certain clinical and radiological characteristics identified in this study may help select those with short myelitis lesions at highest risk of NMO/NMOSD. Therefore, short transverse myelitis lesions do not exclude AQP4-IgG testing nor NMOSD diagnosis.
39.
go back to reference Tanaka M, Tanaka K, Komori M, Saida T. Anti-aquaporin 4 antibody in Japanese multiple sclerosis: the presence of optic spinal multiple sclerosis without long spinal cord lesions and anti-aquaporin 4 antibody. J Neurol Neurosurg Psychiatry. 2007;78(9):990–2. doi:10.1136/jnnp.2006.114165.PubMedCentralPubMed Tanaka M, Tanaka K, Komori M, Saida T. Anti-aquaporin 4 antibody in Japanese multiple sclerosis: the presence of optic spinal multiple sclerosis without long spinal cord lesions and anti-aquaporin 4 antibody. J Neurol Neurosurg Psychiatry. 2007;78(9):990–2. doi:10.​1136/​jnnp.​2006.​114165.PubMedCentralPubMed
41.
go back to reference Storoni M, Davagnanam I, Radon M, Siddiqui A, Plant GT. Distinguishing optic neuritis in neuromyelitis optica spectrum disease from multiple sclerosis: a novel magnetic resonance imaging scoring system. J Neuroophthalmol. 2013;33(2):123–7. doi:10.1097/WNO.0b013e318283c3ed.PubMed Storoni M, Davagnanam I, Radon M, Siddiqui A, Plant GT. Distinguishing optic neuritis in neuromyelitis optica spectrum disease from multiple sclerosis: a novel magnetic resonance imaging scoring system. J Neuroophthalmol. 2013;33(2):123–7. doi:10.​1097/​WNO.​0b013e318283c3ed​.PubMed
42.
go back to reference Ito S, Mori M, Makino T, Hayakawa S, Kuwabara S. “Cloud-like enhancement” is a magnetic resonance imaging abnormality specific to neuromyelitis optica. Ann Neurol. 2009;66(3):425–8. doi:10.1002/ana.21753.PubMed Ito S, Mori M, Makino T, Hayakawa S, Kuwabara S. “Cloud-like enhancement” is a magnetic resonance imaging abnormality specific to neuromyelitis optica. Ann Neurol. 2009;66(3):425–8. doi:10.​1002/​ana.​21753.PubMed
43.
go back to reference Makino T, Ito S, Mori M, Yonezu T, Ogawa Y, Kuwabara S. Diffuse and heterogeneous T2-hyperintense lesions in the splenium are characteristic of neuromyelitis optica. Mult Scler. 2013;19(3):308–15. doi:10.1177/1352458512454772.PubMed Makino T, Ito S, Mori M, Yonezu T, Ogawa Y, Kuwabara S. Diffuse and heterogeneous T2-hyperintense lesions in the splenium are characteristic of neuromyelitis optica. Mult Scler. 2013;19(3):308–15. doi:10.​1177/​1352458512454772​.PubMed
44.
go back to reference Weinshenker BG, Wingerchuk DM, Vukusic S, Linbo L, Pittock SJ, Lucchinetti CF, et al. Neuromyelitis optica IgG predicts relapse after longitudinally extensive transverse myelitis. Ann Neurol. 2006;59(3):566–9. doi:10.1002/ana.20770.PubMed Weinshenker BG, Wingerchuk DM, Vukusic S, Linbo L, Pittock SJ, Lucchinetti CF, et al. Neuromyelitis optica IgG predicts relapse after longitudinally extensive transverse myelitis. Ann Neurol. 2006;59(3):566–9. doi:10.​1002/​ana.​20770.PubMed
46.•
go back to reference Waters PJ, McKeon A, Leite MI, Rajasekharan S, Lennon VA, Villalobos A, et al. Serologic diagnosis of NMO: a multicenter comparison of aquaporin-4-IgG assays. Neurology. 2012;78(9):665–71. doi:10.1212/WNL.0b013e318248dec1. discussion 669. This study demonstrates the greater sensitivity and specificity for NMO diagnosis with AQP4-IgG cell-based assays. Waters PJ, McKeon A, Leite MI, Rajasekharan S, Lennon VA, Villalobos A, et al. Serologic diagnosis of NMO: a multicenter comparison of aquaporin-4-IgG assays. Neurology. 2012;78(9):665–71. doi:10.​1212/​WNL.​0b013e318248dec1​. discussion 669. This study demonstrates the greater sensitivity and specificity for NMO diagnosis with AQP4-IgG cell-based assays.
47.
48.
go back to reference Kitley J, Woodhall M, Waters P, Leite MI, Devenney E, Craig J, et al. Myelin-oligodendrocyte glycoprotein antibodies in adults with a neuromyelitis optica phenotype. Neurology. 2012;79(12):1273–7. doi:10.1212/WNL.0b013e31826aac4e.PubMed Kitley J, Woodhall M, Waters P, Leite MI, Devenney E, Craig J, et al. Myelin-oligodendrocyte glycoprotein antibodies in adults with a neuromyelitis optica phenotype. Neurology. 2012;79(12):1273–7. doi:10.​1212/​WNL.​0b013e31826aac4e​.PubMed
50.
go back to reference Keegan BM, Pittock SJ, Lennon VA. Autoimmune myelopathy associated with collapsin response-mediator protein-5 immunoglobulin G. Ann Neurol. 2008;63(4):531–4. doi:10.1002/ana.21324.PubMed Keegan BM, Pittock SJ, Lennon VA. Autoimmune myelopathy associated with collapsin response-mediator protein-5 immunoglobulin G. Ann Neurol. 2008;63(4):531–4. doi:10.​1002/​ana.​21324.PubMed
51.
go back to reference Cross SA, Salomao DR, Parisi JE, Kryzer TJ, Bradley EA, Mines JA, et al. Paraneoplastic autoimmune optic neuritis with retinitis defined by CRMP-5-IgG. Ann Neurol. 2003;54(1):38–50. doi:10.1002/ana.10587.PubMed Cross SA, Salomao DR, Parisi JE, Kryzer TJ, Bradley EA, Mines JA, et al. Paraneoplastic autoimmune optic neuritis with retinitis defined by CRMP-5-IgG. Ann Neurol. 2003;54(1):38–50. doi:10.​1002/​ana.​10587.PubMed
53.
go back to reference Jarius S, Paul F, Franciotta D, Ruprecht K, Ringelstein M, Bergamaschi R, et al. Cerebrospinal fluid findings in aquaporin-4 antibody positive neuromyelitis optica: results from 211 lumbar punctures. J Neurol Sci. 2011;306(1–2):82–90. doi:10.1016/j.jns.2011.03.038.PubMed Jarius S, Paul F, Franciotta D, Ruprecht K, Ringelstein M, Bergamaschi R, et al. Cerebrospinal fluid findings in aquaporin-4 antibody positive neuromyelitis optica: results from 211 lumbar punctures. J Neurol Sci. 2011;306(1–2):82–90. doi:10.​1016/​j.​jns.​2011.​03.​038.PubMed
55.
56.••
go back to reference Chihara N, Aranami T, Sato W, Miyazaki Y, Miyake S, Okamoto T, et al. Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica. Proc Natl Acad Sci U S A. 2011;108(9):3701–6. doi:10.1073/pnas.1017385108. This study shows that plasmablasts are the key B-cell subset that produces AQP4 autoantibodies in NMO; survival of plasmablasts is dependent on IL-6; these findings have led to trials of IL-6 receptor inhibitors in NMOSD.PubMedCentralPubMed Chihara N, Aranami T, Sato W, Miyazaki Y, Miyake S, Okamoto T, et al. Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica. Proc Natl Acad Sci U S A. 2011;108(9):3701–6. doi:10.​1073/​pnas.​1017385108. This study shows that plasmablasts are the key B-cell subset that produces AQP4 autoantibodies in NMO; survival of plasmablasts is dependent on IL-6; these findings have led to trials of IL-6 receptor inhibitors in NMOSD.PubMedCentralPubMed
59.
go back to reference Lucchinetti CF, Mandler RN, McGavern D, Bruck W, Gleich G, Ransohoff RM, et al. A role for humoral mechanisms in the pathogenesis of Devic's neuromyelitis optica. Brain. 2002;125(Pt 7):1450–61.PubMed Lucchinetti CF, Mandler RN, McGavern D, Bruck W, Gleich G, Ransohoff RM, et al. A role for humoral mechanisms in the pathogenesis of Devic's neuromyelitis optica. Brain. 2002;125(Pt 7):1450–61.PubMed
60.••
go back to reference Hinson SR, Romero MF, Popescu BF, Lucchinetti CF, Fryer JP, Wolburg H, et al. Molecular outcomes of neuromyelitis optica (NMO)-IgG binding to aquaporin-4 in astrocytes. Proc Natl Acad Sci U S A. 2012;109(4):1245–50. doi:10.1073/pnas.1109980108. This study shows the differing effects of AQP4-IgG binding to its two dominant isoforms (M1 and M23) and demonstrates the impact of binding on water flux, highlighting the effect of AQP4-IgG binding at the cellular level.PubMedCentralPubMed Hinson SR, Romero MF, Popescu BF, Lucchinetti CF, Fryer JP, Wolburg H, et al. Molecular outcomes of neuromyelitis optica (NMO)-IgG binding to aquaporin-4 in astrocytes. Proc Natl Acad Sci U S A. 2012;109(4):1245–50. doi:10.​1073/​pnas.​1109980108. This study shows the differing effects of AQP4-IgG binding to its two dominant isoforms (M1 and M23) and demonstrates the impact of binding on water flux, highlighting the effect of AQP4-IgG binding at the cellular level.PubMedCentralPubMed
61.
go back to reference Asavapanumas N, Ratelade J, Verkman AS. Unique neuromyelitis optica pathology produced in naive rats by intracerebral administration of NMO-IgG. Acta Neuropathol. 2014;127(4):539–51. doi:10.1007/s00401-013-1204-8.PubMed Asavapanumas N, Ratelade J, Verkman AS. Unique neuromyelitis optica pathology produced in naive rats by intracerebral administration of NMO-IgG. Acta Neuropathol. 2014;127(4):539–51. doi:10.​1007/​s00401-013-1204-8.PubMed
62.
63.
go back to reference Hinson SR, McKeon A, Fryer JP, Apiwattanakul M, Lennon VA, Pittock SJ. Prediction of neuromyelitis optica attack severity by quantitation of complement-mediated injury to aquaporin-4-expressing cells. Arch Neurol. 2009;66(9):1164–7. doi:10.1001/archneurol.2009.188.PubMed Hinson SR, McKeon A, Fryer JP, Apiwattanakul M, Lennon VA, Pittock SJ. Prediction of neuromyelitis optica attack severity by quantitation of complement-mediated injury to aquaporin-4-expressing cells. Arch Neurol. 2009;66(9):1164–7. doi:10.​1001/​archneurol.​2009.​188.PubMed
65.
go back to reference Hinson SR, Roemer SF, Lucchinetti CF, Fryer JP, Kryzer TJ, Chamberlain JL, et al. Aquaporin-4-binding autoantibodies in patients with neuromyelitis optica impair glutamate transport by down-regulating EAAT2. J Exp Med. 2008;205(11):2473–81. doi:10.1084/jem.20081241.PubMedCentralPubMed Hinson SR, Roemer SF, Lucchinetti CF, Fryer JP, Kryzer TJ, Chamberlain JL, et al. Aquaporin-4-binding autoantibodies in patients with neuromyelitis optica impair glutamate transport by down-regulating EAAT2. J Exp Med. 2008;205(11):2473–81. doi:10.​1084/​jem.​20081241.PubMedCentralPubMed
66.
go back to reference Saadoun S, Waters P, MacDonald C, Bell BA, Vincent A, Verkman AS, et al. Neutrophil protease inhibition reduces neuromyelitis optica-immunoglobulin G-induced damage in mouse brain. Ann Neurol. 2012;71(3):323–33. doi:10.1002/ana.22686.PubMedCentralPubMed Saadoun S, Waters P, MacDonald C, Bell BA, Vincent A, Verkman AS, et al. Neutrophil protease inhibition reduces neuromyelitis optica-immunoglobulin G-induced damage in mouse brain. Ann Neurol. 2012;71(3):323–33. doi:10.​1002/​ana.​22686.PubMedCentralPubMed
68.
go back to reference Lucchinetti CF, Guo Y, Popescu BF, Fujihara K, Itoyama Y, Misu T. The pathology of an autoimmune astrocytopathy: lessons learned from neuromyelitis optica. Brain Pathol. 2014;24(1):83–97. doi:10.1111/bpa.12099.PubMed Lucchinetti CF, Guo Y, Popescu BF, Fujihara K, Itoyama Y, Misu T. The pathology of an autoimmune astrocytopathy: lessons learned from neuromyelitis optica. Brain Pathol. 2014;24(1):83–97. doi:10.​1111/​bpa.​12099.PubMed
69.
71.
go back to reference Filippini G, Brusaferri F, Sibley WA, Citterio A, Ciucci G, Midgard R, et al. Corticosteroids or ACTH for acute exacerbations in multiple sclerosis. Cochrane Database Syst Rev. 2000;4, CD001331. doi:10.1002/14651858.CD001331.PubMed Filippini G, Brusaferri F, Sibley WA, Citterio A, Ciucci G, Midgard R, et al. Corticosteroids or ACTH for acute exacerbations in multiple sclerosis. Cochrane Database Syst Rev. 2000;4, CD001331. doi:10.​1002/​14651858.​CD001331.PubMed
72.
go back to reference Beck RW, Cleary PA, Anderson Jr MM, Keltner JL, Shults WT, Kaufman DI, et al. A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. N Engl J Med. 1992;326(9):581–8. doi:10.1056/NEJM199202273260901.PubMed Beck RW, Cleary PA, Anderson Jr MM, Keltner JL, Shults WT, Kaufman DI, et al. A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. N Engl J Med. 1992;326(9):581–8. doi:10.​1056/​NEJM199202273260​901.PubMed
73.
go back to reference Weinshenker BG, O'Brien PC, Petterson TM, Noseworthy JH, Lucchinetti CF, Dodick DW, et al. A randomized trial of plasma exchange in acute central nervous system inflammatory demyelinating disease. Ann Neurol. 1999;46(6):878–86.PubMed Weinshenker BG, O'Brien PC, Petterson TM, Noseworthy JH, Lucchinetti CF, Dodick DW, et al. A randomized trial of plasma exchange in acute central nervous system inflammatory demyelinating disease. Ann Neurol. 1999;46(6):878–86.PubMed
75.
go back to reference Elsone L, Panicker J, Mutch K, Boggild M, Appleton R, Jacob A. Role of intravenous immunoglobulin in the treatment of acute relapses of neuromyelitis optica: experience in 10 patients. Mult Scler. 2014;20(4):501–4. doi:10.1177/1352458513495938.PubMed Elsone L, Panicker J, Mutch K, Boggild M, Appleton R, Jacob A. Role of intravenous immunoglobulin in the treatment of acute relapses of neuromyelitis optica: experience in 10 patients. Mult Scler. 2014;20(4):501–4. doi:10.​1177/​1352458513495938​.PubMed
76.
go back to reference 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(8):968–74. doi:10.1177/1352458507077189.PubMed 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(8):968–74. doi:10.​1177/​1352458507077189​.PubMed
79.
go back to reference Costanzi C, Matiello M, Lucchinetti CF, Weinshenker BG, Pittock SJ, Mandrekar J, et al. Azathioprine: tolerability, efficacy, and predictors of benefit in neuromyelitis optica. Neurology. 2011;77(7):659–66. doi:10.1212/WNL.0b013e31822a2780.PubMed Costanzi C, Matiello M, Lucchinetti CF, Weinshenker BG, Pittock SJ, Mandrekar J, et al. Azathioprine: tolerability, efficacy, and predictors of benefit in neuromyelitis optica. Neurology. 2011;77(7):659–66. doi:10.​1212/​WNL.​0b013e31822a2780​.PubMed
80.
go back to reference Elsone L, Kitley J, Luppe S, Lythgoe D, Mutch K, Jacob S, et al. Long-term efficacy, tolerability and retention rate of azathioprine in 103 aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder patients: a multicentre retrospective observational study from the UK. Mult Scler. 2014. doi:10.1177/1352458514525870. Elsone L, Kitley J, Luppe S, Lythgoe D, Mutch K, Jacob S, et al. Long-term efficacy, tolerability and retention rate of azathioprine in 103 aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder patients: a multicentre retrospective observational study from the UK. Mult Scler. 2014. doi:10.​1177/​1352458514525870​.
81.
go back to reference Jacob A, Matiello M, Weinshenker BG, Wingerchuk DM, Lucchinetti C, Shuster E, et al. Treatment of neuromyelitis optica with mycophenolate mofetil: retrospective analysis of 24 patients. Arch Neurol. 2009;66(9):1128–33. doi:10.1001/archneurol.2009.175.PubMed Jacob A, Matiello M, Weinshenker BG, Wingerchuk DM, Lucchinetti C, Shuster E, et al. Treatment of neuromyelitis optica with mycophenolate mofetil: retrospective analysis of 24 patients. Arch Neurol. 2009;66(9):1128–33. doi:10.​1001/​archneurol.​2009.​175.PubMed
84.
go back to reference Nakashima I, Takahashi T, Cree BA, Kim HJ, Suzuki C, Genain CP, et al. Transient increases in anti-aquaporin-4 antibody titers following rituximab treatment in neuromyelitis optica, in association with elevated serum BAFF levels. J Clin Neurosci. 2011;18(7):997–8. doi:10.1016/j.jocn.2010.12.011.PubMed Nakashima I, Takahashi T, Cree BA, Kim HJ, Suzuki C, Genain CP, et al. Transient increases in anti-aquaporin-4 antibody titers following rituximab treatment in neuromyelitis optica, in association with elevated serum BAFF levels. J Clin Neurosci. 2011;18(7):997–8. doi:10.​1016/​j.​jocn.​2010.​12.​011.PubMed
85.
go back to reference Kitley J, Elsone L, George J, Waters P, Woodhall M, Vincent A, et al. Methotrexate is an alternative to azathioprine in neuromyelitis optica spectrum disorders with aquaporin-4 antibodies. J Neurol Neurosurg Psychiatry. 2013;84(8):918–21. doi:10.1136/jnnp-2012-304774.PubMed Kitley J, Elsone L, George J, Waters P, Woodhall M, Vincent A, et al. Methotrexate is an alternative to azathioprine in neuromyelitis optica spectrum disorders with aquaporin-4 antibodies. J Neurol Neurosurg Psychiatry. 2013;84(8):918–21. doi:10.​1136/​jnnp-2012-304774.PubMed
86.
go back to reference Meyts I, Jansen K, Renard M, Bossuyt X, Roelens F, Regal L, et al. Neuromyelitis optica-IgG+ optic neuritis associated with celiac disease and dysgammaglobulinemia: a role for tacrolimus? Eur J Paediatr Neurol. 2011;15(3):265–7. doi:10.1016/j.ejpn.2010.09.005.PubMed Meyts I, Jansen K, Renard M, Bossuyt X, Roelens F, Regal L, et al. Neuromyelitis optica-IgG+ optic neuritis associated with celiac disease and dysgammaglobulinemia: a role for tacrolimus? Eur J Paediatr Neurol. 2011;15(3):265–7. doi:10.​1016/​j.​ejpn.​2010.​09.​005.PubMed
87.
go back to reference Kageyama T, Komori M, Miyamoto K, Ozaki A, Suenaga T, Takahashi R, et al. Combination of cyclosporine A with corticosteroids is effective for the treatment of neuromyelitis optica. J Neurol. 2013;260(2):627–34. doi:10.1007/s00415-012-6692-2.PubMed Kageyama T, Komori M, Miyamoto K, Ozaki A, Suenaga T, Takahashi R, et al. Combination of cyclosporine A with corticosteroids is effective for the treatment of neuromyelitis optica. J Neurol. 2013;260(2):627–34. doi:10.​1007/​s00415-012-6692-2.PubMed
88.
go back to reference Weinstock-Guttman B, Ramanathan M, Lincoff N, Napoli SQ, Sharma J, Feichter J, et al. Study of mitoxantrone for the treatment of recurrent neuromyelitis optica (Devic disease). Arch Neurol. 2006;63(7):957–63. doi:10.1001/archneur.63.7.957.PubMed Weinstock-Guttman B, Ramanathan M, Lincoff N, Napoli SQ, Sharma J, Feichter J, et al. Study of mitoxantrone for the treatment of recurrent neuromyelitis optica (Devic disease). Arch Neurol. 2006;63(7):957–63. doi:10.​1001/​archneur.​63.​7.​957.PubMed
90.
go back to reference Yaguchi H, Sakushima K, Takahashi I, Nishimura H, Yashima-Yamada M, Nakamura M, et al. Efficacy of intravenous cyclophosphamide therapy for neuromyelitis optica spectrum disorder. Intern Med. 2013;52(9):969–72.PubMed Yaguchi H, Sakushima K, Takahashi I, Nishimura H, Yashima-Yamada M, Nakamura M, et al. Efficacy of intravenous cyclophosphamide therapy for neuromyelitis optica spectrum disorder. Intern Med. 2013;52(9):969–72.PubMed
91.
go back to reference Araki M, Aranami T, Matsuoka T, Nakamura M, Miyake S, Yamamura T. Clinical improvement in a patient with neuromyelitis optica following therapy with the anti-IL-6 receptor monoclonal antibody tocilizumab. Mod Rheumatol. 2013;23(4):827–31. doi:10.1007/s10165-012-0715-9.PubMedCentralPubMed Araki M, Aranami T, Matsuoka T, Nakamura M, Miyake S, Yamamura T. Clinical improvement in a patient with neuromyelitis optica following therapy with the anti-IL-6 receptor monoclonal antibody tocilizumab. Mod Rheumatol. 2013;23(4):827–31. doi:10.​1007/​s10165-012-0715-9.PubMedCentralPubMed
92.•
go back to reference Araki M, Matsuoka T, Miyamoto K, Kusunoki S, Okamoto T, Murata M, et al. Efficacy of the anti-IL-6 receptor antibody tocilizumab in neuromyelitis optica: a pilot study. Neurology. 2014;82(15):1302–6. doi:10.1212/WNL.0000000000000317. This pilot study shows the potential benefits of IL-6 receptor monoclonal antibodies in NMOSD.PubMedCentralPubMed Araki M, Matsuoka T, Miyamoto K, Kusunoki S, Okamoto T, Murata M, et al. Efficacy of the anti-IL-6 receptor antibody tocilizumab in neuromyelitis optica: a pilot study. Neurology. 2014;82(15):1302–6. doi:10.​1212/​WNL.​0000000000000317​. This pilot study shows the potential benefits of IL-6 receptor monoclonal antibodies in NMOSD.PubMedCentralPubMed
93.
go back to reference Ayzenberg I, Kleiter I, Schroder A, Hellwig K, Chan A, Yamamura T, et al. Interleukin 6 receptor blockade in patients with neuromyelitis optica nonresponsive to anti-CD20 therapy. JAMA Neurol. 2013;70(3):394–7. doi:10.1001/jamaneurol.2013.1246.PubMed Ayzenberg I, Kleiter I, Schroder A, Hellwig K, Chan A, Yamamura T, et al. Interleukin 6 receptor blockade in patients with neuromyelitis optica nonresponsive to anti-CD20 therapy. JAMA Neurol. 2013;70(3):394–7. doi:10.​1001/​jamaneurol.​2013.​1246.PubMed
94.
go back to reference Kieseier BC, Stuve O, Dehmel T, Goebels N, Leussink VI, Mausberg AK, et al. Disease amelioration with tocilizumab in a treatment-resistant patient with neuromyelitis optica: implication for cellular immune responses. JAMA Neurol. 2013;70(3):390–3. doi:10.1001/jamaneurol.2013.668.PubMed Kieseier BC, Stuve O, Dehmel T, Goebels N, Leussink VI, Mausberg AK, et al. Disease amelioration with tocilizumab in a treatment-resistant patient with neuromyelitis optica: implication for cellular immune responses. JAMA Neurol. 2013;70(3):390–3. doi:10.​1001/​jamaneurol.​2013.​668.PubMed
96.••
go back to reference Pittock SJ, Lennon VA, McKeon A, Mandrekar J, Weinshenker BG, Lucchinetti CF, et al. Eculizumab in AQP4-IgG-positive relapsing neuromyelitis optica spectrum disorders: an open-label pilot study. Lancet Neurol. 2013;12(6):554–62. doi:10.1016/S1474-4422(13)70076-0. This open-label pilot study of eculizumab suggests that patients with NMOSD might benefit from eculizumab treatment. After prior studies suggested a role of complement in NMOSD pathogenesis, the promising results of a complement inhibitor brought this research from the bench to the bedside.PubMed Pittock SJ, Lennon VA, McKeon A, Mandrekar J, Weinshenker BG, Lucchinetti CF, et al. Eculizumab in AQP4-IgG-positive relapsing neuromyelitis optica spectrum disorders: an open-label pilot study. Lancet Neurol. 2013;12(6):554–62. doi:10.​1016/​S1474-4422(13)70076-0. This open-label pilot study of eculizumab suggests that patients with NMOSD might benefit from eculizumab treatment. After prior studies suggested a role of complement in NMOSD pathogenesis, the promising results of a complement inhibitor brought this research from the bench to the bedside.PubMed
97.
go back to reference Matiello M, Pittock SJ, Porrata L, Weinshenker BG. Failure of autologous hematopoietic stem cell transplantation to prevent relapse of neuromyelitis optica. Arch Neurol. 2011;68(7):953–5. doi:10.1001/archneurol.2011.38.PubMed Matiello M, Pittock SJ, Porrata L, Weinshenker BG. Failure of autologous hematopoietic stem cell transplantation to prevent relapse of neuromyelitis optica. Arch Neurol. 2011;68(7):953–5. doi:10.​1001/​archneurol.​2011.​38.PubMed
98.
go back to reference Greco R, Bondanza A, Vago L, Moiola L, Rossi P, Furlan R, et al. Allogeneic hematopoietic stem cell transplantation for neuromyelitis optica. Ann Neurol. 2014;75(3):447–53. doi:10.1002/ana.24079.PubMed Greco R, Bondanza A, Vago L, Moiola L, Rossi P, Furlan R, et al. Allogeneic hematopoietic stem cell transplantation for neuromyelitis optica. Ann Neurol. 2014;75(3):447–53. doi:10.​1002/​ana.​24079.PubMed
99.••
go back to reference Tradtrantip L, Zhang H, Saadoun S, Phuan PW, Lam C, Papadopoulos MC, et al. Anti-aquaporin-4 monoclonal antibody blocker therapy for neuromyelitis optica. Ann Neurol. 2012;71(3):314–22. doi:10.1002/ana.22657. This is a proof-of-concept study using a novel patient-derived human monoclonal antibody directed at AQP4 engineered for being incapable of generating complement and cell-mediated cytotoxicity. The monoclonal antibody abrogated NMO lesions in a mouse model of NMO.PubMedCentralPubMed Tradtrantip L, Zhang H, Saadoun S, Phuan PW, Lam C, Papadopoulos MC, et al. Anti-aquaporin-4 monoclonal antibody blocker therapy for neuromyelitis optica. Ann Neurol. 2012;71(3):314–22. doi:10.​1002/​ana.​22657. This is a proof-of-concept study using a novel patient-derived human monoclonal antibody directed at AQP4 engineered for being incapable of generating complement and cell-mediated cytotoxicity. The monoclonal antibody abrogated NMO lesions in a mouse model of NMO.PubMedCentralPubMed
100.
go back to reference Goldstein LH, Dolinsky G, Greenberg R, Schaefer C, Cohen-Kerem R, Diav-Citrin O, et al. Pregnancy outcome of women exposed to azathioprine during pregnancy. Birth Defects Res A Clin Mol Teratol. 2007;79(10):696–701. doi:10.1002/bdra.20399.PubMed Goldstein LH, Dolinsky G, Greenberg R, Schaefer C, Cohen-Kerem R, Diav-Citrin O, et al. Pregnancy outcome of women exposed to azathioprine during pregnancy. Birth Defects Res A Clin Mol Teratol. 2007;79(10):696–701. doi:10.​1002/​bdra.​20399.PubMed
102.
go back to reference Ringelstein M, Harmel J, Distelmaier F, Ingwersen J, Menge T, Hellwig K, et al. Neuromyelitis optica and pregnancy during therapeutic B cell depletion: infant exposure to anti-AQP4 antibody and prevention of rebound relapses with low-dose rituximab postpartum. Mult Scler. 2013;19(11):1544–7. doi:10.1177/1352458513498125.PubMed Ringelstein M, Harmel J, Distelmaier F, Ingwersen J, Menge T, Hellwig K, et al. Neuromyelitis optica and pregnancy during therapeutic B cell depletion: infant exposure to anti-AQP4 antibody and prevention of rebound relapses with low-dose rituximab postpartum. Mult Scler. 2013;19(11):1544–7. doi:10.​1177/​1352458513498125​.PubMed
103.
go back to reference Pellkofer HL, Suessmair C, Schulze A, Hohlfeld R, Kuempfel T. Course of neuromyelitis optica during inadvertent pregnancy in a patient treated with rituximab. Mult Scler. 2009;15(8):1006–8. doi:10.1177/1352458509106512.PubMed Pellkofer HL, Suessmair C, Schulze A, Hohlfeld R, Kuempfel T. Course of neuromyelitis optica during inadvertent pregnancy in a patient treated with rituximab. Mult Scler. 2009;15(8):1006–8. doi:10.​1177/​1352458509106512​.PubMed
106.
go back to reference Min JH, Kim BJ, Lee KH. Development of extensive brain lesions following fingolimod (FTY720) treatment in a patient with neuromyelitis optica spectrum disorder. Mult Scler. 2012;18(1):113–5. doi:10.1177/1352458511431973.PubMed Min JH, Kim BJ, Lee KH. Development of extensive brain lesions following fingolimod (FTY720) treatment in a patient with neuromyelitis optica spectrum disorder. Mult Scler. 2012;18(1):113–5. doi:10.​1177/​1352458511431973​.PubMed
108.
go back to reference Flanagan EP, Aksamit AJ, Kumar N, Morparia NP, Keegan BM, Weinshenker BW. Simultaneous PML-IRIS and myelitis in a patient with neuromyelitis optica spectrum disorder. Neurol Clin Pract. 2013;3(5):448–51. doi:10.1212/CPJ.0b013e3182a78f82. Flanagan EP, Aksamit AJ, Kumar N, Morparia NP, Keegan BM, Weinshenker BW. Simultaneous PML-IRIS and myelitis in a patient with neuromyelitis optica spectrum disorder. Neurol Clin Pract. 2013;3(5):448–51. doi:10.​1212/​CPJ.​0b013e3182a78f82​.
Metadata
Title
Neuromyelitis Optica Spectrum Disorders
Authors
Eoin P. Flanagan
Brian G. Weinshenker
Publication date
01-09-2014
Publisher
Springer US
Published in
Current Neurology and Neuroscience Reports / Issue 9/2014
Print ISSN: 1528-4042
Electronic ISSN: 1534-6293
DOI
https://doi.org/10.1007/s11910-014-0483-3

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