Skip to main content

Advertisement

Log in

What’s new in neuromyelitis optica? A short review for the clinical neurologist

  • Neurological Update
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

The evolution of neuromyelitis optica spectrum disorder (NMOSD) from a rare, incurable and misunderstood disease with almost universally poor outcomes to its present state in just over a decade is unprecedented in neurology and possibly in medicine. Our knowledge of NMOSD biology has led to the recognition of wider phenotypes, new disease mechanisms, and thus clinical trials of new and effective treatments. This article aims to update readers on the recent developments in NMOSD with particular emphasis on clinical advances, the 2015 diagnostic criteria, biomarkers, imaging, and therapeutic interventions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, Nakashima I, Weinshenker BG (2004) A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 364(9451):2106–2112. doi:10.1016/S0140-6736(04)17551-X

    Article  CAS  PubMed  Google Scholar 

  2. Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR (2005) IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med 202(4):473–477. doi:10.1084/jem.20050304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, de Seze J, Fujihara K, Greenberg B, Jacob A, Jarius S, Lana-Peixoto M, Levy M, Simon JH, Tenembaum S, Traboulsee AL, Waters P, Wellik KE, Weinshenker BG (2015) International consensus diagnostic criteria for neuromyelitis optica spectrum disorder. Neurology 85(2):177–189. doi:10.1212/WNL.0000000000001729

    Article  PubMed  PubMed Central  Google Scholar 

  4. Wingerchuk DM, Lennon VA, Pittock SJ, Lucchinetti CF, Weinshenker BG (2006) Revised diagnostic criteria for neuromyelitis optica. Neurology 66(10):1485–1489. doi:10.1212/01.wnl.0000216139.44259.74

    Article  CAS  PubMed  Google Scholar 

  5. Hamid SH, Elsone L, Mutch K, Solomon T, Jacob A (2016) The impact of 2015 neuromyelitis optica spectrum disorders criteria on diagnostic rates. Mult Scler. doi:10.1177/1352458516663853 (Epub ahead of print)

    PubMed  Google Scholar 

  6. Hyun JW, Jeong IH, Joung A, Kim SH, Kim HJ (2016) Evaluation of the 2015 diagnostic criteria for neuromyelitis optica spectrum disorder. Neurology 86(19):1772–1779. doi:10.1212/WNL.0000000000002655

    Article  PubMed  Google Scholar 

  7. Qian P, Lancia S, Alvarez E, Klawiter EC, Cross AH, Naismith RT (2012) Association of neuromyelitis optica with severe and intractable pain. Arch Neurol 69(11):1482–1487. doi:10.1001/archneurol.2012.768

    Article  PubMed  PubMed Central  Google Scholar 

  8. Zhao S, Mutch K, Elsone L, Nurmikko T, Jacob A (2014) Neuropathic pain in neuromyelitis optica affects activities of daily living and quality of life. Mult Scler 20(12):1658–1661. doi:10.1177/1352458514522103

    Article  PubMed  Google Scholar 

  9. Elsone L, Townsend T, Mutch K, Das K, Boggild M, Nurmikko T, Jacob A (2012) Neuropathic pruritis (itch) in neuromyelitis optica. Mult Scler 19(4):475–479. doi:10.1177/1352458512457720

    Article  PubMed  Google Scholar 

  10. Kim SM, Go MJ, Sung JJ, Park KS, Lee KW (2012) Painful tonic spasm in neuromyelitis optica: incidence, diagnostic utility, and clinical characteristics. Arch Neurol 69(8):1026–1031. doi:10.1001/archneurol.2012.112

    Article  PubMed  Google Scholar 

  11. Usmani N, Bedi G, Lam BL, Sheremata WA (2012) Association between paroxysmal tonic spasms and neuromyelitis optica. Arch Neurol 69(1):121–124. doi:10.1001/archneurol.2011.832

    Article  PubMed  Google Scholar 

  12. Pittock SJ, Lennon VA, Krecke K, Wingerchuk DM, Lucchinetti CF, Weinshenker BG (2006) Brain abnormalities in neuromyelitis optica. Arch Neurol 63(3):390–396. doi:10.1001/archneur.63.3.390

    Article  PubMed  Google Scholar 

  13. Misu T, Fujihara K, Nakashima I, Sato S, Itoyama Y (2005) Intractable hiccup and nausea with periaqueductal lesions in neuromyelitis optica. Neurology 65(9):1479–1482. doi:10.1212/01.wnl.0000183151.19351.82

    Article  CAS  PubMed  Google Scholar 

  14. Sato D, Fukihara K (2011) Atypical presentations of neuromyelitis optica. Arq Neuropsiquiatr 69(5):824–828. doi:10.1590/S0004-282X2012000100023

    Article  PubMed  Google Scholar 

  15. Apiwattanakul M, Popescu BF, Matiello M, Weinshenker BG, Lucchinetti CF, Lennon VA, McKeon A, Carpenter AF, Miller GM, Pittock SJ (2010) Intractable vomiting as the initial presentation of neuromyelitis optica. Ann Neurol 68(5):757–761. doi:10.1002/ana.22121

    Article  PubMed  Google Scholar 

  16. Baba T, Nakashima I, Kanbayashi T, Konno M, Takahashi T, Fujihara K, Misu T, Takeda A, Shiga Y, Ogawa H, Itoyama Y (2009) Narcolepsy as an initial manifestation of neuromyelitis optica with antiaquaporin-4 antibody. J Neurol 256(2):287–288. doi:10.1007/s00415-009-0139-4

    Article  PubMed  Google Scholar 

  17. Kanbayashi T, Shimohata T, Nakashima I, Yaguchi H, Yabe I, Nishizawa M, Shimizu T, Nishino S (2009) Symptomatic narcolepsy in patients with neuromyelitis optica and multiple sclerosis: new neurochemical and immunological implications. Arch Neurol 66(12):1563–1566. doi:10.1001/archneurol.2009.264

    Article  PubMed  Google Scholar 

  18. Poppe AY, Lapierre Y, Melançon D, Lowden D, Wardell L, Fullerton LM, Bar-Or A (2005) Neuromyelitis optica with hypothalamic involvement. Mult Scler 11(5):617–621

    Article  PubMed  Google Scholar 

  19. Pu S, Long Y, Yang N, He Y, Shan F, Fan Y, Yin J, Gao Q, Cong G (2015) Syndrome of inappropriate antidiuretic hormone secretion in patients with aquaporin-4 antibody. J Neurol 262(1):101–107. doi:10.1007/s00415-014-7537-y

    Article  CAS  PubMed  Google Scholar 

  20. Blanc F, Zephir H, Lebrun C, Labauge P, Castelnova G, Fleury M, Sellal F, Tranchant C, Dujardin K, Vermersh P, de Seze J (2008) Cognitive functions in neuromyelitis optica. Arch Neurol 65(1):84–88. doi:10.1001/archneurol.2007.16

    Article  PubMed  Google Scholar 

  21. Blanc F, Noblet V, Jung B, Rousseau F, Renard F, Bourre B, Longato N, Cremel N, Bitonto L, Kleitz C, Collongues N, Foucher J, Kremer S, Armspach JP, de Seze J (2012) White matter atrophy and cognitive dysfunctions in neuromyelitis optica. PLoS One 7(4):e33878. doi:10.1371/journal.pone.0033878

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Vanotti S, Cores EV, Eizaquirre B, Melamud L, Rey R, Villa A (2013) Cognitive performance of neuromyelitis optica patients: comparison with multiple sclerosis. Arq Neuropsiquiatr 71(6):357–361. doi:10.1590/0004-282X20130038

    Article  PubMed  Google Scholar 

  23. Liu Y, Fu Y, Schoonheim MM, Zhang N, Fan M, Su L, Shen Y, Yan Y, Yang L, Wang Q, Zhang N, Yu C, Barkhof F, Shi FD (2015) Structural MRI substrates of cognitive impairment in neuromyelitis optica. Neurology 85(17):1491–1499. doi:10.1212/WNL.0000000000002067

    Article  PubMed  Google Scholar 

  24. Meng H, Xu J, Pan C, Cheng J, Hu Y, Hong Y, Shen Y, Dai H (2016) Cognitive dysfunction in neuromyelitis optica: a systematic review and meta-analysis. J Neurol. doi:10.1007/s00415-016-8345-3 (Epub ahead of print)

    PubMed  Google Scholar 

  25. Moore P, Methley A, Pollard C, Mutch K, Hamid S, Elsone L, Jacob A (2016) Cognitive and psychiatric comorbidities in neuromyelitis optica. J Neurol Sci 360:4–9. doi:10.1016/j.jns.2015.11.031

    Article  PubMed  Google Scholar 

  26. Constantinescu C, Chou IJ, Tanasescu R, Tench C, Lim SY, Podda G (2015) Cognitive function and fatigue in patients with neuromyelitis optica: comparison with MS subtypes (P5.256). Neurology 85(14):Supplement P5.256

    Google Scholar 

  27. Zhang N, Li YJ, Fu Y, Shao JH, Luo LL, Yang L, Shi FD, Liu Y (2015) Cognitive impairment in Chinese neuromyelitis optica. Mult Scler 21(14):1839–1846. doi:10.1177/1352458515576982

    Article  PubMed  CAS  Google Scholar 

  28. Mutch K, Methley A, Moore P, Jacob A (2013) Life on hold: the experience of living with neuromyelitis optica. Disabil Rehabil 36(13):1100–1107. doi:10.3109/09638288.2013.833301

    Article  PubMed  Google Scholar 

  29. Shi Z, Chen H, Lian Z, Liu J, Feng H, Zhou H (2015) Factors that impact health-related quality of life in neuromyelitis optica spectrum disorder: anxiety, disability, fatigue and depression. J Neuroimmunol 293:54–58. doi:10.1016/j.jneuroim.2016.02.011

    Article  CAS  Google Scholar 

  30. Weinshenker BG, Wingerchuk DM, Vukusic S, Linbo L, Pittock SJ, Lucchinetti CF, Lennon VA (2006) Neuromyelitis optica IgG predicts relapse after longitudinally extensive transverse myelitis. Ann Neurol 59(3):566–569. doi:10.1002/ana.20770

    Article  CAS  PubMed  Google Scholar 

  31. Matiello M, Lennon VA, Jacob A, Pittock SJ, Lucchinetti CF, Wingerchuk DM, Weinshenker BG (2008) NMO-IgG predicts the outcome of recurrent optic neuritis. Neurology 70(23):2197–2200. doi:10.1212/01.wnl.0000303817.82134.da

    Article  CAS  PubMed  Google Scholar 

  32. Jarius S, Frederikson J, Waters P, Paul F, Akman-Demir G, Marignier R, Ruprecht K, Kuenz B, Rommer P, Kristoferitsch W, Wildemann B, Vincent A (2010) Frequency and prognostic impact of antibodies to aquaporin-4 in patients with optic neuritis. J Neurol Sci 298(1–2):158–162. doi:10.1016/j.jns.2010.07.011

    Article  CAS  PubMed  Google Scholar 

  33. Waters PJ, Pittock SJ, Bennett JL, Jarius S, Weinshenker BG, Wingerchuk DM (2014) Evaluation of aquaporin-4 antibody assays. Clin Exp Neuroimmunol 5(3):290–303. doi:10.1111/cen3.12107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Mader S, Lutterotti A, Di Pauli F, Kuenz B, Schanda K, Aboul-Enein F, Khalil M, Storch MK, Jarius S, Kristoferitsch W, Berger T, Reindl M (2010) Patterns of antibody binding to aquaporin-4 isoforms in neuromyelitis optica. PLoS One 5(5):e10455. doi:10.1371/journal.pone.0010455

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Waters P, Reindl M, Saiz A, Schanda K, Tuller F, Kral V, Nytrova P, Sobek O, Nielson HH, Barington T, Lillevang ST, Illes Z, Rentzsch K, Berthele A, Berki T, Granieri L, Bertolotto A, Giometto B, Zuliani L, Hamann D, van Pelt ED, Hintzen R, Höftberger R, Costa C, Comabella M, Montalban X, Tintoré M, Siva A, Altintas A, Deniz G, Woodhall M, Palace J, Paul F, Hartung HP, Aktas O, Jarius S, Wildemann B, Vedeler C, Ruiz A, Leite MI, Trillenberg P, Probst M, Sachenbrecker S, Vincent A, Marignier R (2016) Multicentre comparison of a diagnostic assay: aquaporin-4 antibodies in neuromyelitis optica. J Neurol Neurosurg Psychiatry 87(9):1005–1015. doi:10.1136/jnnp-2015-312601

    Article  PubMed  PubMed Central  Google Scholar 

  36. Takahashi T, Fujihara K, Nakashima I, Misu T, Miyazawa I, Nakamura M, Watanabe S, Shiga Y, Kanaoka C, Fujimori J, Sato S, Itoyama Y (2007) Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO: a study on antibody titre. Brain 130(Pt 5):1235–1243. doi:10.1093/brain/awm062

    Article  PubMed  Google Scholar 

  37. Mader S, Gredler V, Schanda K, Rostasy K, Dujmovic I, Pfaller K, Lutterotti A, Jarius S, Di Pauli F, Kuenz B, Ehling R, Hegen H, Deisenhammer F, Aboul-Enein F, Storch MK, Koson P, Drulovic J, Kristoferitsch W, Berger T, Reindl M (2011) Complement activating antibodies to myelin oligodendrocyte glycoprotein in neuromyelitis optica and related disorders. J Neuroinflamm 8:184. doi:10.1186/1742-2094-8-184

    Article  CAS  Google Scholar 

  38. Kitley J, Woodhall M, Waters P, Leite MI, Devenney E, Craig J, Palace J, Vincent A (2012) Myelin-oligodendrocyte glycoprotein antibodies in adults with a neuromyelitis optica phenotype. Neurology 79(12):1273–1277. doi:10.1212/WNL.0b013e31826aac4e

    Article  CAS  PubMed  Google Scholar 

  39. Probstel AK, Dornmair K, Bittner R, Sperl P, Jenne D, Magalhaes S, Villalobos A, Breithaupt C, Weissert R, Jacob U, Krumbholz M, Kuempfel T, Blaschek A, Stark W, Gartner J, Pohl D, Rostasy K, Weber F, Forne I, Khademi M, Olsson T, Brillot F, Tantsis E, Dale RC, Wekerle H, Hohlfeld R, Banwell B, Bar-Or A, Meinl E, Derfuss T (2011) Antibodies to MOG are transient in childhood acute disseminated encephalomyelitis. Neurology 77(6):580–588. doi:10.1212/WNL.0b013e318228c0b1

    Article  CAS  PubMed  Google Scholar 

  40. Reindl M, Di Pauli F, Rostasy K, Berger T (2013) The spectrum of MOG autoantibody-associated demyelinating diseases. Nat Rev Neurol 9(8):455–461. doi:10.1038/nrneurol.2013.118

    Article  CAS  PubMed  Google Scholar 

  41. Bettelli E, Baeten D, Jager A, Sobel RA, Kuchroo VK (2006) Myelin oligodendrocyte glycoprotein-specific T and B cells cooperate to induce a devic-like disease in mice. J Clin Investig 116(9):2393–2402. doi:10.1172/JCI28334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Krishnamoorthy G, Lassmann H, Wekerle H, Holz A (2006) Spontaneous opticospinal encephalomyelitis in a double-transgenic mouse model of autoimmune T cell/B cell cooperation. J Clin Investig 116(9):2385–2392. doi:10.1172/JCI28330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Saadoun S, Waters P, Owens GP, Bennett JL, Vincent A, Papadopoulos MC (2014) Neuromyelitis optica MOG-IgG causes reversible lesions in mouse brain. Acta Neuropathol Commun 2:35. doi:10.1186/2051-5960-2-35

    Article  PubMed  PubMed Central  Google Scholar 

  44. Kitley J, Waters P, Woodhall M, Leite I, Murchison A, George J, Küker W, Chandratre S, Vincent A, Palace J (2014) Neuromyelitis optica spectrum disorders with aquaporin-4 and myelin-oligodendrocyte glycoprotein antibodies: a comparative study. JAMA Neurol 71(3):276–283. doi:10.1001/jamaneurol.2013.5857

    Article  PubMed  Google Scholar 

  45. Sato DK, Callegaro D, Lana-Peixoto MA, Waters PJ, de Haidar Jorge FM, Takahashi T, Nakashima I, Apostolos-Pereira SL, Talim N, Simm RF, Martins Lino AM, Misu T, Leite MI, Aoki M, Fujihara K (2014) Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders. Neurology 82(6):474–481. doi:10.1212/WNL.0000000000000101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Jarius S, Ruprecht K, Kleiter I, Boristow N, Asgari N, Pitarokoli K, Pache F, Stich O, Beume LA, Hümmert MW, Ringelstein M, Trebst C, Winkelmann A, Schwarz A, Buttmann M, Zimmermann H, Kuchling J, Franciotta D, Capobianco M, Siebert E, Lukas C, Korporal-Kuhnke M, Hass J, Fechner K, Brandt A, Schanda K, Aktas O, Paul F, Reindl M, Wildemann B (2016) MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 2: epidemiology, clinical presentation, radiological and laboratory features, treatment responses, and long-term outcome. J Neuroinflamm 13:280. doi:10.1186/s12974-016-0718-0

    Article  Google Scholar 

  47. Jarius S, Ruprecht K, Wildemann B, Kuempfel T, Ringelstein M, Geis C, Kleiter I, Kleinschnitz C, Berthele A, Brettschneider J, Hellwig K, Hemmer B, Linker RA, Lauda F, Mayer CA, Tumani H, Melms A, Trebst C, Stangel M, Marziniak M, Hoffmann F, Schippling S, Faiss JH, Neuhaus O, Ettrich B, Zentner C, Guthke K, Hofstadt-van Oy U, Reuss R, Pellkofer H, Ziemann U, Kern P, Wandinger KP, Bergh FT, Boettcher T, Langel S, Liebetrau M, Rommer PS, Niehaus S, Münch C, Winkelmann A, Zetti UUK, Metz I, Veauthier C, Sieb JP, Wilke C, Hartung HP, Aktas O, Paul F (2012) Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: a multicentre study of 175 patients. J Neuroinflamm 9:14. doi:10.1186/1742-2094-9-14

    Article  CAS  Google Scholar 

  48. Liedtke W, Edelmann W, Bieri PL, Chiu FC, Cowan NJ, Kucherlapati R, Raine CS (1996) GFAP is necessary for the integrity of CNS white matter architecture and long-term maintenance of myelination. Neuron 17(4):607–615

    Article  CAS  PubMed  Google Scholar 

  49. Misu T, Takano R, Fujihara K, Takahashi T, Sato S, Itoyama Y (2009) Marked increase in cerebrospinal fluid glial fibrillar acidic protein in neuromyelitis optica: an astrocytic damage marker. J Neurol Neurosurg Psychiatry 80(5):575–577. doi:10.1136/jnnp.2008.150698

    Article  CAS  PubMed  Google Scholar 

  50. Takano R, Misu T, Takahashi T, Sato S, Fujihara K, Itoyama Y (2010) Astrocytic damage is far more severe than demyelination in NMO: a clinical CSF biomarker study. Neurology 75(3):208–216. doi:10.1212/WNL.0b013e3181e2414b

    Article  CAS  PubMed  Google Scholar 

  51. Storoni M, Verbeek MM, Illes Z, Marignier R, Teunissen CE, Grabowska M, Confavreux C, Plant GT, Petzold A (2012) Serum GFAP levels in optic neuropathies. J Neurol Sci 317(1–2):117–122. doi:10.1016/j.jns.2012.02.012

    Article  CAS  PubMed  Google Scholar 

  52. Fang B, McKeon A, Hinson SR, Kryzer TJ, Pittock SJ, Aksamit AJ, Lennon VA (2016) Autoimmune glial fibrillary acidic protein astrocytopathy: a novel meningoencephalomyelitis. JAMA Neurol 73(11):1297–1307. doi:10.1001/jamaneurol.2016.2549

    Article  PubMed  Google Scholar 

  53. Uzawa A, Mori M, Ito M, Uchida T, Hayakawa S, Masuda S, Kuwabara S (2009) Markedly increased CSF interleukin-6 levels in neuromyelitis optica, but not in multiple sclerosis. J Neurol 256(12):2082–2084. doi:10.1007/s00415-009-5274-4

    Article  CAS  PubMed  Google Scholar 

  54. Içöz S, Tüzün E, Kürtüncü M, Durmus H, Mutlu M, Eraksoy M, Akman-Demir G (2010) Enhanced IL-6 production in aquaporin-4 anti-body positive neuromyelitis optica patients. Int J Neurosci 120(1):71–75. doi:10.3109/00207450903428970

    Article  PubMed  Google Scholar 

  55. Uzawa A, Mori M, Arai K, Sato Y, Hayakawa S, Masuda S, Taniguchi J, Kuwabara S (2010) Cytokine and chemokine profiles in neuromyelitis optica: significance of interleukin-6. Mult Scler 16(12):1443–1452. doi:10.1177/1352458510379247

    Article  CAS  PubMed  Google Scholar 

  56. Linhares UC, Schiavoni PB, Barros OB, Kasahara TM, Teixeira B, Ferreira TB, Alvarenga R, Hygino J, Vieira MMM, Bittencourt VCB, Andrade RM, Andrade AF, Bento CAM (2013) The ex vivo pro- duction of IL-6 and IL-21 by CD41 T cells is directly associated with neurological disability in neuromyelitis optica patients. J Clin Immunol 33(1):179–189. doi:10.1007/s10875-012-9780-2

    Article  CAS  PubMed  Google Scholar 

  57. Chihara N, Aranami T, Sato W, Miyazaki Y, Miyake S, Okamoto T, Ogawa M, Toda T, Yamamura T (2011) Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmoblasts in neuromyelitis optica. Proc Natl Acad Sci 108(9):3701–3706. doi:10.1073/pnas.1017385108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Uwara A, Mori M, Sato Y, Masuda S, Kuwabara S (2012) CSF interleukin-6 level predicts recovery from neuromyelitis optica relapse. J Neurol Neurosurg Psychiatry 83(3):339–340. doi:10.1136/jnnp.2011.241760

    Article  Google Scholar 

  59. Barros PO, Cassano T, Hygino J, Ferreira TB, Centuriao N, Kasahara TM, Andrade RM, Linhares UC, Andrade AFB, Vasconcelos CCF, Alvarenga R, Marignier R, Bento CA (2015) Predication of disease severity in neuromyelitis optica by levels of interleukin (IL)-6 produced during remission. Clin Exp Immunol 183(3):480–489. doi:10.1111/cei.12733

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Flanagan EP, Weinshenker BG, Krecke KN, Lennon VA, Lucchinetti CF, McKeon A, Wingerchuk DM, Shuster EA, Jiao Y, Horta ES, Pittock SJ (2015) Short myelitis lesions in aquaporin-4-IgG-positive neuromyelitis optica spectrum. JAMA Neurol 72(1):81–87. doi:10.1001/jamaneurol.2014.2137

    Article  PubMed  PubMed Central  Google Scholar 

  61. Matthews L, Marasco R, Jenkinson M, Küker W, Lupper S, Leite MI, Giorgio A, De Stefano N, Robertson N, Johansen-Berg H, Evangelou N, Palace J (2013) Distinction of seropositive NMO spectrum disorder and MS brain lesion distribution. Neurology 80(14):1330–1337. doi:10.1212/WNL.0b013e3182887957

    Article  PubMed  PubMed Central  Google Scholar 

  62. Lu Z, Zhang B, Qiu W, Kang Z, Shen L, Long Y, Huang J, Hu X (2011) Comparative brain stem lesions on MRI of acute disseminated encephalomyelitis, neuromyelitis optica and multiple sclerosis. PLoS One 6(8):e22766. doi:10.1371/journal.pone.0022766

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Iorio R, Damato V, Mirabella M, Evoli A, Marti A, Plantone D, Frisullo G, Batocchi AP (2013) Distinctive clinical and neuroimaging characteristics of longitudinally extensive transverse myelitis associated with aquaporin-4 autoantibodies. J Neurol 260(9):2396–2402. doi:10.1007/s00415-013-6997-9

    Article  PubMed  Google Scholar 

  64. Matthews LA, Palace JA (2014) The role of imaging in diagnosing neuromyelitis optica spectrum disorder. Mult Scler Relat Disord 3(3):284–293. doi:10.1016/j.msard.2013.11.003

    Article  PubMed  Google Scholar 

  65. ClinicalTrials.gov. Search results for “neuromyelitis optica”. https://clinicaltrials.gov/ct2/results?term=neuromyelitis+optica&Search=Search. Accessed 14 Dec 2016

  66. Abboud H, Petrak A, Mealy M, Sasidharan S, Siddique L, Levy M (2016) Treatment of acute relapses in neuromyelitis optica: steroids alone versus steroids plus plasma exchange. Mult Scler 22(2):185–192. doi:10.1177/1352458515581438

    Article  CAS  PubMed  Google Scholar 

  67. Kleiter I, Gahlen A, Borisow N, Fischer K, Wernecke KD, Wegner B, Hellwig K, Pache F, Ruprecht K, Havla J, Krumbholz M, Kumpfel T, Aktas O, Hartung HP, Ringelstein M, Geis C, Kleinschnitz C, Berthele A, Hemmer B, Angstwurm K, Stellmann JP, Schuster S, Stangel M, Lauda F, Tumani H, Mayer C, Zeltner L, Ziemann U, Linker R, Schwab M, Marziniak M, Bergh FT, Hofstadt-van Oy U, Neuhaus O, Winkelmann A, Marouf W, Faiss J, Wildemann B, Friedemann P, Jarius S, Trebst C, On behalf of the Neuromyelitis Optica Study Group (2016) Neuromyelitis optica: evaluation of 871 attacks and 1,153 treatment courses. Ann Neurol 79(2):206–216. doi:10.1002/ana.24554

    Article  CAS  PubMed  Google Scholar 

  68. Elsone L, Panicker J, Mutch K, Boggild M, Appleton R, Jacob A (2014) Role of intravenous immunoglobulin in the treatment of acute relapses of neuromyelitis optica: experience in 10 patients. Mult Scler 20(4):501–504. doi:10.1177/1352458513495938

    Article  CAS  PubMed  Google Scholar 

  69. Absoud M, Gadian J, Hellier J, Brex PA, Ciccarelli O, Giovannoni G, Kelly J, McCrone P, Murphy C, Palace J, Pickles A, Pike M, Robertson N, Jacob A, Lim M (2015) Protocol for a multicentre randomised controlled TRial of IntraVEnous immunoglobulin versus standard therapy for the treatment of transverse myelitis in adults and children (STRIVE). BMJ Open 5(5):e008312. doi:10.1136/bmjopen-2015-008312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Levy M, Mealy M (2014) Purified human C1-esterase inhibitor is safe in acute relapses of neuromyelitis optica. Neurol Neuroimmunol Neuroinflamm 1(1):e5. doi:10.1212/NXI.0000000000000005

    Article  PubMed  PubMed Central  Google Scholar 

  71. Shimizu J, Hatanaka Y, Hasegawa M, Iwata A, Sugimoto I, Date H, Goto J, Shimizu T, Takatsu M, Sakurai Y, Nakase H, Uesaka Y, Hashida H, Hashimoto K, Komiya T, Tsuji S (2010) IFNbeta-1b may severely exacerbate Japanese optic-spinal MS in neuromyelitis optica spectrum. Neurology 75(16):1423–1427. doi:10.1212/WNL.0b013e3181f8832e

    Article  CAS  PubMed  Google Scholar 

  72. Palace J, Leite MI, Nairne A, Vincent A (2010) Interferon Beta treatment in neuromyelitis optica: increase in relapses and aquaporin 4 antibody titers. Arch Neurol 67(8):1016–1017. doi:10.1001/archneurol.2010.188

    Article  PubMed  Google Scholar 

  73. Barnett MH, Prineas JW, Buckland ME, Parratt JD, Pollard JD (2012) Massive astrocyte destruction in neuromyelitis optica despite natalizumab therapy. Mult Scler 18(1):108–112. doi:10.1177/1352458511421185

    Article  CAS  PubMed  Google Scholar 

  74. Jacob A, Hutchinson M, Elsone L, Kelly S, Ali R, Saukans I, Tubridy N, Boggild M (2012) Does natalizumab therapy worsen neuromyelitis optica? Neurology 79(10):1065–1066. doi:10.1212/WNL.0b013e31826845fe

    Article  PubMed  Google Scholar 

  75. Kleiter I, Hellwig K, Berthele A, Kumpfel T, Linker RA, Hartung HP, Paul F, Aktas O, Neuromyelitis Optica Study Group (2012) Failure of natalizumab to prevent relapses in neuromyelitis optica. Arch Neurol 69(2):239–245. doi:10.1001/archneurol.2011.216

    Article  PubMed  Google Scholar 

  76. Min JH, Kim BJ, Lee KH (2012) Development of extensive brain lesions following fingolimod (FTY720) treatment in a patient with neuromyelitis optica spectrum disorder. Mult Scler 18(1):113–115. doi:10.1177/1352458511431973

    Article  CAS  PubMed  Google Scholar 

  77. Ayzenberg I, Schollhammer J, Hoepner R, Hellwig K, Ringelstein M, Aktas O, Kumpfel T, Krumbholz M, Trebst C, Paul F, Pache F, Obermann M, Zeltner L, Schwab M, Berthele A, Jarius S, Kleiter I (2016) Efficacy of glatiramer acetate in neuromyelitis optica spectrum disorder: a multicenter retrospective study. J Neurol 263:575–582. doi:10.1007/s00415-015-7991-1

    Article  CAS  PubMed  Google Scholar 

  78. Azzopardi L, Cox AL, McCarthy CL, Jones JL, Coles AJ (2016) Alemtuzumab use in neuromyelitis optica spectrum disorders: a brief case series. J Neurol 263:25–29. doi:10.1007/s00415-015-7925-y

    Article  PubMed  Google Scholar 

  79. Kimbrough DJ, Fukihara K, Jacob A, Lana-Peixoto MA, Leite MI, Levy M, Marignier R, Nakashima I, Palace J, de Seze J, Stuve O, Tenembaum SN, Traboulsee A, Waubant E, Weinshenker BG, Wingerchuk DM (2012) Treatment of neuromyelitis optica: review and recommendations. Mult Scler Relat Disord 1:180–187. doi:10.1016/j.msard.2012.06.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Trebst C, Jarius S, Berthele A, Paul F, Schippling S, Wildemann B, Borisow N, Kleiter I, Aktas O, Kumpfel T, Neuromyelitis Optica Study Group (2014) Update on the diagnosis and treatment of neuromyelitis optica: Recommendations of the Neuromyelitis Optica Study Group (NEMOS). Neurology 261(1):1–16. doi:10.1007/s00415-013-7169-7

    Article  CAS  Google Scholar 

  81. Kessler RA, Mealy MA, Levy M (2016) Treatment of neuromyelitis optica spectrum disorder: acute, preventative, and symptomatic. Curr Treat Options Neurol 18(1):2. doi:10.1007/s11940-015-0387-9

    Article  PubMed  PubMed Central  Google Scholar 

  82. Palace J, Leite I, Jacob A (2012) A practical guide to the treatment of neuromyelitis optica. Pract Neurol 12(4):209–214. doi:10.1136/practneurol-2012-000237

    Article  PubMed  Google Scholar 

  83. Stroopinsky D, Katz T, Rowe JM, Melamed D, Avivi I (2012) Rituximab-induced direct inhibition of T-cell activation. Cancer Immunol Immunother 61(8):1233–1241. doi:10.1007/s00262-011-1168-2

    Article  CAS  PubMed  Google Scholar 

  84. Graves J, Vinayagasundaram U, Mowry EM, Matthews IR, Marino JA, Cheng J, Waubant E (2014) Effects of rituximab on lymphocytes in multiple sclerosis and neuromyelitis optica. Mult Scler Relat Disord 3(2):244–252. doi:10.1016/j.msard.2013.10.003

    Article  PubMed  Google Scholar 

  85. Cree BAC, Lamb S, Morgan K, Chen A, Waubant E, Genain C (2005) An open label study of the effects of rituximab in neuromyelitis optica. Neurology 64(7):1270–1272. doi:10.1212/01.WNL.0000159399.81861.D5

    Article  CAS  PubMed  Google Scholar 

  86. Jacob A, Weinshenker BG, Violich I, McLinskey N, Krupp L, Fox RJ, Wingerchuk DM, Boggild M, Constantinescu CS, Miller A, De Angelis T, Matiello M, Cree BAC (2008) Treatment of neuromyelitis optica with rituximab: retrospective analysis of 25 patients. Arch Neurol 65(11):1443–1448. doi:10.1001/archneur.65.11.noc80069

    Article  PubMed  Google Scholar 

  87. Kim SH, Huh SY, Lee SJ, Joung A, Kim HJ (2013) A 5-year follow-up of rituximab treatment in patients with neuromyelitis optica spectrum disorder. JAMA Neurol 70(9):1110–1118. doi:10.1001/jamaneurol.2013.3071

    Article  PubMed  Google Scholar 

  88. Mealy MA, Wingerchuk DM, Palace J, Greenberg M, Levy M (2014) Comparison of relapse and treatment failure rates among patients with neuromyelitis optica: multicenter study of treatment efficacy. JAMA Neurol 71(3):324–330. doi:10.1001/jamaneurol.2013.5699

    Article  PubMed  Google Scholar 

  89. Kim SH, Jeong IH, Hyun JW, Joung A, Jo HJ, Hwang SH, Yun S, Joo J, Kim HJ (2015) Treatment outcomes with rituximab in 100 patients with neuromyelitis optica. Influence of FCGR3A polymorphisms on the therapeutic response to rituximab. JAMA Neurol 72(9):989–995. doi:10.1001/jamaneurol.2015.1276

    Article  PubMed  Google Scholar 

  90. Zéphir H, Bernard-Valnet R, Lebrun C, Outteryck O, Audoin B, Bourre B, Pittion S, Wiertlewski S, Ouallet JC, Neau JP, Ciron J, Clavelou P, Marignier R, Brassat D (2015) Rituximab as first-line therapy in neuromyelitis optica: efficiency and tolerability. J Neurol 262(10):2329–2335. doi:10.1007/s00415-015-7852-y

    Article  PubMed  CAS  Google Scholar 

  91. Radaelli M, Moiola L, Sangalli F, Esposito F, Barcella V, Ferre L, Rodegher M, Colombo B, Fazio R, Martinelli V, Comi G (2016) Neuromyelitis optica spectrum disorders: long-term safety and efficacy of rituximab in Caucasian patients. Mult Scler 22(4):511–519. doi:10.1177/1352458515594042

    Article  CAS  PubMed  Google Scholar 

  92. Annovazzi P, Capobianco M, Moiola L, Patti F, Frau J, Uccelli A, Centonze D, Perini P, Tortorella C, Prosperini L, Lus G, Fuiani A, Falcini M, Martinelli V, Comi G, Ghezzi A (2016) Rituximab in the treatment of neuromyelitis optica: a multicentre Italian observational study. J Neurol 263(9):1727–1735. doi:10.1007/s00415-016-8188-y

    Article  CAS  PubMed  Google Scholar 

  93. Kim SH, Kim W, Li XF, Jung IJ, Kim HJ (2011) Repeated treatment with rituximab based on the assessment of peripheral circulating memory B cells in patients with relapsing neuromyelitis optica over 2 years. Arch Neurol 68(11):1412–1419. doi:10.1001/archneurol.2011.154

    Article  PubMed  Google Scholar 

  94. Greenberg BM, Graves D, Remington G, Hardeman P, Mann M, Karandikar N, Stuve O, Monson N, Frohman E (2012) Rituximab dosing and monitoring strategies in neuromyelitis optica patients: creating strategies for therapeutic success. Mult Scler 18(7):1022–1026. doi:10.1177/1352458511432896

    Article  PubMed  Google Scholar 

  95. Yang CS, Yang L, Li T, Zhang DQ, Jin WN, Li MS, Su N, Zhangning N, Liu Q, Shao ZH, Yu C, Shi FD (2013) Responsiveness to reduced dosage of rituximab in Chinese patients with neuromyelitis optica. Neurology 81(8):710–713. doi:10.1212/WNL.0b013e3182a1aac7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Clifford DB, Ances B, Costello C, Rosen-Schmidt S, Andersson M, Parks D, Perry A, Yerra R, Schmidt R, Alvarez E, Tyler KL (2011) Rituximab-associated progressive multifocal leukoencephalopathy in rheumatoid arthritis. Arch Neurol 68(9):1156–1164. doi:10.1001/archneurol.2011.103

    Article  PubMed  PubMed Central  Google Scholar 

  97. Kim SH, Hyun JW, Jeong IH, Joung A, Yeon JL, Dehmel T, Adams O, Kieseier BC, Kim HJ (2015) Anti-JC virus antibodies in rituximab-treated patients with neuromyelitis optica spectrum disorder. J Neurol 262(3):696–700. doi:10.1007/s00415-014-7629-8

    Article  CAS  PubMed  Google Scholar 

  98. Dubey D, Kieseier BC, Hartung HP, Hemmer B, Miller-Little WA, Stuve O (2014) Clinical management of multiple sclerosis and neuromyelitis optica with therapeutic monoclonal antibodies: approved therapies and emerging candidates. Expert Rev Clin Immunol 11(1):93–108. doi:10.1586/1744666X.2015.992881

    Article  PubMed  CAS  Google Scholar 

  99. Kieseier BC, Stüve O, Dehmel T, Goebels N, Leussink VI, Mausberg AK, Ringelstein M, Turowski B, Aktas O, Antoch G, Hartung HP (2013) Disease amelioration with tocilizumab in a treatment-resistant patient with neuromyelitis optica. JAMA Neurol 70(3):390–393. doi:10.1001/jamaneurol.2013.668

    Article  PubMed  Google Scholar 

  100. Ayzenberg I, Kleiter I, Schroder A, Hellwig K, Chan A, Yamamura T, Gold R (2013) Interleukin 6 receptor blockade in patients with neuromyelitis optica nonresponsive to anti-CD20 therapy. JAMA Neurol 70(3):394–397. doi:10.1001/jamaneurol.2013.1246

    Article  PubMed  Google Scholar 

  101. Araki M, Aranami T, Matsuoka T, Nakamura M, Miyake S, Yamamura T (2012) Clinical improvement in a patient with neuromyelitis optica following therapy with the anti-IL-6 receptor monoclonal antibody tocilizumab. Mod Rheumatol 23(4):827–831. doi:10.1007/s10165-012-0715-9

    Article  PubMed  PubMed Central  Google Scholar 

  102. Harmel J, Ringelstein M, Ingwersen J, Mathys C, Goebels N, Hartung HP, Jarius S, Aktas O (2014) Interferon-β-related tumefactive brain lesion in a Caucasian patient with neuromyelitis optica and clinical stabilization with tocilizumab. BMC Neurol 14(1):473–475. doi:10.1186/s12883-014-0247-3

    Article  CAS  Google Scholar 

  103. Lauenstein AS, Stettner M, Kieseier BC, Lensch E (2014) Treating neuromyelitis optica with the interleukin-6 receptor antagonist tocilizumab. BMJ Case Rep 26(03):2014. doi:10.1136/bcr-2013-202939 (published online)

    Google Scholar 

  104. Ringelstein M, Ayzenberg I, Harmel J, Lauenstein AS, Lensch E, Stögbauer F, Hellwig K, Ellrichmann G, Stettner M, Chan A, Hartung HP, Kieseier B, Gold R, Aktas O, Kleiter I (2015) Long-term therapy with interleukin 6 receptor blockade in highly active neuromyelitis optica spectrum disorder. JAMA Neurol 72(7):756–758. doi:10.1001/jamaneurol.2015.0533

    Article  PubMed  Google Scholar 

  105. Komai T, Shoda H, Yamaguchi K, Sakurai K, Shibuya M, Kubo K, Takahashi T, Fujio K, Yamamoto K (2016) Neuromyelitis optica spectrum disorder complicated with Sjogren syndrome successfully treated with tocilizumab: a case report. Mod Rheumatol 26(2):294–296. doi:10.3109/14397595.2013.861333

    PubMed  Google Scholar 

  106. Chugai Pharmaceutical Co., LTD. SMART-Ig (recycling antibody). http://www.chugai-pharm.co.jp/english/ir/rd/technologies_popup1.html#. Accessed 14 Dec 2016

  107. Rother RP, Rollins SA, Mojcik CF, Brodsky RA, Bell L (2007) Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nat Biotechnol 25(11):1256–1264. doi:10.1038/nbt1344

    Article  CAS  PubMed  Google Scholar 

  108. Hinson SR, McKeon A, Fryer JP, Apiwattanakul M, Lennon VA, Pittock SJ (2009) Prediction of neuromyelitis optica attack severity by quantitation of complement-mediated injury to aquaporin-4-expressing cells. Arch Neurol 66(9):1164–1167. doi:10.1001/archneurol.2009.188

    Article  PubMed  Google Scholar 

  109. Pittock SJ, Lennon VA, McKeon A, Mandrekar J, Weinshenker BG, Lucchinetti CF, O’Toole O, Wingerchuk DM (2013) Eculizumab in AQP4-IgG-positive relapsing neuromyelitis optica spectrum disorders: an open-label pilot study. Lancet Neurol 12(6):554–562. doi:10.1016/S1474-4422(13)70076-0

    Article  CAS  PubMed  Google Scholar 

  110. Matiello M, Pittock SJ, Porrata L, Weinshenker BG (2011) Failure of autologous haematopoietic to prevent relapse of neuromyelitis optica. Arch Neurol 68(7):953–955. doi:10.1001/archneurol.2011.38

    Article  PubMed  Google Scholar 

  111. Greco R, Bondanza A, Oliveira MC, Badoglio M, Burman J, Piehl F, Hagglund H, Krasulova E, Simoes B, Pinto CK, Pohlreich D, Labopin M, Saccardi R, Comi G, Mancardi GL, Bacigalupo A, Ciceri F, Farge D (2015) Autologous haematopoietic stem cell transplantation in neuromyelitis optica: a registry study of the EBMT Autoimmune Diseases Working Party. Mult Scler 21(2):189–197. doi:10.1177/1352458514541978

    Article  PubMed  Google Scholar 

  112. Le Blanc K, Mougiakakos D (2012) Multipotent mesenchymal stromal cells and the innate immune system. Nat Rev Immunol 12(5):383–396. doi:10.1038/nri3209

    Article  PubMed  CAS  Google Scholar 

  113. Kokaia Z, Martino G, Schwartz M, Lindvall O (2012) Cross-talk between neural stem cells and immune cells: the key to better brain repair? Nat Neurosci 15(8):1078–1087. doi:10.1038/nn.3163

    Article  CAS  PubMed  Google Scholar 

  114. Lu Z, Ye D, Qian L, Zhu L, Wang C, Guan D, Zhang X, Xu Y (2012) Human umbilical cord mesenchymal stem cell therapy on neuromyelitis optica. Curr Neurovasc Res 9(4):250–255. doi:10.2174/156720212803530708

    Article  PubMed  Google Scholar 

  115. Fu Y, Yan Y, Qi Y, Yang L, Li T, Zhang N, Yu C, Su L, Zhang R, Shen Y, Lin S, Liu Q, Shao Z, Han Z, Shi FD (2016) Impact of autologous mesenchymal stem cell infusion on neuromyelitis optica spectrum disorder: a pilot, 2-year observational study. CNS Neurosci Ther 22(8):677–685. doi:10.1111/cns.12559

    Article  CAS  PubMed  Google Scholar 

  116. Levy M, Boulis N, Rao M, Svendsen CN (2016) Regenrative cellular therapies for neurologic diseases. Brain Res 1638(Pt A):88–96. doi:10.1016/j.brainres.2015.06.053

    Article  CAS  PubMed  Google Scholar 

  117. Lida S, Nakamura M, Wate R, Kaneko S, Kusaka H (2015) Successful treatment of paroxysmal tonic spasms with topiramate in a patient with neuromyelitis optica. Mult Scler Relat Disord 4(5):457–459. doi:10.1016/j.msard.2015.07.011

    Article  Google Scholar 

  118. Clerc C, Bourre B, Mathieu B, Zephir H, Jean-Baptiste C, Collongues N, Blanc F, Zaencker C, Vermersch P, de Seze J (2015) Dalfampridine for symptomatic treatment of neuromyelitis optica (P5.263). Neurology 84(14):Supplement P5.263

    Google Scholar 

  119. Mutch KP, Wilson M, Manohar R, Zhao S, Leggett H, Hamid S, Elsone L, Jacob A (2015) Efficacy of fampridine modified-release on ambulation in neuromyelitis optica: a pilot study. ECTRIMS Online Library: Poster P1175. http://onlinelibrary.ectrims-congress.eu/ectrims/2015/31st/116184/kerry.mutch.efficacy.of.fampridine.modified-release.on.ambulation.in.html?f=m1. Accessed 14 Dec 2016

  120. Moore P, Jackson C, Mutch K, Methley A, Pollard C, Hamid S, Jacob A (2016) Patient-reported outcome measure for neuromyelitis optica: pretesting of preliminary instrument and protocol for further development in accordance with international guidelines. BMJ Open 6:e011142. doi:10.1136/bmjopen-2016-011142

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The UK NMO Service is funded by the National Health Service, through the Highly Specialised Commissioning Group.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Anu Jacob.

Ethics declarations

Conflicts of interest

Dr. Jacob has received research grants from Biogen Idec, Alexion Pharmaceuticals and speakers fees from Biogen, Chugai, Sanofi-Genzyme and Terumo-BCT. Drs. Whittam, Wilson, Hamid, Keir and Bhojak have no relevant disclosures.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Whittam, D., Wilson, M., Hamid, S. et al. What’s new in neuromyelitis optica? A short review for the clinical neurologist. J Neurol 264, 2330–2344 (2017). https://doi.org/10.1007/s00415-017-8445-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-017-8445-8

Keywords

Navigation