Neuromyelitis Optica

Authors: P. Nytrová;  D. Horáková
Authors‘ workplace: Neurologická klinika a Centrum klinických neurověd 1. LF UK a VFN v Praze
Published in: Cesk Slov Neurol N 2015; 78/111(2): 130-137
Category: Minimonography
doi: 10.14735/amcsnn2015130


Neuromyelitis optica (NMO), also known as Devic‘s disease, is a devastating autoimmune disorder of the central nervous system and is clinically characterized by inflammation of the optic nerve, spinal cord, and, less frequently, brainstem. The discovery of antibodies against aquaporin‑4 (NMO‑ IgG/ AQP4- IgG) has definitively distinguished this disease from multiple sclerosis. AQP4- IgG testing is crucial in differential dia­gnosis that also includes magnetic resonance imaging of the brain and spinal cord. Typically, spinal cord lesions exceeding the length of three vertebral segments are found. Changes in magnetic resonance imaging of the brain do not exclude the dia­gnosis of NMO; by contrast, they are relatively common and are fairly typical. Optical coherence tomography provides important information, and quantifies the involvement of the retina and optic nerve. Neurologic deficit in this disease is a result of disease relapse, and it is therefore crucial to establish the dia­gnosis early and initiate an appropriate treatment that can change the unfavorable prognosis. The main therapeutic strategies include aggressive treatment of relapses (with high‑dose corticosteroids or plasmapheresis), followed by chronic therapy (first choice drugs include azathioprine and rituximab).

Key words:
neuromyelitis optica – autoantibodies against aquaporin-4 – neuromyelitis optica spectrum disorders

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manu­script met the ICMJE “uniform requirements” for biomedical papers.


1. Wingerchuk DM, Hogancamp WF, O‘Brien PC, Weinshenker BG. The clinical courseof neuromyelitis optica (Devic‘s syndrome). Neurology 1999; 53(5): 1107– 1114.

2. de Seze J, Stojkovic T, Ferriby D, Gauvrit JY, Montagne C,Mounier‑ Vehier F et al. Devic‘s neuromyelitis optica: clinical, laboratory, MRI and outcome profile. J Neurol Sci 2002; 197(1– 2): 57– 61.

3. 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– 2112.

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

5. Hasegawa H, Ma T, Skach W, Matthay MA, Verkman AS. Molecular cloning of a mercurial‑ insensitive water chan­nel expressed in selected water‑ transporting tissues. J Biol Chem 1994; 269(8): 5497– 5500.

6. Rash JE, Yasumura T, Hudson CS, Agre P, Nielsen S. Direct immunogold labeling of aquaporin‑4 in square arrays of astrocyte and ependymocyte plasma membranes in rat brain and spinal cord. Proc Natl Acad Sci U S A 1998; 95(20): 11981– 11986.

7. Marrie RA, Gryba C. The incidence and prevalence of neuromyelitis optica: a systematic review. Int J MS Care 2013; 15(3): 113– 118. doi: 10.7224/ 1537‑ 2073.2012‑ 048.

8. Wingerchuk DM, Lennon VA, Lucchinetti CF, Pittock SJ, Weinshenker BG. The spectrum of neuromyelitis optica. Lancet Neurol 2007; 6(9): 805– 815.

9. Hinson SR, Pittock SJ, Lucchinetti CF, Roemer SF, Fryer JP,Kryzer TJ et al. Pathogenic potential of IgG binding to water channel extracellular domain in neuromyelitis optica. Neurology 2007; 69(24): 2221– 2231.

10. Saadoun S, Waters P, Bell BA, Vincent A, Verkman AS, Papadopoulos MC. Intra‑ cerebral injection of neuromyelitis optica immunoglobulin G and human complement produces neuromyelitis optica lesions in mice. Brain 2010; 133(2): 349– 361. doi: 10.1093/ brain/ awp309.

11. 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(7): 1450– 1461.

12. Nytrova P, Potlukova E, Kemlink D, Woodhall M, Horakova D, Waters P et al. Complement activation in patients with neuromyelitis optica. J Neuroimmunol 2014; 274(1– 2): 185– 191. doi: 10.1016/ j.jneuroim.2014.07.001.

13. Jarius S, Paul F, Franciotta D, Waters P, Zipp F, Hohlfeld Ret al. Mechanisms of disease: aquaporin‑4 antibodies in neuromyelitis optica. Nat Clin Pract Neurol 2008; 4(4): 202– 214. doi: 10.1038/ ncpneuro0764.

14. Roemer SF, Parisi JE, Lennon VA, Benarroch EE, Las­smann H, Bruck W et al. Pattern‑ specific loss of aquaporin‑4 immunoreactivity distinguishes neuromyelitis optica from multiple sclerosis. Brain 2007; 130(5): 1194– 1205.

15. Iorio R, Lucchinetti CF, Lennon VA, Farrugia G, Pasricha PJ, Weinshenker BG et al. Intractable nausea and vomiting from autoantibodies against a brain water chan­nel. Clin Gastroenterol Hepatol 2013; 11(3): 240– 245. doi: 10.1016/ j.cgh.2012.11.021.

16. Chan KH, Tse CT, Chung CP, Lee RL, Kwan JS, Ho PW et al. Brain involvement in neuromyelitis optica spectrum disorders. Arch Neurol 2011; 68(11): 1432– 1439. doi: 10.1001/ archneurol.2011.249.

17. Samart K, Phanthumchinda K. Neuromyelitis optica with hypothalamic involvement: a case report. J Med Assoc Thai 2010; 93(4): 505– 509.

18. 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– 682. doi: 10.1136/ jnnp.2008.157693.

19. Zavada J, Nytrova P, Wandinger KP, Jarius S, Svobodova R, Probst C et al. Seroprevalence and specificity of NMO‑ IgG (anti‑aquaporin 4 antibodies) in patients with neuropsychiatric systemic lupus erythematosus. Rheumatol Int 2013; 33(1): 259– 263. doi: 10.1007/ s00296‑ 011‑ 2176‑ 4.

20. Wingerchuk DM, Weinshenker BG. Neuromyelitis optica: clinical predictors of a relapsing course and survival. Neurology 2003; 60(5): 848– 853.

21. 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– 1849. doi: 10.1093/ brain/ aws109.

22. Tackley G, Kuker W, Palace J. Magnetic resonance imaging in neuromyelitis optica. Mult Scler 2014. pii:1352458514531087. [Epub ahead of print].

23. Kim W, Park MS, Lee SH, Kim SH, Jung IJ, Takahashi Tet al. Characteristic brain magnetic resonance imag­ing abnormalities in central nervous system aquaporin‑4 autoimmunity. Mult Scler 2010; 16(10): 1229– 1236. doi: 10.1177/ 1352458510376640.

24. Pittock SJ, Lennon VA, Krecke K, Wingerchuk DM, Lucchinetti CF, Weinshenker BG. Brain abnormalities in neuromyelitis optica. Arch Neurol 2006; 63(3): 390– 396.

25. Sinnecker T, Dorr J, Pfueller CF, Harms L, Ruprecht K,Jarius S et al. Distinct lesion morphology at 7– T MRI dif­ferentiates neuromyelitis optica from multiple sclerosis. Neurology 2012; 79(7): 708– 714. doi: 10.1212/ WNL.0b013e3182648bc8.

26. Jarius S, Wildemann B. Aquaporin‑4 antibodies (NMO‑ IgG) as a serological marker of neuromyelitis optica: a critical review of the literature. Brain Pathol 2013; 23(6): 661– 683. doi: 10.1111/ bpa.12084.

27. 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.

28. Ringelstein M, Kleiter I, Ayzenberg I, Borisow N, Paul F,Ruprecht K et al. Visual evoked potentials in neuromyelitis optica and its spectrum disorders. Mult Scler 2014; 20(5): 617– 620. doi: 10.1177/ 1352458513503053.

29. Wingerchuk DM, Lennon VA, Pittock SJ, Lucchinetti CF, Weinshenker BG. Revised dia­gnostic criteria for neuromyelitis optica. Neurology 2006; 66(10): 1485– 1489.

30. 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.

31. Jiao Y, Fryer JP, Lennon VA, McKeon A, Jenkins SM, Smith CY et al. Aquaporin 4 IgG serostatus and outcome in recurrent longitudinally extensive transverse myelitis. JAMA Neurol 2014; 71(1): 48– 54. doi: 10.1001/ jamaneurol.2013.5055.

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

33. 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– 1277. doi: 10.1212/ WNL.0b013e31826aac4e.

34. Woodhall M, Coban A, Waters P, Ekizoglu E, Kurtuncu M,Shugaiv E et al. Glycine receptor and myelin oligodendrocyte glycoprotein antibodies in Turkish patients with neuromyelitis optica. J Neurol Sci 2013; 335(1– 2): 221– 223. doi: 10.1016/ j.jns.2013.08.034.

35. Trebst C, Jarius S, Berthele A, Paul F, Schippling S, Wildemann B et al. Update on the dia­gnosis and treatment of neuromyelitis optica: recommendations of the Neuromyelitis Optica Study Group (NEMOS). J Neurol 2014; 261(1): 1– 16. doi: 10.1007/ s00415‑ 013‑ 7169‑ 7.

36. Papadopoulos MC, Bennett JL, Verkman AS. Treatment of neuromyelitis optica: state‑ of‑ the‑ art and emerging therapies. Nat Rev Neurol 2014; 10(9): 493– 506. doi: 10.1038/ nrneurol.2014.141.

37. Shimizu J, Hatanaka Y, Hasegawa M, Iwata A, Sugimoto I, Date H et al. IFNbeta‑1b may severely exacerbate Japanese optic‑ spinal MS in neuromyelitis optica spectrum. Neurology 2010; 75(16): 1423– 1427. doi: 10.1212/ WNL.0b013e3181f8832e.

38. Papeix C, Vidal JS, de Seze J, Pierrot‑ Deseilligny C, Tourbah A, Stankoff B et al. Immunosuppressive therapy is more effective than interferon in neuromyelitis optica. Mult Scler 2007; 13(2): 256– 259.

39. Kleiter I, Hellwig K, Berthele A, Kumpfel T, Linker RA, Hartung HP et al. Failure of natalizumab to prevent relapses in neuromyelitis optica. Arch Neurol 2012; 69(2): 239– 245. doi: 10.1001/ archneurol.2011.216.

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

41. 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– 115. doi: 10.1177/ 1352458511431973.

42. Wingerchuk DM, Weinshenker BG. Neuromyelitis optica. Curr Treat Options Neurol 2008; 10(1): 55– 66.

43. Pellkofer HL, Krumbholz M, Berthele A, Hemmer B,Gerdes LA, Havla J et al. Long‑term follow‑up of patients with neuromyelitis optica after repeated therapy with rituximab. Neurology 2011; 76(15): 1310– 1315. doi: 10.1212/ WNL.0b013e3182152881.

44. Kim SH, Huh SY, Lee SJ, Joung A, Kim HJ. A 5‑year fol­low‑up of rituximab treatment in patients with neuromyelitis optica spectrum disorder. JAMA Neurol 2013; 70(9): 1110– 1117.

45. Sellner J, Boggild M, Clanet M, Hintzen RQ, Illes Z, Montalban X et al. EFNS guidelines on dia­gnosis and management of neuromyelitis optica. Eur J Neurol 2010; 17(8): 1019– 1032. doi: 10.1111/ j.1468‑ 1331.2010.03066.x.

46. 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– 562. doi: 10.1016/ S1474‑ 4422(13)70076‑ 0.

47. 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– 1306. doi: 10.1212/ WNL.0000000000000317.

48. Greco R, Bondanza A, Oliveira MC, Badoglio M, Burman J, Piehl F et al. Autologous hematopoietic stem cell transplantation in neuromyelitis optica: a registry study of the EBMT Autoimmune Diseases Working Party. Mult Scler 2014; 21(2): 189– 197. doi: 10.1177/ 1352458514541978.

49. Fragoso YD, Adoni T, Bichuetti DB, Brooks JB, Ferreira ML, Oliveira EM et al. Neuromyelitis optica and pregnancy. J Neurol 2013; 260(10): 2614– 2619. doi: 10.1007/s00415‑ 013‑ 7031‑ y.

Paediatric neurology Neurosurgery Neurology

Article was published in

Czech and Slovak Neurology and Neurosurgery

Issue 2

2015 Issue 2

Most read in this issue
Forgotten password

Don‘t have an account?  Create new account

Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.


Don‘t have an account?  Create new account