Skip to main content

Advertisement

SpringerLink
Log in

Headache in Neuromyelitis Optica

  • Secondary Headache (M Robbins, Section Editor)
  • Published:
Current Pain and Headache Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Neuromyelitis optica (NMO) classically features a clinical presentation that includes longitudinally extensive transverse myelitis and optic neuritis. However, many other pathognomonic phenomena have more recently been described in patients diagnosed with NMO, including intractable hiccups, vomiting, and painful tonic spasms, but less has been reported regarding the relationship between NMO and headache. Though headache is well established as both a symptom and comorbidity of multiple sclerosis (MS), it has been much less described thus far in the NMO literature and warrants more careful evaluation. Many questions remain unanswered about the relationship between NMO and headache, including headache prevalence in certain groups, distribution of primary and symptomatic headache disorders that are seen most frequently and the specific neuroimaging findings that are associated with an increased risk of headache.

Recent Findings

Various types of headache, such as cervicogenic headache and trigeminal autonomic cephalalgia-like headache, have been reported as the initial clinical presentation of NMO. Other publications have emphasized the association of NMO and other etiologies of headache, such as trigeminal neuralgia, PRES, and preeclampsia. Certain MR imaging findings such as medullary lesions in patients with NMO have also been associated with headache.

Summary

The link between headache and NMO is evident not only in limited case reports and clinical studies but also with both MR imaging and even with some potential common underlying biomarkers such as pentraxin-3 and interleukin-6. Developing a further understanding in the association between these two diseases may lead to better management of headache in patients with NMO and potentially lead to earlier diagnosis of NMO in whom headache may serve as an initial presenting symptom and may even herald a disease exacerbation.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. Lennon VA et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet. 2004;364(9451):2106–12.

    Article  CAS  PubMed  Google Scholar 

  2. Flanagan EP et al. Epidemiology of aquaporin-4 autoimmunity and neuromyelitis optica spectrum. Ann Neurol. 2016;70(5):775–83.

    Article  Google Scholar 

  3. Wingerchuk et al. The spectrum of neuromyelitis optica. Lancet Neurol. 2007;6:805–15.

    Article  CAS  PubMed  Google Scholar 

  4. Popescu BF, Lennon VA, Parisi JE, Howe CL, Weigand SD, Cabrera-Gómez JA, et al. Neuromyelitis optica unique area postrema lesions: nausea, vomiting, and pathogenic implications. Neurology. 2011;76:1229–37.

    Article  PubMed  PubMed Central  Google Scholar 

  5. 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;68:757–61.

    Article  PubMed  Google Scholar 

  6. Kremer L et al. Brainstem manifestations in neuromyelitis optica: a multicenter study of 258 patients. Mult Scler. 2014;20(7):843–7.

    Article  CAS  PubMed  Google Scholar 

  7. Pittock et al. Neuromyelitis optica brain lesions localized at sites of high aquaporin 4 expression. Arch Neurol. 2006;63:964–8.

    Article  PubMed  Google Scholar 

  8. Hsu C-L et al. Persistent hyperthermia in a patient with aquaporin-4 antibody positive neuromyelitis optica spectrum disorder. J Clin Neurol. 2016;12(4):515–6.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Watanabe M et al. Galactorrhea in a patient with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder: a case report and review of the literature. Neurologist. 2015;20(6):101–3.

    Article  PubMed  Google Scholar 

  10. Baba T, Nakashima I, Kanbayashi T, Konno M, Takahashi T, Fujihara K, et al. Narcolepsy as an initial manifestation of neuromyelitis optica with anti-aquaporin-4 antibody. J Neurol. 2009;256:287–8.

    Article  PubMed  Google Scholar 

  11. Elsone et al. Neuropathic pruritis (itch) in neuromyelitis optica. Mult Scler. 2013;19(4):475–9.

    Article  PubMed  Google Scholar 

  12. Hyun J-W et al. Evaluation of the 2015 diagnostic criteria for neuromyelitis optica spectrum disorder. Neurology. 2015;86(19):1772–9.

    Article  Google Scholar 

  13. •• Wingerchuk et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015;85(2):177–89. This publication reevaluated the diagnostic criteria for NMOSD and highlighted the different clinical and radiological findings that are necessary for diagnosis of NMOSD depending on AQP4 antibody status.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Yang X et al. The role of AQP4 in neuromyelitis optica: more answers, more questions. J Neuroimmunol. 2016;298:63–70.

    Article  CAS  PubMed  Google Scholar 

  15. D’Amico D et al. Prevalence of primary headaches in people with multiple sclerosis. Cephalalgia. 2004;24(11):980–4.

    Article  PubMed  Google Scholar 

  16. Ergun U et al. Headaches in the different phases of relapsing-remitting multiple sclerosis: a tendency for stabbing headaches during relapses. Neurologist. 2009;15(4):212–6.

    Article  PubMed  Google Scholar 

  17. Villani V et al. Primary headache and multiple sclerosis: preliminary results of a prospective study. Neurol Sci. 2008;29(1):146–8.

    Article  Google Scholar 

  18. Tortorella P et al. Assessment of MRI abnormalities of the brainstem from patients with migraine and multiple sclerosis. J Neurol Sci. 2006;244(1-2):137–41.

    Article  PubMed  Google Scholar 

  19. Gee JR et al. The association of brainstem lesions with migraine-like headache: an imaging study of multiple sclerosis. Headache. 2005;45(6):670–7.

    Article  PubMed  Google Scholar 

  20. Lin GY et al. Multiple sclerosis presenting initially with a worsening of migraine symptoms. J Headache Pain. 2013;14:70.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Fragoso YD, Brooks JBB. Two cases of lesions in brainstem in multiple sclerosis and refractory migraine. Headache. 2007;14:852–4.

    Article  Google Scholar 

  22. Gonzalez-Quintanilla V et al. Cluster-tic syndrome as the initial manifestation of multiple sclerosis. J Headache Pain. 2012;14:425–9.

    Article  Google Scholar 

  23. Kister I et al. Tension-type headache and migraine in multiple sclerosis. Curr Pain Headache Rep. 2010;14(6):441–8.

    Article  PubMed  Google Scholar 

  24. Qian P et al. Association of neuromyelitis optica with severe and intractable pain. Arch Neurol. 2012;69(11):1482–7.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Kanamori Y et al. Pain in neuromyelitis optica and its effect on quality of life: a cross-sectional study. Neurology. 2011;77(7):652–8.

    Article  CAS  PubMed  Google Scholar 

  26. Carnero Contentti et al. Neuromyelitis optica: association with paroxysmal painful tonic spasms. Neurologia. 2016;31:8.

    Article  Google Scholar 

  27. Morrow M, Wingerchuk D. Neuromyelitis optica. J Neuroophthalmol. 2012;32(2):154–66.

    Article  PubMed  Google Scholar 

  28. Kim SM, et al. Gender effect on neuromyelitis optica spectrum disorder with aquaporin4-immunoglobulin G. Mult Scler. 2016. epub.

  29. Cruccu G et al. Trigeminal neuralgia: new classification and diagnostic grading for practice and research. Neurology. 2016;87(2):220–8.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Truini A et al. A dual concurrent mechanism explains trigeminal neuralgia in patients with multiple sclerosis. Neurology. 2016;86(22):2094–9.

    Article  PubMed  Google Scholar 

  31. Sugiyama A et al. Trigeminal root entry zone involvement in neuromyelitis optica and multiple sclerosis. J Neurol Sci. 2015;355(1-2):147–9.

    Article  PubMed  Google Scholar 

  32. Cruccu G et al. Trigeminal neuralgia and pain related to multiple sclerosis. Pain. 2009;143(3):186–91.

    Article  CAS  PubMed  Google Scholar 

  33. Hinchey J et al. A reversible posterior leukoencephalopathy syndrome. N Eng J Med. 1996;334(8):494.

    Article  CAS  Google Scholar 

  34. Magana SM et al. Posterior reversible encephalopathy syndrome in neuromyelitis optica spectrum disorders. Neurology. 2009;72(8):712–7.

    Article  CAS  PubMed  Google Scholar 

  35. Papadopoulous M, Verkman AS. Aquaporin 4 and neuromyelitis optica. Lancet Neurol. 2012;11(6):535–44.

    Article  Google Scholar 

  36. Cheng C et al. Clinical, radiographic characteristics and immunomodulating changes in neuromyelitis optica with extensive brain lesions. BMC Neurol. 2013;13:72.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Berger JR et al. Posterior reversible encephalopathy syndrome masquerading as progressive multifocal leukoencephalopathy in rituximab treated neuromyelitis optica. Mult Scler Relat Disord. 2014;3(6):728–31.

    Article  PubMed  Google Scholar 

  38. Saadoun S et al. Neuromyelitis optica IgG causes placental inflammation and fetal death. J Immunol. 2013;191(6):2999–3005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Reuss R et al. A woman with acute myelopathy in pregnancy: case outcome. BMJ. 2009;339:b4026.

    Article  PubMed  Google Scholar 

  40. Davoudi V et al. Immunology of neuromyelitis optica during pregnancy. Neurol Neuroimmunol Neuroinflamm. 2016;3(6):e288.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Gold SM et al. Pregnancy and multiple sclerosis: from molecular mechanisms to clinical applications. Semin Immunopathol. 2016;38(6):709–18.

    Article  CAS  PubMed  Google Scholar 

  42. Bourre B et al. Neuromyelitis optica and pregnancy. Neurology. 2012;78(12):875–9.

    Article  CAS  PubMed  Google Scholar 

  43. Skliut M, Jamieson DG. Imaging of headache in pregnancy. Curr Pain Headache Rep. 2016;20:56.

    Article  PubMed  Google Scholar 

  44. Rubio-Ochoa J et al. Physical examination tests for screening and diagnosis of cervicogenic headache: a systematic review. Man Ther. 2016;21:35–40.

    Article  CAS  PubMed  Google Scholar 

  45. Choi S et al. A case of neuromyelitis optica misdiagnosed as cervicogenic headache. Korean J Pain. 2014;27:77–80.

    Article  PubMed  Google Scholar 

  46. Zhao S et al. Neuropathic pain in neuromyelitis optica affects activities of daily living and quality of life. Mult Scler J. 2014;20(12):1658–61.

    Article  Google Scholar 

  47. Horbinski C et al. A 10-year old girl with neck pain. Brain Pathol. 2010;20(2):519–22.

    Article  PubMed  Google Scholar 

  48. Wang JY et al. Meningoencephalitis as an initial manifestation of neuromyelitis optica spectrum disorder. Mult Scler. 2013;19(5):639–43.

    Article  PubMed  Google Scholar 

  49. Fujikura. A case of neuromyelitis optica presenting marked pleocytosis and hypogylcorrhachia. Rinsho Shinkeigaku. 2016;56(8):569–72.

    Article  PubMed  Google Scholar 

  50. Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition beta. Cephalalgia. 2013;33(9):629–808.

    Article  Google Scholar 

  51. Mathew T et al. Trigeminal autonomic cephalalgia as a presenting feature of neuromyelitis optica: “a rare combination of two uncommon disorders”. Mult Scler Relat Disord. 2016;6:73–4.

    Article  PubMed  Google Scholar 

  52. Zhao S et al. An unusual case of ‘itchy paralysis’: neuromyelitis optica presenting with severe neuropathic itch. Pract Neurol. 2015;15:149–51.

    Article  PubMed  Google Scholar 

  53. Xiao L et al. Intractable pruritis in neuromyelitis optica. Neurol Sci. 2016;37(6):949–54.

    Article  PubMed  Google Scholar 

  54. Netravathi, Manjunath, et al. Is pruritis an indicator of aquaporin-positive neuromyelitis optica? Mult Scler. 2016; 1–8. doi:10.1177/1352458516665497.

  55. Doi H et al. Frequency of chronic headaches in Japanese patients with multiple sclerosis: with special reference to opticospinal and common forms of multiple sclerosis. Headache. 2009;49(10):1513–20.

    Article  PubMed  Google Scholar 

  56. Wang Y et al. Comparative clinical characteristics of neuromyelitis optica spectrum disorders with and without medulla oblongata lesions. J Neurol. 2014;261(5):954–62.

    Article  PubMed  Google Scholar 

  57. Pittock S et al. Neuromyelitis optica and non-organ specific autoimmunity. Arch Neurol. 2008;65(1):78–83.

    Article  PubMed  Google Scholar 

  58. Alexopoulos H et al. Anti-aquaporin-4 autoantibodies in systemic lupus erythematosus persist for years and induce astrocytic cytotoxicity but not CNS disease. J Neuroimmunol. 2015;289:8–11.

    Article  CAS  PubMed  Google Scholar 

  59. Tjensvoll AB et al. Migraine is frequent in patients with systemic lupus erythematosus: a case-control study. Cephalalgia. 2011;31(4):401–8.

    Article  PubMed  Google Scholar 

  60. Zhong, Y.H., et al. Comparisons of presentations and outcomes of neuromyelitis optica patients with and without Sjogren’s syndrome. Neurol Sci. 2017;38(2):271–7.

  61. Carvalho D et al. Sjogren syndrome and neuromyelitis optica spectrum disorder co-exist in a common autoimmune milieu. Arg Neurossiquiatr. 2014;72(8):619–24.

    Google Scholar 

  62. Morreale M et al. Neurological involvement in primary Sjogren syndrome: a focus on central nervous system. PLoS One. 2014;9(1):e84605.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Moreira I et al. Frequent involvement of central nervous system in primary Sjogren syndrome. Rheumatol Int. 2015;35(2):289–94.

    Article  PubMed  Google Scholar 

  64. Katsumata Y et al. Semiquantitative measurement of aquaporin-4 antibodies as a possible surrogate marker of neuromyelitis optica spectrum disorders with systemic autoimmune diseases. Mod Rheumatol. 2012;22(5):676–84.

    Article  CAS  PubMed  Google Scholar 

  65. Makhani N, Bigi S, Banwell B, Shroff M. Diagnosing neuromyelitis optica. Neuroimaging Clin N Am. 2013;23:279–91.

    Article  PubMed  Google Scholar 

  66. Pekcevik Y et al. What do we know about brain contrast enhancement patterns in neuromyelitis optica? Clin Imaging. 2016;40:573–80.

    Article  PubMed  Google Scholar 

  67. Cassinotto C et al. MRI of the spinal cord in neuromyelitis optica and recurrent longitudinal extensive myelitis. J Neuroradiol. 2009;36(4):199–205.

    Article  CAS  PubMed  Google Scholar 

  68. Asgari N et al. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  69. •• Kim HJ et al. MRI characteristics of neuromyelitis optica spectrum disorder: an international update. Neurology. 2015;84(11):1165–73. This publication emphasizes distinctions in imaging findings between NMOSD and other pathology such as MS, which has important implications in appropriate treatment.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Stankewitz A et al. Trigeminal nociceptive transmission in migraineurs predicts migraine attacks. J Neurosci. 2011;31(6):1937–43.

    Article  CAS  PubMed  Google Scholar 

  71. •• Bradl M et al. Pain in neuromyelitis optica—prevalance, pathogenesis and therapy. Nat Rev Neurol. 2014;10:529–36. This publication extensively reviewed the pathophysiology of pain in NMO and proposed specific therapies for treatment.

    Article  PubMed  Google Scholar 

  72. O’Connor AB et al. Pain associated with multiple sclerosis: systematic review and proposed classification. Pain. 2008;137(1):96–111.

    Article  PubMed  Google Scholar 

  73. Ceylan M et al. Serum levels of pentraxin-3 and other inflammatory biomarkers in migraine: association with migraine characteristics. Cephalalgia. 2016;36(6):518–25.

    Article  PubMed  Google Scholar 

  74. Wang H et al. Increased plasma levels of pentraxin 3 in patients with multiple sclerosis and neuromyelitis optica. Mult Scler. 2013;19(7):926–31.

    Article  CAS  PubMed  Google Scholar 

  75. Seok JM et al. Clinical characteristics of disabling attacks at onset in patients with neuromyelitis optica spectrum disorder. J Neurol Sci. 2016;368:209–13.

    Article  PubMed  Google Scholar 

  76. Wang F et al. Association of serum levels of intercellular adhesion molecule-1 and interleukin-6 with migraine. Neurol Sci. 2015;36(4):535–40.

    Article  PubMed  Google Scholar 

  77. Chavarro VS et al. Insufficient treatment of severe depression in neuromyelitis optica spectrum disorder. Neurol Neuroimmunol Neuroinflamm. 2016;3(6):286. –abstract.

    Article  Google Scholar 

  78. Igel C et al. Neuromyelitis optica in pregnancy complicated by posterior reversible encephalopathy syndrome, eclampsia and fetal death. J Clin Med Res. 2015;7(3):193–5.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Saul R Korey Department of Neurology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA

    Alina Masters-Israilov & Matthew S. Robbins

  2. Montefiore Headache Center, Bronx, USA

    Matthew S. Robbins

Authors
  1. Alina Masters-Israilov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matthew S. Robbins
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Matthew S. Robbins.

Ethics declarations

Conflict of Interest

Alina Masters-Israilov declares no conflicts of interest.

Matthew S. Robbins declares he is a site PI for clinical trials with eNeura, Inc., and the funds were given directly to his institution; he also declares book royalties from Wiley.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Secondary Headache

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Masters-Israilov, A., Robbins, M.S. Headache in Neuromyelitis Optica. Curr Pain Headache Rep 21, 20 (2017). https://doi.org/10.1007/s11916-017-0620-1

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11916-017-0620-1

Keywords

Search

Navigation