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Headache and Its Management in Patients With Multiple Sclerosis

Headache (JR Couch, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Headache

Abstract

Purpose of review

The purpose of this review was to discuss the prevalence, impact, pathophysiology, and treatment of headaches (H/As) in patients with multiple sclerosis (MS).

Recent findings

Headaches and multiple sclerosis are more common in women than in men with the ratio of female to male being 3:1. It is not entirely clear if there is a correlation or an incidental comorbidity of two neurological conditions. A review of the literature shows a variable prevalence of H/As in MS patients. Using the International Classification of Headache Disorders (ICHD) criteria, the primary type of H/As, especially migraine, is the most common type seen in patients with MS. One of the theories of the pathophysiologic mechanisms of migraine in MS patients is inflammation leading to demyelinating lesions in the pain-producing centers in the midbrain. Secondary H/As due to MS medications such as interferons are also frequently present.

Summary

H/As can be a cause for significant comorbidity in patients with MS. The treatment of H/As in patients with MS should be addressed in the same fashion as in the non-MS population, which is a combination of pharmacological and non-pharmacological methods. Preventive medicines for the H/As should be carefully selected because of their side effect profiles. Acute attacks of migraines can be treated with medications such as triptans. Patients with MS who have migraine H/As should be educated about the phenomenon of overuse H/As, keeping headache journals, avoiding stress, and monitoring sleeping habits. The presence of depression in patients with MS and migraine affects quality of life (QOL) and should also be addressed for better outcomes.

Keywords

Prevalence Pathogenesis Multiple sclerosis Headaches Mimics Treatment 

Abbreviations

H/As

Headaches

EM

Episodic migraine

CM

Chronic migraine

CDH

Chronic daily headaches

ICHD

International Classification of Headache Disorders

IHS

International Headache Society

SLE

Systemic lupus erythematosus

QOL

Quality of life

HIT-6

Headache Impact Test

MIDAS

Migraine Disability Assessment

DMT

Disease-modifying therapy

IFN-B

Interferon beta

PRES

Posterior reversible encephalopathy syndrome

CADASIL

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

CGRP

Calcitonin gene-related peptide

CNSV

Central nervous system vasculitis

NSAIDs

Non-steroidal anti-inflammatory drugs

Notes

Compliance with Ethical Standards

Conflict of Interest

Farhat Husain and Meheroz Rabadi declare no conflict of interest.

Gabriel Pardo is a consultant for Bayer and is a consultant and on speaker’s bureau for Biogen, Genentech, Genzyme, Novartis, Serono, and Teva.

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.

References and Recommended Reading

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

  1. 1.
    Lipton R, Stewart W, Diamond S, Diamond M, Reed M. Prevalence and burden of migraine in the United States. Data from the American migraine study 11. Headache. 2001;41:646–57.CrossRefPubMedGoogle Scholar
  2. 2.
  3. 3.
    Evans et al. Incidence and prevalence of multiple sclerosis in the Americas: a systemic review. Neuroepidemiology 2013; 40(3):195–210.Google Scholar
  4. 4.
    • Bove R, Chitnis T. The role of gender and sex hormones in determining the onset and outcome of multiple sclerosis. Mult Scler J. 2014;20(5):520–6. This review addresses the sex differences in susceptibility to MS and addresses the interactions of hormonal genetic and epigenetic factors.CrossRefGoogle Scholar
  5. 5.
    Lublin F. New multiple sclerosis phenotypic classification. Eur Neurol. 2014;72(sup 11):1–5.  https://doi.org/10.1159/000367614.CrossRefPubMedGoogle Scholar
  6. 6.
    • Mohrke J, Kropp P, Zettl. Headaches in multiple sclerosis might imply an Inflammatorial process. PLoS One. 2013;8(8):e69570. This study found a higher incidence of headaches in the relapsing remitting type of MSCrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    International Association for the Study of Pain, 2011. https://s3.amazonaws.com/.../HeadacheFactSheets/1-Epidemiology.pdf.
  8. 8.
    Tabby D, Hassan M, Youngman B, Wilcox J. Headache in multiple sclerosis. Int J MS Care. 2013:73–80.Google Scholar
  9. 9.
    Lenore L, Terwindt G, Ferrari M. The prevalence and characteristics of migraine in a populationbased cohort: the GEM study. Neurology. 1999;53(3):537–42.CrossRefGoogle Scholar
  10. 10.
    Jensen R, Stovner LJ. Epidemiology and comorbidity of headache. Lancet Neurol. 2008;7:354–61.CrossRefPubMedGoogle Scholar
  11. 11.
    Buse D, Manack A, Serrano D, Reed M, Varon S, Turkel C, et al. Headache impact of chronic and episodic migraine; results from American migraine prevalence and prevention study. Headache. 2012;52(1):3–17.CrossRefPubMedGoogle Scholar
  12. 12.
    Kosinski M, Bayliss MS, Bjorner JB, et al. A six-item short-form survey for measuring headache impact. The HIT-6. Qual Life Res. 2003;12:963–74.CrossRefPubMedGoogle Scholar
  13. 13.
    Finocchi C, Strada L. Sex -related differences in migraine. Neurol Sci. 2014;35(Suppl 1):S207–13.CrossRefGoogle Scholar
  14. 14.
    La Mantia L, Prone V. Headache in multiple sclerosis and autoimmune disorders. Neurol Sci. 2015;36(Suppl 1):S75–8.CrossRefGoogle Scholar
  15. 15.
    ICHD-3 beta. Cephalalgia. 2013;33(9):629–808.  https://doi.org/10.1177/03331024134856.
  16. 16.
    Manzoni GC, Bonavita V, Bussone G, et al. Chronic migraine classification: current knowledge and future perspectives. J Headache Pain. 2011;12:585–92.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Dodick D. Chronic daily headache. NEJM. 2006;354:158–65.CrossRefPubMedGoogle Scholar
  18. 18.
    Compston N, McAlpine D. Some aspects of the natural history of disseminated sclerosis. Q J Med. 1952;21:135–67.PubMedGoogle Scholar
  19. 19.
    Villani V, De Giglio L, Prosperini L, Sette G, Pozzilli C, Salvetti M, et al. Determinants of severity of comorbid migraine in multiple sclerosis. Neurol Sci. 2012;33:1345–53.CrossRefPubMedGoogle Scholar
  20. 20.
    • Kister I, Caminero AB, Monteith A, et al. Migraine is comorbid with multiple sclerosis and associated with a more symptomatic course. J Headache Pain. 2010;11:417–25. Study demonstrated higher frequency of rates of depression, anxiety and episodic neurologic dysfunction in patient with MS who also have migraines.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Kister I, Caminero A, Herbert J, Lipton RB. Tension-type headache and migraine in multiple sclerosis. Curr Pain Headache Rep. 2010;14:441–8.CrossRefPubMedGoogle Scholar
  22. 22.
    Villani V, Prosperini L, Ciuffoli A, Pizzolato R, Salvetti M, Pozzilli C, et al. Primary headache and multiple sclerosis: preliminary results of a prospective study. Neurol Sci. 2008;29:S146–8.CrossRefPubMedGoogle Scholar
  23. 23.
    Maarbjerg S, Di Stefano G, Bendtsen L, Cruccu G. Trigeminal neuralgia –diagnosis and treatment. Cephalalgia. 2016:1–10.  https://doi.org/10.1177/0333102416687280.
  24. 24.
    Boneschi FM, Colombo B, Annovazzi P, Martinelli V, Bernasconi L, Solaro C, et al. Lifetime and actual prevalence of pain and headache in multiple sclerosis. Mult Scler. 2008;14:514–21.CrossRefGoogle Scholar
  25. 25.
    Fallata A, Salter A, Tyry T, Cutter G, Marrie R. Trigeminal neuralgia commonly precedes diagnosis of multiple sclerosis. IJMSC. 2017;19:240–6.PubMedPubMedCentralGoogle Scholar
  26. 26.
    Santi L, Annunziata P. Symptomatic cranial neuralgias in multiple sclerosis. Clinical features and treatment. Clin Neurol Neurosurg. 2012:101–7.Google Scholar
  27. 27.
    Minagar A, Sheremata WA. Glossopharyngeal neuralgia and MS. Neurology. 2000;54:1368–70.CrossRefPubMedGoogle Scholar
  28. 28.
    •• Patti F, Nicoletti A, Pappalardo A, et al. Frequency and severity of headache is worsened by interferon-ß therapy in patients with multiple sclerosis. Acta Neurol Scand. 2012;125:91–5. Study shows that treatment with IFN -β can worsen pre-existing and also cause new H/As in patients with MS.CrossRefPubMedGoogle Scholar
  29. 29.
    Polman C, O’Connor P, Havrdova E, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006;354(9):899–910.CrossRefPubMedGoogle Scholar
  30. 30.
    •• Magliozzi R, Howell O, Reeves C, et al. A gradient of neuronal loss and meningeal inflammation in multiple sclerosis. Ann Neurol. 2010;68:477–93. Discovery of B -follicles in meningeal infiltrates may be cause of irritation and serve as a trigger for primary headaches in MSCrossRefPubMedGoogle Scholar
  31. 31.
    Pakpoor J, Handel A, Giovannoni G, Dobson R, Ramagopalan S. Meta-analysis of the relationship between Mutiple sclerosis and migraine. PLoS One. 2012;7(9):e45295.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Merkler D, Klinker F, Jurgens T, et al. Propagation of spreading depression inversely correlates with cortical myelin content. Ann Neurol. 2009;66:355–65.CrossRefPubMedGoogle Scholar
  33. 33.
    Gee J, Chang J, Dublin A, Vijayan N. The association of brainstem lesions with migraine-like headache: an imaging study of multiple sclerosis. Headache. 2005;45(6):670–7.CrossRefPubMedGoogle Scholar
  34. 34.
    Marrie R, Cohen J, Stuve O, Trojano M, Sorensen P, Reingold S, et al. A systematic review of the incidence and prevalence of comorbidity in multiple sclerosis: overview. Mult Scler J. 2015;21(3):263–81.CrossRefGoogle Scholar
  35. 35.
    Marrie R, Fisk J, Tremlett H, et al. Differences in the burden of psychiatric comorbidity in MS vs the general population. Neurology. 2015;85:1972–9.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    •• Marrie R, Reingold S, Cohen J, Stuve O, Trojano M, Soelberg S, et al. The incidence and prevalence of psychiatric disorders in multiple sclerosis: a systematic review. Mult Scler J. 2015;21(3):305–17. This review establishes comorbidity of psychiatric disorders in patients with MSCrossRefGoogle Scholar
  37. 37.
    Feinstein A. Multiple sclerosis and depression. Mult Scler J. 2011;17(11):1276–81.CrossRefGoogle Scholar
  38. 38.
    Murphy R, O’Donoghue, Counihan T, et al. Neuropsychiatric syndromes of multiple sclerosis. J Neurol Neurosurg Psychiatry. 2017;88:697–708.CrossRefPubMedGoogle Scholar
  39. 39.
    D’Amico D, Libro G, Prudenzano MP, et al. Stress and chronic headache. J Headache Pain. 2000;1:S49–52.CrossRefPubMedCentralGoogle Scholar
  40. 40.
    Lampl C, Thomas H, Tassorelli C, et al. Headache, depression and anxiety: associations in the Eurolight project. J Headache Pain. 2016;17:59.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Manack A, Buse D, Lipton R. Chronic migraine: epidemiology and disease burden. Curr Pain Headache Rep. 2011;15:70–8.CrossRefPubMedGoogle Scholar
  42. 42.
    Marrie RA, Horwitz R, Cutter, et al. Cumulative impact of comorbidity on quality of life in MS. Acta Neurol Scand. 2012;125:180–6.CrossRefPubMedGoogle Scholar
  43. 43.
    Elliott D. Migraine in multiple sclerosis. Int Rev Neurobiol. 79:281–301.Google Scholar
  44. 44.
    Jacobs L, Cookfair D, Rudick R, et al. Intramuscular interferon Beta 1-a for disease progression in relapsing Mutiple sclerosis. Ann Neurol. 1996;39:285–96.CrossRefPubMedGoogle Scholar
  45. 45.
    Nicoletti P, Pappalaedo A, Castioglione A, et al. Frequency and severity of headache is worsened by interferon-β therapy in patients with multiple sclerosis. Acta Neurol Scand. 2012;125:91–5.PubMedGoogle Scholar
  46. 46.
    Mantia L. Interferon treatment may trigger primary headaches in multiple sclerosis patients. Mult Scler. 12:476–80.Google Scholar
  47. 47.
    Gelfand A, Gelfand J, Goadsby P. Migraine and multiple sclerosis: epidemiology and approach to treatment. Mult Scler Relat Disord. 2013;2:73–9.CrossRefPubMedGoogle Scholar
  48. 48.
    Polman C, O’Connor P, Havrdova E, et al. A randomized, placebo-controlled trial of Natalizumab for Rlapsing multiple sclerosis. NEJM. 2006;354:899–910.CrossRefPubMedGoogle Scholar
  49. 49.
    Villani V, Prosperini L, Giglio L, Pozzilli C, Salvetti M, Sette G. The impact of interferon Beta and Natalizumab on comorbid migraine in Mutiple sclerosis. Headache. 2012;52:1130–5.CrossRefPubMedGoogle Scholar
  50. 50.
    Kappos L, Radue E-W, O’Connor P, et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med. 2010;362(5):387–401.CrossRefPubMedGoogle Scholar
  51. 51.
    O’Connor P, Wolinsky J, et al. Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med. 2011;365(14):1293–303.CrossRefPubMedGoogle Scholar
  52. 52.
    Kappos L, Gold R et al. Efficacy and safety of oral fumarate in patients with relapsing-remitting multiple sclerosis: a multicenter, randomized, double-blind, placebo-controlled phase 11b study. www. the lancet.com. 2008;372:1463–1472.
  53. 53.
    CAMMS223 Trial Investigators. Alemtuzumab vs. interferon Beta 1-a in early multiple sclerosis. N Engl J Med. 2008;359(17):1786–801.CrossRefGoogle Scholar
  54. 54.
    Hauser S, Bar-Or A, Comi G et al. Ocrelizumab versus Interferon Beta- 1a in relapsing multiple sclerosis. Headache. 2014;376(3): 221–234.Google Scholar
  55. 55.
    Kappos L, Wiendl H, Selmaj K, et al. Daclizumab HYP versus interferon Beta -1a in relapsing multiple sclerosis. N Engl J Med. 2015;373(15):1418–28.CrossRefPubMedGoogle Scholar
  56. 56.
    •• Solomon A, Bourdette D, Cross A, et al. The contemporary spectrum of multiple sclerosis misdiagnosis. Neurology. 2016;87:1393–9. This review emphasizes the frequency of migraine being misdiagnosed as MS and recommends the correct use of McDonald criteria to avoid unnecessary exposure to MS treatments with potential side effectsCrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Kastiari C, Vikelis M, Paraskevopoulou, Sfikakis P, Misikostas. Headache in systematic lupus erythematosus vs multiple sclerosis: a prospective comparative study. Headache. 2011;51:1398–407.Google Scholar
  58. 58.
    John S, Hajj-Ali RA. Headache in autoimmune diseases. Headache. 2014; 572–582.Google Scholar
  59. 59.
    Mantia L, Erbetta A. Headache and inflammatory disorders of the central nervous system. Neurol Sci. 2004;25:S148–53.CrossRefPubMedGoogle Scholar
  60. 60.
    Cuadrado MJ, Sanna G. Headache and systemic lupus erythematosus. Lupus. 2003;12:943–6.CrossRefPubMedGoogle Scholar
  61. 61.
    Toledano M, Weinshenker B, Solomon A. A clinical approach to the differential diagnosis of multiple sclerosis. Curr Neurol Neurosci Rep. 2015;15:57.  https://doi.org/10.1007/s11910-015-0576-7.CrossRefPubMedGoogle Scholar
  62. 62.
    Alroughani R, Ahmed S, Khan R, Al-Hashel J. Status migrainosus as an initial presentation of multiple sclerosis. Alroughani et al. Springer Plus. 2015;4:28.Google Scholar
  63. 63.
    Lin G-Y, Wang C-W, Chiang T, Peng G-S, Yang F-C. Multiple sclerosis presenting initially with a worsening of migraine symptoms. J Headache Pain. 2013; 14:70.Google Scholar
  64. 64.
    Gebhardt M, Kropp P, Jurgens T, Hoffmann F. Headache in the first manifestation of Multiple Sclerosis-Prospective, multicenter study. Brain Behav. 2017: e00852.  https://doi.org/10.1002/brb3.852.
  65. 65.
    Okuda D. Incidental lesions suggesting multiple sclerosis. Continuum. 2016;22(3):730–43.PubMedGoogle Scholar
  66. 66.
    Applebee A. The clinical overlap of multiple sclerosis and headache. Headache. 2012;52(S2):111–6.CrossRefPubMedGoogle Scholar
  67. 67.
    Polman C, Reingold S, Banwell B, et al. Diagnostic criteria for multiple sclerosis. 2010 revisions to the mc Donald criteria. Ann Neurol. 2011;69(2):292–302.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Thompson A, Banwell B, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018;17(2):162–73.CrossRefPubMedGoogle Scholar
  69. 69.
    Lipton R, Bigal M, Diamond M, et al. Migraine prevalence, disease burden, and the need for preventive study. Neurology. 2007;68:343–9.CrossRefPubMedGoogle Scholar
  70. 70.
    •• Estemalik E, Tepper S. Preventive treatment in migraine and the new US guidelines. Neuropsychiatr Dis Treat. 2013;9:709–20. Article describes updated guidelines for preventive treatment in migraine and discusses mode of action of different agents.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Ayata C, Jin H, Kudo C, Dalkara T, Moskowitz. Suppression of cortical spreading depression in migraine prophylaxis. Ann Neurol. 2006;59:652–61.CrossRefPubMedGoogle Scholar
  72. 72.
    Silberstein S, Holland S, Freitag F, Dodick D, Argoff C, Ashman E. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults. Neurology. 2012;78:1337–45.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    D’Amico D, Tepper S. Prophylaxis of migraine: general principles and patient acceptance. Neuropsychiatr Dis Treat. 2008;4(6):1155–67.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Silberstein S. Preventive migraine treatment. Continuum. 2015;21(4):973–89.PubMedPubMedCentralGoogle Scholar
  75. 75.
    Schaefer S, Gottschalk C, Jabbari B. Treatment of chronic migraine with focus on botulinum neurotoxins. Toxins. 2015;7:2615–28.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Barbanti P, Ferroni P. Onabotulinum toxin a in the treatment of chronic migraine: patient selection and special considerations. J Pain Res. 2017;10:2319–29.CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Rizzoli P. Acute and preventive treatment of migraine. Continuum. 2012;18(4):764–82.PubMedGoogle Scholar
  78. 78.
    • Charles A. Migraine. N Engl J Med. 2017;377:553–61. Article discusses diagnostic criteria for migraine and discusses treatment strategies for acute attacks and preventive treatment.CrossRefPubMedGoogle Scholar
  79. 79.
    Colman I, Friedman B, Brown M, Innes G, Grafstein E, Roberts T, et al. Parenteral dexamethasone for acute severe migraine headache: meta –analysis of randomized controlled trials for preventing recurrence. BMJ. 2008;336(7657):1359–61.  https://doi.org/10.1136/bmj.39566.806725.BE.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Jette N, Amoozegar F, Patten S. Depression in epilepsy, migraine and multiple sclerosis. Neurol Clin Pract. 2017;7(2):118–27.CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Harden C, Pennell P, Koppel B, et al. Management issues for women with epilepsy. Epilepsia. 2009;50(5):1247–55.CrossRefPubMedGoogle Scholar
  82. 82.
    Tepper S, Ashina M, Reuter U, et al. Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomized, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2017;16:425–34.CrossRefPubMedGoogle Scholar
  83. 85.••
    Silberstein S, Dodick D, Bigal M Et al. Fremanezumab for the preventive treatment of chronic migraine. N Engl J Med. 2017. 377(22):2113–2132. This paper reports positive results from a phase 3 trial of the use of the monoclonal antibody targeting CGRP in chronic migraine.Google Scholar
  84. 84.
    Kabat-Zinn J. Wherever you go, there you are: Mindfulness meditation in everyday life. Hyperion 1994. ISBN. 10: 1401307787.Google Scholar
  85. 85.
    Andrasik F, Grazzi L, D’Amico D, Sansone E, Leonardi M, Raggi A, et al. Mindfulness and headache: a “new” old treatment, with new findings. Cephalalgia. 2016;36(12):1192–205.CrossRefPubMedGoogle Scholar
  86. 86.
    Gilbertson R, Klatt M. Mindfulness in motion for people with multiple sclerosis: a feasibility study. Int J MS Care. 2017:225–31.Google Scholar
  87. 87.
    Vickers A, Rees R, Zollman C et al. Acupuncture for chronic headache in primary care: large, pragmatic, randomized trial. BMJ 2004. doi: https://doi.org/10.1136/bmj.38029.421863.EB.
  88. 88.
    Zhao L, Chen J, LiY ETAL. The long-term effect of acupuncture for migraine prophylaxis. A randomized clinical trial. JAMA Intern Med. 2017;177(4):508–15.CrossRefPubMedGoogle Scholar

Copyright information

© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2018

Authors and Affiliations

  1. 1.Department of Neurology/RehabilitationOklahoma City VA Medical CenterOklahoma CityUSA
  2. 2.Oklahoma Medical Research FoundationMS Center of ExcellenceOklahoma CityUSA

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