Headache and Its Management in Patients With Multiple Sclerosis
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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).
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.
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.
KeywordsPrevalence Pathogenesis Multiple sclerosis Headaches Mimics Treatment
Chronic daily headaches
International Classification of Headache Disorders
International Headache Society
Systemic lupus erythematosus
Quality of life
Headache Impact Test
Migraine Disability Assessment
Posterior reversible encephalopathy syndrome
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy
Calcitonin gene-related peptide
Central nervous system vasculitis
Non-steroidal anti-inflammatory drugs
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
- 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.• 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
- 7.International Association for the Study of Pain, 2011. https://s3.amazonaws.com/.../HeadacheFactSheets/1-Epidemiology.pdf.
- 8.Tabby D, Hassan M, Youngman B, Wilcox J. Headache in multiple sclerosis. Int J MS Care. 2013:73–80.Google Scholar
- 15.ICHD-3 beta. Cephalalgia. 2013;33(9):629–808. https://doi.org/10.1177/03331024134856.
- 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
- 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.
- 26.Santi L, Annunziata P. Symptomatic cranial neuralgias in multiple sclerosis. Clinical features and treatment. Clin Neurol Neurosurg. 2012:101–7.Google Scholar
- 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
- 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
- 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
- 43.Elliott D. Migraine in multiple sclerosis. Int Rev Neurobiol. 79:281–301.Google Scholar
- 46.Mantia L. Interferon treatment may trigger primary headaches in multiple sclerosis patients. Mult Scler. 12:476–80.Google Scholar
- 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.
- 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
- 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.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.John S, Hajj-Ali RA. Headache in autoimmune diseases. Headache. 2014; 572–582.Google Scholar
- 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.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.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.
- 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
- 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.Kabat-Zinn J. Wherever you go, there you are: Mindfulness meditation in everyday life. Hyperion 1994. ISBN. 10: 1401307787.Google Scholar
- 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.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.