Skip to main content

Advertisement

SpringerLink
Log in

Dissecting the Association Between Migraine and Stroke

  • Headache (RB Halker, Section Editor)
  • Published:
Current Neurology and Neuroscience Reports Aims and scope Submit manuscript

Abstract

Migraine is a common disabling neurological disorder resulting from excessive cortical excitation and trigeminovascular afferent sensitization. In addition to aberrant neuronal processing, migraineurs are also at significant risk of vascular disease. Consequently, the impact of migraine extends well beyond the ictal headache and includes a well-documented association with acute ischemic stroke, particularly in young women with a history of migraine with aura. The association between migraine and stroke has been acknowledged for 40 years or more. However, examining the pathobiology of this association has become a more recent and critically important undertaking. The diversity of mechanisms underlying the association between migraine and stroke likely reflects the heterogenous nature of this disorder. Vasospasm, endothelial injury, platelet aggregation and prothrombotic states, cortical spreading depression, carotid dissection, genetic variants, and traditional vascular risk factors have been offered as putative mechanisms involved in migraine-related stroke risk. Assimilating these seemingly divergent pathomechanisms into a cogent understanding of migraine-related stroke will inform future studies and the development of new strategies for the prevention and treatment of migraine and stroke.

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.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Article Open access 20 February 2023

Lou Grangeon, Kristin Sophie Lange, … on behalf of the European Headache Federation School of Advanced Studies (EHF-SAS)

References

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

  1. The international classification of headache disorders, 3rd edition (beta version). Cephalalgia. 2013;33:629–808.

  2. Manzoni GC, Farina S, Lanfranchi M, Solari A. Classic migraine—clinical findings in 164 patients. Eur Neurol. 1985;24:163–9.

    CAS  PubMed  Google Scholar 

  3. Jensen K, Tfelt-Hansen P, Lauritzen M, Olesen J. Classic migraine. A prospective recording of symptoms. Acta Neurol Scand. 1986;73:359–62.

    CAS  PubMed  Google Scholar 

  4. Vincent MB, Hadjikhani N. Migraine aura and related phenomena: beyond scotomata and scintillations. Cephalalgia. 2007;27:1368–77.

    PubMed Central  CAS  PubMed  Google Scholar 

  5. Smitherman TA, Burch R, Sheikh H, Loder E. The prevalence, impact, and treatment of migraine and severe headaches in the United States: a review of statistics from national surveillance studies. Headache. 2013;53:427–36.

    PubMed  Google Scholar 

  6. Stewart WF, Lipton RB, Celentano DD, Reed ML. Prevalence of migraine headache in the United States. Relation to age, income, race, and other sociodemographic factors. JAMA. 1992;267:64–9.

    CAS  PubMed  Google Scholar 

  7. Victor TW, Hu X, Campbell JC, Buse DC, Lipton RB. Migraine prevalence by age and sex in the United States: a life-span study. Cephalalgia. 2010;30:1065–72.

    CAS  PubMed  Google Scholar 

  8. Lipton RB, Stewart WF, Scher AI. Epidemiology and economic impact of migraine. Curr Med Res Opin. 2001;17 Suppl 1:s4–s12.

    PubMed  Google Scholar 

  9. Stewart WF, Roy J, Lipton RB. Migraine prevalence, socioeconomic status, and social causation. Neurology. 2013;81:948–55.

    PubMed Central  PubMed  Google Scholar 

  10. Stewart WF, Wood GC, Manack A, Varon SF, Buse DC, Lipton RB. Employment and work impact of chronic migraine and episodic migraine. J Occup Environ Med. 2010;52:8–14.

    PubMed  Google Scholar 

  11. Furie KL, Kasner SE, Adams RJ, et al. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011;42:227–76.

    PubMed  Google Scholar 

  12. Kissela BM, Khoury JC, Alwell K, et al. Age at stroke: temporal trends in stroke incidence in a large, biracial population. Neurology. 2012;79:1781–7.

    PubMed Central  PubMed  Google Scholar 

  13. Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med. 1995;333:1581–1587.

  14. Rutten-Jacobs LC, Arntz RM, Maaijwee NA, et al. Long-term mortality after stroke among adults aged 18 to 50 years. JAMA. 2013;309:1136–44.

    CAS  PubMed  Google Scholar 

  15. Rutten-Jacobs LC, Maaijwee NA, Arntz RM, et al. Long-term risk of recurrent vascular events after young stroke: The FUTURE study. Ann Neurol. 2013;74:592–601.

    PubMed  Google Scholar 

  16. Putaala J, Haapaniemi E, Metso AJ, et al. Recurrent ischemic events in young adults after first-ever ischemic stroke. Ann Neurol. 2010;68:661–71.

    PubMed  Google Scholar 

  17. Hall GC, Brown MM, Mo J, MacRae KD. Triptans in migraine: the risks of stroke, cardiovascular disease, and death in practice. Neurology. 2004;62:563–8.

    CAS  PubMed  Google Scholar 

  18. Velentgas P, Cole JA, Mo J, Sikes CR, Walker AM. Severe vascular events in migraine patients. Headache. 2004;44:642–51.

    PubMed  Google Scholar 

  19. Kurth T, Slomke MA, Kase CS, et al. Migraine, headache, and the risk of stroke in women: a prospective study. Neurology. 2005;64:1020–6.

    CAS  PubMed  Google Scholar 

  20. Kurth T, Gaziano JM, Cook NR, Logroscino G, Diener HC, Buring JE. Migraine and risk of cardiovascular disease in women. JAMA. 2006;296:283–91.

    CAS  PubMed  Google Scholar 

  21. Donaghy M, Chang CL, Poulter N. Duration, frequency, recency, and type of migraine and the risk of ischaemic stroke in women of childbearing age. J Neurol Neurosurg Psychiatry. 2002;73:747–50.

    PubMed Central  CAS  PubMed  Google Scholar 

  22. Oral contraceptives and stroke in young women. Associated risk factors. JAMA. 1975;231:718–722.

  23. Henrich JB, Horwitz RI. A controlled study of ischemic stroke risk in migraine patients. J Clin Epidemiol. 1989;42:773–80.

    CAS  PubMed  Google Scholar 

  24. Tzourio C, Iglesias S, Hubert JB, et al. Migraine and risk of ischaemic stroke: a case-control study. BMJ. 1993;307:289–92.

    PubMed Central  CAS  PubMed  Google Scholar 

  25. Tzourio C, Tehindrazanarivelo A, Iglesias S, et al. Case-control study of migraine and risk of ischaemic stroke in young women. BMJ. 1995;310:830–3.

    PubMed Central  CAS  PubMed  Google Scholar 

  26. Carolei A, Marini C, De Matteis G. History of migraine and risk of cerebral ischaemia in young adults. The Italian National Research Council Study Group on Stroke in the Young. Lancet. 1996;347:1503–6.

    CAS  PubMed  Google Scholar 

  27. Chang CL, Donaghy M, Poulter N. Migraine and stroke in young women: case-control study. The World Health Organisation Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. BMJ. 1999;318:13–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  28. MacClellan LR, Giles W, Cole J, et al. Probable migraine with visual aura and risk of ischemic stroke: the stroke prevention in young women study. Stroke. 2007;38:2438–45.

    PubMed  Google Scholar 

  29. Haapaniemi H, Hillbom M, Juvela S. Lifestyle-associated risk factors for acute brain infarction among persons of working age. Stroke. 1997;28:26–30.

    CAS  PubMed  Google Scholar 

  30. Lidegaard O, Kreiner S. Contraceptives and cerebral thrombosis: a five-year national case-control study. Contraception. 2002;65:197–205.

    CAS  PubMed  Google Scholar 

  31. Nightingale AL, Farmer RD. Ischemic stroke in young women: a nested case-control study using the UK General Practice Research Database. Stroke. 2004;35:1574–8.

    PubMed  Google Scholar 

  32. Schurks M, Rist PM, Bigal ME, Buring JE, Lipton RB, Kurth T. Migraine and cardiovascular disease: systematic review and meta-analysis. BMJ. 2009;339:b3914.

    PubMed Central  PubMed  Google Scholar 

  33. Merikangas KR, Fenton BT, Cheng SH, Stolar MJ, Risch N. Association between migraine and stroke in a large-scale epidemiological study of the United States. Arch Neurol. 1997;54:362–8.

    CAS  PubMed  Google Scholar 

  34. Kittner SJ, Stern BJ, Wozniak M, et al. Cerebral infarction in young adults: the Baltimore-Washington Cooperative Young Stroke Study. Neurology. 1998;50:890–4.

    CAS  PubMed  Google Scholar 

  35. Sochurkova D, Moreau T, Lemesle M, Menassa M, Giroud M, Dumas R. Migraine history and migraine-induced stroke in the Dijon stroke registry. Neuroepidemiology. 1999;18:85–91.

    CAS  PubMed  Google Scholar 

  36. Marini C, Carolei A, Roberts RS, et al. Focal cerebral ischemia in young adults: a collaborative case-control study. Nat Res Counc Study Group Neuroepidemiology. 1993;12:70–81.

    CAS  Google Scholar 

  37. Welch KM, Levine SR. Migraine-related stroke in the context of the International Headache Society classification of head pain. Arch Neurol. 1990;47:458–62.

    CAS  PubMed  Google Scholar 

  38. Etminan M, Takkouche B, Isorna FC, Samii A. Risk of ischaemic stroke in people with migraine: systematic review and meta-analysis of observational studies. BMJ. 2005;330:63.

    PubMed Central  PubMed  Google Scholar 

  39. Cole JW, Kittner SJ. Meta-analysis of results from case control and cohort studies finds that migraine is associated with approximately twice the risk of ischaemic stroke. Evid Based Med. 2010;15:193–4.

    PubMed  Google Scholar 

  40. Spector JT, Kahn SR, Jones MR, Jayakumar M, Dalal D, Nazarian S. Migraine headache and ischemic stroke risk: an updated meta-analysis. Am J Med. 2010;123:612–24. The authors provide a review and meta-analysis of 13 case control and 8 cohort studies examining the association between migraine and stroke. The results summarize the current observations that migraine is associated with a doubled risk of acute ischemic stroke.

    PubMed Central  PubMed  Google Scholar 

  41. Gudmundsson LS, Scher AI, Aspelund T, et al. Migraine with aura and risk of cardiovascular and all cause mortality in men and women: prospective cohort study. BMJ. 2010;341:c3966.

    PubMed Central  PubMed  Google Scholar 

  42. Rist PM, Buring JE, Kase CS, Schurks M, Kurth T. Migraine and functional outcome from ischemic cerebral events in women. Circulation. 2010;122:2551–7.

    PubMed Central  PubMed  Google Scholar 

  43. Lizarelli PM, Martins WP, Vieira CS, et al. Both a combined oral contraceptive and depot medroxyprogesterone acetate impair endothelial function in young women. Contraception. 2009;79:35–40.

    CAS  PubMed  Google Scholar 

  44. Mueck AO, Seeger H, Wallwiener D. Medroxyprogesterone acetate versus norethisterone: effect on estradiol-induced changes of markers for endothelial function and atherosclerotic plaque characteristics in human female coronary endothelial cell cultures. Menopause. 2002;9:273–81.

    PubMed  Google Scholar 

  45. Csordas A, Bernhard D. The biology behind the atherothrombotic effects of cigarette smoke. Nat Rev Cardiol. 2013;10:219–30.

    CAS  PubMed  Google Scholar 

  46. Messner B, Bernhard D. Smoking and cardiovascular disease: mechanisms of endothelial dysfunction and early atherogenesis. Arterioscler Thromb Vasc Biol. 2014;34:509–15.

    CAS  PubMed  Google Scholar 

  47. Danese E, Montagnana M, Lippi G. Platelets and migraine. Thromb Res. 2014;134:17–22.

    CAS  PubMed  Google Scholar 

  48. Uzar E, Evliyaoglu O, Toprak G, et al. Increased asymmetric dimethylarginine and nitric oxide levels in patients with migraine. J Headache Pain. 2011;12:239–43.

    PubMed Central  CAS  PubMed  Google Scholar 

  49. Rodriguez-Osorio X, Sobrino T, Brea D, Martinez F, Castillo J, Leira R. Endothelial progenitor cells: a new key for endothelial dysfunction in migraine. Neurology. 2012;79:474–9.

    PubMed  Google Scholar 

  50. Busija DW, Bari F, Domoki F, Horiguchi T, Shimizu K. Mechanisms involved in the cerebrovascular dilator effects of cortical spreading depression. Prog Neurobiol. 2008;86:379–95.

    CAS  PubMed  Google Scholar 

  51. Imamura K, Takeshima T, Fusayasu E, Nakashima K. Increased plasma matrix metalloproteinase-9 levels in migraineurs. Headache. 2008;48:135–9.

    PubMed  Google Scholar 

  52. Gao HM, Li L, Zhang KL, Chen XH, Tian SQ, Zhang ZL. Impact of migraine attacks on the blood-brain barrier. Chin Med J (Engl). 2010;123:2559–61.

    Google Scholar 

  53. Meier B, Kalesan B, Mattle HP, et al. Percutaneous closure of patent foramen ovale in cryptogenic embolism. N Engl J Med. 2013;368:1083–91.

    CAS  PubMed  Google Scholar 

  54. Arboix A, Massons J, Garcia-Eroles L, Oliveres M, Balcells M, Targa C. Migrainous cerebral infarction in the Sagrat Cor Hospital of Barcelona stroke registry. Cephalalgia. 2003;23:389–94.

    CAS  PubMed  Google Scholar 

  55. Milhaud D, Bogousslavsky J, van Melle G, Liot P. Ischemic stroke and active migraine. Neurology. 2001;57:1805–11.

    CAS  PubMed  Google Scholar 

  56. Tsai CF, Chen CC, Wang SC, Yip PK. Reversible vasospasm in migrainous infarction: a transcranial Doppler follow-up study. J Ultrasound Med. 2010;29:481–4.

    PubMed  Google Scholar 

  57. Marshall N, Maclaurin WA, Koulouris G. MRA captures vasospasm in fatal migrainous infarction. Headache. 2007;47:280–3.

    PubMed  Google Scholar 

  58. Gomez CR, Gomez SM, Puricelli MS, Malik MM. Transcranial Doppler in reversible migrainous vasospasm causing cerebellar infarction: report of a case. Angiology. 1991;42:152–6.

    CAS  PubMed  Google Scholar 

  59. Spierings EL. Angiographic changes suggestive of vasospasm in migraine complicated by stroke. Headache. 1990;30:727–8.

    CAS  PubMed  Google Scholar 

  60. Sanin LC, Mathew NT. Severe diffuse intracranial vasospasm as a cause of extensive migrainous cerebral infarction. Cephalalgia. 1993;13:289–92.

    CAS  PubMed  Google Scholar 

  61. Stone GM, Burns RJ. Cerebral infarction caused by vasospasm. Med J Aust. 1982;1:556–9.

    CAS  PubMed  Google Scholar 

  62. Solomon S, Lipton RB, Harris PY. Arterial stenosis in migraine: spasm or arteriopathy? Headache. 1990;30:52–61.

    CAS  PubMed  Google Scholar 

  63. Masuzawa T, Shinoda S, Furuse M, Nakahara N, Abe F, Sato F. Cerebral angiographic changes on serial examination of a patient with migraine. Neuroradiology. 1983;24:277–81.

    CAS  PubMed  Google Scholar 

  64. Call GK, Fleming MC, Sealfon S, Levine H, Kistler JP, Fisher CM. Reversible cerebral segmental vasoconstriction. Stroke. 1988;19:1159–70.

    CAS  PubMed  Google Scholar 

  65. Calabrese LH, Dodick DW, Schwedt TJ, Singhal AB. Narrative review: reversible cerebral vasoconstriction syndromes. Ann Intern Med. 2007;146:34–44.

    PubMed  Google Scholar 

  66. Hampton KK, Esack A, Peatfield RC, Grant PJ. Elevation of plasma vasopressin in spontaneous migraine. Cephalalgia. 1991;11:249–50.

    CAS  PubMed  Google Scholar 

  67. Tietjen EG. Migraine and ischaemic heart disease and stroke: potential mechanisms and treatment implications. Cephalalgia. 2007;27:981–7.

    PubMed  Google Scholar 

  68. Baggott CD, Aagaard-Kienitz B. Cerebral vasospasm. Neurosurg Clin N Am. 2014;25:497–528.

    PubMed  Google Scholar 

  69. Saengjaroentham C, Supornsilpchai W, Ji-Au W, Srikiatkhachorn A, Maneesri-le Grand S. Serotonin depletion can enhance the cerebrovascular responses induced by cortical spreading depression via the nitric oxide pathway. Int J Neurosci. 2014.

  70. Heckmann JG, Tomandl B, Kraus B, Gerlach R, Neundorfer B. A case of diffuse cerebral vasospasm—possibly ergotamine-associated? Cerebrovasc Dis. 2000;10:417–8.

    CAS  PubMed  Google Scholar 

  71. Silberstein SD. The pharmacology of ergotamine and dihydroergotamine. Headache. 1997;37 Suppl 1:S15–25.

    PubMed  Google Scholar 

  72. Humphrey PP. How it started. Cephalalgia. 2001;21 Suppl 1:2–5.

    PubMed  Google Scholar 

  73. Chabrier PE. The role of endothelin in the vessel wall. Baillieres Clin Haematol. 1993;6:577–91.

    CAS  PubMed  Google Scholar 

  74. Nattero G, Mengozzi G, Inconis T, Paradisi L. Nitric oxide, endothelin-1, and transcranial Doppler in migraine. Findings in interictal conditions and during migraine attack. Headache. 1996;36:307–11.

    CAS  PubMed  Google Scholar 

  75. Farkkila M, Palo J, Saijonmaa O, Fyhrquist F. Raised plasma endothelin during acute migraine attack. Cephalalgia. 1992;12:383–4. discussion 340.

    CAS  PubMed  Google Scholar 

  76. Kallela M, Farkkila M, Saijonmaa O, Fyhrquist F. Endothelin in migraine patients. Cephalalgia. 1998;18:329–32.

    CAS  PubMed  Google Scholar 

  77. Hasselblatt M, Kohler J, Volles E, Ehrenreich H. Simultaneous monitoring of endothelin-1 and vasopressin plasma levels in migraine. Neuroreport. 1999;10:423–5.

    CAS  PubMed  Google Scholar 

  78. Dreier JP, Kleeberg J, Alam M, et al. Endothelin-1-induced spreading depression in rats is associated with a microarea of selective neuronal necrosis. Exp Biol Med (Maywood). 2007;232:204–13.

    CAS  Google Scholar 

  79. Dreier JP, Kleeberg J, Petzold G, et al. Endothelin-1 potently induces Leao’s cortical spreading depression in vivo in the rat: a model for an endothelial trigger of migrainous aura? Brain. 2002;125:102–12.

    PubMed  Google Scholar 

  80. Cardell LO, Uddman R, Edvinsson L. Endothelins: a role in cerebrovascular disease? Cephalalgia. 1994;14:259–65.

    CAS  PubMed  Google Scholar 

  81. Ziv I, Fleminger G, Djaldetti R, Achiron A, Melamed E, Sokolovsky M. Increased plasma endothelin-1 in acute ischemic stroke. Stroke. 1992;23:1014–6.

    CAS  PubMed  Google Scholar 

  82. Salom JB, Torregrosa G, Alborch E. Endothelins and the cerebral circulation. Cerebrovasc Brain Metab Rev. 1995;7:131–52.

    CAS  PubMed  Google Scholar 

  83. Petzold GC, Einhaupl KM, Dirnagl U, Dreier JP. Ischemia triggered by spreading neuronal activation is induced by endothelin-1 and hemoglobin in the subarachnoid space. Ann Neurol. 2003;54:591–8.

    CAS  PubMed  Google Scholar 

  84. Hassan A, Hunt BJ, O’Sullivan M, et al. Markers of endothelial dysfunction in lacunar infarction and ischaemic leukoaraiosis. Brain. 2003;126:424–32.

    PubMed  Google Scholar 

  85. Kelleher RJ, Soiza RL. Evidence of endothelial dysfunction in the development of Alzheimer’s disease: is Alzheimer’s a vascular disorder? Am J Cardiovasc Dis. 2013;3:197–226.

    PubMed Central  PubMed  Google Scholar 

  86. Hamed SA. The vascular risk associations with migraine: relation to migraine susceptibility and progression. Atherosclerosis. 2009;205:15–22.

    CAS  PubMed  Google Scholar 

  87. Munno I, Marinaro M, Bassi A, Cassiano MA, Causarano V, Centonze V. Immunological aspects in migraine: increase of IL-10 plasma levels during attack. Headache. 2001;41:764–7.

    CAS  PubMed  Google Scholar 

  88. Munno I, Centonze V, Marinaro M, et al. Cytokines and migraine: increase of IL-5 and IL-4 plasma levels. Headache. 1998;38:465–7.

    CAS  PubMed  Google Scholar 

  89. Perini F, D’Andrea G, Galloni E, et al. Plasma cytokine levels in migraineurs and controls. Headache. 2005;45:926–31.

    PubMed  Google Scholar 

  90. Sarchielli P, Alberti A, Baldi A, et al. Proinflammatory cytokines, adhesion molecules, and lymphocyte integrin expression in the internal jugular blood of migraine patients without aura assessed ictally. Headache. 2006;46:200–7.

    PubMed  Google Scholar 

  91. Tietjen GE, Herial NA, White L, Utley C, Kosmyna JM, Khuder SA. Migraine and biomarkers of endothelial activation in young women. Stroke. 2009;40:2977–82.

    CAS  PubMed  Google Scholar 

  92. Tietjen GE, Al-Qasmi MM, Athanas K, Dafer RM, Khuder SA. Increased von Willebrand factor in migraine. Neurology. 2001;57:334–6.

    CAS  PubMed  Google Scholar 

  93. Cesar JM, Garcia-Avello A, Vecino AM, Sastre JL, Alvarez-Cermeno JC. Increased levels of plasma von Willebrand factor in migraine crisis. Acta Neurol Scand. 1995;91:412–3.

    CAS  PubMed  Google Scholar 

  94. Morancho A, Rosell A, Garcia-Bonilla L, Montaner J. Metalloproteinase and stroke infarct size: role for anti-inflammatory treatment? Ann N Y Acad Sci. 2010;1207:123–33.

    CAS  PubMed  Google Scholar 

  95. Chaturvedi M, Kaczmarek L. Mmp-9 inhibition: a therapeutic strategy in ischemic stroke. Mol Neurobiol. 2014;49:563–73.

    PubMed Central  CAS  PubMed  Google Scholar 

  96. Leira R, Sobrino T, Rodriguez-Yanez M, Blanco M, Arias S, Castillo J. Mmp-9 immunoreactivity in acute migraine. Headache. 2007;47:698–702.

    PubMed  Google Scholar 

  97. Bernecker C, Pailer S, Kieslinger P, et al. Increased matrix metalloproteinase activity is associated with migraine and migraine-related metabolic dysfunctions. Eur J Neurol. 2011;18:571–6.

    CAS  PubMed  Google Scholar 

  98. Lee ST, Chu K, Jung KH, et al. Decreased number and function of endothelial progenitor cells in patients with migraine. Neurology. 2008;70:1510–7.

    PubMed  Google Scholar 

  99. Oterino A, Toriello M, Palacio E, et al. Analysis of endothelial precursor cells in chronic migraine: a case-control study. Cephalalgia. 2013;33:236–44.

    PubMed  Google Scholar 

  100. Liman TG, Bachelier-Walenta K, Neeb L, et al. Circulating endothelial microparticles in female migraineurs with aura. Cephalalgia. 2014.

  101. Couch JR, Hassanein RS. Platelet aggregability in migraine. Neurology. 1977;27:843–8.

    CAS  PubMed  Google Scholar 

  102. Sarchielli P, Alberti A, Coppola F, et al. Platelet-activating factor (PAF) in internal jugular venous blood of migraine without aura patients assessed during migraine attacks. Cephalalgia. 2004;24:623–30.

    CAS  PubMed  Google Scholar 

  103. Patel RR, Adam R, Maldjian C, Lincoln CM, Yuen A, Arneja A. Cervical carotid artery dissection: current review of diagnosis and treatment. Cardiol Rev. 2012;20:145–52.

    PubMed  Google Scholar 

  104. Tzourio C, Benslamia L, Guillon B, et al. Migraine and the risk of cervical artery dissection: a case-control study. Neurology. 2002;59:435–7.

    CAS  PubMed  Google Scholar 

  105. Metso TM, Tatlisumak T, Debette S, et al. Migraine in cervical artery dissection and ischemic stroke patients. Neurology. 2012;78:1221–8.

    CAS  PubMed  Google Scholar 

  106. Rist PM, Diener HC, Kurth T, Schurks M. Migraine, migraine aura, and cervical artery dissection: a systematic review and meta-analysis. Cephalalgia. 2011;31:886–96. The authors performed a meta-analysis that included 5 case-control studies demonstrating an association between migraine and cervical artery dissection which may explain in part the association between migraine and stroke risk.

    PubMed Central  PubMed  Google Scholar 

  107. Lucas C, Lecroart JL, Gautier C, et al. Impairment of endothelial function in patients with spontaneous cervical artery dissection: evidence for a general arterial wall disease. Cerebrovasc Dis. 2004;17:170–4.

    CAS  PubMed  Google Scholar 

  108. Tzourio C, El Amrani M, Robert L, Alperovitch A. Serum elastase activity is elevated in migraine. Ann Neurol. 2000;47:648–51.

    CAS  PubMed  Google Scholar 

  109. Hadjikhani N, Sanchez Del Rio M, Wu O, et al. Mechanisms of migraine aura revealed by functional MRI in human visual cortex. Proc Natl Acad Sci U S A. 2001;98:4687–92.

    PubMed Central  CAS  PubMed  Google Scholar 

  110. Eikermann-Haerter K. Spreading depolarization may link migraine and stroke. Headache. 2014;54:1146–57.

    PubMed  Google Scholar 

  111. Hashemi P, Bhatia R, Nakamura H, et al. Persisting depletion of brain glucose following cortical spreading depression, despite apparent hyperaemia: evidence for risk of an adverse effect of Leao’s spreading depression. J Cereb Blood Flow Metab. 2009;29:166–75.

    CAS  PubMed  Google Scholar 

  112. Dohmen C, Sakowitz OW, Fabricius M, et al. Spreading depolarizations occur in human ischemic stroke with high incidence. Ann Neurol. 2008;63:720–8.

    PubMed  Google Scholar 

  113. Eikermann-Haerter K, Lee JH, Yuzawa I, et al. Migraine mutations increase stroke vulnerability by facilitating ischemic depolarizations. Circulation. 2012;125:335–45.

    PubMed Central  PubMed  Google Scholar 

  114. Piilgaard H, Lauritzen M. Persistent increase in oxygen consumption and impaired neurovascular coupling after spreading depression in rat neocortex. J Cereb Blood Flow Metab. 2009;29:1517–27.

    CAS  PubMed  Google Scholar 

  115. Takano T, Tian GF, Peng W, et al. Cortical spreading depression causes and coincides with tissue hypoxia. Nat Neurosci. 2007;10:754–62.

    CAS  PubMed  Google Scholar 

  116. Stam AH, van den Maagdenberg AM, Haan J, Terwindt GM, Ferrari MD. Genetics of migraine: an update with special attention to genetic comorbidity. Curr Opin Neurol. 2008;21:288–93.

    PubMed  Google Scholar 

  117. Knierim E, Leisle L, Wagner C, et al. Recurrent stroke due to a novel voltage sensor mutation in Cav2.1 responds to verapamil. Stroke. 2011;42:e14–7.

    CAS  PubMed  Google Scholar 

  118. Chabriat H, Vahedi K, Iba-Zizen MT, et al. Clinical spectrum of CADASIL: a study of 7 families. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Lancet. 1995;346:934–9.

    CAS  PubMed  Google Scholar 

  119. Jen J, Cohen AH, Yue Q, et al. Hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS). Neurology. 1997;49:1322–30.

    CAS  PubMed  Google Scholar 

  120. Ophoff RA, DeYoung J, Service SK, et al. Hereditary vascular retinopathy, cerebroretinal vasculopathy, and hereditary endotheliopathy with retinopathy, nephropathy, and stroke map to a single locus on chromosome 3p21.1-p21.3. Am J Hum Genet. 2001;69:447–53.

    PubMed Central  CAS  PubMed  Google Scholar 

  121. Goodfellow JA, Dani K, Stewart W, et al. Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes: an important cause of stroke in young people. Postgrad Med J. 2012;88:326–34.

    CAS  PubMed  Google Scholar 

  122. Freilinger T, Anttila V, de Vries B, et al. Genome-wide association analysis identifies susceptibility loci for migraine without aura. Nat Genet. 2012;44:777–82.

    PubMed Central  CAS  PubMed  Google Scholar 

  123. Law C, Bunyan D, Castle B, et al. Clinical features in a family with an R460H mutation in transforming growth factor beta receptor 2 gene. J Med Genet. 2006;43:908–16.

    PubMed Central  CAS  PubMed  Google Scholar 

  124. Allain B, Jarray R, Borriello L, et al. Neuropilin-1 regulates a new VEGF-induced gene, Phactr-1, which controls tubulogenesis and modulates lamellipodial dynamics in human endothelial cells. Cell Signal. 2012;24:214–23.

    CAS  PubMed  Google Scholar 

  125. Jarray R, Allain B, Borriello L, et al. Depletion of the novel protein PHACTR-1 from human endothelial cells abolishes tube formation and induces cell death receptor apoptosis. Biochimie. 2011;93:1668–75.

    CAS  PubMed  Google Scholar 

  126. Fuentealba RA, Liu Q, Kanekiyo T, Zhang J, Bu G. Low density lipoprotein receptor-related protein 1 promotes anti-apoptotic signaling in neurons by activating Akt survival pathway. J Biol Chem. 2009;284:34045–53.

    PubMed Central  CAS  PubMed  Google Scholar 

  127. Liu Q, Trotter J, Zhang J, et al. Neuronal LRP1 knockout in adult mice leads to impaired brain lipid metabolism and progressive, age-dependent synapse loss and neurodegeneration. J Neurosci. 2010;30:17068–78.

    PubMed Central  CAS  PubMed  Google Scholar 

  128. Lillis AP, Van Duyn LB, Murphy-Ullrich JE, Strickland DK. LDL receptor-related protein 1: unique tissue-specific functions revealed by selective gene knockout studies. Physiol Rev. 2008;88:887–918.

    PubMed Central  CAS  PubMed  Google Scholar 

  129. Muratoglu SC, Belgrave S, Hampton B, et al. LRP1 protects the vasculature by regulating levels of connective tissue growth factor and HtrA1. Arterioscler Thromb Vasc Biol. 2013;33:2137–46.

    PubMed Central  CAS  PubMed  Google Scholar 

  130. Hopkins PN. Molecular biology of atherosclerosis. Physiol Rev. 2013;93:1317–542.

    CAS  PubMed  Google Scholar 

  131. Gutierrez-Fernandez M, Rodriguez-Frutos B, Fuentes B, et al. CDP-choline treatment induces brain plasticity markers expression in experimental animal stroke. Neurochem Int. 2012;60:310–7.

    CAS  PubMed  Google Scholar 

  132. Polavarapu R, Gongora MC, Yi H, et al. Tissue-type plasminogen activator-mediated shedding of astrocytic low-density lipoprotein receptor-related protein increases the permeability of the neurovascular unit. Blood. 2007;109:3270–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  133. Chasman DI, Schurks M, Anttila V, et al. Genome-wide association study reveals three susceptibility loci for common migraine in the general population. Nat Genet. 2011;43:695–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  134. Anttila V, Winsvold BS, Gormley P, et al. Genome-wide meta-analysis identifies new susceptibility loci for migraine. Nat Genet. 2013;45:912–7. The authors identify several genetic susceptibility loci associated with migraine. The identification of these loci may provide putative variants that may link migraine and stroke.

    PubMed Central  CAS  PubMed  Google Scholar 

  135. MacClellan LR, Howard TD, Cole JW, et al. Relation of candidate genes that encode for endothelial function to migraine and stroke: the Stroke Prevention in Young Women study. Stroke. 2009;40:e550–7.

    PubMed Central  PubMed  Google Scholar 

  136. Tzourio C, El Amrani M, Poirier O, Nicaud V, Bousser MG, Alperovitch A. Association between migraine and endothelin type A receptor (ETA −231 A/G) gene polymorphism. Neurology. 2001;56:1273–7.

    CAS  PubMed  Google Scholar 

  137. Weigand KM, Swarts HG, Russel FG, Koenderink JB. Biochemical characterization of sporadic/familial hemiplegic migraine mutations. Biochim Biophys Acta. 1838;2014:1693–700.

    Google Scholar 

  138. Yang GY, Chen SF, Kinouchi H, Chan PH, Weinstein PR. Edema, cation content, and ATPase activity after middle cerebral artery occlusion in rats. Stroke. 1992;23:1331–6.

    CAS  PubMed  Google Scholar 

  139. Kirchmann M, Thomsen LL, Olesen J. The CACNA1A and ATP1A2 genes are not involved in dominantly inherited migraine with aura. Am J Med Genet B Neuropsychiatr Genet. 2006;141B:250–6.

    CAS  PubMed  Google Scholar 

  140. Todt U, Dichgans M, Jurkat-Rott K, et al. Rare missense variants in ATP1A2 in families with clustering of common forms of migraine. Hum Mutat. 2005;26:315–21.

    CAS  PubMed  Google Scholar 

  141. Harriott AM, Dueker N, Cheng YC, et al. Polymorphisms in migraine-associated gene, and ischemic stroke risk in a biracial population: the genetics of early onset stroke study. Springerplus. 2013;2:46.

    PubMed Central  PubMed  Google Scholar 

  142. Pezzini A, Grassi M, Del Zotto E, et al. Migraine mediates the influence of C677T MTHFR genotypes on ischemic stroke risk with a stroke-subtype effect. Stroke. 2007;38:3145–51.

    CAS  PubMed  Google Scholar 

  143. Schurks M, Rist PM, Kurth T. MTHFR 677C>T and ACE D/I polymorphisms in migraine: a systematic review and meta-analysis. Headache. 2010;50:588–99.

    PubMed Central  PubMed  Google Scholar 

  144. Pezzini A, Grassi M, Lodigiani C, et al. Predictors of migraine subtypes in young adults with ischemic stroke: the Italian project on stroke in young adults. Stroke. 2011;42:17–21.

    PubMed  Google Scholar 

  145. Scher AI, Terwindt GM, Picavet HS, Verschuren WM, Ferrari MD, Launer LJ. Cardiovascular risk factors and migraine: the GEM population-based study. Neurology. 2005;64:614–20.

    CAS  PubMed  Google Scholar 

  146. Sinclair AJ, Matharu M. Migraine, cerebrovascular disease and the metabolic syndrome. Ann Indian Acad Neurol. 2012;15:S72–7.

    PubMed Central  PubMed  Google Scholar 

  147. Bigal ME, Kurth T, Santanello N, et al. Migraine and cardiovascular disease: a population-based study. Neurology. 2010;74:628–35.

    PubMed Central  CAS  PubMed  Google Scholar 

  148. Kruit MC, Launer LJ, Ferrari MD, van Buchem MA. Infarcts in the posterior circulation territory in migraine. The population-based MRI CAMERA study. Brain. 2005;128:2068–77.

    PubMed  Google Scholar 

  149. Kruit MC, van Buchem MA, Hofman PA, et al. Migraine as a risk factor for subclinical brain lesions. JAMA. 2004;291:427–34.

    CAS  PubMed  Google Scholar 

  150. Hougaard A, Amin FM, Ashina M. Migraine and structural abnormalities in the brain. Curr Opin Neurol. 2014;27:309–14.

    PubMed  Google Scholar 

  151. Fisher CM. Late-life migraine accompaniments—further experience. Stroke. 1986;17:1033–42.

    CAS  PubMed  Google Scholar 

  152. Fisher CM. Late-life migraine accompaniments as a cause of unexplained transient ischemic attacks. Can J Neurol Sci. 1980;7:9–17.

    CAS  PubMed  Google Scholar 

  153. Wijman CA, Wolf PA, Kase CS, Kelly-Hayes M, Beiser AS. Migrainous visual accompaniments are not rare in late life: the Framingham Study. Stroke. 1998;29:1539–43.

    CAS  PubMed  Google Scholar 

  154. Carroll JD, Saver JL, Thaler DE, et al. Closure of patent foramen ovale versus medical therapy after cryptogenic stroke. N Engl J Med. 2013;368:1092–100.

    CAS  PubMed  Google Scholar 

  155. Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45:2160–236. The goals for secondary stroke prevention in migraineurs should be the same as those for the general stroke population until unique modifiable risks and treatment options are discovered. The authors review the guidelines for secondary stroke prevention in the general stroke population.

    PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Margaret Alice McKinney, Medical Illustrator, Creative Media, Mayo Clinic Rochester, for providing the illustration.

Compliance with Ethics Guidelines

ᅟ

Conflict of Interest

Andrea M. Harriott and Kevin M. Barrett declare that they have no conflict of interest.

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.

Author information

Authors and Affiliations

  1. Department of Neurology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA

    Andrea M. Harriott & Kevin M. Barrett

Authors
  1. Andrea M. Harriott
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kevin M. Barrett
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andrea M. Harriott.

Additional information

This article is part of the Topical Collection on Headache

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Harriott, A.M., Barrett, K.M. Dissecting the Association Between Migraine and Stroke. Curr Neurol Neurosci Rep 15, 5 (2015). https://doi.org/10.1007/s11910-015-0530-8

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11910-015-0530-8

Keywords

Search

Navigation