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The Risk of Stroke in Patients with Migraine and Implications for Migraine Management

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Abstract

Assessing the risk of stroke in persons with migraine is complicated by the intricate relationship between these two conditions. Both migraine and stroke are common and co-morbidity may, in some cases, be coincidental. Given the overlap of clinical symptoms in stroke and migraine, each condition may also mimic the other. Numerous studies have, however, shown that migraine is an independent risk factor for stroke both during, and remote from, the migraine attack. Women of childbearing age and those with aura are at greatest risk of migraine-related stroke. Additional risk of stroke in migraineurs occurs in those using oral contraceptive pills and who smoke cigarettes. Elevated blood pressure, an important stroke risk factor, is less common in migraineurs. Acquired antiphospholipid antibodies, not clearly a cause of migraine per se, may raise the risk of infarction in migraineurs. Hereditary conditions, including CADASIL (cerebral autosomal dominant arteriopathy with sub-cortical infarcts and leukoencephalopathy), MELAS (mitochondrial myopathy, encephalopathy, lactacidosis and stroke) and hereditary haemorrhagic telangiectasia, appear to predispose to both migraine and stroke. Purported mechanisms for migraine-associated stroke include involvement of the vasculature (including vasospasm, arterial dissection and small vessel arteriopathy), hypercoagulability (elevated von Willebrand Factor, platelet activation) and elevated risk of cardioembolism (patent foramen ovale, atrial septal aneurysm). Triptans and ergotamines, used to treat acute migraine attacks, appear to be safe in low-risk populations. These medications should be avoided in persons with haemiplegic migraine, basilar migraine, vascular risk factor and prior cerebral or cardiac ischaemia.

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References

  1. Launer LJ, Terwindt GM, Ferrari MD. The prevalence and characteristics of migraine in a population-based cohort: the GEM study. Neurology 1999; 53: 537–42

    PubMed  CAS  Google Scholar 

  2. Bogousslavsky J, Regli F, Van Meile G, et al. Migraine stroke. Neurology 1988; 38: 223–7

    PubMed  CAS  Google Scholar 

  3. Wijman CA, Wolf PA, Kase CS, et al. Migrainous visual accompaniments are not rare in late life: the Framingham Study. Stroke 1998; 29: 1539–43

    PubMed  CAS  Google Scholar 

  4. Ramadan NM, Tietjen GE, Levine SR, et al. Scintillating scotomata associated with internal carotid artery dissection: report of three cases. Neurology 1991; 41(7): 1084–7

    PubMed  CAS  Google Scholar 

  5. Bredt DS. Endogenous nitric oxide synthesis: biological functions and pathophysiology. Free Radic Res 1995; 31: 477–96

    Google Scholar 

  6. Castillo J, Martinez F, Corredera E, et al. Amino acid transmitters in patients with headache during the acute phase of cerebrovascular ischemic disease. Stroke 1995; 26: 2035–9

    PubMed  CAS  Google Scholar 

  7. Collaborative Group for the Study of Stroke in Young Women. Oral contraceptives and stroke in young women. JAMA 1975; 231: 718–22

    Google Scholar 

  8. Tzourio C, Iglesias S, Hubert JB, et al. Migraine and risk of ischemic stroke: a case-control study. BMJ 1993; 308: 289–92

    Google Scholar 

  9. Carolei A, Marini C, De Matteis G. History of migraine and risk of cerebral ischaemia in young adults. Lancet 1996; 347:1503–6

    PubMed  CAS  Google Scholar 

  10. Schwaag S, Nabavi DG, Frese A, et al. The association between migraine and juvenile stroke: a case-control study. Headache 2003; 43: 90–5

    PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  12. Lidegaard O. Oral contraceptives, pregnancy and the risk of cerebral thromboembolism: the influence of diabetes, hypertension, migraine and previous thrombotic disease. Br J Obstet Gynaecol 1995; 102: 153–9

    PubMed  CAS  Google Scholar 

  13. Chang CL, Donaghy M, Poulter NR, et al. Migraine and stroke in young women: case-control study. BMJ 1999; 318(7175): 13–8

    PubMed  CAS  Google Scholar 

  14. Buring JE, Herbert P, Romero J, et al. Migraine and the subsequent risk of stroke in the Physicians Health Study. Arch Neurol 1995; 52: 129–34

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  16. Mosek A, Marom R, Korczyn AD, et al. A history of migraine is not a risk factor to develop an ischemic stroke in the elderly. Headache 2001; 41: 399–401

    PubMed  CAS  Google Scholar 

  17. Milhaud D, Bogousslavsky J, van Mell G, et al. Ischemic stroke and active migraine. Neurology 2001; 57: 1805–11

    PubMed  CAS  Google Scholar 

  18. Mitchell P, Wang JJ, Currie J, et al. Prevalence and vascular associations with migraine in older Australians. Aust N Z J Med 1988; 28: 627–32

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  21. Headache Classification Committee of the International Headache Society. Diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia 1988; 8Suppl. 7: 20

    Google Scholar 

  22. Henrich JB, Sandercock PAG, Warlow CP, et al. Stroke and migraine in the Oxfordshire Community Stroke Project. J Neurol 1986; 23: 257–62

    Google Scholar 

  23. Broderick JP, Swanson JW. Migraine-related strokes: clinical profile and prognosis in 20 patients. Arch Neurol 1987; 44: 868–71

    PubMed  CAS  Google Scholar 

  24. Sacquegna T, Andreoli A, Baldrati A, et al. Ischemic stroke in young adults: the relevance of migrainous infarction. Cephalalgia 1989; 9: 255–8

    PubMed  CAS  Google Scholar 

  25. 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

    PubMed  CAS  Google Scholar 

  26. Kristensen B, Malm J, Carlberg B, et al. Epidemiology and etiology of ischemic stroke in young adults aged 18 to 44 years in northern Sweden. Stroke 1997; 28: 1702–9

    PubMed  CAS  Google Scholar 

  27. Arboix A, Massons J, Garcia-Eroles L, et al. Migrainous cerebral infarction in the Sagrat Cor Hospital of Barcelona stroke registry. Cephalalgia 2003; 23: 389–94

    PubMed  CAS  Google Scholar 

  28. Rothrock JF, Walicke P, Swenson MR, et al. Migrainous stroke. Arch Neurol 1988; 45: 63–7

    PubMed  CAS  Google Scholar 

  29. Tzourio C, Gagniere B, El Amrani M, et al. Relationship between migraine, blood pressure, and carotid thickness: a population-based study in the elderly. Cephalalgia 2003; 23: 914–20

    PubMed  CAS  Google Scholar 

  30. Hagen K, Stovner LJ, Vatten L, et al. Blood pressure and risk of headache: a prospective study of 22 685 adults in Norway. J Neurol Neurosurg Psychiatry 2002; 72: 463–6

    PubMed  CAS  Google Scholar 

  31. Wiehe M, Fuchs SC, Moreira LB, et al. Migraine is more frequent in individuals with optimal and normal blood pressure: a population-based study. J Hypertens 2002; 20: 1303–6

    PubMed  CAS  Google Scholar 

  32. WHO Collaborative Study. Cardiovascular disease and steroid hormone contraception: ischemic stroke and combined oral contraceptives. Results of an international, multicentre, case-control study. Lancet 1996; 348: 498–505

    Google Scholar 

  33. Hannaford PC, Croft PR, Kay CR. Oral contraception and stroke: evidence from the Royal College of General Practioners’ oral contraception study. Stroke 1994; 25: 935–42

    PubMed  CAS  Google Scholar 

  34. Pettiti DB, Sidney S, Bernstein A, et al. Stroke in users of low-dose oral contraceptives. N Engl J Med 1996; 335: 8–15

    Google Scholar 

  35. Schwartz SM, Petitti DB, Siscovick DS, et al. Stroke and use of low-dose oral contraceptives in young women: a pooled analysis of two US studies. Stroke 1998; 29: 2277–84

    PubMed  CAS  Google Scholar 

  36. Lidegaard O. Oral contraception and risk of a cerebral thromboembolic attack: results of a case control study. BMJ 1993; 306: 956–63

    PubMed  CAS  Google Scholar 

  37. Kemmeren JM, Tanis BC, Maurice AAJ, et al. Risk of Arterial Thrombosis in Relation to Oral Contraceptives (RATIO) study: oral contraceptives and the risk of ischemic stroke. Stroke 2002; 33: 1202–8

    PubMed  Google Scholar 

  38. Gillum LA, Mamidipudi SK, Johnston SC. Ischemic stroke risk with oral contraceptives: a meta-analysis. JAMA 2000; 284: 72–8

    PubMed  CAS  Google Scholar 

  39. Becker WJ. Use of oral contraceptives in patients with migraine. Neurology 1999; 53(4 Suppl. 1): S19–25

    PubMed  CAS  Google Scholar 

  40. Brey RL, Stallworth CL, McGlasson DL, et al. Antiphospholipid antibodies and stroke in young women. Stroke 2002; 33: 2396–401

    PubMed  CAS  Google Scholar 

  41. Montalban J, Titus F, Ordi J, et al. Anticardiolipin antibodies and migraine-related strokes [letter]. Arch Neurol 1988; 45: 603

    PubMed  CAS  Google Scholar 

  42. Silvestrini M, Matteis M, Troisi E, et al. Migrainous stroke and antiphospholipid antibodies. Eur Neurol 1994; 34: 316–9

    PubMed  CAS  Google Scholar 

  43. Tietjen GE, Day M, Norris L, et al. Role of anticardiolipin antibodies in young persons with migraine and transient focal neurological events. Neurology 1998; 50: 1433–40

    PubMed  CAS  Google Scholar 

  44. Chabriat H, Bousser MG. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Adv Neurol 2003; 92: 147–50

    PubMed  Google Scholar 

  45. Ohno K, Isotani E, Hirakawa K. MELAS presenting as migraine complicated by stroke: case report. Neuroradiology 1997; 39: 781–4

    PubMed  CAS  Google Scholar 

  46. Kolb SJ, Costello F, Lee AG, et al. Distinguishing ischemic stroke from the stroke-lesions of MELAS using apparent diffusion coefficient mapping. J Neurol Sci 2003; 216: 11–5

    PubMed  Google Scholar 

  47. Steele JG, Nath PU, Burn J, et al. An association between migrainous aura and hereditary haemorrhagic telangiectasia. Headache 1993; 33: 145–8

    PubMed  CAS  Google Scholar 

  48. Leao APP. Spreading depression of activity in cerebral cortex. J Neurophysiol 1944; 7: 379–90

    Google Scholar 

  49. Cao Y, Welch KMA, Aurora S, et al. Functional MRI-BOLD of visually triggered headache in patients with migraine. Arch Neurol 1999; 56: 548–54

    PubMed  CAS  Google Scholar 

  50. Friberg L, Olesen J, Lassen NA, et al. Cerebral oxygen extraction, oxygen consumption, and regional cerebral blood flow during the aura phase of migraine. Stroke 1994; 25: 974–9

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  52. 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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  54. De Benedittis G, Lorenzetti A, Sina C, et al. Magnetic resonance imaging in migraine and tension-type headache. Headache 1995; 35: 264–8

    PubMed  Google Scholar 

  55. Igarashi H, Sakai F, Kan S, et al. Magnetic resonance imaging of the brain in patients with migraine. Cephalalgia 1991; 11: 69–74

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  57. Salobir B, Sabovic M, Peternel P, et al. Classic risk factors, hypercoagulability, and migraine in young women with cerebral lacunar infarctions. Acta Neurol Scand 2002; 105: 189–95

    PubMed  CAS  Google Scholar 

  58. Robertson WM, Welch KM, Levine SR, et al. The effects of aging on cerebral blood flow in migraine. Neurology 1989; 39: 947–51

    PubMed  CAS  Google Scholar 

  59. Tietjen GE, Gottwald L, Al-Qasmi MM, et al. Migraine is associated with livedo reticularis: a prospective study. Headache 2002; 42: 263–7

    PubMed  Google Scholar 

  60. Tietjen GE, Hill T, Dennis MJ, et al. Cerebral vascular reactivity is lower in female migraineurs with livedo reticularis: a prospective functional perfusion MRI study [abstract]. Headache 2003; 43: 515–6

    Google Scholar 

  61. Overell JR, Bone I, Lees KR. Interatrial septal abnormalities and stroke: a meta-analysis of case-control studies. Neurology 2000; 55: 1172–9

    PubMed  CAS  Google Scholar 

  62. Lamy C, Giannesini C, Zuber M, et al. Clinical and imaging findings in cryptogenic stroke patients with and without patent foramen ovale. The PFO-ASA Study. Stroke 2002; 33: 706–11

    CAS  Google Scholar 

  63. Del Sette M, Angeli S, Leandri M, et al. Migraine with aura and right to left shunt on transcranial Doppler: a case-control study. Cerebrovasc Dis 1998; 8: 327–30

    PubMed  Google Scholar 

  64. Anzola GP, Magoni M, Guindani M, et al. Potential source of cerebral embolism in migraine with aura: a transcranial Doppler study. Neurology 1999; 52: 1622–5

    PubMed  CAS  Google Scholar 

  65. Wilmhurst P, Nightingale S. Relationship between migraine and cardiac and pulmonary right-to-left shunts. Clin Sci 2001; 100: 215–20

    Google Scholar 

  66. Carej S, Narbone C, Zito C, et al. Prevalence of atrial septal aneurysm in patients with migraine: an echocardiographic study. Headache 2003; 43: 725–8

    Google Scholar 

  67. Arquizan C, Coste J, Touboul PJ, et al. Is patent foramen ovale a family trait? A transcranial Doppler sonographic study. Stroke 2001; 32: 1563–6

    PubMed  CAS  Google Scholar 

  68. Wilmhurst P, Nightingale S, Walsh KP, et al. Effect on migraine of closure of cardiac right-to-left shunts to prevent recurrence of decompression illness or stroke or for hemodynamic reasons. Lancet 2000; 356: 1648–51

    Google Scholar 

  69. Schwerzmann M, Wiher S, Nedeltchev K, et al. Percutaneous closure of patent foramen ovale reduces the frequency of migraine attacks. Neurology 2004; 62(8): 1399–401

    PubMed  CAS  Google Scholar 

  70. Post MC, Thijis V, Herroelen L, et al. Closure of a patent foramen ovale is associated with a decrease in prevalence of migraine. Neurology 2004; 62(8): 1439–40

    PubMed  Google Scholar 

  71. Crassard I, Conrad J, Bousser M-G. Migraine and haemostasis. Cephalalgia 2001; 21: 630–6

    PubMed  CAS  Google Scholar 

  72. Hering-Hanit R, Friedman Z, Schlesinger I, et al. Evidence for activation of the coagulation system in migraine with aura. Cephalalgia 2001; 21: 137–9

    PubMed  CAS  Google Scholar 

  73. D’Andrea G, Toldo M, Cortelazzo S, et al. Platelet activity in migraine. Headache 1992; 22: 207–12

    Google Scholar 

  74. Cesar JM, Garcia-Avello A, Vecino AM, et al. Increased levels of plasma von Willebrand factor in migraine crisis. Acta Neurol Scand 1995; 91: 412–3

    PubMed  CAS  Google Scholar 

  75. Tietjen GE, Al-Qasmi MM, Athanas K, et al. Increased von Willebrand factor in migraine. Neurology 2001; 57: 334–6

    PubMed  CAS  Google Scholar 

  76. Folsom AR, Wu KK, Rosamond WD, et al. Prospective study of hemostatic factors and incidence of coronary heart disease: the Atherosclerosis Risk In Community (ARIC) studies. Circulation 1997; 96: 1102–8

    PubMed  CAS  Google Scholar 

  77. Iniesta JA, Corral J, Gonzalez-Conejero R, et al. Prothrombotic genetic risk factors in patients with coexisting migraine ischemic cerebrovascular disease. Headache 1999; 39: 486–9

    PubMed  CAS  Google Scholar 

  78. Whitty CWM, Hockaday JM, Whitty MM. The effect of oral contraceptives on migraine. Lancet 1966; I(7442): 856–9

    Google Scholar 

  79. Conrad J, Samama MM. Oral contraceptives, hormone replacement and haemostasis. Cephalalgia 2000; 20: 175–82

    Google Scholar 

  80. Goadsby PJ. The pharmacology of headache. Prog Neurobiol 2000; 62: 509–22

    PubMed  CAS  Google Scholar 

  81. Parsons AA, Walley ET, Feniuk W, et al. 5 HT1-like receptors mediate 5-hydroxytryptamine-induced contraction of human basilar artery. Br J Pharmacol 1989; 96: 434–49

    PubMed  CAS  Google Scholar 

  82. Papademetriou V. Cardiovascular risk assessment and triptans. Headache 2004; 44Suppl. 1: S31–9

    PubMed  Google Scholar 

  83. Data on file, Product Surveillance Report, GlaxoSmithKline, 2001 Mar 31

  84. Welch KMA, Mathew NT, Stone P, et al. Tolerability of sumatriptan: clinical trials and postmarketing experience. Cephalalgia 2000; 20: 687–95

    PubMed  CAS  Google Scholar 

  85. Ferrari MD, Roon KI, Lipton RB, et al. Oral triptan (serotonin 5HT 1B/1D agonists) in acute migraine treatment: a meta-analysis of 53 trials. Lancet 2001; 358: 1668–75

    PubMed  CAS  Google Scholar 

  86. Luman W, Gray RS. Adverse reactions associated with sumatriptan. Lancet 1993; 341: 1091–2

    PubMed  CAS  Google Scholar 

  87. Cavazos JE, Caress JB, Chilukuri VR, et al. Sumatriptan-induced stroke in sagittal sinus thrombosis. Lancet 1994; 343: 1105–6

    PubMed  CAS  Google Scholar 

  88. Jayamaha JEL, Street MK. Fatal cerebellar infarction in a migraine sufferer whilst receiving sumatriptan. Intensive Care Med 1995; 21: 82–3

    PubMed  CAS  Google Scholar 

  89. Meschia JF, Malkoff MD, Biller J. Reversible segmental arterial spasm and cerebral infarction. Arch Neurol 1998; 55: 712–4

    PubMed  CAS  Google Scholar 

  90. Vijayan N, Peacock JH. Spinal cord infarction during use of zolmitriptan: a case report. Headache 2000; 40: 57–60

    PubMed  CAS  Google Scholar 

  91. Combremont PC, Marcus EM. Intracranial hemorrhages associated with sumatriptan. Neurology 2001; 56: 1243–4

    PubMed  CAS  Google Scholar 

  92. Combremont PC, Marcus EM. Intracranial hemorrhages associated with sumatriptan [letter]. Neurology 2001; 57: 2322

    Google Scholar 

  93. Velentgas PT, Cole A, Mo J, et al. Severe vascular events in migraine patients. Headache 2004; 44(7): 642–51

    PubMed  Google Scholar 

  94. Tfelt-Hansen P. The effect of ergotamine on arterial system in man. Acta Pharmacol Toxicol 1986; 59: 1–30

    Google Scholar 

  95. Lindboe CF, Dahl T, Rostad B. Fatal stroke in migraine: a case report with autopsy findings. Cephalalgia 1989; 9: 277–8

    PubMed  CAS  Google Scholar 

  96. Lipton RB. Ergotamine tartrate and dihydroergotamine mesylate: safety profiles. Headache 1997; 37Suppl. 1: S33–41

    PubMed  Google Scholar 

  97. Alvarez SJ, Molins A, Turon A, et al. Migraine infarct in patients treated with beta-blockers. Rev Clin Esp 1993; 192: 228–30

    Google Scholar 

  98. Bardwell A, Trott JA. Stroke and migraine as a consequence of propranolol. Headache 1987; 27: 381–3

    PubMed  CAS  Google Scholar 

  99. Gilbert GJ. An occurrence of complicated migraine during propranolol therapy. Headache 1982; 22: 81–3

    PubMed  CAS  Google Scholar 

  100. Katz B. Migrainous central retinal artery occlusion. J Clin Neuroophthalmol 1986; 6: 69–75

    PubMed  CAS  Google Scholar 

  101. Massiou H, Bousser MG. Influence of female hormones on migraine. In: Olesen J, Tfelt-Hansen P, Welch KMA, editors. The headaches. 2nd rev. ed. Philadelphia (PA): Lippincott-Williams & Wilkins, 2000: 261–67

    Google Scholar 

  102. Prendes JL. Considerations on the use of propranolol and complicated migraine. Headache 1980; 20: 93–5

    PubMed  CAS  Google Scholar 

  103. Sharpe CJ. Propranolol in the treatment of migraine [letter]. BMJ 1974; 34: 522

    Google Scholar 

  104. Evans RW, Lipton RB. Topics in migraine management: a survey of headache specialists highlights some controversies. Neurol Clin 2001; 19(1): 1–21

    PubMed  CAS  Google Scholar 

  105. Bousser MG, Conrad J, Kittner S, et al., on behalf of The International Headache Society Task Force on Combined Oral Contraceptives and Hormone Replacement Therapy. Recommendations on the risk of ischaemic stroke associated with use of combined oral contraceptives and hormone replacement therapy in women with migraine. Cephalalgia 2000; 20: 155–6

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The author’s work on functional MRI in migraineurs with livedo reticularis[60] was funded by the American Headache Society and Merck. The author has served on the GlaxoSmithKline national scientific advisory committee and has had grant support from GlaxoSmithKline.

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Tietjen, G.E. The Risk of Stroke in Patients with Migraine and Implications for Migraine Management. CNS Drugs 19, 683–692 (2005). https://doi.org/10.2165/00023210-200519080-00004

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