Migraine is a common neurological disorder with a great impact on the quality of life and social activities. Pulmonary arteriovenous malformations (PAVMs) are mostly congenital, with a prevalence of 5–50% in patients with hereditary hemorrhagic telangiectasia (HHT). A high prevalence of PAVMs is found in patients with HHT and migraine. Embolization of PAVMs seems to decrease the prevalence of migraine. Different pathophysiological hypotheses have been proposed to explain the association between migraine and the different right-to-left shunts. This review article describes the association between a pulmonary right-to-left shunt and the occurrence of migraine.

Keywords:
Hereditary hemorrhagic telangiectasia, Migraine, Pulmonary arteriovenous malformations, Right-to-left shunt
1.
Wilmshurst PT, Nightingale S, Walsh KP, Morrison WL: Effect on migraine of closure of cardiac right-to-left shunts to prevent recurrence of decompression illness or stroke or for haemodynamic reasons. Lancet 2000;356:1648–1651.
2.
Holmes DR Jr: Strokes and holes and headaches: are they a package deal? Lancet 2004;364:1840–1842.
3.
The International Classification of Headache Disorders, ed 2. Cephalalgia 2004;24 (suppl 1):9–160.
4.
Silberstein SD: Migraine. Lancet 2004;363:381–391.
5.
Stewart WF, Shechter A, Rasmussen BK: Migraine prevalence. A review of population-based studies. Neurology 1994;44:17–23.
6.
Launer LJ, Terwindt GM, Ferrari MD: The prevalence and characteristics of migraine in a population-based cohort: the GEM study. Neurology 1999;53:537–542.
7.
Lipton RB: Fair winds and foul headaches: risk factors and triggers of migraine. Neurology 2000;54:280–281.
8.
Gardner KL: Genetics of migraine: an update. Headache 2006;46(suppl 1):S19–S24.
9.
Goadsby PJ, Edvinsson L: The trigeminovascular system and migraine: studies characterizing cerebrovascular and neuropeptide changes seen in humans and cats. Ann Neurol 1993;33:48–56.
10.
Olesen J, Friberg L, Olsen TS, Iversen HK, Lassen NA, Andersen AR, Karle A: Timing and topography of cerebral blood flow, aura, and headache during migraine attacks. Ann Neurol 1990;28:791–798.
11.
Olesen J, Larsen B, Lauritzen M: Focal hyperemia followed by spreading oligemia and impaired activation of rCBF in classic migraine. Ann Neurol 1981;9:344–352.
12.
Shovlin CL, Letarte M: Hereditary haemorrhagic telangiectasia and pulmonary arteriovenous malformations: issues in clinical management and review of pathogenic mechanisms. Thorax 1999;54:714–729.
13.
Letteboer TG, Mager JJ, Snijder RJ, Koeleman BP, Lindhout D, Ploos van Amstel JK, Westermann CJ: Genotype-phenotype relationship in hereditary haemorrhagic telangiectasia. J Med Genet 2006;43:371–377.
14.
McAllister KA, Grogg KM, Johnson DW, Gallione CJ, Baldwin MA, Jackson CE, Helmbold EA, Markel DS, McKinnon WC, Murrell J: Endoglin, a TGF-beta binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1. Nat Genet 1994;8:345–351.
15.
Johnson DW, Berg JN, Baldwin MA, Gallione CJ, Marondel I, Yoon SJ, Stenzel TT, Speer M, Pericak-Vance MA, Diamond A, Guttmacher AE, Jackson CE, Attisano L, Kucherlapati R, Porteous ME, Marchuk DA: Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2. Nat Genet 1996;13:189–195.
16.
Westermann CJ, Rosina AF, De Vries V, de Coteau PA: The prevalence and manifestations of hereditary hemorrhagic telangiectasia in the Afro-Caribbean population of the Netherlands Antilles: a family screening. Am J Med Genet A 2003;116:324–328.
17.
Begbie ME, Wallace GM, Shovlin CL: Hereditary haemorrhagic telangiectasia (Osler-Weber-Rendu syndrome): a view from the 21st century. Postgrad Med J 2003;79:18–24.
18.
Remy J, Remy-Jardin M, Wattinne L, Deffontaines C: Pulmonary arteriovenous malformations: evaluation with CT of the chest before and after treatment. Radiology 1992;182:809–816.
19.
Kjeldsen AD, Oxhoj H, Andersen PE, Elle B, Jacobsen JP, Vase P: Pulmonary arteriovenous malformations: screening procedures and pulmonary angiography in patients with hereditary hemorrhagic telangiectasia. Chest 1999;116:432–439.
20.
Mager JJ, Overtoom TT, Blauw H, Lammers JW, Westermann CJ: Embolotherapy of pulmonary arteriovenous malformations: long-term results in 112 patients. J Vasc Interv Radiol 2004;15:451–456.
21.
Puskas JD, Allen MS, Moncure AC, Wain JC Jr, Hilgenberg AD, Wright C, Grillo HC, Mathisen DJ: Pulmonary arteriovenous malformations: therapeutic options. Ann Thorac Surg 1993;56:253–257.
22.
White RI Jr, Lynch-Nyhan A, Terry P, Buescher PC, Farmlett EJ, Charnas L, Shuman K, Kim W, Kinnison M, Mitchell SE: Pulmonary arteriovenous malformations: techniques and long-term outcome of embolotherapy. Radiology 1988;169:663–669.
23.
Moussouttas M, Fayad P, Rosenblatt M, Hashimoto M, Pollak J, Henderson K, Ma TY, White RI: Pulmonary arteriovenous malformations: cerebral ischemia and neurologic manifestations. Neurology 2000;55:959–964.
24.
Wilmshurst P, Nightingale S: Relationship between migraine and cardiac and pulmonary right-to-left shunts. Clin Sci (Lond) 2001;100:215–220.
25.
Hodgson CH, Burchell HB, Good CA, Clagett OT: Hereditary hemorrhagic telangiectasia and pulmonary arteriovenous fistula: survey of a large family. N Engl J Med 1959;261:625–636.
26.
Post MC, Letteboer TG, Mager JJ, Plokker TH, Kelder JC, Westermann CJ: A pulmonary right-to-left shunt in patients with hereditary hemorrhagic telangiectasia is associated with an increased prevalence of migraine. Chest 2005;128:2485–2489.
27.
Thenganatt J, Schneiderman J, Hyland RH, Edmeads J, Mandzia JL, Faughnan ME: Migraines linked to intrapulmonary right-to-left shunt. Headache 2006;46:439–443.
28.
Bayrak-Toydemir P, McDonald J, Markewitz B, Lewin S, Miller F, Chou LS, Gedge F, Tang W, Coon H, Mao R: Genotype-phenotype correlation in hereditary hemorrhagic telangiectasia: mutations and manifestations. Am J Med Genet A 2006;140:463–470.
29.
Steele JG, Nath PU, Burn J, Porteous ME: An association between migrainous aura and hereditary haemorrhagic telangiectasia. Headache 1993;33:145–148.
30.
Cottin V, Chinet T, Lavole A, Corre R, Marchand E, Reynaud-Gaubert M, Plauchu H, Cordier JF: Pulmonary arteriovenous malformations in hereditary hemorrhagic telangiectasia: a series of 126 patients. Medicine (Baltimore) 2007;86:1–17.
31.
Post MC, Thijs V, Schonewille WJ, Budts W, Snijder RJ, Plokker HW, Westermann CJ: Embolization of pulmonary arteriovenous malformations and decrease in prevalence of migraine. Neurology 2006;66:202–205.
32.
Stang PE, Carson AP, Rose KM, Mo J, Ephross SA, Shahar E, Szklo M: Headache, cerebrovascular symptoms, and stroke: the Atherosclerosis Risk in Communities Study. Neurology 2005;64:1573–1577.
33.
Kurth T, Slomke MA, Kase CS, Cook NR, Lee IM, Gaziano JM, Diener HC, Buring JE: Migraine, headache, and the risk of stroke in women: a prospective study. Neurology 2005;64:1020–1026.
34.
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.
35.
Kruit MC, van Buchem MA, Hofman PA, Bakkers JT, Terwindt GM, Ferrari MD, Launer LJ: Migraine as a risk factor for subclinical brain lesions. JAMA 2004;291:427–434.
36.
Fragoso YD: Reduction of migraine attacks during the use of warfarin. Headache 1997;37:667–668.
37.
Lipton RB, Goldstein J, Baggish JS, Yataco AR, Sorrentino JV, Quiring JN: Aspirin is efficacious for the treatment of acute migraine. Headache 2005;45:283–292.
38.
Shovlin CL, Guttmacher AE, Buscarini E, Faughnan ME, Hyland RH, Westermann CJ, Kjeldsen AD, Plauchu H: Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome). Am J Med Genet 2000;91:66–67.
39.
Wilmshurst P, Nightingale S: The role of cardiac and pulmonary pathology in migraine: a hypothesis. Headache 2006;46:429–434.
40.
Post MC, Budts W: The relationship between migraine and right-to-left shunt: fact or fiction? Chest 2006;130:896–901.
41.
Post MC, Luermans JG, Plokker HW, Budts W: Patent foramen ovale and migraine. Catheter Cardiovasc Interv 2007;69:9–14.
42.
Roman G, Fisher M, Perl DP, Poser CM: Neurological manifestations of hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease): report of 2 cases and review of the literature. Ann Neurol 1978;4:130–144.
43.
Cottin V, Dupuis-Girod S, Lesca G, Cordier JF: Pulmonary vascular manifestations of hereditary hemorrhagic telangiectasia (Rendu-Osler disease). Respiration 2007;74:361–378.
44.
Marchesani F, Cecarini L, Pela R, Catalini G, Sabbatini A, Fianchini A, Sanguinetti CM: Pulmonary arteriovenous fistula in a patient with Rendu-Osler-Weber syndrome. Respiration 1997;64:367–370.
45.
Aamodt AH, Borch-Iohnsen B, Hagen K, Stovner LJ, Asberg A, Zwart JA: Headache prevalence related to haemoglobin and ferritin. The HUNT Study. Cephalalgia 2004;24:758–762.
46.
Whyte MK, Hughes JM, Jackson JE, Peters AM, Hempleman SC, Moore DP, Jones HA: Cardiopulmonary response to exercise in patients with intrapulmonary vascular shunts. J Appl Physiol 1993;75:321–328.
47.
O’Connor TP, van der Koov D: Enrichment of a vasoactive neuropeptide (calcitonin gene related peptide) in the trigeminal sensory projection to the intracranial arteries. J Neurosci 1988;8:2468–2476.
48.
Van Gelderen EM, Du XY, Schoemaker RG, Saxena PR: Carotid blood flow distribution, haemodynamics and inotropic responses following calcitonin gene-related peptide in the pig. Eur J Pharmacol 1995;284:51–60.
49.
Post MC, Thijs V, Herroelen L, Budts WI: Closure of a patent foramen ovale is associated with a decrease in prevalence of migraine. Neurology 2004;62:1439–1440.
50.
Wilmshurst PT, Pearson MJ, Nightingale S, Walsh KP, Morrison WL: Inheritance of persistent foramen ovale and atrial septal defects and the relation to familial migraine with aura. Heart 2004;90:1315–1320.
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