The Genetics of Cerebral Aneurysms and Other Vascular Malformations

  • Jennifer E. Fugate
  • Robert D. BrownJr.


Stroke can be caused by vascular malformations and cerebral aneurysms. This chapter discusses the importance of these conditions and the genetic screening that could be used. This chapter also describes the most recent genes that have been associated with these conditions.


Intracranial Aneurysm Autosomal Dominant Polycystic Kidney Disease Hereditary Hemorrhagic Telangiectasia Intracranial Aneurysm Cavernous Malformation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Ingall T, Asplund K, Mahonen M, Bonita R. A multinational comparison of subarachnoid hemorrhage epidemiology in the WHO MONICA stroke study. Stroke. 2000;31(5):1054–61.PubMedGoogle Scholar
  2. 2.
    Brown Jr RD, Wiebers DO, Torner JC, O’Fallon WM. Frequency of intracranial hemorrhage as a presenting symptom and subtype analysis: a population-based study of intracranial vascular malformations in Olmsted Country, Minnesota. J Neurosurg. 1996;85(1):29–32.PubMedGoogle Scholar
  3. 3.
    Broderick JP, Brott T, Tomsick T, Huster G, Miller R. The risk of subarachnoid and intracerebral hemorrhages in blacks as compared with whites. N Engl J Med. 1992;326(11):733–6.PubMedGoogle Scholar
  4. 4.
    Fogelholm R. Subarachnoid hemorrhage in Finland. Stroke. 1992;23(3):437.PubMedGoogle Scholar
  5. 5.
    Thrift AG, Dewey HM, Macdonell RA, McNeil JJ, Donnan GA. Incidence of the major stroke subtypes: initial findings from the North East Melbourne stroke incidence study (NEMESIS). Stroke. 2001;32(8):1732–8.PubMedGoogle Scholar
  6. 6.
    Longstreth Jr WT, Koepsell TD, Yerby MS, van Belle G. Risk factors for subarachnoid hemorrhage. Stroke. 1985;16(3):377–85.PubMedGoogle Scholar
  7. 7.
    Juvela S. Prevalence of risk factors in spontaneous intracerebral hemorrhage and aneurysmal subarachnoid hemorrhage. Arch Neurol. 1996;53(8):734–40.PubMedGoogle Scholar
  8. 8.
    Kissela BM, Sauerbeck L, Woo D, Khoury J, Carrozzella J, Pancioli A, et al. Subarachnoid hemorrhage: a preventable disease with a heritable component. Stroke. 2002;33(5):1321–6.PubMedGoogle Scholar
  9. 9.
    Sankai T, Iso H, Shimamoto T, Kitamura A, Naito Y, Sato S, et al. Prospective study on alcohol intake and risk of subarachnoid hemorrhage among Japanese men and women. Alcohol Clin Exp Res. 2000;24(3):386–9.PubMedGoogle Scholar
  10. 10.
    Donahue RP, Abbott RD, Reed DM, Yano K. Alcohol and hemorrhagic stroke. The Honolulu Heart Program. JAMA. 1986;255(17):2311–4.PubMedGoogle Scholar
  11. 11.
    Chyatte D, Chen TL, Bronstein K, Brass LM. Seasonal fluctuation in the incidence of intracranial aneurysm rupture and its relationship to changing climatic conditions. J Neurosurg. 1994;81(4):525–30.PubMedGoogle Scholar
  12. 12.
    Feigin VL, Anderson CS, Anderson NE, Broad JB, Pledger MJ, Bonita R. Is there a temporal pattern in the occurrence of subarachnoid hemorrhage in the southern hemisphere? Pooled data from 3 large, population-based incidence studies in Australasia, 1981 to 1997. Stroke. 2001;32(3):613–9.PubMedGoogle Scholar
  13. 13.
    Gallerani M, Portaluppi F, Maida G, Chieregato A, Calzolari F, Trapella G, et al. Circadian and circannual rhythmicity in the occurrence of subarachnoid hemorrhage. Stroke. 1996;27(10):1793–7.PubMedGoogle Scholar
  14. 14.
    Rinkel GJ, Djibuti M, Algra A, van Gijn J. Prevalence and risk of rupture of intracranial aneurysms: a systematic review. Stroke. 1998;29(1):251–6.PubMedGoogle Scholar
  15. 15.
    Atkinson JL, Sundt Jr TM, Houser OW, Whisnant JP. Angiographic frequency of anterior circulation intracranial aneurysms. J Neurosurg. 1989;70(4):551–5.PubMedGoogle Scholar
  16. 16.
    Vernooij MW, Ikram MA, Tanghe HL, Vincent AJ, Hofman A, Krestin GP, et al. Incidental findings on brain MRI in the general population. N Engl J Med. 2007;357(18):1821–8.PubMedGoogle Scholar
  17. 17.
    Ronkainen A, Hernesniemi J, Puranen M, Niemitukia L, Vanninen R, Ryynanen M, et al. Familial intracranial aneurysms. Lancet. 1997;349(9049):380–4.PubMedGoogle Scholar
  18. 18.
    Raaymakers TW. Aneurysms in relatives of patients with subarachnoid hemorrhage: frequency and risk factors. MARS Study Group. Magnetic resonance angiography in relatives of patients with subarachnoid hemorrhage. Neurology. 1999;53(5):982–8.PubMedGoogle Scholar
  19. 19.
    Schievink WI, Schaid DJ, Michels VV, Piepgras DG. Familial aneurysmal subarachnoid hemorrhage: a community-based study. J Neurosurg. 1995;83(3):426–9.PubMedGoogle Scholar
  20. 20.
    Schievink WI, Schaid DJ, Rogers HM, Piepgras DG, Michels VV. On the inheritance of intracranial aneurysms. Stroke. 1994;25(10):2028–37.PubMedGoogle Scholar
  21. 21.
    De Braekeleer M, Perusse L, Cantin L, Bouchard JM, Mathieu J. A study of inbreeding and kinship in intracranial aneurysms in the Saguenay Lac-Saint-Jean region (Quebec, Canada). Ann Hum Genet. 1996;60(Pt 2):99–104.PubMedGoogle Scholar
  22. 22.
    Wang PS, Longstreth Jr WT, Koepsell TD. Subarachnoid hemorrhage and family history. A population-based case-control study. Arch Neurol. 1995;52(2):202–4.PubMedGoogle Scholar
  23. 23.
    Broderick JP, Brown Jr RD, Sauerbeck L, Hornung R, Huston 3rd J, Woo D, et al. Greater rupture risk for familial as compared to sporadic unruptured intracranial aneurysms. Stroke. 2009;40(6):1952–7.PubMedGoogle Scholar
  24. 24.
    Wiebers DO, Whisnant JP, Huston 3rd J, Meissner I, Brown Jr RD, Piepgras DG, et al. Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet. 2003;362(9378):103–10.PubMedGoogle Scholar
  25. 25.
    Woo D, Khoury J, Haverbusch MM, Sekar P, Flaherty ML, Kleindorfer DO, et al. Smoking and family history and risk of aneurysmal subarachnoid hemorrhage. Neurology. 2009;72(1):69–72.PubMedGoogle Scholar
  26. 26.
    Bromberg JE, Rinkel GJ, Algra A, van Duyn CM, Greebe P, Ramos LM, et al. Familial subarachnoid hemorrhage: distinctive features and patterns of inheritance. Ann Neurol. 1995;38(6):929–34.PubMedGoogle Scholar
  27. 27.
    Wills S, Ronkainen A, van der Voet M, Kuivaniemi H, Helin K, Leinonen E, et al. Familial intracranial aneurysms: an analysis of 346 multiplex Finnish families. Stroke. 2003;34(6):1370–4.PubMedGoogle Scholar
  28. 28.
    Onda H, Kasuya H, Yoneyama T, Takakura K, Hori T, Takeda J, et al. Genomewide-linkage and haplotype-association studies map intracranial aneurysm to chromosome 7q11. Am J Hum Genet. 2001;69(4):804–19.PubMedGoogle Scholar
  29. 29.
    Hashikata H, Liu W, Inoue K, Mineharu Y, Yamada S, Nanayakkara S, et al. Confirmation of an association of single-nucleotide polymorphism rs1333040 on 9p21 with familial and sporadic intracranial aneurysms in Japanese patients. Stroke. 2010;41(6):1138–44.PubMedGoogle Scholar
  30. 30.
    van der Voet M, Olson JM, Kuivaniemi H, Dudek DM, Skunca M, Ronkainen A, et al. Intracranial aneurysms in Finnish families: confirmation of linkage and refinement of the interval to chromosome 19q13.3. Am J Hum Genet. 2004;74(3):564–71.PubMedGoogle Scholar
  31. 31.
    Farnham JM, Camp NJ, Neuhausen SL, Tsuruda J, Parker D, MacDonald J, et al. Confirmation of chromosome 7q11 locus for predisposition to intracranial aneurysm. Hum Genet. 2004;114(3):250–5.PubMedGoogle Scholar
  32. 32.
    Ruigrok YM, Seitz U, Wolterink S, Rinkel GJ, Wijmenga C, Urban Z. Association of polymorphisms and haplotypes in the elastin gene in Dutch patients with sporadic aneurysmal subarachnoid hemorrhage. Stroke. 2004;35(9):2064–8.PubMedGoogle Scholar
  33. 33.
    Akagawa H, Tajima A, Sakamoto Y, Krischek B, Yoneyama T, Kasuya H, et al. A haplotype spanning two genes, ELN and LIMK1, decreases their transcripts and confers susceptibility to intracranial aneurysms. Hum Mol Genet. 2006;15(10):1722–34.PubMedGoogle Scholar
  34. 34.
    Berthelemy-Okazaki N, Zhao Y, Yang Z, Camp NJ, Farnham J, Parker D, et al. Examination of ELN as a candidate gene in the Utah intracranial aneurysm pedigrees. Stroke. 2005;36(6):1283–4.PubMedGoogle Scholar
  35. 35.
    Mineharu Y, Inoue K, Inoue S, Yamada S, Nozaki K, Takenaka K, et al. Association analysis of common variants of ELN, NOS2A, APOE and ACE2 to intracranial aneurysm. Stroke. 2006;37(5):1189–94.PubMedGoogle Scholar
  36. 36.
    Yamada S, Utsunomiya M, Inoue K, Nozaki K, Miyamoto S, Hashimoto N, et al. Absence of linkage of familial intracranial aneurysms to 7q11 in highly aggregated Japanese families. Stroke. 2003;34(4):892–900.PubMedGoogle Scholar
  37. 37.
    Hofer A, Hermans M, Kubassek N, Sitzer M, Funke H, Stogbauer F, et al. Elastin polymorphism haplotype and intracranial aneurysms are not associated in Central Europe. Stroke. 2003;34(5):1207–11.PubMedGoogle Scholar
  38. 38.
    McColgan P, Thant KZ, Sharma P. The genetics of sporadic ruptured and unruptured intracranial aneurysms: a genetic meta-analysis of 8 genes and 13 polymorphisms in approximately 20,000 individuals. J Neurosurg. 2010;112(4):714–21.PubMedGoogle Scholar
  39. 39.
    Foroud T, Sauerbeck L, Brown R, Anderson C, Woo D, Kleindorfer D, et al. Genome screen to detect linkage to intracranial aneurysm susceptibility genes: the familial intracranial aneurysm (FIA) study. Stroke. 2008;39(5):1434–40.PubMedGoogle Scholar
  40. 40.
    Brown Jr RD, Huston J, Hornung R, Foroud T, Kallmes DF, Kleindorfer D, et al. Screening for brain aneurysm in the familial intracranial aneurysm study: frequency and predictors of lesion detection. J Neurosurg. 2008;108(6):1132–8.PubMedGoogle Scholar
  41. 41.
    Ronkainen A, Miettinen H, Karkola K, Papinaho S, Vanninen R, Puranen M, et al. Risk of harboring an unruptured intracranial aneurysm. Stroke. 1998;29(2):359–62.PubMedGoogle Scholar
  42. 42.
    Bederson JB, Connolly Jr ES, Batjer HH, Dacey RG, Dion JE, Diringer MN, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke. 2009;40(3):994–1025.PubMedGoogle Scholar
  43. 43.
    Bor AS, Koffijberg H, Wermer MJ, Rinkel GJ. Optimal screening strategy for familial intracranial aneurysms: a cost-effectiveness analysis. Neurology. 2010;74(21):1671–9.PubMedGoogle Scholar
  44. 44.
    Chapman AB, Rubinstein D, Hughes R, Stears JC, Earnest MP, Johnson AM, et al. Intracranial aneurysms in autosomal dominant polycystic kidney disease. N Engl J Med. 1992;327(13):916–20.PubMedGoogle Scholar
  45. 45.
    Huston 3rd J, Torres VE, Sulivan PP, Offord KP, Wiebers DO. Value of magnetic resonance angiography for the detection of intracranial aneurysms in autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 1993;3(12):1871–7.PubMedGoogle Scholar
  46. 46.
    Saifuddin A, Dathan JR. Adult polycystic kidney disease and intracranial aneurysms. Br Med J (Clin Res Ed). 1987;295(6597):526.Google Scholar
  47. 47.
    Schievink WI. Marfan syndrome and intracranial aneurysms. Stroke. 1999;30(12):2767–8.PubMedGoogle Scholar
  48. 48.
    Schievink WI, Michels VV, Piepgras DG. Neurovascular manifestations of heritable connective tissue disorders. A review. Stroke. 1994;25(4):889–903.PubMedGoogle Scholar
  49. 49.
    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(2):130–44.PubMedGoogle Scholar
  50. 50.
    Schievink WI. Genetics and aneurysm formation. Neurosurg Clin N Am. 1998;9(3):485–95.PubMedGoogle Scholar
  51. 51.
    Ho KL. Intraventricular aneurysm associated with tuberous sclerosis. Arch Neurol. 1980;37(6):385–6.PubMedGoogle Scholar
  52. 52.
    Butler WE, Barker 2nd FG, Crowell RM. Patients with polycystic kidney disease would benefit from routine magnetic resonance angiographic screening for intracerebral aneurysms: a decision analysis. Neurosurgery. 1996;38(3):506–15; discussion 15–6.PubMedGoogle Scholar
  53. 53.
    Giombini S, Morello G. Cavernous angiomas of the brain. Account of fourteen personal cases and review of the literature. Acta Neurochir (Wien). 1978;40(1–2):61–82.Google Scholar
  54. 54.
    Rigamonti D, Hadley MN, Drayer BP, Johnson PC, Hoenig-Rigamonti K, Knight JT, et al. Cerebral cavernous malformations. Incidence and familial occurrence. N Engl J Med. 1988;319(6):343–7.PubMedGoogle Scholar
  55. 55.
    Al-Shahi R, Bhattacharya JJ, Currie DG, Papanastassiou V, Ritchie V, Roberts RC, et al. Prospective, population-based detection of intracranial vascular malformations in adults: the Scottish Intracranial Vascular Malformation Study (SIVMS). Stroke. 2003;34(5):1163–9.PubMedGoogle Scholar
  56. 56.
    McCormick WF. The pathology of vascular (“arteriovenous”) malformations. J Neurosurg. 1966;24(4):807–16.PubMedGoogle Scholar
  57. 57.
    Otten P, Pizzolato GP, Rilliet B, Berney J. 131 cases of cavernous angioma (cavernomas) of the CNS, discovered by retrospective analysis of 24,535 autopsies. Neurochirurgie. 1989;35(2):128–31.Google Scholar
  58. 58.
    Kim DS, Park YG, Choi JU, Chung SS, Lee KC. An analysis of the natural history of cavernous malformations. Surg Neurol. 1997;48(1):9–17. discussion 17–8.PubMedGoogle Scholar
  59. 59.
    Del Curling Jr O, Kelly Jr DL, Elster AD, Craven TE. An analysis of the natural history of cavernous angiomas. J Neurosurg. 1991;75(5):702–8.PubMedGoogle Scholar
  60. 60.
    Robinson JR, Awad IA, Little JR. Natural history of the cavernous angioma. J Neurosurg. 1991;75(5):709–14.PubMedGoogle Scholar
  61. 61.
    Sage MR, Brophy BP, Sweeney C, Phipps S, Perrett LV, Sandhu A, et al. Cavernous haemangiomas (angiomas) of the brain: clinically significant lesions. Australas Radiol. 1993;37(2):147–55.PubMedGoogle Scholar
  62. 62.
    Zabramski JM, Wascher TM, Spetzler RF, Johnson B, Golfinos J, Drayer BP, et al. The natural history of familial cavernous malformations: results of an ongoing study. J Neurosurg. 1994;80(3):422–32.PubMedGoogle Scholar
  63. 63.
    Hayman LA, Evans RA, Ferrell RE, Fahr LM, Ostrow P, Riccardi VM. Familial cavernous angiomas: natural history and genetic study over a 5-year period. Am J Med Genet. 1982;11(2):147–60.PubMedGoogle Scholar
  64. 64.
    Dashti SR, Hoffer A, Hu YC, Selman WR. Molecular genetics of familial cerebral cavernous malformations. Neurosurg Focus. 2006;21(1):e2.PubMedGoogle Scholar
  65. 65.
    Maraire JN, Awad IA. Intracranial cavernous malformations: lesion behavior and management strategies. Neurosurgery. 1995;37(4):591–605.PubMedGoogle Scholar
  66. 66.
    Tekkok IH, Ventureyra EC. De novo familial cavernous malformation presenting with hemorrhage 12.5 years after the initial hemorrhagic Ictus: natural history of an infantile form. Pediatr Neurosurg. 1996;25(3):151–5.PubMedGoogle Scholar
  67. 67.
    Detwiler PW, Porter RW, Zabramski JM, Spetzler RF. De novo formation of a central nervous system cavernous malformation: implications for predicting risk of hemorrhage. Case report and review of the literature. J Neurosurg. 1997;87(4):629–32.PubMedGoogle Scholar
  68. 68.
    Larson JJ, Ball WS, Bove KE, Crone KR, Tew Jr JM. Formation of intracerebral cavernous malformations after radiation treatment for central nervous system neoplasia in children. J Neurosurg. 1998;88(1):51–6.PubMedGoogle Scholar
  69. 69.
    Chang SD, Vanefsky MA, Havton LA, Silverberg GD. Bilateral cavernous malformations resulting from cranial irradiation of a choroid plexus papilloma. Neurol Res. 1998;20(6):529–32.PubMedGoogle Scholar
  70. 70.
    Ogilvy CS, Moayeri N, Golden JA. Appearance of a cavernous hemangioma in the cerebral cortex after a biopsy of a deeper lesion. Neurosurgery. 1993;33(2):307–9; discussion 9.PubMedGoogle Scholar
  71. 71.
    Ciricillo SF, Dillon WP, Fink ME, Edwards MS. Progression of multiple cryptic vascular malformations associated with anomalous venous drainage. Case report. J Neurosurg. 1994;81(3):477–81.PubMedGoogle Scholar
  72. 72.
    Dubovsky J, Zabramski JM, Kurth J, Spetzler RF, Rich SS, Orr HT, et al. A gene responsible for cavernous malformations of the brain maps to chromosome 7q. Hum Mol Genet. 1995;4(3):453–8.PubMedGoogle Scholar
  73. 73.
    Craig HD, Gunel M, Cepeda O, Johnson EW, Ptacek L, Steinberg GK, et al. Multilocus linkage identifies two new loci for a mendelian form of stroke, cerebral cavernous malformation, at 7p15–13 and 3q25.2–27. Hum Mol Genet. 1998;7(12):1851–8.PubMedGoogle Scholar
  74. 74.
    Gunel M, Awad IA, Anson J, Lifton RP. Mapping a gene causing cerebral cavernous malformation to 7q11.2-q21. Proc Natl Acad Sci USA. 1995;92(14):6620–4.PubMedGoogle Scholar
  75. 75.
    Mindea SA, Yang BP, Shenkar R, Bendok B, Batjer HH, Awad IA. Cerebral cavernous malformations: clinical insights from genetic studies. Neurosurg Focus. 2006;21(1):e1.PubMedGoogle Scholar
  76. 76.
    Revencu N, Vikkula M. Cerebral cavernous malformation: new molecular and clinical insights. J Med Genet. 2006;43(9):716–21.PubMedGoogle Scholar
  77. 77.
    Liquori CL, Berg MJ, Squitieri F, Leedom TP, Ptacek L, Johnson EW, et al. Deletions in CCM2 are a common cause of cerebral cavernous malformations. Am J Hum Genet. 2007;80(1):69–75.PubMedGoogle Scholar
  78. 78.
    Denier C, Labauge P, Bergametti F, Marchelli F, Riant F, Arnoult M, et al. Genotype-phenotype correlations in cerebral cavernous malformations patients. Ann Neurol. 2006;60(5):550–6.PubMedGoogle Scholar
  79. 79.
    Chen L, Tanriover G, Yano H, Friedlander R, Louvi A, Gunel M. Apoptotic functions of PDCD10/CCM3, the gene mutated in cerebral cavernous malformation 3. Stroke. 2009;40(4):1474–81.PubMedGoogle Scholar
  80. 80.
    Schleider E, Stahl S, Wustehube J, Walter U, Fischer A, Felbor U. Evidence for anti-angiogenic and pro-survival functions of the cerebral cavernous malformation protein 3. Neurogenetics. 2011;12(1):83–6.PubMedGoogle Scholar
  81. 81.
    Zhu Y, Wu Q, Xu JF, Miller D, Sandalcioglu IE, Zhang JM, et al. Differential angiogenesis function of CCM2 and CCM3 in cerebral cavernous malformations. Neurosurg Focus. 2010;29(3):E1.PubMedGoogle Scholar
  82. 82.
    Zawistowski JS, Serebriiskii IG, Lee MF, Golemis EA, Marchuk DA. KRIT1 Association with the integrin-binding protein ICAP-1: a new direction in the elucidation of cerebral cavernous malformations (CCM1) pathogenesis. Hum Mol Genet. 2002;11(4):389–96.PubMedGoogle Scholar
  83. 83.
    Zhang J, Rigamonti D, Dietz HC, Clatterbuck RE. Interaction between krit1 and malcavernin: implications for the pathogenesis of cerebral cavernous malformations. Neurosurgery. 2007;60(2):353–9; discussion 9.PubMedGoogle Scholar
  84. 84.
    D’Angelo R, Marini V, Rinaldi C, Origone P, Dorcaratto A, Avolio M, et al. Mutation analysis of CCM1, CCM2 and CCM3 genes in a cohort of Italian patients with cerebral cavernous malformation. Brain Pathol. 2011;21(2):215–24.PubMedGoogle Scholar
  85. 85.
    Labauge P, Denier C, Bergametti F, Tournier-Lasserve E. Genetics of cavernous angiomas. Lancet Neurol. 2007;6(3):237–44.PubMedGoogle Scholar
  86. 86.
    Furlan AJ, Whisnant JP, Elveback LR. The decreasing incidence of primary intracerebral hemorrhage: a population study. Ann Neurol. 1979;5(4):367–73.PubMedGoogle Scholar
  87. 87.
    Perret G, Nishioka H. Report on the cooperative study of intracranial aneurysms and subarachnoid hemorrhage. IV. Cerebral angiography. An analysis of the diagnostic value and complications of carotid and vertebral angiography in 5,484 patients. J Neurosurg. 1966;25(1):98–114.PubMedGoogle Scholar
  88. 88.
    Fleetwood IG, Steinberg GK. Arteriovenous malformations. Lancet. 2002;359(9309):863–73.PubMedGoogle Scholar
  89. 89.
    Berman MF, Sciacca RR, Pile-Spellman J, Stapf C, Connolly Jr ES, Mohr JP, et al. The epidemiology of brain arteriovenous malformations. Neurosurgery. 2000;47(2):389–96; discussion 97.PubMedGoogle Scholar
  90. 90.
    Stapf C, Mast H, Sciacca RR, Berenstein A, Nelson PK, Gobin YP, et al. The New York Islands AVM Study: design, study progress, and initial results. Stroke. 2003;34(5):e29–33.PubMedGoogle Scholar
  91. 91.
    ApSimon HT, Reef H, Phadke RV, Popovic EA. A population-based study of brain arteriovenous malformation: long-term treatment outcomes. Stroke. 2002;33(12):2794–800.PubMedGoogle Scholar
  92. 92.
    Hofmeister C, Stapf C, Hartmann A, Sciacca RR, Mansmann U, TerBrugge K, et al. Demographic, morphological, and clinical characteristics of 1289 patients with brain arteriovenous malformation. Stroke. 2000;31(6):1307–10.PubMedGoogle Scholar
  93. 93.
    Padget DH. The cranial venous system in man in reference to development, adult configuration, and relation to the arteries. Am J Anat. 1956;98(3):307–55.PubMedGoogle Scholar
  94. 94.
    Stein BM, Wolpert SM. Arteriovenous malformations of the brain. I: current concepts and treatment. Arch Neurol. 1980;37(1):1–5.PubMedGoogle Scholar
  95. 95.
    Mullan S, Mojtahedi S, Johnson DL, Macdonald RL. Embryological basis of some aspects of cerebral vascular fistulas and malformations. J Neurosurg. 1996;85(1):1–8.PubMedGoogle Scholar
  96. 96.
    Gonzalez LF, Bristol RE, Porter RW, Spetzler RF. De novo presentation of an arteriovenous malformation. Case report and review of the literature. J Neurosurg. 2005;102(4):726–9.PubMedGoogle Scholar
  97. 97.
    Kader A, Goodrich JT, Sonstein WJ, Stein BM, Carmel PW, Michelsen WJ. Recurrent cerebral arteriovenous malformations after negative postoperative angiograms. J Neurosurg. 1996;85(1):14–8.PubMedGoogle Scholar
  98. 98.
    Lasjaunias P. A revised concept of the congenital nature of cerebral arteriovenous malformations. Interv Neuroradiol. 1997;3(4):275–81.PubMedGoogle Scholar
  99. 99.
    Deshpande DH, Vidyasagar C. Histology of the persistent embryonic veins in arteriovenous malformations of brain. Acta Neurochir (Wien). 1980;53(3–4):227–36.Google Scholar
  100. 100.
    Nussbaum ES, Heros RC, Madison MT, Awasthi D, Truwit CL. The pathogenesis of arteriovenous malformations: insights provided by a case of multiple arteriovenous malformations developing in relation to a developmental venous anomaly. Neurosurgery. 1998;43(2):347–51; discussion 51–2.PubMedGoogle Scholar
  101. 101.
    Leblanc R, Melanson D, Wilkinson RD. Hereditary neurocutaneous angiomatosis. Report of four cases. J Neurosurg. 1996;85(6):1135–42.PubMedGoogle Scholar
  102. 102.
    Yokoyama K, Asano Y, Murakawa T, Takada M, Ando T, Sakai N, et al. Familial occurrence of arteriovenous malformation of the brain. J Neurosurg. 1991;74(4):585–9.PubMedGoogle Scholar
  103. 103.
    van Beijnum J, van der Worp HB, Schippers HM, van Nieuwenhuizen O, Kappelle LJ, Rinkel GJ, et al. Familial occurrence of brain arteriovenous malformations: a systematic review. J Neurol Neurosurg Psychiatry. 2007;78(11):1213–7.PubMedGoogle Scholar
  104. 104.
    Inoue S, Liu W, Inoue K, Mineharu Y, Takenaka K, Yamakawa H, et al. Combination of linkage and association studies for brain arteriovenous malformation. Stroke. 2007;38(4):1368–70.PubMedGoogle Scholar
  105. 105.
    Snead 3rd OC, Acker JD, Morawetz R. Familial arteriovenous malformation. Ann Neurol. 1979;5(6):585–7.PubMedGoogle Scholar
  106. 106.
    Boyd MC, Steinbok P, Paty DW. Familial arteriovenous malformations. Report of four cases in one family. J Neurosurg. 1985;62(4):597–9.PubMedGoogle Scholar
  107. 107.
    Brilli RJ, Sacchetti A, Neff S. Familial arteriovenous malformations in children. Pediatr Emerg Care. 1995;11(6):376–8.PubMedGoogle Scholar
  108. 108.
    Pawlikowska L, Tran MN, Achrol AS, Ha C, Burchard E, Choudhry S, et al. Polymorphisms in transforming growth factor-beta-related genes ALK1 and ENG are associated with sporadic brain arteriovenous malformations. Stroke. 2005;36(10):2278–80.PubMedGoogle Scholar
  109. 109.
    Hashimoto T, Lawton MT, Wen G, Yang GY, Chaly Jr T, Stewart CL, et al. Gene microarray analysis of human brain arteriovenous malformations. Neurosurgery. 2004;54(2):410–23; discussion 23–5.PubMedGoogle Scholar
  110. 110.
    Young WL, Yang GY. Are there genetic influences on sporadic brain arteriovenous malformations? Stroke. 2004;35(11 Suppl 1):2740–5.PubMedGoogle Scholar
  111. 111.
    Shenkar R, Elliott JP, Diener K, Gault J, Hu LJ, Cohrs RJ, et al. Differential gene expression in human cerebrovascular malformations. Neurosurgery. 2003;52(2):465–77; discussion 77–8.PubMedGoogle Scholar

Copyright information

© Springer-Verlag London 2013

Authors and Affiliations

  1. 1.Department of NeurologyMayo ClinicRochesterUSA
  2. 2.Department of NeurologyMayo Clinic College of MedicineRochesterUSA

Personalised recommendations