title: A hierarchical model for the development of cerebral arteriovenous malformations.
abstract: OBJECTIVE
  Cerebral arteriovenous malformations (AVMs) are vascular lesions whose pathogenesis, although not fully elucidated, is likely multifactorial. Recent research investigating vessel development suggests a potential hierarchical model in which capillary sprouts from higher-flow arteries give rise to lower-flow veins. It is possible that an embryologic structural vascular dysgenesis in this hierarchical development heavily contributes to the formation of AVMs. Subsequent genetic "second hits" may then allow development of a clinically significant cerebral AVM. We review this vascular developmental process and describe a novel proposal for the embryogenesis of AVMs and its implications in relation to recent research on polymorphisms and AVMs.
  
  
  METHODS
  A comprehensive literature search was performed using PubMed for recent research relative to cerebral AVMs, embryologic vascular development, and polymorphisms involved in AVM pathology.
  
  
  RESULTS
  It has recently been shown that both centrally, in the axial embryo, and peripherally, in the embryonic yolk sac, veins form via capillary sprouting from parent arteries. In developing intracranial vessels, a derangement in this embryonic process may lead to a primitive arteriovenous shunt. After this structural "first hit," we suggest that single nucleotide polymorphisms (SNPs) are a major component in allowing AVM growth into symptomatic clinical lesions.
  
  
  CONCLUSIONS
  This is a novel theory for the embryologic formation of cerebral AVMs. Hierarchical vessel development, where higher-flow parent arteries give rise to lower-flow veins, provides a potential mechanism for the formation of primitive arteriovenous shunts that, with the influence of polymorphisms, allows AVMs to develop.
authors.affiliation: Division of Neurological Surgery, Department of Surgery, The University of Arizona, Tucson, USA; Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, USA.
authors.forename: Wyatt L
authors.initials: WL
authors.lastname: Ramey
authors.affiliation: Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, USA.
authors.forename: Nikolay L
authors.initials: NL
authors.lastname: Martirosyan
authors.affiliation: Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Zabramski
authors.affiliation: Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, USA.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Spetzler
authors.affiliation: Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, USA. Electronic address: Neuropub@dignityhealth.org.
authors.forename: M Yashar S
authors.initials: MY
authors.lastname: Kalani
mesh_terms: D006801:Humans; D002538:Intracranial Arteriovenous Malformations / Q000196:embryology* / Q000209:etiology*; D008959:Models, Neurological
keywords: Arteriovenous malformation; Embryology; Polymorphism; Vasculogenesis