A hierarchical model for the development of cerebral arteriovenous malformations

Wyatt L. Ramey, Nikolay L. Martirosyan, Joseph M. Zabramski, Robert F. Spetzler, M. Yashar S. Kalani

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)126-129
Number of pages4
JournalClinical Neurology and Neurosurgery
StatePublished - Nov 2014


  • Arteriovenous malformation
  • Embryology
  • Polymorphism
  • Vasculogenesis

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology


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