{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T14:27:44Z","timestamp":1783088864749,"version":"3.54.6"},"reference-count":60,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,1]]},"abstract":"<jats:p>Cerebral arteriovenous malformations (AVMs) are a leading cause of intracerebral hemorrhage in both children and young adults. With the continued advancement of science and technology, the understanding of the pathophysiology behind the development of these lesions has evolved. From early theory published by Harvey Cushing and Percival Bailey in 1928, <jats:italic>Tumors Arising from the Blood-vessels of the Brain: Angiomatous Malformations and Hemangioblastoma<\/jats:italic>, which regarded AVMs as tumors arising from blood vessels, to the meticulous artistry of Dorcas Padget\u2019s embryological cataloguing of the cerebral vasculature in 1948, to the proliferative capillaropathy theory of Ya\u015fargil in 1987, to Ramey\u2019s 2014 hierarchical model of vascular development, there have been multiple hypotheses of congenital, developmental, and genetic two-hit theories in the pathogenesis of AVMs. Most recent evidence implicates somatic KRAS mutations in the cerebral endothelium, producing an important understanding of the pathogenesis of this disease, which is critical to the development of targeted therapeutics. The authors present the historical progression of their understanding of AVM pathogenesis. They focus on the foundation laid by early pioneers, discussing embryological anatomy and vasculogenesis, the prominent theories of AVM development that have emerged over time, and culminate in an overview of the most current understanding of the pathogenesis of these complex vascular lesions and the clinical implications of our scientific progress.<\/jats:p>","DOI":"10.3171\/2023.12.jns232233","type":"journal-article","created":{"date-parts":[[2024,3,23]],"date-time":"2024-03-23T01:30:49Z","timestamp":1711157449000},"page":"323-332","source":"Crossref","is-referenced-by-count":5,"title":["A comprehensive review on the development of sporadic cerebral arteriovenous malformations: from Padget to next-generation sequencing"],"prefix":"10.3171","volume":"141","author":[{"given":"Stephanie A.","family":"Coffman","sequence":"first","affiliation":[{"name":"Department of Neurological Surgery, Wake Forest School of Medicine, Winston-Salem, North Carolina; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyan","family":"Peterson","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Vanderbilt University, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Contillo","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Wake Forest School of Medicine, Winston-Salem, North Carolina; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle M.","family":"Fargen","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Wake Forest School of Medicine, Winston-Salem, North Carolina; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey Q.","family":"Wolfe","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Wake Forest School of Medicine, Winston-Salem, North Carolina; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"issue":"19","key":"b1","series-title":"N Engl J Med","first-page":"1859","article-title":"Arteriovenous malformations of the brain","volume":"376","author":"Solomon RA","year":"2017","unstructured":"Solomon RA, Connolly ES. 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