{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T02:45:14Z","timestamp":1783651514128,"version":"3.55.0"},"reference-count":78,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,1]]},"abstract":"<jats:p>Pediatric arteriovenous malformations (AVMs) are rare but carry a risk of devastating neurological morbidity and mortality. Rupture of a cerebral AVM is the most common cause of spontaneous intracranial hemorrhage in children, with an unruptured AVM having an approximate hemorrhage risk of 2%\u20134% per year.<\/jats:p>\n<jats:p>The complex etiology of pediatric AVMs persists as an impediment to a comprehensive understanding of pathogenesis and subsequent targeted gene therapies. While AVMs secondary to vascular malformation syndromes have a clearer pathogenesis, a variety of gene mutations have been identified within sporadic AVM cases. The Ephrin B2\/EphB4 (<jats:italic>RASA-1, KRAS<\/jats:italic>, and <jats:italic>MEK<\/jats:italic>) signaling axis, hemorrhagic telangiectasia, NOTCH, and TIE2 receptor complexes (<jats:italic>PIK3CA<\/jats:italic> and <jats:italic>mTOR<\/jats:italic>), in addition to other isolated gene variants, have been implicated in AVM pathogenesis. Furthering the understanding of the molecular mechanisms of AVM pathogenesis will lead to future novel therapies and treatment paradigms.<\/jats:p>\n<jats:p>Given the expected lifespan of a child, pediatric patients have an unacceptably high cumulative lifetime risk of hemorrhage. AVM treatment strategies are dependent on AVM grade, provider preference, and institutional resources. While open microsurgery is the mainstay of treatment for some AVMs, radiosurgery for definitive treatment and adjunctive endovascular embolization are also used extensively. There is increasing evidence indicating that all three modalities play important and potentially synergistic roles in the armamentarium for pediatric AVM treatment. This review serves to report current understanding in the genetic and molecular mechanisms of pediatric AVMs, review clinical diagnostic and classification criteria, and detail treatment options and subsequent outcomes of pediatric AVM patients.<\/jats:p>","DOI":"10.3171\/2024.6.peds22354","type":"journal-article","created":{"date-parts":[[2024,9,7]],"date-time":"2024-09-07T02:18:56Z","timestamp":1725675536000},"page":"509-518","source":"Crossref","is-referenced-by-count":7,"title":["Current trends, molecular insights, and future directions toward precision medicine in the management of pediatric cerebral arteriovenous malformations"],"prefix":"10.3171","volume":"34","author":[{"given":"H. Westley","family":"Phillips","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Stanford School of Medicine, Palo Alto, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regan M.","family":"Shanahan","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clementina","family":"Aiyudu","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Allegheny General Hospital, Pittsburgh, Pennsylvania; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy A.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilary Y.","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Greene","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Duke University School of Medicine, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"issue":"3","key":"b1","series-title":"Neurosurgery","first-page":"540","article-title":"Management of pediatric intracranial arteriovenous malformations: experience with multimodality therapy","volume":"69","author":"Darsaut TE","year":"2011","unstructured":"Darsaut TE, Guzman R, Marcellus ML,  Management of pediatric intracranial arteriovenous malformations: experience with multimodality therapy. 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