Arteriovenous Malformations (AVMs): Molecular Pathogenesis, Clinical Features, and Emerging Therapeutic Strategies

Arteriovenous malformations (AVMs) are fast‑flow vascular malformations formed by direct artery–to-vein shunts without an intervening capillary bed, increasing the risk of hemorrhage and organ‑specific damage. A synthesis of recent advances shows that AVMs arise from interplay between germline susceptibility (ENG, ACVRL1, SMAD4, RASA1, EPHB4), somatic mosaicism (KRAS, MAP2K1, PIK3CA), perturbed signaling (TGF‑β/BMP, Notch, VEGF, PI3K/AKT, RAS/MAPK), hemodynamic stress, and inflammation. Multi-modal imaging—digital subtraction angiography (DSA), MRI/MRA with perfusion and susceptibility sequences, CTA, Doppler ultrasound, and 3D rotational angiography, un-derpins diagnosis and risk stratification, while arterial spin labeling and 4D flow tech-niques refine hemodynamic assessment. Management is individualized and multidisci-plinary, combining endovascular embolization, microsurgical resection, and stereotactic radiosurgery (SRS); a non-surgical approach and monitoring remain reasonable for some asymptomatic AVMs. Device and technique innovations (detachable‑tip microcatheters, pressure‑cooker approaches, newer liquid embolic such as PHIL and Squid) have broad-ened candidacy, and precision‑medicine strategies including pathway‑targeted pharma-cotherapy are emerging for syndromic and somatic‑mutation–driven AVMs. Animal models and computational/radiomics tools increasingly guide hypothesis generation and treatment selection. We outline practical updates and future priorities: integrated ge-nomic–imaging risk scores, genotype‑informed medical therapy, rational hybrid se-quencing, and long‑term outcome standards focused on hemorrhage prevention and quality of life.