Genetics and Emerging Therapies for Brain Arteriovenous Malformations

Authors

Lea Scherschinski, Barrow Aneurysm and AVM Research Center, Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA; Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.
Redi Rahmani, Barrow Aneurysm and AVM Research Center, Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA; Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.
Visish M. Srinivasan, Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.
Joshua S. Catapano, Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.Follow
S Paul Oh, Barrow Aneurysm and AVM Research Center, Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.
Michael T. Lawton, Barrow Aneurysm and AVM Research Center, Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA; Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA. Electronic address: Neuropub@barrowneuro.org.Follow

Document Type

Article

Abstract

Brain arteriovenous malformations (AVMs) are characterized by a high-pressure, low-resistance vascular nidus created by direct shunting of blood from feeding arteries into arterialized veins, bypassing intervening capillaries. AVMs pose a risk of spontaneous rupture because the vessel walls are continuously exposed to increased shear stress and abnormal flow phenomena, which lead to vessel wall inflammation and distinct morphologic changes. The annual rupture rate is estimated at 2%, and once an AVM ruptures, the risk of rerupture increases 5-fold. The ability of AVMs to grow, regress, recur, and undergo remodeling shows their dynamic nature. Identifying the underlying cellular and molecular pathways of AVMs not only helps us understand their natural physiology but also allows us to directly block vital pathways, thus preventing AVM development and progression. Management of AVMs is challenging and often necessitates a multidisciplinary approach, including neurosurgical, endovascular, and radiosurgical expertise. Because many of these procedures are invasive, carry a risk of inciting hemorrhage, or are controversial, the demand for pharmacologic treatment options is increasing. In this review, we introduce novel findings of cellular and molecular AVM physiology and highlight key signaling mediators that are potential targets for AVM treatment. Furthermore, we give an overview of syndromes associated with hereditary and nonhereditary AVM formation and discuss causative genetic alterations.

Medical Subject Headings

Arteriovenous Malformations (complications); Brain (metabolism); Capillaries; Humans; Intracranial Arteriovenous Malformations (complications, genetics, therapy); Nervous System Malformations (complications); Radiosurgery

Publication Date

3-1-2022

Publication Title

World neurosurgery

E-ISSN

1878-8769

Volume

159

First Page

327

Last Page

337

PubMed ID

35255632

Digital Object Identifier (DOI)

10.1016/j.wneu.2021.10.127

Recommended Citation

Scherschinski, Lea; Rahmani, Redi; Srinivasan, Visish M.; Catapano, Joshua S.; Oh, S Paul; and Lawton, Michael T., "Genetics and Emerging Therapies for Brain Arteriovenous Malformations" (2022). Neurosurgery. 1577.
https://scholar.barrowneuro.org/neurosurgery/1577