The Role and Therapeutic Implications of Inflammation in the Pathogenesis of Brain Arteriovenous Malformations

Brain arteriovenous malformations (bAVMs) are focal vascular lesions composed of abnormal vascular channels without an intervening capillary network. As a result, high-pressure arterial blood shunts directly into the venous outflow system. These high-flow, low-resistance shunts are composed of dilated, tortuous, and fragile vessels, which are prone to rupture. BAVMs are a leading cause of hemorrhagic stroke in children and young adults. Current treatments for bAVMs are limited to surgery, embolization, and radiosurgery, although even these options are not viable for similar to 20% of AVM patients due to excessive risk. Critically, inflammation has been suggested to contribute to lesion progression. Here we summarize the current literature discussing the role of the immune system in bAVM pathogenesis and lesion progression, as well as the potential for targeting inflammation to prevent bAVM rupture and intracranial hemorrhage. We conclude by proposing that a dysfunctional endothelium, which harbors the somatic mutations that have been shown to give rise to sporadic bAVMs, may drive disease development and progression by altering the immune status of the brain.

Automated summary

This paper discusses the role of the immune system in the development and progression of brain arteriovenous malformations (bAVMs) and the potential for targeting inflammation to prevent bAVM rupture and intracranial hemorrhage. Inflammation has been suggested as a contributor to lesion progression, and a dysfunctional endothelium may drive disease development and progression by altering the immune status of the brain.