• Menno R Germans, Wenhua Sun, Martina Sebök, Annika Keller, and Luca Regli.
• Department of Neurosurgery, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland. Electronic address: Menno.Germans@usz.ch.
• World Neurosurg. 2022 Jan 1; 157: 143-151.

BackgroundThe mechanisms of brain arteriovenous malformation (bAVM) development, formation, and progress are still poorly understood. By gaining more knowledge about the molecular signature of bAVM in relation to hemorrhage, we might be able to find biomarkers associated with this serious complication, which can function as a goal for further research and can be a potential target for gene therapy.AimsTo provide a comprehensive overview of the molecular signature of bAVM-related hemorrhage We conducted a systematic review, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, of articles published in Embase, Medline, Cochrane central, Scopus, and Chinese databases (CNKI, Wanfang).Summary Of ReviewOur search identified 3944 articles, of which 3108 remained after removal of duplicates. After title, abstract, and full-text screening, 31 articles were included for analysis. The results show an overview of molecular characteristics. Several genetic polymorphisms are identified that increase the risk of bAVM rupture by increasing the expression of certain inflammatory cytokines (interleukin [IL]-6, IL-17A, IL-1β, and tumor necrosis factor-α), NOTCH pathways, matrix metalloproteinase-9, and vascular endothelial growth factor-α.ConclusionsSeveral molecular factors are associated with the risk of bAVM-related hemorrhage. These factors are associated with increased inflammation on the cellular level and changes in the endothelium leading to instability of the vessel wall. Further investigation of these biomarkers regarding hemorrhage rates, together with their relationship with noninvasive diagnostic methods, should be a goal of future studies to improve the patient specific risk estimation and future treatment options.Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

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