Risk of first intracranial hemorrhage risk in unruptured brain AVMs lower than anticipated: JAMA
A recent study published in the Journal of the American Medical Association found that the risk of a first intracranial hemorrhage (ICH) from unruptured brain arteriovenous malformations (AVMs) is significantly lower than traditionally believed. The Multicenter Arteriovenous Malformation Research Study (MARS) from 2017 to 2023 across 9 major international cohorts, reports an annual hemorrhage rate of just 1.4%, challenging the widely cited 2–4% figure used in clinical settings for decades.
AVMs are often detected incidentally or following neurological symptoms such as seizures. While rupture can lead to life-threatening bleeding, treatment decisions have long been hampered by uncertainty over the natural risk of bleeding in unruptured cases.
The MARS project combined data from 2 population-based and 7 referral-based cohorts, making it one of the largest analyses of its kind. The study included a total of the 3,030 participants with unruptured brain AVMs (median age 38 years; 50.3% female). Nearly half of the patients (45%) presented with seizures at diagnosis, and the median AVM size was about 3.1 cm.
Detailed angiographic assessments revealed that 10% of AVMs had exclusively deep venous drainage, 11% were located in cerebellar or supratentorial deep regions, and 19% had associated arterial aneurysms that can increase bleeding risk.
During the follow-up period totaling 11,339 person-years, 159 first hemorrhages were recorded, which resulted in the revised ICH rate of 1.4 per 100 person-years (95% CI, 1.20–1.64). This research then identified several key independent risk factors that increase the risk of a first hemorrhage.
Age emerged as a significant variable, with patients over 60 years old showing a more than 2-fold higher risk (hazard ratio [HR], 2.01) when compared to those younger than 20. Middle-aged groups (40–59 years) had a moderate risk increase (HR, 1.23), while those aged 20–39 showed slightly reduced risk when compared to the youngest patients.
The presence of associated arterial aneurysms raised the bleeding risk by 66% (HR, 1.66), while AVMs located in deep or cerebellar brain regions nearly doubled the risk (HR, 1.87) relative to more superficial sites. Overall, this study highlights the importance of personalized management strategies which balances the modest annual bleeding risk against the potential complications of surgical or endovascular interventions.
Reference:
Kim, H., Nelson, J., McCulloch, C. E., Hess, C., Hetts, S. W., Flemming, K., Lanzino, G. S., 2nd, Koroknay-Pál, P., Oulasvirta, E., Laakso, A., Lawton, M. T., Mohr, J. P., Morgan, M. K., Moayeri, N., Zaroff, J. G., Stefani, M. A., Chen, X., Zhao, Y., & Al-Shahi Salman, R. (2025). Risk of future hemorrhage from unruptured brain arteriovenous malformations: The Multicenter Arteriovenous Malformation Research Study (MARS): The multicenter arteriovenous malformation research study (MARS). JAMA Neurology. https://doi.org/10.1001/jamaneurol.2025.3581
