Risk of intracranial hemorrhage in brain arteriovenous malformations: a systematic review and meta-analysis

Abstract

Background and objective: Brain arteriovenous malformations (bAVMs) carry a risk of hemorrhage. We aim to identify factors associated with subsequent hemorrhages.

Methods: Systematic searches were conducted across the ScienceDirect, Medline, and Cochrane databases. Assessed risk factors included bAVM size, bAVM volume, hemorrhage and seizure presentations, presence of deep venous drainage, deep-seated bAVMs, associated aneurysms, and Spetzler-Martin grade. Subgroup analyses were conducted on prior treatments, hemorrhage presentation, AVM size, and type of management.

Results: The meta-analysis included 8 cohort studies and 2 trials, with 4,240 participants. Initial hemorrhage presentation (HR 2.41; 95% CI 1.94-2.98; p < 0.001), any deep venous drainage (HR 1.52; 95% CI 1.09-2.13; p = 0.01), and associated aneurysms (HR 1.78; 95% CI 1.41-2.23; p < 0.001) increased secondary hemorrhage risk. Conversely, higher Spetzler-Martin grades (HR 0.77; 95% CI 0.68-0.87; p < 0.001) and larger malformation volumes (HR 0.87; 95% CI 0.76-0.99; p = 0.04) reduced risk. Subgroups showed any deep venous drainage in patients without prior treatment (HR 1.64; 95% CI 1.25-2.15; p < 0.001), bAVM > 3 cm (HR 1.79; 95% CI 1.15-2.78; p = 0.01), and multimodal interventions (HR 1.69; 95% CI 1.12-2.53; p = 0.01) increased risk. The reverse effect was found for patients initially presented without hemorrhage (HR 0.79; 95% CI 0.67-0.93; p = 0.01). Deep bAVM was a risk factor in > 3 cm cases (HR 2.72; 95% CI 1.61-4.59; p < 0.001) and multimodal management (HR 2.77; 95% CI 1.66-4.56; p < 0.001). Kaplan-Meier analysis revealed increased hemorrhage risk for initial hemorrhage presentation, while cumulative survival was higher in intervened patients over 72 months.

Conclusion: Significant risk factors for bAVMs hemorrhage include initial hemorrhage, any deep venous drainage, and associated aneurysms. Deep venous drainage involvement is a risk factor in cases without prior treatment, those with bAVM > 3 cm, and cases managed with multimodal interventions. Deep bAVM involvement also emerges as a risk factor in cases > 3 cm and those managed with multimodal approaches.

Keywords: Arteriovenous malformation; Hemorrhage; Secondary intracranial hemorrhage; Unruptured brain arteriovenous malformation.