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

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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.

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