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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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Data availability

All data relevant to the study are included in the article or uploaded as supplementary information.

Abbreviations

ARUBA:

A Randomized Trial of Unruptured Brain Arteriovenous Malformations

bAVM:

Brain arteriovenous malformation

CI:

Confidence interval

CT:

Computed tomography

HRs:

Hazard ratios

MRI:

Magnetic resonance imaging

NOS:

Newcastle–Ottawa scale

PRISMA:

Preferred Reporting Items for Systematic Reviews and Meta-Analyses

PROSPERO:

International Prospective Register of Systematic Reviews

REML:

Restricted maximum likelihood

RCT:

Randomized controlled trial

SIVMS:

Steering Committee and the Oxford Vascular Study

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Acknowledgements

The authors also acknowledge the contribution of the Department of Neurology, Universitas Udayana for the supports given.

Funding

The authors did not receive any grant or funding for this research from any funding agency in the public, commercial or not-for-profit sectors.

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Authors and Affiliations

  1. Faculty of Medicine, Prof. I.G.N.G Ngoerah General Hospital, Universitas Udayana, Denpasar, Bali, Indonesia

    Bryan Gervais de Liyis, Anak Agung Istri Kosalya Arini & Chrysanta Paramitha Karuniamaya

  2. Department of Neurology, Faculty of Medicine, Prof. I.G.N.G Ngoerah General Hospital, Universitas Udayana, Denpasar, Bali, Indonesia

    Nyoman Angga Krishna Pramana, Kumara Tini & I. Putu Eka Widyadharma

  3. Department of Neurology, Faculty of Medicine, Sardjito General Hospital, Universitas Gadjah Mada, Yogyakarta, Indonesia

    Ismail Setyopranoto

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  1. Bryan Gervais de Liyis
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Contributions

BGdL: acquisition of data, analysis and interpretation of data, wrote the first draft, study supervision. AAIKA: analysis and interpretation of data, wrote the first draft. CPK: wrote the first draft. NAKP: critical revision of manuscript for intellectual content. KT: critical revision of manuscript for intellectual content. IPEW: study concept and design, critical revision of manuscript for intellectual content. ISP: critical revision of manuscript for intellectual content. BGdL is the guarantor.

Corresponding author

Correspondence to I. Putu Eka Widyadharma.

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de Liyis, B.G., Arini, A.A.I.K., Karuniamaya, C.P. et al. Risk of intracranial hemorrhage in brain arteriovenous malformations: a systematic review and meta-analysis. J Neurol 271, 2274–2284 (2024). https://doi.org/10.1007/s00415-024-12235-1

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  • DOI: https://doi.org/10.1007/s00415-024-12235-1

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