Comparative Effectiveness Of Treatment Modalities For Unruptured Brain Arteriovenous Malformations: A Systematic Review And Meta-Analysis Of 6,124 Patients

Background The optimal management of unruptured brain arteriovenous malformations (AVMs) remains controversial, with conflicting evidence regarding conservative versus interventional approaches, especially in the light of the ARUBA trials. This meta-analysis aims to provide comprehensive, grade-specific outcomes across treatment modalities to guide clinical decision-making. Methods We conducted a PRISMA-compliant meta-analysis of 16 studies (n = 6,124 patients) comparing conservative management, microsurgery, stereotactic radiosurgery (SRS), embolization, and hybrid therapy. Databases searched included MEDLINE (PubMed), Embase (Ovid), Cochrane Central Register, and Web of Science (2000–2025). Risk of bias was assessed using the Cochrane Risk of Bias Tool 2.0 for RCTs and Newcastle-Ottawa Scale for cohort studies. Data were synthesized using random-effects models (DerSimonian-Laird method), with heterogeneity quantified via the I² statistic. Primary outcomes were hemorrhage risk and obliteration rates; secondary outcomes included functional status (mRS ≥ 2), new-onset seizures, and mortality. Results Microsurgery achieved the highest obliteration rates (99% for Spetzler-Martin [SM] I-II, 86% for SM III) and lowest hemorrhage risk (0.6%/yr for SM I-II, 1.3%/yr for SM III), with superior functional outcomes (8% disability [95% CI 5–11%] vs. 11% for conservative management; p = 0.04). SRS showed moderate efficacy (76% obliteration for SM I-II, 47% for SM III-IV) with higher latency-period hemorrhage risk (1.1–2.1%/yr) and disability rates comparable to conservative management (13% [95% CI 10–16%]; p = 0.18). New-onset seizures occurred in 9.1% of microsurgery and 4.9% of SRS cases. Mortality was low across treatments (1–2%), with conservative management at 1.1% and SRS at 1.6%. Conservative management had a 1.9–2.6%/yr hemorrhage risk without procedural morbidity. Conclusions Microsurgery is preferred for operable SM I-II AVMs due to superior obliteration, hemorrhage protection, and functional outcomes, despite higher seizure risk. SRS is suitable for inoperable cases, while conservative management remains reasonable for high-grade AVMs unless high-risk features exist.