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BACKGROUND AND OBJECTIVES: The literature about the role of serum homocysteine (Hcy) in intracranial aneurysms (IAs) is controversial, and its association with aneurysm topography remains unexplored. We evaluated the impact of Hcy levels on IA rupture and location. METHODS: A dual approach was performed: an institutional cross-sectional review and a PRISMA-compliant meta-analysis (PROSPERO ID: CRD420261325415). The cross-sectional analysis included 342 patients with confirmed IA rupture status, analyzed using non-parametric tests (Mann-Whitney U). To prevent topographical overlap bias, spatial analysis and multivariable logistic regression were restricted to a pure single-aneurysm cohort (N = 205), utilizing the Kruskal-Wallis test. The meta-analysis pooled data using a random-effects model with a leave-one-out sensitivity analysis. RESULTS: Our institutional data (N = 342) showed no significant difference in median Hcy levels between unruptured and ruptured IAs (11.4 IQR: 5.84 vs. 10.7 IQR: 4.68 µmol/L; p = 0.414). Our meta-analysis of 1,457 patients confirmed this lack of association (SMD = 0.30, 95% CI: -0.12 to 0.71, p = 0.158). However, institutional data revealed significant variance in median Hcy across aneurysm topographies (p = 0.011). Multivariable regression demonstrated that elevated Hcy is independently associated with posterior circulation aneurysms (OR = 1.14, 95% CI: 1.03-1.27, p = 0.011), remaining robust after adjusting for aneurysm morphology (p = 0.006). CONCLUSION: Our findings suggestthat serum Hcy does not impact IA rupture risk. However, elevated Hcy is independently associated with posterior circulation IAs. These hypothesis-generating findings suggest a location-specific pathophysiological role for Hcy, warranting prospective multicenter replication.
Júnior et al. (Mon,) studied this question.