Natural Course and Clinical Outcomes of Patients With Hemorrhagic Moyamoya Disease: A Large Cohort Study.

Abstract

Given the natural history of hemorrhagic moyamoya disease (hMMD) is unclear and research on long-term outcomes following indirect revascularization is limited, this study sought to assess its natural course and the efficacy of indirect revascularization. We conducted a retrospective analysis of patients with hMMD admitted to the Chinese PLA General Hospital from April 2002 to March 2022. Clinical characteristics, radiologic findings, rebleeding events, and prognostic outcomes were evaluated. Logistic and Cox regression models identified risk factors for poor outcomes and rebleeding in the natural history. After overlap weighting to balance the encephaloduroarteriosynangiosis (EDAS) and conservative groups, weighted regression models were used to compare outcomes. This study enrolled 1,050 patients with hMMD. The mean age at first bleeding was 37.0 ± 12.3 years, and 577 (55.0%) were female. Among them, 123 were in the natural history group and 927 in the EDAS group. The natural history group had a significantly older mean age (43.7 ± 12.1 vs 36.1 ± 12.1 years, <i>p</i> < 0.001), while the proportion of female patients was similar between the 2 groups (55.7% vs 49.6%, <i>p</i> = 0.204). In the natural history course, anterior choroidal artery (AChA) dilation (hazard ratio [HR] 8.64, 95% CI 3.03-24.67, <i>p</i> < 0.001) was associated with rebleeding. Female sex (OR 3.93, 95% CI 1.27-12.13, <i>p</i> = 0.017), AChA dilation (OR 3.41, 95% CI 1.32-8.82, <i>p</i> = 0.012), and bilateral lesions (OR 5.45, 95% CI 1.45-20.52, <i>p</i> = 0.012) were associated with poor outcomes in patients with hMMD. After overlap weighting, treatment with EDAS was associated with a lower incidence of rebleeding events (HR 0.49, 95% CI 0.30-0.81, <i>p</i> = 0.006) and improved outcomes (OR 0.85, 95% CI 0.79-0.93, <i>p</i> < 0.001). In conclusion, hMMD occurs mainly in adult patients. In the natural history of hMMD, AChA dilation was associated with rebleeding, while female sex, AChA dilation, and bilateral lesions were associated with poor outcomes. This study suggests that EDAS is associated with a reduced incidence of rebleeding and improved outcomes, indicating that EDAS may be an effective treatment for hMMD. However, given the retrospective design, prospective validation is needed.