In a large cohort of hemorrhagic moyamoya disease patients, anterior choroidal artery dilation, female sex, and bilateral lesions were associated with poor natural history outcomes, while EDAS treatment was associated with reduced rebleeding (HR 0.49) and improved outcomes compared to conservative management.
Key Findings
Results
Hemorrhagic moyamoya disease predominantly affects adults with a mean age at first bleeding of 37.0 years, with a slight female predominance.
The study enrolled 1,050 patients with hMMD admitted to Chinese PLA General Hospital from April 2002 to March 2022.
Mean age at first bleeding was 37.0 ± 12.3 years.
577 patients (55.0%) were female.
123 patients were in the natural history group and 927 in the EDAS treatment group.
The natural history group had a significantly older mean age compared to the EDAS group (43.7 ± 12.1 vs 36.1 ± 12.1 years, p < 0.001).
Results
Anterior choroidal artery (AChA) dilation was independently associated with rebleeding in the natural history of hemorrhagic moyamoya disease.
AChA dilation was identified using Cox regression modeling in the natural history group.
Hazard ratio for rebleeding with AChA dilation: HR 8.64, 95% CI 3.03–24.67, p < 0.001.
This was the primary radiologic risk factor identified for rebleeding in natural course patients.
Results
Female sex, AChA dilation, and bilateral lesions were each independently associated with poor outcomes in patients with hemorrhagic moyamoya disease following natural history.
Female sex: OR 3.93, 95% CI 1.27–12.13, p = 0.017.
AChA dilation: OR 3.41, 95% CI 1.32–8.82, p = 0.012.
Bilateral lesions: OR 5.45, 95% CI 1.45–20.52, p = 0.012.
Risk factors were identified using logistic regression models in the natural history group.
Results
EDAS treatment was associated with a significantly lower incidence of rebleeding compared to conservative management after overlap weighting.
Overlap weighting was used to balance the EDAS and conservative groups before comparison.
Weighted Cox regression showed: HR 0.49, 95% CI 0.30–0.81, p = 0.006 for rebleeding.
This represents approximately a 51% relative reduction in rebleeding hazard with EDAS.
927 patients were in the EDAS group versus 123 in the conservative/natural history group.
Results
EDAS treatment was associated with improved clinical outcomes compared to conservative management after overlap weighting.
Weighted logistic regression showed: OR 0.85, 95% CI 0.79–0.93, p < 0.001 for poor outcomes.
Overlap weighting methodology was employed to balance baseline characteristics between the two treatment groups prior to outcome comparison.
Authors note the retrospective design as a limitation and call for prospective validation.
Results
The proportion of female patients was similar between the natural history and EDAS groups, suggesting sex did not drive treatment allocation.
Female proportion: 55.7% in the natural history group vs 49.6% in the EDAS group, p = 0.204.
Age differed significantly between groups (43.7 ± 12.1 vs 36.1 ± 12.1 years, p < 0.001), indicating older patients were more likely to receive conservative management.
Overlap weighting was applied to address these baseline differences.
What This Means
Moyamoya disease is a rare brain condition where the main arteries supplying blood to the brain become progressively narrowed, causing the body to grow fragile substitute blood vessels. In some patients, these substitute vessels rupture and cause bleeding in the brain — a condition called hemorrhagic moyamoya disease (hMMD). This large study followed 1,050 such patients over two decades at a major Chinese hospital to understand what happens to these patients over time and whether a surgical procedure called EDAS (encephaloduroarteriosynangiosis), which promotes new blood vessel growth on the brain's surface, can help.
This research suggests that without treatment, patients with hMMD face meaningful risks of rebleeding and disability. Specific features identified as red flags include enlargement of a blood vessel called the anterior choroidal artery, being female, and having the disease affect both sides of the brain — all of which were linked to worse outcomes. When comparing patients who underwent EDAS surgery to those managed conservatively (after using statistical methods to make the two groups more comparable), EDAS was associated with roughly half the risk of rebleeding and meaningfully better overall outcomes.
These findings matter because hMMD is a serious and potentially life-threatening condition that mainly strikes working-age adults, with an average age at first bleeding of 37 years. The study is the largest of its kind and provides clinicians with clearer information about which patients are at highest risk and suggests that EDAS surgery may be a beneficial treatment option. However, because this was a retrospective study — meaning it looked back at existing records rather than randomly assigning patients to treatments — the authors emphasize that prospective clinical trials are needed to confirm these findings before definitive treatment recommendations can be made.
Chen C, Gao G, Wang H, Zhang Q, Fu H, Zou Z, et al.. (2026). Natural Course and Clinical Outcomes of Patients With Hemorrhagic Moyamoya Disease: A Large Cohort Study.. Neurology. https://doi.org/10.1212/WNL.0000000000218493