Distinct Clinical Phenotypes in Moyamoya Disease: A Multicenter Comparison of Ischemic and Hemorrhagic Presentations

Moyamoya disease (MMD) is a progressive occlusive arteriopathy marked by stenosis of the major cerebral arteries and the development of fragile basal collaterals. Although ischemic and hemorrhagic phenotypes of MMD are well described, comparative evidence evaluating differences in surgical safety and long-term treatment response between these subgroups remains limited. This study aimed to compare perioperative complications and long-term stroke risk after revascularization surgery in patients with ischemic-type vs hemorrhagic-type MMD.

We conducted a multicenter retrospective cohort study across 13 North American academic centers (2008-2022), including 485 patients with 502 revascularized hemispheres for angiographically confirmed MMD. Hemispheres were stratified by presenting phenotype. Primary outcomes were overall postoperative complications and long-term stroke events. Propensity score matching (2:1) and multivariable logistic regression were used. A sensitivity analysis including only hemispheres with ≥2 years of follow-up was performed.

Of 502 hemispheres, 423 (84%) presented with ischemia and 79 (16%) with hemorrhage. Before and after matching, ischemic-onset MMD demonstrated significantly higher overall postoperative complication rates (post-match: 10% vs 2.6%, P = .043). Stroke patterns at long-term follow-up reflected initial presentation: ischemic-onset hemispheres experienced predominantly ischemic recurrences, whereas hemorrhagic-onset hemispheres showed higher rates of hemorrhagic or mixed-pattern strokes (P < .001). In the sensitivity cohort (≥2-year follow-up; mean 78.5 months), hemorrhagic presentation was independently associated with an 8-fold higher risk of long-term stroke, as compared with ischemic presentation (adjusted odds ratio 8.23; 95% CI 1.84-36.8; P = .006). Stroke risk did not differ significantly between hemorrhage subtypes.

Ischemic and hemorrhagic MMD represent distinct clinical phenotypes with meaningful differences in safety and long-term response to surgical revascularization. Ischemic-type MMD is more prone to postoperative complications, whereas hemorrhagic-type MMD was associated with a substantially elevated long-term stroke risk. These findings underscore the need to consider MMD phenotypes as separate entities when counseling patients, choosing treatment strategies, and initiating long-term surveillance.