Moyamoya disease (MMD) is a rare cerebro-occlusive disease with unknown etiology that can cause both ischemic and hemorrhagic stroke. MMD is characterized by progressive stenosis of the terminal internal carotid artery (ICA) and development of basal brain collaterals. Early-stage MMD is known to cause hemodynamic insufficiency despite mild or moderate stenosis of the intracranial arteries, but the exact mechanism underlying this pathophysiological condition is undetermined. We used highresolution Large eddy Simulations to investigate multiple complex hemodynamic phenomena that led to cerebral ischemia in five patients with early-stage MMD. The effects of transitional flow, coherent flow structures and blood shear-thinning properties through regions of tortuous and stenosed arteries were explored and linked to symptomatology. It is evidently shown that in some cases complex vortex structures, such as Rankine-type vortices, redirects blood flow away from some arteries causing significant reduction in blood flow. Moreover, partial blood hammer (PBH) phenomenon was detected in some cases and led to significant hemodynamic insufficiency. PBH events were attributed to the interaction between shear-thinning properties, transitional flow structures and loss of upstream pressure-velocity phase lag. We clearly show that the hemodynamic complexities in early-stage MMD could induce ischemia and explain the non-responsiveness to antiplatelet therapy.Moyamoya disease (MMD) is a rare cerebrovascular disease, characterized by bilateral occlusive changes at the internal carotid artery (ICA) terminus and an abnormal collaterals development at the base of the brain 1 . MMD is more prevalent in East Asian populations and can present as either ischemic or hemorrhagic stroke 2 . MMD can occur in pediatric or adult populations 2-4 and can present as bilateral or unilateral disease involvement 5 . The basic pathology of MMD, including its temporal profile, is clearly indicated by Suzuki's angiographic staging 1 , demonstrating the pathologic conversion of the cerebral vascular supply from internal carotid (IC) to the external carotid (EC) system 6 . Insufficiency of this 'IC-EC conversion system' could result in either ischemic or hemorrhage MMD presentations.Recent advance in high resolution magnetic resonance (HR-MR) vascular wall imaging enabled us to diagnose MMD even in its early stage, by demonstrating the characteristic vascular wall structure such as outer-diameter narrowing and the concentric stenosis of the affected intracranial arteries 7-9 . All of these characteristic findings by HR-MR vascular wall imaging are precisely reflected by vascular wall pathology of MMD including medial layer thinning and the waving of internal elastic lamina 10,11 . Accurate diagnosis of the early-stage MMD is clinically important because it could manifest as transient ischemic attacks (TIA) and/or cerebral infarction due to the significant hemodynamic compromise, despite its mild or moderate stenosis. Nonetheless, the mechanism