**2.1 The role of antithrombotic therapy in Moyamoya disease**

Antithrombotic therapy consists of antiplatelet, anticoagulant, and thrombolytic agents. The rationale of antithrombotic is to prevent thrombogenesis [7]. It is not very confident that the ischemic event in Moyamoya disease is associated with thrombogenesis. The disease's pathogenesis lacks cerebral blood flow due to progressive stenosis of corresponding arteries rather than thrombo-embolism causes brain ischemia in Moyamoya patients. The role of antithrombotic therapy for ischemic prevention in Moyamoya disease is also not absolute.

However, hemodynamic failure may not be the only mechanism responsible for cerebral ischemia in Moyamoya disease. Larson et al. demonstrated that Moyamoya patients are predisposed to a pro-thrombotic state [8]. Shulman et al. reported evidence of artery-to-artery emboli in two separate Moyamoya cases. In the first patient, the emboli were visualized distally from the stenotic artery during bypass surgery. In the second case, the authors detected the emboli as a high-intensity transient signal (HITS) by transcranial Doppler (TCD) [9]. Jeon et al. reported the correlation between the emboli detected as HITS by TCD and the recent cerebral infarct [10]. The results of these two studies imply that hemodynamic compromise might not be the only mechanism for cerebral ischemia in Moyamoya patients. The evidence of artery-to-artery emboli opens up the role of antithrombotic therapy in Moyamoya disease. However, no clinical trial supports the use of antithrombotic drugs in Moyamoya disease.

Although there is no evidence to support clinical benefit, physicians still prescribe an antiplatelet agent as cerebral ischemic prevention in Moyamoya patients with symptomatic ischemic events or transient ischemic attacks (TIAs) [11, 12]. The single antiplatelet regimen with Aspirin is the most popular among the physicians. Most physicians prefer no antithrombotic treatment in asymptomatic Moyamoya patients [11]. Surgeons usually prescribe an antiplatelet agent after revascularization surgery [5, 11, 13–15]. After the surgery, antiplatelet treatment benefits include improving circulation to preserve cerebral perfusion, preventing small thrombus, and maintaining blood flow through surgical bypass [11, 14–16]. Aspirin remains the most popular antiplatelet agent prescribed by surgeons after surgery [15, 17]. Onozuka et al. reported that nearly 2,000 patients from Japan with non-hemorrhagic Moyamoya disease who received antiplatelet therapy before admission had better functional status than those who did not [18].

Other antiplatelet agents, such as Clopidogrel and Cilostazol, are also useful for ischemic prevention in Moyamoya disease [11]. Japanese and Korean physicians have the most experienced using Cilostazol in Moyamoya patients [19, 20]. Seo et al.'s upcoming report showed that nearly 10,000 patients from Korea who were
