In contrast, and a retrospective mul- reported no difference between direct and indirect modalities. 2. Although traditionally thought to result from poor perfusion, there is some evidence that many instances of ischemia in moyamoya disease actu- ally result from thromboembolic phenomenon.406 In a propensity score matched analysis, Onozuka found that prehospital antiplatelet use was significantly associated with good functional sta- tus on hospital admission for patients with non- hemorrhagic moyamoya disease in Japan. Several meta-analyses and case series have compared antiplatelet therapy with surgical bypass or obser- vation alone with mixed results.393,397 399 Although some found a benefit or no difference with anti- others found surgery to However, many studies include patients with both ischemic and hemorrhagic CLINICAL STATEMENTS AND GUIDELINES Kleindorfer moyamoya disease, and conclusions are often based on subgroup analyses. Antiplatelet therapy may also be of benefit in conjunction with surgi- An international survey of perceived experts in the treatment of moyamoya disease reported that the majority of non-Asian respondents recommended antiplatelet therapy, in contrast to their Asian counterparts, perhaps reflecting a difference in the typical pattern of dis- ease seen in the 2 geographic regions.407 Knowledge Gaps and Future Research Significant knowledge gaps exist in our understand- ing of moyamoya disease. No prospective RCT exists comparing medical management with surgical interven- tion for either the primary or secondary prevention of ischemic events in patients with moyamoya disease. Similarly, there are no prospective RCTs comparing the efficacy of the most common surgical revascular- ization procedures used for the prevention of ischemic events in this patient population. Numerous obstacles to the performance of such trials exist, including a lack of equipoise among many treating neurologists and neurosurgeons, particularly for symptomatic patients. Consideration should therefore also be given to com- prehensive, adjudicated long-term registries as an alternative means of investigation. 