Effects of Extracranial–Intracranial Bypass for Patients With Hemorrhagic Moyamoya Disease

See related article, p 1245. Moyamoya disease is a unique cerebrovascular disease characterized by progressive occlusion of the bilateral internal carotid arteries at their terminal portions and unusual secondarily formed vascular networks (moyamoya vessels) that act as collateral pathways. Unlike pediatric patients, who usually present with transient ischemic attacks (TIAs) or cerebral infarction, about one half of adult patients have intracranial hemorrhage that seriously affects their prognosis. Long-term hemodynamic stress to the collateral vessels is thought to induce vascular pathologies leading to hemorrhage. Although the rate of recurrent bleeding is known to be extremely high, no therapeutic method of preventing rebleeding attacks has yet been established. Extracranial–intracranial bypass surgery is often used for ischemic moyamoya disease, and angiographic diminishment of moyamoya vessels can be observed after surgery, which is regarded as decreased hemodynamic stress to these vessels. A hypothesis has therefore emerged that bypass surgery can also reduce this stress, even in hemorrhagic moyamoya disease, and prevent rebleeding attacks. In fact, many cases of bypass surgery for hemorrhagic moyamoya disease have been reported, but all are retrospective studies and the benefit of bypass surgery has not yet been scientifically clarified. To resolve this, the Japan Adult Moyamoya (JAM) Trial was Background and Purpose—About one half of those who develop adult-onset moyamoya disease experience intracranial hemorrhage. Despite the extremely high frequency of rebleeding attacks and poor prognosis, measures to prevent rebleeding have not been established. The purpose of this study is to determine whether extracranial–intracranial bypass can reduce incidence of rebleeding and improve patient prognosis. Methods—This study was a multicentered, prospective, randomized, controlled trial conducted by 22 institutes in Japan. Adult patients with moyamoya disease who had experienced intracranial hemorrhage within the preceding year were given either conservative care or bilateral extracranial–intracranial direct bypass and were observed for 5 years. Primary and secondary end points were defined as all adverse events and rebleeding attacks, respectively. Results—Eighty patients were enrolled (surgical, 42; nonsurgical, 38). Adverse events causing significant morbidity were observed in 6 patients in the surgical group (14.3%) and 13 patients in the nonsurgical group (34.2%). Kaplan–Meier survival analysis revealed significant differences between the 2 groups (3.2%/y versus 8.2%/y; P=0.048). The hazard ratio of the surgical group calculated by Cox regression analysis was 0.391 (95% confidence interval, 0.148–1.029). Rebleeding attacks were observed in 5 patients in the surgical group (11.9%) and 12 in the nonsurgical group (31.6%), significantly different in the Kaplan–Meier survival analysis (2.7%/y versus 7.6%/y; P=0.042). The hazard ratio of the surgical group was 0.355 (95% confidence interval, 0.125–1.009). Conclusions—Although statistically marginal, Kaplan–Meier analysis revealed the significant difference between surgical and nonsurgical group, suggesting the preventive effect of direct bypass against rebleeding. Clinical Trial Registration—URL: http://www.umin.ac.jp/ctr/index.htm. Unique identifier: C000000166. (Stroke. 2014;45:1415-1421.)