title: Significance of the Hemorrhagic Site for Recurrent Bleeding: Prespecified Analysis in the Japan Adult Moyamoya Trial.
abstract: OBJECTIVE
  The primary results of the Japan Adult Moyamoya Trial revealed the statistically marginal superiority of bypass surgery over medical treatment alone in preventing rebleeding in moyamoya disease. The purpose of this analysis is to test the prespecified subgroup hypothesis that the natural course and surgical effects vary depending on the hemorrhagic site at onset.
  
  
  METHODS
  The hemorrhagic site, classified as either anterior or posterior, was the only stratifying variable for randomization. Statistical analyses were focused on the assessment of effect modification according to the hemorrhagic site and were based on tests of interaction.
  
  
  RESULTS
  Of 42 surgically treated patients, 24 were classified as anterior hemorrhage and 18 as posterior hemorrhage; of 38 medically treated patients, 21 were classified as anterior and 17 as posterior. The hazard ratio of the primary end points (all adverse events) for the surgical group relative to the nonsurgical group was 0.07 (95% confidence interval, 0.01-0.55) for the posterior group, as compared with 1.62 (95% confidence interval, 0.39-6.79) for the anterior group (P=0.013 for interaction). Analysis within the nonsurgical group revealed that the incidence of the primary end point was significantly higher in the posterior group than in the anterior group (17.1% per year versus 3.0% per year; hazard ratio, 5.83; 95% confidence interval, 1.60-21.27).
  
  
  CONCLUSIONS
  Careful interpretation of the results suggests that patients with posterior hemorrhage are at higher risk of rebleeding and accrue greater benefit from surgery, subject to verification in further studies.
  
  
  BACKGROUND
  URL: http://www.umin.ac.jp/ctr/index.htm. Unique identifier: C000000166.
authors.affiliation: From the Department of Neurosurgery (J.C.T.) and Integrative Stroke Imaging Center (J.N.), National Cerebral and Cardiovascular Center, Suita, Japan; Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan (T.F., K.Y., S.M.); Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan (K.H.); Department of Neurosurgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan (T.I.); Department of Neurosurgery, Iwate Medical University, Morioka, Japan (K.O.); and Department of Neurosurgery, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan (S.K.).
authors.forename: Jun C
authors.initials: JC
authors.lastname: Takahashi
authors.affiliation: From the Department of Neurosurgery (J.C.T.) and Integrative Stroke Imaging Center (J.N.), National Cerebral and Cardiovascular Center, Suita, Japan; Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan (T.F., K.Y., S.M.); Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan (K.H.); Department of Neurosurgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan (T.I.); Department of Neurosurgery, Iwate Medical University, Morioka, Japan (K.O.); and Department of Neurosurgery, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan (S.K.).
authors.forename: Takeshi
authors.initials: T
authors.lastname: Funaki
authors.affiliation: From the Department of Neurosurgery (J.C.T.) and Integrative Stroke Imaging Center (J.N.), National Cerebral and Cardiovascular Center, Suita, Japan; Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan (T.F., K.Y., S.M.); Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan (K.H.); Department of Neurosurgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan (T.I.); Department of Neurosurgery, Iwate Medical University, Morioka, Japan (K.O.); and Department of Neurosurgery, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan (S.K.).
authors.forename: Kiyohiro
authors.initials: K
authors.lastname: Houkin
authors.affiliation: From the Department of Neurosurgery (J.C.T.) and Integrative Stroke Imaging Center (J.N.), National Cerebral and Cardiovascular Center, Suita, Japan; Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan (T.F., K.Y., S.M.); Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan (K.H.); Department of Neurosurgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan (T.I.); Department of Neurosurgery, Iwate Medical University, Morioka, Japan (K.O.); and Department of Neurosurgery, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan (S.K.).
authors.forename: Tooru
authors.initials: T
authors.lastname: Inoue
authors.affiliation: From the Department of Neurosurgery (J.C.T.) and Integrative Stroke Imaging Center (J.N.), National Cerebral and Cardiovascular Center, Suita, Japan; Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan (T.F., K.Y., S.M.); Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan (K.H.); Department of Neurosurgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan (T.I.); Department of Neurosurgery, Iwate Medical University, Morioka, Japan (K.O.); and Department of Neurosurgery, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan (S.K.).
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Ogasawara
authors.affiliation: From the Department of Neurosurgery (J.C.T.) and Integrative Stroke Imaging Center (J.N.), National Cerebral and Cardiovascular Center, Suita, Japan; Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan (T.F., K.Y., S.M.); Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan (K.H.); Department of Neurosurgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan (T.I.); Department of Neurosurgery, Iwate Medical University, Morioka, Japan (K.O.); and Department of Neurosurgery, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan (S.K.).
authors.forename: Jyoji
authors.initials: J
authors.lastname: Nakagawara
authors.affiliation: From the Department of Neurosurgery (J.C.T.) and Integrative Stroke Imaging Center (J.N.), National Cerebral and Cardiovascular Center, Suita, Japan; Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan (T.F., K.Y., S.M.); Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan (K.H.); Department of Neurosurgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan (T.I.); Department of Neurosurgery, Iwate Medical University, Morioka, Japan (K.O.); and Department of Neurosurgery, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan (S.K.).
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kuroda
authors.affiliation: From the Department of Neurosurgery (J.C.T.) and Integrative Stroke Imaging Center (J.N.), National Cerebral and Cardiovascular Center, Suita, Japan; Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan (T.F., K.Y., S.M.); Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan (K.H.); Department of Neurosurgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan (T.I.); Department of Neurosurgery, Iwate Medical University, Morioka, Japan (K.O.); and Department of Neurosurgery, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan (S.K.).
authors.forename: Keisuke
authors.initials: K
authors.lastname: Yamada
authors.affiliation: From the Department of Neurosurgery (J.C.T.) and Integrative Stroke Imaging Center (J.N.), National Cerebral and Cardiovascular Center, Suita, Japan; Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan (T.F., K.Y., S.M.); Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan (K.H.); Department of Neurosurgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan (T.I.); Department of Neurosurgery, Iwate Medical University, Morioka, Japan (K.O.); and Department of Neurosurgery, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan (S.K.). miy@kuhp.kyoto-u.ac.jp.
authors.forename: Susumu
authors.initials: S
authors.lastname: Miyamoto
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002543:Cerebral Hemorrhage / Q000175:diagnosis* / Q000453:epidemiology*; D005260:Female; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009072:Moyamoya Disease / Q000175:diagnosis* / Q000453:epidemiology*; D012008:Recurrence; D055815:Young Adult
keywords: Japan; cerebral revascularization; confidence intervals; incidence; intracerebral hemorrhage; moyamoya disease