title: Untreated brain arteriovenous malformation: patient-level meta-analysis of hemorrhage predictors.
abstract: OBJECTIVE
  To identify risk factors for intracranial hemorrhage in the natural history course of brain arteriovenous malformations (AVMs) using individual patient data meta-analysis of 4 existing cohorts.
  
  
  METHODS
  We harmonized data from Kaiser Permanente of Northern California (n = 856), University of California San Francisco (n = 787), Columbia University (n = 672), and the Scottish Intracranial Vascular Malformation Study (n = 210). We censored patients at first treatment, death, last visit, or 10-year follow-up, and performed stratified Cox regression analysis of time-to-hemorrhage after evaluating hemorrhagic presentation, sex, age at diagnosis, deep venous drainage, and AVM size as predictors. Multiple imputation was performed to assess impact of missing data.
  
  
  RESULTS
  A total of 141 hemorrhage events occurred during 6,074 patient-years of follow-up (annual rate of 2.3%, 95% confidence interval [CI] 2.0%-2.7%), higher for ruptured (4.8%, 3.9%-5.9%) than unruptured (1.3%, 1.0%-1.7%) AVMs at presentation. Hemorrhagic presentation (hazard ratio 3.86, 95% CI 2.42-6.14) and increasing age (1.34 per decade, 1.17-1.53) independently predicted hemorrhage and remained significant predictors in the imputed dataset. Female sex (1.49, 95% CI 0.96-2.30) and exclusively deep venous drainage (1.60, 0.95-2.68, p = 0.02 in imputed dataset) may be additional predictors. AVM size was not associated with intracerebral hemorrhage in multivariable models (p > 0.5).
  
  
  CONCLUSIONS
  This large, individual patient data meta-analysis identified hemorrhagic presentation and increasing age as independent predictors of hemorrhage during follow-up. Additional AVM cohort data may further improve precision of estimates, identify new risk factors, and allow validation of prediction models.
authors.affiliation: From the Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care (H.K., W.L.Y.), and Departments of Epidemiology and Biostatistics (H.K., C.E.M.), Neurological Surgery (W.L.Y.), and Neurology (W.L.Y.), University of California, San Francisco; Division of Clinical Neurosciences (R.A.-S.S.), Centre for Clinical Brain Sciences, University of Edinburgh, UK; and Neurovasc-Paris Sorbonne (C.S.), Univ Paris Diderot-Sorbonne Paris Cité, and Department of Neurology, APHP-Hôpital Lariboisière, Paris, France. kimhel@anesthesia.ucsf.edu.
authors.forename: Helen
authors.initials: H
authors.lastname: Kim
authors.affiliation: From the Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care (H.K., W.L.Y.), and Departments of Epidemiology and Biostatistics (H.K., C.E.M.), Neurological Surgery (W.L.Y.), and Neurology (W.L.Y.), University of California, San Francisco; Division of Clinical Neurosciences (R.A.-S.S.), Centre for Clinical Brain Sciences, University of Edinburgh, UK; and Neurovasc-Paris Sorbonne (C.S.), Univ Paris Diderot-Sorbonne Paris Cité, and Department of Neurology, APHP-Hôpital Lariboisière, Paris, France.
authors.forename: Rustam
authors.initials: R
authors.lastname: Al-Shahi Salman
authors.affiliation: From the Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care (H.K., W.L.Y.), and Departments of Epidemiology and Biostatistics (H.K., C.E.M.), Neurological Surgery (W.L.Y.), and Neurology (W.L.Y.), University of California, San Francisco; Division of Clinical Neurosciences (R.A.-S.S.), Centre for Clinical Brain Sciences, University of Edinburgh, UK; and Neurovasc-Paris Sorbonne (C.S.), Univ Paris Diderot-Sorbonne Paris Cité, and Department of Neurology, APHP-Hôpital Lariboisière, Paris, France.
authors.forename: Charles E
authors.initials: CE
authors.lastname: McCulloch
authors.affiliation: From the Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care (H.K., W.L.Y.), and Departments of Epidemiology and Biostatistics (H.K., C.E.M.), Neurological Surgery (W.L.Y.), and Neurology (W.L.Y.), University of California, San Francisco; Division of Clinical Neurosciences (R.A.-S.S.), Centre for Clinical Brain Sciences, University of Edinburgh, UK; and Neurovasc-Paris Sorbonne (C.S.), Univ Paris Diderot-Sorbonne Paris Cité, and Department of Neurology, APHP-Hôpital Lariboisière, Paris, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Stapf
authors.affiliation: From the Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care (H.K., W.L.Y.), and Departments of Epidemiology and Biostatistics (H.K., C.E.M.), Neurological Surgery (W.L.Y.), and Neurology (W.L.Y.), University of California, San Francisco; Division of Clinical Neurosciences (R.A.-S.S.), Centre for Clinical Brain Sciences, University of Edinburgh, UK; and Neurovasc-Paris Sorbonne (C.S.), Univ Paris Diderot-Sorbonne Paris Cité, and Department of Neurology, APHP-Hôpital Lariboisière, Paris, France.
authors.forename: William L
authors.initials: WL
authors.lastname: Young
mesh_terms: D000328:Adult; D000367:Age Factors; D002543:Cerebral Hemorrhage / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology*; D002560:Cerebrovascular Circulation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D002538:Intracranial Arteriovenous Malformations / Q000150:complications* / Q000453:epidemiology* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D012044:Regression Analysis; D012307:Risk Factors; D012737:Sex Factors; D016019:Survival Analysis; D013997:Time Factors