title: Natural history of cavernous malformation: Systematic review and meta-analysis of 25 studies.
abstract: OBJECTIVE
  We pooled the results of studies on natural history of cavernous malformations (CM) to calculate point estimates and investigate main sources of heterogeneity.
  
  
  METHODS
  We searched MEDLINE, EMBASE, and ISI Web of Science for relevant studies published before May 2015. We used fixed or random effects models and meta-regression to pool the data.
  
  
  RESULTS
  Twenty-five studies were entered into the meta-analysis (90-1,295 patients depending on the analysis). Bleeding was defined as symptomatic hemorrhage plus radiologic evidence of hemorrhage. Sources of heterogeneity were identified as mixture of hemorrhage and rehemorrhage, mixture of rehemorrhage before and after 2 years of first bleeding, brainstem vs other locations, and calculation method. The rehemorrhage rate was higher than the hemorrhage rate (incidence rate ratio 16.5, p < 0.001, 95% confidence interval [CI] 9.7-28.0). Rehemorrhage within 2 years of the first hemorrhage was higher than after that (incidence rate ratio 1.8, p = 0.042, 95% CI 1.5-2.0). In two metaregression models, rough estimate of the annual incidence rate of hemorrhage was 0.3% (95% CI 0.1%-0.5%) and 2.8% (2.5%-3.3%) per person year in nonbrainstem and brainstem lesions and rough estimate of annual rehemorrhage rate per person year was 6.3% (3%-13.2%) and 32.3% (19.8%-52.7%) in nonbrainstem and brainstem lesions. Median time to rehemorrhage was 10.5 months. Posthemorrhage full recovery was 38.8%/person-year (28.7%-48.8%). Posthemorrhage full recovery or minimal disability was 79.5%/person-year (74.3%-84.8%). Mortality after bleeding was 2.2%.
  
  
  CONCLUSIONS
  The incidence of symptomatic hemorrhage or rehemorrhage is higher in brainstem lesions. First symptomatic hemorrhage increases the chance of symptomatic rehemorrhage, which decreases after 2 years.
authors.affiliation: From the Division of Neurosurgery (S.T.), University of Toronto, Canada; Department of Psychiatry (A.M.), Icahn School of Medicine, Mount Sinai Hospital, New York, NY; Department of Neurosurgery (S.A.-H.), University of Illinois at Chicago; Neurosurgical Service (F.G.B.), Massachusetts General Hospital, Harvard Medical School, Boston; Division of Neurosurgery (R.L.M.), St. Michael's Hospital, Labatt Family Centre of Excellence in Brain Injury and Trauma Research, Keenan Research Centre for Biomedical Science; and the Department of Surgery (R.L.M.), Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Canada.
authors.forename: Shervin
authors.initials: S
authors.lastname: Taslimi
authors.affiliation: From the Division of Neurosurgery (S.T.), University of Toronto, Canada; Department of Psychiatry (A.M.), Icahn School of Medicine, Mount Sinai Hospital, New York, NY; Department of Neurosurgery (S.A.-H.), University of Illinois at Chicago; Neurosurgical Service (F.G.B.), Massachusetts General Hospital, Harvard Medical School, Boston; Division of Neurosurgery (R.L.M.), St. Michael's Hospital, Labatt Family Centre of Excellence in Brain Injury and Trauma Research, Keenan Research Centre for Biomedical Science; and the Department of Surgery (R.L.M.), Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Canada.
authors.forename: Amirhossein
authors.initials: A
authors.lastname: Modabbernia
authors.affiliation: From the Division of Neurosurgery (S.T.), University of Toronto, Canada; Department of Psychiatry (A.M.), Icahn School of Medicine, Mount Sinai Hospital, New York, NY; Department of Neurosurgery (S.A.-H.), University of Illinois at Chicago; Neurosurgical Service (F.G.B.), Massachusetts General Hospital, Harvard Medical School, Boston; Division of Neurosurgery (R.L.M.), St. Michael's Hospital, Labatt Family Centre of Excellence in Brain Injury and Trauma Research, Keenan Research Centre for Biomedical Science; and the Department of Surgery (R.L.M.), Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Canada.
authors.forename: Sepideh
authors.initials: S
authors.lastname: Amin-Hanjani
authors.affiliation: From the Division of Neurosurgery (S.T.), University of Toronto, Canada; Department of Psychiatry (A.M.), Icahn School of Medicine, Mount Sinai Hospital, New York, NY; Department of Neurosurgery (S.A.-H.), University of Illinois at Chicago; Neurosurgical Service (F.G.B.), Massachusetts General Hospital, Harvard Medical School, Boston; Division of Neurosurgery (R.L.M.), St. Michael's Hospital, Labatt Family Centre of Excellence in Brain Injury and Trauma Research, Keenan Research Centre for Biomedical Science; and the Department of Surgery (R.L.M.), Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Canada.
authors.forename: Fred G
authors.initials: FG
authors.lastname: Barker
authors.affiliation: From the Division of Neurosurgery (S.T.), University of Toronto, Canada; Department of Psychiatry (A.M.), Icahn School of Medicine, Mount Sinai Hospital, New York, NY; Department of Neurosurgery (S.A.-H.), University of Illinois at Chicago; Neurosurgical Service (F.G.B.), Massachusetts General Hospital, Harvard Medical School, Boston; Division of Neurosurgery (R.L.M.), St. Michael's Hospital, Labatt Family Centre of Excellence in Brain Injury and Trauma Research, Keenan Research Centre for Biomedical Science; and the Department of Surgery (R.L.M.), Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Canada. macdonaldlo@smh.ca.
authors.forename: R Loch
authors.initials: RL
authors.lastname: Macdonald
mesh_terms: D001933:Brain Stem / Q000503:physiopathology; D016543:Central Nervous System Neoplasms / Q000453:epidemiology* / Q000503:physiopathology; D002543:Cerebral Hemorrhage / Q000453:epidemiology / Q000503:physiopathology; D020786:Hemangioma, Cavernous, Central Nervous System / Q000453:epidemiology* / Q000503:physiopathology; D006801:Humans; D012008:Recurrence