title: Treatment of cerebral cavernous malformations: a systematic review and meta-regression analysis.
abstract: OBJECTIVE
  The reported effects of treating cerebral cavernous malformations (CCMs) by neurosurgical excision or stereotactic radiosurgery are imprecise and vary between studies.
  
  
  METHODS
  We searched Ovid Medline, EMBASE and The Cochrane Library for peer-reviewed publications of cohort studies describing outcomes of treating 20 or more patients with CCM with at least 80% completeness of follow-up. Two reviewers extracted data to quantify the incidence of a composite outcome (death, non-fatal intracranial haemorrhage, or new/worse persistent focal neurological deficit) after CCM treatment. We explored associations between summary measures of study characteristics and outcome using Poisson meta-regression analyses.
  
  
  RESULTS
  We included 63 cohorts, involving 3424 patients. The incidence of the composite outcome was 6.6 (95% CI 5.7 to 7.5) per 100 person-years after neurosurgical excision (median follow-up 3.3 years) and 5.4 (95% CI 4.5 to 6.4) after stereotactic radiosurgery (median follow-up 4.1 years). After neurosurgical excision the incidence of the composite outcome increased with every per cent point increase in patients with brainstem CCM (rate ratio (RR) 1.03, 95% CI 1.01 to 1.05), and decreased with each more recent study midyear (RR 0.91, 95% CI 0.85 to 0.98) and each per cent point increase in patients presenting with haemorrhage (RR 0.98, 95% CI 0.96 to 1.00). We did not find significant associations in studies of stereotactic radiosurgery.
  
  
  CONCLUSIONS
  The reported risks of CCM treatment (and the lower risks of neurosurgical excision over time, from recently bled CCMs, and for CCMs outside the brainstem) compare favourably with the risks of recurrent haemorrhage from CCM. Long-term effects, especially important for stereotactic radiosurgery, are unknown.
authors.affiliation: Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Michiel H F
authors.initials: MH
authors.lastname: Poorthuis
authors.affiliation: Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Catharina J M
authors.initials: CJ
authors.lastname: Klijn
authors.affiliation: Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Ale
authors.identifier: http://orcid.org/0000-0003-2858-5808
authors.initials: A
authors.lastname: Algra
authors.affiliation: Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Gabriel J E
authors.initials: GJ
authors.lastname: Rinkel
authors.affiliation: Division of Clinical Neurosciences, Centre for Clinical Brain Sciences, University of Edinburgh, Western General Hospital, Edinburgh, UK.
authors.forename: Rustam
authors.identifier: http://orcid.org/0000-0002-2108-9222
authors.initials: R
authors.lastname: Al-Shahi Salman
mesh_terms: D020786:Hemangioma, Cavernous, Central Nervous System / Q000401:mortality / Q000601:surgery*; D006801:Humans; D016012:Poisson Distribution; D016634:Radiosurgery / Q000009:adverse effects; D012307:Risk Factors; D016896:Treatment Outcome
keywords: Cerebrovascular