Hemorrhage from cavernous malformations of the brain: definition and reporting standards. Angioma Alliance Scientific Advisory Board

Stroke. 2008 Dec;39(12):3222-30. doi: 10.1161/STROKEAHA.108.515544. Epub 2008 Oct 30.


Background and purpose: Cavernous malformations of the brain (CMs) cause intracranial hemorrhage, but its reported frequency varies, partly attributable to study design. To improve the validity of future research, we aimed to develop a robust definition of CM hemorrhage.

Methods: We systematically reviewed the published literature (Ovid Medline and Embase to June 1, 2007) for definitions of CM hemorrhage used in studies of the untreated clinical course of >or=20 participants with CM(s), to inform the development of a consensus statement on the clinical and imaging features of CM hemorrhage at a scientific workshop of the Angioma Alliance.

Results: A systematic review of 1426 publications about CMs in humans, revealed 15 studies meeting our inclusion criteria. Although 14 (93%) studies provided a definition of CM hemorrhage, data were less complete on the confirmatory type(s) of imaging (87%), whether CM hemorrhage should be clinically symptomatic (73%), and whether hemorrhage had to extend outside the CM or not (47%). We define a CM hemorrhage as requiring acute or subacute onset symptoms (any of: headache, epileptic seizure, impaired consciousness, or new/worsened focal neurological deficit referable to the anatomic location of the CM) accompanied by radiological, pathological, surgical, or rarely only cerebrospinal fluid evidence of recent extra- or intralesional hemorrhage. The definition includes neither an increase in CM diameter without other evidence of recent hemorrhage, nor the existence of a hemosiderin halo.

Conclusions: A consistent approach to clinical and brain imaging classification of CM hemorrhage will improve the external validity of future CM research.

Publication types

  • Consensus Development Conference
  • Guideline
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Algorithms
  • Biomarkers
  • Cerebral Hemorrhage / classification
  • Cerebral Hemorrhage / diagnosis
  • Cerebral Hemorrhage / epidemiology
  • Cerebral Hemorrhage / etiology*
  • Clinical Trials as Topic / standards*
  • Consciousness Disorders / etiology
  • Diagnostic Imaging / methods
  • Diagnostic Imaging / standards
  • Humans
  • Intracranial Arteriovenous Malformations / complications*
  • Intracranial Arteriovenous Malformations / diagnosis
  • Magnetic Resonance Imaging
  • Movement Disorders / etiology
  • Seizures / etiology
  • Sensation Disorders / etiology
  • Tomography, X-Ray Computed


  • Biomarkers