title: Bleeding propensity of cavernous malformations: impact of tight junction alterations on the occurrence of overt hematoma.
abstract: OBJECTIVE
  Endothelial tight junction (TJ) expression is mostly absent in cerebral cavernous malformations (CMs), which causes increased perilesional erythrocyte and fluid oozing. However, in a subset of CM lesions, foci of preserved TJ staining are observed along endothelial cell contacts. The clinical relevance of this finding is unclear. This study investigates the relevance of the focal TJ protein expression and its association with CM bleeding propensity.
  
  
  METHODS
  Immunohistochemical staining for the TJ proteins claudin-5, occludin, and ZO-1 was performed on 32 CM specimens that were resected during 2008-2010. The patients were allocated to 2 groups according to TJ protein expression, and the clinical and radiological parameters of aggressiveness were analyzed and compared. RESULTS Complete absence of TJ expression was identified in 20 specimens, and focal TJ protein expression in 12. CMs without TJ immunoreactivity were significantly larger (p = 0.022) and had a significantly greater propensity for development of frank hematomas (p = 0.028) and perilesional edema (p = 0.013). Symptom severity, multiplicity, developmental venous anomaly (DVA) presence, and CM location did not show a significant difference depending on TJ expression.
  
  
  CONCLUSIONS
  In a univariate analysis the authors observed significantly less propensity for frank hematomas and perilesional edema as well as smaller size in CM lesions with focal TJ expression compared with CMs without TJ expression. The observed difference in TJ protein expression might be the reason for differences in bleeding propensity of the CM lesions. Although this finding cannot be used in predictive manner at this time, it is a basis for further multivariate analyses of possible CM biological predictors.
authors.affiliation: Department of Neurosurgery and.
authors.forename: Dejan
authors.initials: D
authors.lastname: Jakimovski
authors.forename: Hannah
authors.initials: H
authors.lastname: Schneider
authors.forename: Karl
authors.initials: K
authors.lastname: Frei
authors.forename: Lieven N
authors.initials: LN
authors.lastname: Kennes
authors.forename: Helmut
authors.initials: H
authors.lastname: Bertalanffy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002543:Cerebral Hemorrhage / Q000453:epidemiology*; D002648:Child; D002675:Child, Preschool; D062507:Claudin-5 / Q000378:metabolism; D005260:Female; D020786:Hemangioma, Cavernous, Central Nervous System / Q000150:complications*; D006406:Hematoma / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D062793:Occludin / Q000378:metabolism; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors; D019108:Tight Junctions / Q000378:metabolism*; D055815:Young Adult; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D062507:Claudin-5; D062793:Occludin; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein
keywords: CM = cavernous malformation; DVA = developmental venous anomaly; GLUT-1 = glucose transporter 1; PBS = phosphate-buffered saline; TJ = tight junction; ZO-1; cavernous malformation; claudin-5; hemorrhage; occludin; tight junction; vascular disorders