Introduction: Endothelial tight junction (TJ) expression in cerebral cavernous malformations (CCM) is mostly absent, which causes increased perilesional erythrocyte and fluid oozing. However, in a subset of CCM 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 CCM bleeding propensity.
Methods: Immunohistochemical staining for the TJ proteins claudin-5, occludin and ZO-1 was performed on 32 CCM specimens, surgically resected in the period 2008-2010. The patients were allocated in two groups according to TJ protein expression and the clinical and radiological parameters of aggressiveness were analyzed and compared.
Results: Complete absence was identified in 20 and focal TJ protein expression in 12 specimen. CCM’s with absent TJ immunoreactivity had significantly larger size (p=0.022) as well as higher propensity for development of frank hematomas (p=0.028) and perilesional edema (p=0.013). Symptom severity, multiplicity, DVA presence and CCM location did not show a significant difference depending on TJ expression.
Conclusions: In a univariate analysis we observed significantly lesser propensity for frank hematomas and perilesional edema as well as smaller size in CCM lesions with focal TJ expression. The observed difference in TJ protein expression might be the rational for different bleeding propensity of the CCM lesions. Although this finding cannot be used in predictive manner at this time, it is a basis for further multivariate analyses of possible CCM biologic predictors.
Patient Care: Although this finding cannot be used in predictive manner at this time, it is a basis for further multivariate analyses of possible CCM biologic predictors which in turn could be used to validate a clinically useful decision analysis that might guide clinical care.
Learning Objectives: By the conclussion of this session, participants should be able to: 1)describe the importance of tight junction expression as a possible predictor of the bleeding propensity of cavernomas, 2)discuss the methods for external validation of the results and correlation with genetic or imaging surrogates, 3)Identify a clinically useful decision analysis that might guide clinical care.