Evidence of increased endothelial cell turnover in brain arteriovenous malformations

OBJECTIVE: We hypothesized that human brain arteriovenous malformations (BA VMs) are nonstatic vascular lesions with active angiogenesis or vascular re modeling. To test this hypothesis, we assessed endothelial cell turnover in BAVMs. METHODS: We identified nonresting endothelial cells by use of immunohistoch emistry for the Ki-67 antigen. From archived paraffin blocks, we selected B AVM vessels without intravascular thrombosis or embolic material in areas n onadjacent to the nidus edge. For controls, we used 50- to 100-mum diameter cortical vessels from temporal lobe cortex removed for epilepsy treatment. The Ki-67 index was calculated as a percentage of Ki-67-positive endotheli al cells. The data were analyzed by the nonparametric Mann-Whitney test and reported as mean +/- standard deviation. RESULTS: Thirty-seven specimens that met the above criteria were selected. There were 26 +/- 15 vessels counted in each BAVM specimen versus 18 +/- 5 in each control cortex (n = 5). The mean Ki-67 index was higher for BAVM ve ssels than control cortical vessels (0.7 +/- 0.6 versus 0.1 +/- 0.2%; P = 0 .005), which represented an approximately seven-fold increase in the number of nonresting endothelial cells. In the BAVM group, there was a trend for younger patients to have a wider variation and higher Ki-67 index than olde r patients; no trend was evident in the control group. CONCLUSION: Compared with control vessels, BAVM vessels have higher endothe lial cell turnover, which suggests the presence of active angiogenesis or v ascular remodeling in BAVMs.