Background: Since growth and de novo generation of cerebrovascular malformations were demonstrated, a strictly congenital model cannot be further supported as unique factor in the pathogenesis of cerebral arteriovenous malformations (AVMs). Vascular endothelial growth factor (VEGF) has previously been demonstrated to be highly expressed in AVMs by immunohistochemical methods. However, systemic VEGF levels have not been analysed previously. This study aimed to investigate VEGF plasma concentrations as a possible plasma marker for neovascularization in patients with cerebral AVMs compared to healthy controls. Methods: The study included 17 patients with cerebral AVMs and 40 healthy controls. VEGF plasma concentrations were measured by a specific enzyme immuno-assay. Results: VEGF plasma concentrations were significantly higher in patients with cerebral AVMs (mean 140.9 pg/ml, SD 148.5 pg/ml and median 63.0 pg/ml) compared to a healthy control group (mean 44.7 pg/ml, SD 36.4 pg/ml and median 35.0 pg/ml), p = 0.0003. Conclusions: Our findings suggest that VEGF plasma concentrations might play a role in the pathogenesis of cerebral AVMs. Further studies are necessary and would contribute to an improved understanding of the pathogenesis of cerebral AVMs.

Aneurysm growth appears to be associated with an increased risk of rupture. Therefore, it may be of interest to identify mechanisms contributing to aneurysm growth. Angiogenic factors, particularly vascular endothelial growth factor (VEGF), appear to play an important role in the pathogenesis and growth of cerebrovascular malformations. We aimed to study systemic VEGF levels as a potential systemic marker in patients with non-ruptured intracranial aneurysms compared with healthy controls. Mean VEGF plasma concentrations were found to be increased in patients with non-ruptured intracranial aneurysms compared with healthy controls (85.2 pg/ml versus 44.1 pg/ml). This difference did not reach significance in the analyzed study cohort (p=0.05) but only when the analysis was restricted to male patients (p=0.04). Female patients and controls demonstrated significantly increased VEGF plasma levels only on correlation with age but not with the presence of aneurysms. Neither the presence of multiple aneurysms nor aneurysm location were correlated with VEGF levels. Although overall VEGF plasma difference was not statistically significant, we found significantly increased levels in male patients. Furthermore, we identified a distinct group of female patients with intracranial aneurysms who presented excessively increased VEGF plasma levels to an amount that was not observed in the controls. Further studies may clarify the relationship of aneurysm growth and VEGF.

Background: The natural history of cerebral arteriovenous malformations (AVMs) is yet to be determined. It has been shown that angiogenic factors are involved in the pathogenesis of AVMs, in particular in partially embolized lesions. This study was conducted to investigate the expression of angiogenic and proliferative factors in relation to different clinical conditions and treatment modalities. Methods: Immunohistochemistry was performed for 145 consecutive cases of cerebral AVMs. The specimens were stained with antibodies against VEGF, bFGF, Ki 67, CD 34 and CD 31. Expression was correlated with clinical presentation (haemorrhage, seizures or other symptoms), AVM localization, size, eloquence and venous drainage, as well as with preoperative AVM embolization. Results: Whereas no correlation was found between the expression of angiogenic factors and different clinical conditions, we observed a significantly increased proliferation activity as shown by Ki 67 expression in patients with intracerebral haemorrhage (p = 0.02) and in patients with preoperative embolization (p = 0.02). Conclusions: Increased proliferation activity in partially embolized AVMs supports a ‘no-touch’ strategy and clinical observation in high-risk AVMs and demands complete AVM elimination in treatable lesions.