Little is known of the molecular mechanisms mediating the genesis and subsequent biological behavior of central nervous system vascular malformations. The role of angiogenic and permeability-inducing factors in the pathogenesis of these lesions has not bee previously explored. In this study, we subject specimens from 12 cases of excised vascular malformation to a battery of immunostaining for vascular endothelial growth factor, basic fibroblast growth factor, and selected structural and matrix proteins. The lesions consisted of seven arteriovenous malformations (AVMs), including one angiographically occult AVM, one arterialized vein from a dural AVM, and five cavernous malformations (CMs). Vascular endothelial growth factor was expressed by all lesions and was localized predominantly in the subendothelial layer and in perivascular spaces. Four of seven AVMs and four of five CMs demonstrated faint basic fibroblast growth factor expression that was localized to the media of AVM vessels and the subendothelial layer and intercavernous matrix of CMs. This pattern of angiogenic factor immunostaining was correlated with the expression of structural and matrix proteins in the same lesions. Laminin was not expressed in any of the CMs, confirming previous reports from our laboratory. By contrast, fibronectin expression was more prominent in CMs than in AVMs. Collagen Type IV and alpha smooth muscle actin expression occurred in every lesion. We conclude that angiogenic growth factors are expressed in all types of vascular malformations of the central nervous system. The pattern of expression suggests diffuse activation of angiogenesis without specific relation to individual vessel types or recent clinical behavior. Defining the role of angiogenesis in vascular malformations might provide insight into their pathogenesis and suggest novel strategies for modification of their behavior.

Peritumoral vasogenic brain edema (PVBE) is a common accompaniment of malignant gliomas. It results from microvascular extravasation of plasma fluid and proteins through the interendothelial spaces. Tumor-associated cysts (TACs) are observed more commonly with benign gliomas that are not associated with PVBE. This study investigates the hypothesis that these morphologically distinct epiphenomena of microvascular extravasation are linked by a common pathophysiological mechanism involving vascular endothelial growth/permeability factor (VEG/PF), which has been implicated in vascular leak phenomena including ascites, malignant effusions, and brain edema. Furthermore, VEG/PF has been isolated from cultured glioma cells, and both VEG/PF protein and messenger RNA transcripts are expressed in brain tumor tissue. To further elucidate the relationship of VEG/PF to PVBE and TACs, the authors examined 34 pathological specimens for VEG/PF expression. Nineteen primary low-grade tumors, 11 primary high-grade tumors, and four gliosis controls were immunostained with a polyclonal anti-VEG/PF immunoglobulin G antibody. Magnetic resonance imaging was used to quantitate PVBE and to determine the presence of TACs and tumor enhancement. The study revealed that eight VEG/PF-negative specimens exhibited no significant edema, whereas 26 VEG/PF-positive tumors exhibited either significant PVBE or TACs. Notably, eight of nine benign TACs that were not associated with PVBE immunostained positive for VEG/PF. These data indicate a high degree of correlation between VEG/PF expression by gliomas and the occurrence of PVBE or TACs, irrespective of tumor grade, thus supporting VEG/PF's pivotal role as the common pathophysiological link between these processes.

Acute or subacute neurological deterioration without evidence of hemorrhage in a patient with a spinal arteriovenous (AV) malformation has been referred to as "Foix-Alajouanine syndrome." This clinical entity has been considered to be the result of progressive vascular thrombosis resulting in a necrotic myelopathy; it has therefore been thought to be largely irreversible and hence untreatable. The authors report five patients with dural AV fistulas who presented in this manner, and who improved substantially after embolic and surgical therapy. The outcome of these patients indicates that acute and subacute progression of myelopathy in cases of spinal dural AV fistulas may be caused by venous congestion and not necessarily by thrombosis. Therefore, a clinical diagnosis of Foix-Alajouanine syndrome is of little practical use, as spinal cord dysfunction from venous congestion is a potentially reversible process whereas thrombotic infarction is not. This diagnosis may result in suboptimal management. The recognition of nonhemorrhagic acute or subacute myelopathy as a complication of a spinal dural AV fistula is important since what appears to be irreversible cord injury is often treatable by standard surgical techniques.