Pathogenesis Of Dural Arteriovenous Fistulas Research Articles

Role of surgery in management of intracranial dural arteriovenous fistulas.

Intracranial dural arteriovenous fistulas (DAVF) are abnormal connections between intracranial arterial and venous systems within the dural layers. Intracranial DAVFs are rare but can occur wherever dural components exist. The pathogenesis of DAVFs is controversial. Venous hypertension is considered as a main cause of clinical symptoms which are subclassified into asymptomatic, benign and aggressive manifestations. To date, several classification schemes have been proposed to stratify the natural course and risks of DAVFs. Currently, endovascular therapy is the main treatment modality. Moreover, the use of radiosurgery and radiotherapy has been limited. Open surgery is also selectively performed as a main treatment modality for specific types of DAVFs and an adjunctive modality for the endovascular approach. Herein, we present a review of the general perspectives of intracranial DAVFs with an emphasis on the role of surgery.

Frequency and characteristics associated with inherited thrombophilia in patients with intracranial dural arteriovenous fistula.

The pathogenesis of dural arteriovenous fistulas (DAVFs) remains poorly defined. Prior studies on thrombophilia as a risk factor for DAVF development are limited by small sample sizes and poor generalizability. In this longitudinal observational study, all patients with intracranial DAVFs evaluated at the University of California, San Francisco from December 1994 through April 2014 were identified. After obtaining patient consent, 3 thrombophilic mutations, factor V Leiden (rs6025), MTHFR (rs1801133), and prothrombin G20210A, were genotyped. The authors evaluated the association of thrombophilia status (presence of any thrombophilic mutation) and clinical and angiographic characteristics using either a 2-sample t-test or Fisher's exact test. A total of 116 patients with diagnosed intracranial DAVFs were included in the study. Twenty-five (22%) patients met criteria for thrombophilia. Focal neurological deficits tended to occur more frequently in the thrombophilia group (78% vs 57%, p = 0.09). Angiographic characteristics of DAVFs, including high-risk venous flow pattern, multiplicity of DAVF, and the presence of venous sinus thrombosis, did not differ significantly between the 2 groups but tended to be more common in the thrombophilic than in the nonthrombophilic group. This study is one of the largest of thrombophilia and DAVF to date. The frequency of mutations associated with thrombophilia in this study was higher than that in the general population.

Meningioma-related dural arteriovenous fistula fed via a vascular tumor bed: A case report and literature review

Dural arteriovenous fistulas (AVFs) are defined as arterioveous shunts within dural leaflet. The pathogenesis of dural AVFs is till unknown. Although congenital dural AVFs have been reported, ost dural AVFs are considered to be acquired secondary to trauma, hrombophlebitis, surgery and infection [3]. It has been previously reported that intracranial tumors occludng the major sinus might be associated with dural AVF [2,4,8]. hese previous reports support the hypothesis that dural AVFs re acquired lesions and that venous outflow obstruction is a conributing factor [6,7]. However, this hypothesis cannot explain the ndings that there have been several cases with tumor-related ural AVF who are not associated with sinus occlusion [1,5]. It uggests that the other factors are contributing to dural AVFs foration. We report a case of dural AVF of the right transverse sinus assoiated with a tentorial meningioma and discuss the mechanism of ormation and post-surgical disappearance of tumor-related dural VF.

The relationship between venous hypertension and expression of vascular endothelial growth factor: hemodynamic and immunohistochemical examinations in a rat venous hypertension model

Background Venous hypertension is regarded as an important factor in the pathogenesis of dural arteriovenous fistula (DAVF). We investigate histologic reaction of dural sinus under the condition of venous hypertension using a rat venous hypertension model to present hemodynamic and immunohistochemical effect in the development of DAVF. Methods Twenty-four Sprague-Dawley male rats were divided into venous hypertension and control groups. Venous hypertension was induced with a left common carotid artery–external jugular vein anastomosis and an occlusion of a right posterior facial vein. Measurements of systemic mean arterial pressure, draining vein pressure (DVP), and cerebral perfusion pressure (CPP) were conducted on the next day, at 7 days, and at 28 days after surgery, and the rats were killed for histologic examinations. Results Postoperative DVP increased significantly in venous hypertension group compared to control group (35 ± 5 vs 13 ± 2 mm Hg, P < .05). Increased DVP remained above 30 mm Hg throughout the observation period. Postoperative CPP decreased significantly in venous hypertension group compared to control group (49 ± 8 vs 86 ± 9 mm Hg, P < .05). In venous hypertension group, there was a significant difference between days 1 and 28 (49 ± 8 vs 64 ± 8 mm Hg, P < .05). Histologic examination revealed thickening of connective tissues, proliferation of fibroblasts, and strong expression of vascular endothelial growth factor (VEGF) in endothelium under venous hypertension condition. Immunostained VEGF cells decreased significantly from day 7 to day 28 (100 ± 16 vs 72 ± 19 cells, P < .05). A positive correlation was observed between DVP and VEGF expression (Pearson correlation coefficient; r = 0.671, P = .0017). There was a negative correlation between CPP and immunostained VEGF cells ( r = −0.702, P = .0089). Conclusions These results suggest that venous hypertension is associated with increased expression of VEGF, and a decreased CPP may have a potential effect in VEGF expression under venous hypertension condition. These factors are speculated to play an important role in progression of DAVF.

Immunohistochemical study in dural arteriovenous fistulas and possible role of local hypoxia for the de novo formation of dural arteriovenous fistulas

Objective : Although previous clinical and experimental studies investigated the pathogenesis of dural arteriovenous fistulas (DAVFs), the biological process leading to intracranial DAVFs so far remains unknown. In this study, we investigated the expression of vascular growth factors in order to elucidate the possible role of these factors in the development of DAVFs. Methods : We examined the histological features, proliferative and angiogenic capacities of the tissue specimens obtained from eight patients who underwent surgery at our institution. Immunohistochemical staining for vascular endothelial growth factor (VEGF), its receptors Flk-1 and Flt-1, transforming growth factor alpha (TGFα), basic fibroblast growth factor (bFGF), hypoxia inducible factor 1α (Hif-1α), MIB-1 and proliferating cell nuclear antigen (PCNA) was performed using standard immunohistochemical techniques. Results : A positive immunostaining was found for all antibodies studied except MIB-1, whereas nuclear endothelial expression of PCNA was observed in only 3/8 cases. Hif-1α and VEGF stained positive in all of the available specimens (7/7). Flk-1 showed a positive immunoreaction in only 2/8 cases and Flt-1 in 5/7 cases. TGFα and bFGF were expressed in the majority (6/8) of cases. Conclusion : These results indicate the possible role of local tissue hypoxia as the initial step causing neoangiogenesis and a low degree of endothelial proliferation in DAVFs. Such hypoxia might be caused by venous hypertension or venous thrombosis as it was previously suggested by other authors.

Transarterial Wedged-catheter, Flow-arrest, N-butyl Cyanoacrylate Embolization of Three Dural Arteriovenous Fistulae in a Single Patient

The pathogenesis of dural arteriovenous fistulas (DAVFs) is currently unknown, with multiple DAVFs being rare. For patients with limited venous access secondary to sinus thrombosis, or for patients where parent sinus occlusion would not be tolerated, transvenous embolization may not be possible and other treatment methods must be considered. A 69-year-old female patient with a two-year history of progressive headaches, memory loss, and unsteady gait underwent cerebral angiography that revealed three separate DAVFs with congested cortical venous drainage overlying both frontal lobes. Using an application of a transarterial wedged-catheter, flow-arrest technique, N-butyl cyanoacrylate was deposited across all three pathologic arteriovenous connections providing a definitive cure. Transarterial NBCA embolization may provide curative treatment of DAVFs, and is of particular utility in situations where access to the draining venous structures is limited.

Significantly increased prevalence of factor V Leiden in patients with dural arteriovenous fistulas.

Resistance to activated protein C (APCR) is the most common genetic risk factor for venous thrombosis and is generally caused by a mutation in the factor V (FV) gene leading to FV Leiden. The recent finding of FV Leiden in three of seven patients with dural arteriovenous fistulas (DAVFs) prompted us to evaluate systematically the role of APCR due to FV Leiden in the pathogenesis of DAVFs in 22 patients and age- and sex-matched controls. We found a significantly higher frequency of APCR and FV Leiden in the patient group than among controls (5/22 vs. 0/22, P=0.048, Fisher's exact test). We conclude that APCR due to FV Leiden is of pathogenetic significance in a subgroup of DAVFs.

Expression of angiogenic growth factors in dural arteriovenous fistula.

Although various mechanisms of the development of dural arteriovenous fistula (AVF) have been described, the exact course of its pathogenesis, including molecular processes mediating its genesis, is still unknown. Recently, the importance of sinus thrombosis and venous hypertension has been reported in experimental and clinical studies. Additionally, a role of angiogenic growth factors in the pathogenesis of vascular malformations of the central nervous system has been reported. In this study, the authors investigated the existence of sinus thrombosis in dural AVF and the expression of angiogenic growth factors (basic fibroblast growth factor [bFGF] and vascular endothelial growth factor [VEGF]) in nine patients with dural AVFs that were surgically resected. The authors examined histological features of dural AVFs that involved the transverse/sigmoid sinus in seven patients and the superior sagittal sinus in two. Sinus thrombosis was verified angiographically in seven cases and histologically in all cases. In surgically resected specimens the angiogenic growth factors bFGF and VEGF were examined immunohistochemically in nine patients with dural AVFs, with five dural sinuses from cadavers with unrelated central nervous system diseases serving as a normal control group. The media and perivascular connective tissues of the arteries in the wall of the normal dural sinuses stained faintly for bFGF; on the other hand, the expression of VEGF was not detected. In all patients with dural AVFs, the thick wall of the dural sinus stained strongly for bFGF, mainly in the subendothelial layer and media of the strongly proliferative vessels in the sinus wall, in addition to the perivascular connective tissues. In all nine cases VEGF was expressed in the endothelium of the sinus and perivascular connective tissues. In two cases, VEGF was expressed in many capillaries proliferating in the granulation-like tissues in sinuses that were obliterated by organized thrombi. It is concluded that the pathogenesis of dural AVF is still unknown, but that angiogenic growth factors, which might be produced by the healing process due to sinus thrombosis, may participate in the genesis of dural AVF. Understanding the mechanism of molecular pathogenesis in the development of dural AVF might aid in the establishment of a new therapeutic strategy for this dynamic vascular disease.

Association of resistance to activated protein C and dural arteriovenous fistulas.

Resistance to activated protein C (APCR), shown to be the most common genetic risk factor for venous thrombosis, is mostly caused by a mutation in the factor V (FV) gene leading to FV Leiden. As dural arteriovenous fistulas (DAVFs) are associated with cerebral venous thrombosis, we looked for the FV Leiden mutation in seven patients with such fistulas. The APCR ratio was determined according to standard procedures. For APCR ratios considered pathological (less than 2.0), mutation analysis was done by a reverse hybridization assay. Three of the seven patients with DAVFs showed pathological APCR ratios and heterozygosity for FV Leiden mutation. Thus, it is hypothesized that FV Leiden might be involved in the pathogenesis of DAVFs.

O-4-53 - Dural arteriovenous fistula of the posterior fossa developing after surgical occlusion of the sigmoid sinus

✓ In this article, the authors present five cases of dural arteriovenous fistula (AVF) that developed in the transverse—sigmoid sinus 2 to 6 years after sacrifice of the sigmoid sinus because of tumor involvement. The original tumor was meningioma in two patients and neurinoma, glomus jugulare tumor, and ameloblastoma in one patient each. The involved sigmoid sinus was resected along with the tumor and ligated at the normal edge; all that remained of the sigmoid sinus was a small stump on the retrosigmoid portion. Serial angiography performed before and after tumor surgery revealed no abnormal arteriovenous communications or dural AVF in any of the cases. Although many reports have suggested that sinus thrombosis is a precipitating factor in the pathogenesis of dural AVFs, this has been difficult to verify because of the small number of cases in which serial angiography was performed before the development of a dural AVF. In all of the cases presented in this article, surgical resection of a dural AVF and...

Dural arteriovenous fistula of the posterior fossa developing after surgical occlusion of the sigmoid sinus

In this article, the authors present five cases of dural arteriovenous fistula (AVF) that developed in the transverse-sigmoid sinus 2 to 6 years after sacrifice of the sigmoid sinus because of tumor involvement. The original tumor was meningioma in two patients and neurinoma, glomus jugulare tumor, and ameloblastoma in one patient each. The involved sigmoid sinus was resected along with the tumor and ligated at the normal edge; all that remained of the sigmoid sinus was a small stump on the retrosigmoid portion. Serial angiography performed before and after tumor surgery revealed no abnormal arteriovenous communications or dural AVF in any of the cases. Although many reports have suggested that sinus thrombosis is a precipitating factor in the pathogenesis of dural AVFs, this has been difficult to verify because of the small number of cases in which serial angiography was performed before the development of a dural AVF. In all of the cases presented in this article, surgical resection of a dural AVF and histological examination were performed. Subintimal fibrous thickening was marked, and the sinus wall was found to contain many dural vessels. Organized thrombosis with neovascularization was seen in only two patients. These cases demonstrate that subintimal fibrous thickening a hypertrophied sinus wall secondary to increased intrasinus pressure or sinus thrombosis occurring after sinus occlusion can provoke the development of a dural AVF within the course of a lifetime. Maintenance of intrasinus blood flow may be very important to prevent this late postoperative complication.