Intracranial dural arteriovenous ﬁ stulas: A Review

Dural arteriovenous ﬁ stulas are ﬁ stulas connecting the branches of dural arteries to dural veins or a venous sinus. Digital subtraction angiography remains the gold standard for diagnosing these ﬁ stulas. Endovascular treatment is one of the ﬁ rst line options available for their management. This review article reviews the etiopathogenesis, natural history, common classiﬁ cation systems and various available treatment options.


Introduction
Yasargill noted that Rizzoli, in 1881, was the Þ rst to describe an arteriovenous malformation (AVM) that involved the dura mater and Sachs reported the first, angiographic description in 1931. Subsequently cranial dural Þ stulas have been most frequently described at the transverse sinus and cavernous sinus, although they occur at every cranial dural sinus. Dural arteriovenous Þ stulas (DAVFs) can occur anywhere within the intracranial dura mater. DAVFs are rare vascular abnormalities. They consist of numerous tiny connections between branches of dural arteries and veins or a venous sinus. [1] The true incidence of DAVFs is unknown. [2] However, the reported incidence of intracranial DAVFs is approximately 10-15% of all intracranial vascular abnormalities. A good percentage of DAVFs remain clinically silent or involute spontaneously and therefore the true incidence may be much more. [3] Present evidence suggests that DAVFs are acquired lesions and present later in life than AVMs. [4] Etiopathology Before the mid-1970s DAVFs were thought to be congenital in origin and to be associated with other vascular lesions. In the late 1970s, Castaigne and Djindjian proposed an acquired etiology. They suggested that DAVFs may develop due to the opening up of existing micro shunts within the dura and by angioneogenesis, leading to the development of new shunts. Various etiologies are postulated: e.g., anomalies of venous system, venous thrombosis, head trauma, transcranial surgery, association with pregnancy, delivery and menopause, increased systemic thrombotic activity, cortical vein thrombosis (CVT), role of hormonal changes (use of oral contraceptive and pregnancy) causing increased angiogenesis, tumors (meningiomas obstruct dural venous outß ow), general surgery, otitis, and sinusitis. [5] Understanding of the pathophysiology of DAVFs came from the school of La Salpetriere, which emphasized the role of the cortical venous drainage of these dural shunts. [5] Henceforth, the role of the subarachnoid and subpial venous drainage could be correlated with the type of neurological manifestation and the natural history of dural shunts. Conditions associated with DAVFs include stenosis or occlusion of the draining dural sinuses, sinus thrombosis, prothrombin gene mutation, resistance to activated protein (APCR), mutation in factor V gene, and presence of antiphospholipid antibodies.
DAVFs in adulthood are an acquired disease and there is no relationship to hereditary or developmental disorders. On the other hand, we have seen brain AVMs as well as cavernomas occur in patients with DAVFs. Vascular diseases associated with dural arteriovenous shunts include cerebral AVM, maxillofacial AVM, hereditary hemorrhagic telangiectasia, bone AVM, cavernomas, and intradural or extradural arterial aneurysms. [5] Multiple DAVFs at separate locations in the same patient have also been reported. [5,6] The common predisposing factor for DAVFs appears to be venous sinus thrombosis. [7] The venous hypertension developing after venous thrombosis opens up the microvascular connections within the dura. [8] Without intervention, these channels become hypertrophied resulting in direct shunting between the arteries and veins [ Table 1]. [7] When the Þ stula grows and becomes more diff use, it recruits pial supply from parenchymal vessels. This may lead to the angiomatous network of multiple feeding arteries and numerous AV shunts within a partially recanalized sinus that is frequently seen at angiography. The involved dural sinus receives arterialized blood ß ow that can lead to mechanical obstruction of the sinus and result in retrograde drainage of blood away from the sinus and into the cortical veins. Histopathological analysis of excised DAVFs has revealed thrombosis and angiographic progression of sinus thrombosis to DAVF. In addition, dilatation of the cortical veins may occur, predisposing the patient to intracranial hemorrhage.
Another mechanism for DAVF evolution is the release of angiogenic growth factors such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), which promotes neovascularization and development of a DAVF [Tables 2 and 3]. These factors by themselves should therefore not be considered as the direct cause of DAVFs, but rather they make up an environment that may be conducive to the development of DAVF, depending on the individual host response to their presence. DAVF in adults are triggered by factors that stimulate angiogenesis. If this angiogenic process is simultaneously associated with loss of some of the venular surface properties, then venous thrombosis is likely to occur. It has been noted that angiogenic growth factors such as basic Þ broblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) are expressed in the DAVFs. In DAVFs with a patent sinus, cortical venous pathways usually do not develop and hemorrhagic complications with these DAVFs are infrequent. [9] Osteodural-venous complex At birth, the total cerebral venous drainage is directed towards the posterior sinuses, i.e. a true sinusal system. [5] Few months aft er birth that the so-called cavernous capture of sylvian vein will occur and off er the infant brain an alternate drainage via the cavernous plexus toward the orbit or the pterygoid plexus and into the external jugular venous system. The dura mater along the convexity of the cranial vault has a diff erent origin from the dural along the base of the skull (membranous vs. cartilaginous bone). Septations may occur within the dural sinuses and result in separate venous channels, one of these channels may be used for the brain to drain while the other is sometimes exclusively used for the drainage of the DAVF and may be the speciÞ c target for treatment. [10] A peculiar group of lesions are the intracranial arteriovenous shunts fed by the dural arteries (that also supply the bone), which are located with in the bony structures along the convexity or at the base of the skull: the so called osteodural AVFs.
The incidence of DAVF at various locations as reported in literature is as follows: transverse sinus 50%, cavernous sinus 16%, tentorium cerebelli 12%, and superior sagitt al sinus, 8%. [6] Natural history The natural history of DAVFs is poorly documented and mostly reviewed retrospectively. Davis et al, followed 102 patients with intracranial DAVFs for an average of 33 months, with complete follow up in 91%. In his series, 55 patients had DAVFs without leptomeningeal and cortical venous reß ux and, of these, 32 received no treatment. Among the patients who received no treatment, 81% had symptom improvement or complete resolution as compared to 86% of the treated patients with the same angioarchitecture. In the same series, there were 46 patients who had DAVFs with leptomeningeal or cortical venous reß ux and 14 of these declined further treatment. At follow-up, this group had an 11% nonhemorrhagic neurological deÞ cit rate per year and a 20% intracerebral hemorrhage (ICH) rate per year. [5] In an updated review of 118 patients with DAVFs and leptomeningeal reß ux, the Toronto team demonstrated an annual risk for nonhemorrhagic neurological deÞ cit of 6.9% and a risk of 8.1% for hemorrhage, with an annual mortality rate of 10.4%. [5] Many DAVFs remain stable and do not change on follow-up. Some involute spontaneously; this may be due to thrombosis following DSA. Some DAVFs undergo progressive recruitment of pachymeningeal feeders with the worsening of symptoms. The actual progress of lesions once symptoms develop is unknown. By location, an aggressive course is seen in 75% of anterior fossa lesions, 79% of tentorial lesions, 60% of foramen magnum lesions, Symptoms of DAVFs may be characterized further as either nonaggressive (e.g., tinnitus) or aggressive (e.g., intracerebral, subarachnoid, or subdural hemorrhage and neurologic deÞ cits). [5,10] These aggressive features are usually due to venous hypertension, although neurological deÞ cits may be secondary to arterial steal. [6] A DAVF demonstrating venous occlusive disease is at a higher risk for complications from the arterialized collateral venous system. Aggressive neurological symptoms are more common in male patients who have aggressive angiographic features like retrograde leptomeningeal venous drainage, variceal or aneurysmal venous structures, and galenic venous drainage. [12] Earlier treatment of DAVFs that have these features is important to prevent complications. The risk of conversion from a benign to an aggressive DAVF is small but repeat angiography is indicated if the clinical picture appears to progress. [13]

ClassiÞ cation system
The initial classiÞ cation of DAVFs proposed in 1978 by Djindjian and Merland was based on venous drainage; [14] it was recently modified by Cognard et al, [15]  PET-based regional cerebral blood ß ow (rCBF) studies indicate that decreased rCBF may be important in the pathogenesis of the neurological symptoms. In patients with normal cortical venous drainage, values for rCBF, regional cerebral metabolic rate of oxygen (rCMRO), and regional oxygen extraction fraction (rOEF) were normal. Reduced rCBF and mildly or markedly increased rOEF is seen in patients with clinical symptoms and cortical venous drainage. [11] Angiography Angiography remains the gold standard for diagnosis and planning of therapy. In addition to diagnosis, anatomical and hemodynamic assessment of the Þ stula needs to be performed. The aim is not only to identify the arterial feeders and the site of the Þ stula but also to identify the patt ern and direction of venous drainage of the Þ stula and normal cerebral parenchyma. Selective injection of all potential arteries that may contribute to the region of dural pathology needs to be done. The acquisition of images should begin in the early arterial phase and continue into the late venous phase of the study. A dual arterial injection (competitive angiogram) may be required to study the venous drainage of fistula and normal brain. In this technique Þ rst selective injection is done in ICA followed by ECA. Then by using resubtraction and changing of the mask runs, drainage of the Þ stula and normal brain parenchyma can be superimposed. The angiogram should be analyzed for feeders, type of venous drainage, retrograde flow, occlusion of sinuses, and circulation time. The angiogram should be analyzed for feeders, type of venous drainage, retrograde ß ow, occlusion of sinuses, and circulation time.
The common angiographic Þ ndings seen are feeders from pial and dural branches, AV shunting, venous ectasia, stenosis, calcifications, impaired drainage of cerebral parenchyma with delayed venous drainage, and cortical venous collaterals.

Cortical rerouting
Aggressive symptoms are shown by those DAVFs, which drain retrogradely by leptomeningeal cortical venous channels. Awad et al, pointed out the aggressive factors as leptomeningeal cortical venous drainage, galenic deep venous drainage, variceal or aneurismal dilatations and lesions located at the tentorial incisura. [12] Houser et al, [8] point out that the sinus need not even be thrombosed to cause retrograde venous drainage into cortical veins. Partial Þ lling of sinuses by the high-pressure arterial blood can impede antegrade venous drainage. A high frequency of hemorrhage is reported in DAVFs involving the anterior cranial fossa and tentorium. These DAVFs almost always drain into intradural veins. [17] Apart from hemorrhage, retrograde venous ß ow accompanied by increased venous pressure can lead to chronic passive congestion and venous infarcts, which are a major cause of focal neurologic deÞ cits in DAVFs. Hydrocephalus is another complication of DAVF. It is due to decreased absorption of cerebrospinal ß uid due to increased venous pressure or mechanical compression of the aqueduct by mesencephalic veins.

Treatment
General treatment approaches for the treatment of DAVFs include the following: 1. Conservative treatment 2. Neuroradiological endovascular intervention, which comprises of: i. Particulate embolization ii. Glue or onyx injection through arterial or venous route iii. Coiling with or without glue or onyx injection [ Figures  1-3] iv. Venous stenting 3. Radiation therapy 4. Surgery 5. Combination of above, i.e., RT + intervention or intervention + surgery

Conservative treatment
Conservative treatment involves mainly symptomatic treatment and supportive measures. Spontaneous regression of dural DAVFs has been reported. [18] 2. Endovascular neuroradiological intervention Transarterial route i. Particulate embolization: Embolization of external carotid branches with particles is easily performed and can reduce shunt ß ow. Transarterial particulate embolization typically is not curative. Total obliteration is diffi cult to achieve with this method because some feeding arteries cannot be catheterized and because of the recruitment of blood supply from collateral arteries. [19] Therefore, it is generally used to relieve symptoms or in combination with other procedures such as irradiation, surgery, or transvenous embolization (TVE).
ii. N-butyl-2-cyanoacrylate or onyx embolization: Deposition of glue into the collecting vein or fistula through the transarterial route may also result in cure, but it is less controllable than coil embolization and thus may present a higher risk. Transarterial embolization (TAE) with N-butyl-2-cyanoacrylate is regularly used to treat complex DAVFs if percutaneous transvenous catheterization is not possible. [20] Onyx is a new nonadhesive liquid embolic agent. It is supplied in ready-to-use vials and is a mixture of EVOH, DMSO, and tantalum. Onyx, aft er coming in contact with blood, gets precipitated and occludes the vessels but is nonadherent to the vessel wall. This non-adhesive property of onyx eliminates the risk of gluing of the microcatheter to the vessels. This also allows a slow and prolonged single injection of the embolic agent with concomitant check angiograms. Good positioning of the microcatheter and slow injection can completely Þ ll the Þ stula and enable a complete cure.
Currently onyx is available in two concentrations (FDAapproved) in the United States for presurgical cerebral AVM embolization. [21] Depending on the need, onyx or glue in mild to moderate concentration (20, 25, or 33%) may be injected.
iii. Coiling via transvenous route: Coils are now regularly used for curative purposes. Many studies have reported their usefulness. Complete occlusion may occur in 80-100% of cases. [22] An angiographically nonvisualized inferior petrosal sinus (IPS) can be successfully catheterized in 30-50% of patients. [9] When this is thrombosed, the transvenous access may be tried out via the superior petrosal sinus (SPS) facial vein, angular vein, pterygoid sinus, and superior ophthalmic vein (SOV) [23] Inadequate embolization leads

Radiation therapy
Good results have been reported from the use of stereotactic radiotherapy for the treatment of DAVFs, with complete occlusion being reported in 44-87% of cases. [26,27] This method, although reported to be eff ective in several case reports or small series, carries an unacceptable delay of 1-3 years in the cure of DAVFs with cortical venous reß ux (CVR) and therefore is not recommended as a primary therapeutic measure for these lesions. [28] The advantages of radiotherapy include decreased invasiveness of the procedure and fewer short-term complications; the major disadvantage is the latency of 6-12 months aft er irradiation before there are tangible beneÞ ts. The combined use of stereotactic radiotherapy and TAE with particles is in practice and it enhances the eff ectiveness of both the techniques. Combined treatment gives good results and reduces the risk of worsening symptoms during the follow-up period. [29,30]

Surgery
Endovascular management has become a Þ rst-line treatment for dural DAVFs. However, some DAVFs of the anterior cranial fossa can oft en be treated more easily and safely with surgical disconnection of the venous drainage. [29] Combination Gupta et al.: Intracranial DAVFs to a worsening of symptoms.
The use of detachable coils before onyx or glue injection slows and decreases ß ow in the Þ stula and provides secure anchoring to the onyx or glue cast.
iv. Stent placement: Some authors have tried to close the shunts in the dural arteriovenous Þ stulas with the help of with endovascular procedures is required in diffi cult cases where sinus isolation and resection are needed.

Conclusions
DAVFs with retrograde leptomeningeal venous drainage carry a high risk for neurological sequelae or death, both at presentation and in the natural course of disease progression. With presently available treatment modalities most of these lesions are either curable or, at the very least, patients may get signiÞ cant clinical improvement. The natural history of the condition suggests that these lesions are aggressive and need prompt diagnosis and treatment.