Natural history, current concepts, classification, factors impacting endovascular therapy, and pathophysiology of cerebral and spinal dural arteriovenous fistulas.

G Model CLINEU-3603; No. of Pages 12

ARTICLE IN PRESS Clinical Neurology and Neurosurgery xxx (2014) xxx–xxx

Contents lists available at ScienceDirect

Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro

Review

Natural history, current concepts, classification, factors impacting endovascular therapy, and pathophysiology of cerebral and spinal dural arteriovenous fistulas Lotfi Hacein-Bey a,∗ , Angelos Aristeidis Konstas b , John Pile-Spellman c,d a

Radiological Associates of Sacramento Medical Group Inc, 1500 Expo Parkway, Sacramento, 95815, USA UCLA Medical Center, Radiology Department, Los Angeles, USA c Neurological Surgery, P.C., 600 Northern Boulevard, Suite 118, Great Neck, 11021, USA d Columbia University, Department of Biomedical Engineering, New York, USA b

a r t i c l e

i n f o

Article history: Received 23 October 2013 Received in revised form 12 January 2014 Accepted 19 January 2014 Available online xxx Keywords: Dural Arteriovenous fistula Endovascular Angiography Magnetic resonance imaging

a b s t r a c t Dural arteriovenous fistulas (DAVFs) may occur anywhere there is a dural or meningeal covering around the brain or spinal cord. Clinical manifestations are mostly related to venous hypertension, and may be protean, acute or chronic, ranging from minor to severe, from non-disabling tinnitus to focal neurological deficits, seizures, hydrocephalus, psychiatric disturbances, and developmental delay in pediatric patients. Although low-grade lesions may have a benign course and spontaneous involution may occasionally occur (i.e. cavernous sinus DAVFs), the risk of hemorrhage is considerable in high grade lesions. Angiographic features of DAVFs have been clarified since the 1970s when venous drainage pattern was clearly identified as the most significant risk predictor and as a major determinant of success or failure of treatment. The mainstay of therapy is interruption of arteriovenous shunting, which has traditionally been accomplished surgically. Currently, endovascular therapy is generally considered the first line of treatment, allowing elimination of the lesion in most patients, with surgery and stereotactic radiosurgery reserved for complex situations. This review discusses major aspects of DAVFs, including grading systems, clinical presentation, diagnostic evaluation, various issues impacting endovascular therapy, and pathophysiology. © 2014 Elsevier B.V. All rights reserved.

Contents 1. 2. 3. 4. 5. 6.

7.

8.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Grading systems, natural history and prognostication factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Clinical presentation: highly variable . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Diagnostic evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . General facts about endovascular therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Practical aspects of endovascular therapy based on venous collector structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.1. Shunting into dural sinus (sinus-type DAVF) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.2. Shunting into leptomeningeal veins (non-sinus-type DAVF) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.3. Shunting into venous confluence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.4. Spinal DAVFs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pathophysiology and mechanism of formation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.1. Molecular factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2. Anatomical factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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∗ Corresponding author. Tel.: +1 916 646 8300; fax: +1 916 920 4434. E-mail address: [email protected] (L. Hacein-Bey). 0303-8467/$ – see front matter © 2014 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.clineuro.2014.01.018

Please cite this article in press as: Hacein-Bey L, et al. Natural history, current concepts, classification, factors impacting endovascular therapy, and pathophysiology of cerebral and spinal dural arteriovenous fistulas. Clin Neurol Neurosurg (2014), http://dx.doi.org/10.1016/j.clineuro.2014.01.018


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1. Introduction Dural arteriovenous fistulas (DAVFs) have been estimated to account for less than 10% of all cerebral vascular malformations [1,2]. Although DAVFs are uncommon in all populations, true prevalence is unknown. An epidemiological study conducted in Japan between 1998 and 2002 reported a detection rate for DAVFs of 0.29 per 100,000 adults per year [3]. Also, there are significant geographic variations in DAVF location, as most DAVFs diagnosed in the United States and Europe involve the sigmoid and transverse sinuses, while the cavernous sinus is the most commonly reported location in Asia, particularly Japan [3]. Since DAVFs involve dural and meningeal coverings, clinical presentation is in part determined by anatomical location. For instance, transverse-sigmoid junction and cavernous sinus DAVFs (the two most common locations) present respectively with pulsatile tinnitus and/or headache (tranverse-sigmoid sinus), or with cranial nerve deficits and ocular symptoms (cavernous sinus). DAVFs in other locations may present a variety of ways, the most dreaded being spontaneous hemorrhage. The major determinant of hemorrhagic risk is venous drainage pattern, especially cortical venous reflux; the severity of cortical venous reflux [2,4–6] correlates directly with “aggressive clinical presentation”, defined as either intracranial hemorrhage or nonhemorrhagic neurological deficit [5]. Interruption of arteriovenous shunting, which is the mainstay of therapy, was traditionally accomplished by open surgery, although endovascular therapy (transvenous and transarterial) has now become the preferred first line treatment modality. Adequate identification of the collecting venous structure which receives the arteriovenous shunts is a major determinant of treatment success, which is compounded by the additional difficulty that venous collectors may have a variety of configurations. 2. Grading systems, natural history and prognostication factors The annual risk of hemorrhage for unruptured DAVFs has been estimated to be 1.5–1.8% [6,7]. A recent study reported that patients presenting with hemorrhage experienced excess mortality until 7 years after admission [8]. However the risk of hemorrhage varies greatly for different DAVFs and depends mainly on two factors: (1) venous drainage pattern, particularly cortical venous reflux [2,4,5,7,9], and (2) the presence or absence of aggressive symptoms on clinical presentation [10]. Djindjian and Merland were the first in the 1970s to link angiographic findings to hemorrhagic risk in DAVFs, and their classification provides a foundation for the two most widely used subsequent grading systems [7], respectively devised by Cognard

[2] and Borden [4] (Table 1). All grading systems associate venous drainage pattern to risk of hemorrhage and neurological deficit. Increased hemorrhagic risk in high grade lesions is clearly related to retrograde venous drainage into thin-walled cortical veins [2,9,10]. In all classifications, low grade DAVFs (Grade I Merland–Djindjian, Grade I–IIa Cognard, Grade I Borden) have an annual risk of hemorrhage of 0%, intermediate lesions (Grade II Merland–Djindjian, Grade IIb, IIa+b Cognard, Grade II Borden) have a 6% annual hemorrhagic risk, and high-grade lesions (Grade III Merland–Djindjian, Grade III–V Cognard, Grade III Borden) have an annual risk of hemorrhage of 10% [9]. Cognard et al. also reported a dramatic increase in the incidence of aggressive clinical presentation with higher grade lesions. Low grade DAVFs had a 10% incidence of aggressive presentation, intermediate lesions had a 54% incidence of aggressive symptoms and high grade DAVFs had an 89% incidence of aggressive clinical presentation [2]. The presence of intracranial venous hypertension in intermediate and high grade lesions is the ultimate determinant of poor long term prognosis, either due to intracranial hemorrhage or non-hemorrhagic neurologic deficits [11]. However, not all intermediate or high grade DAVFs present with intracranial hemorrhage or neurologic deficits, although they are characterized by angiographic cortical venous drainage [2,10]. It has been suggested that the angiographic demonstration of cortical venous drainage does not necessarily indicate intracranial venous hypertension [10]. Asymptomatic or mildly symptomatic patients with cortical venous drainage have been reported to have a less aggressive clinical course [12], with a 10-fold lower annual event rate when compared to patients with cortical venous drainage and aggressive symptoms at presentation. Soderman et al. reported that the annual risk of hemorrhage was 7.4% in patients presenting with an intracranial bleed versus 1.5% in those not presenting with a hemorrhage [6]. Although no intracranial location is immune from harboring lesions with an aggressive presentation, two locations appear to have a higher hemorrhagic risk. In a series of 102 DAVFs, 69% of hemorrhages occurred either in anterior cranial fossa or in tentorial DAVFs, a disproportionately high rate given that these two locations accounted for 18% of the lesions in the series [5]. The higher risk of hemorrhage is thought to reflect the higher proportion of high grade lesions in these locations [5,13]. The natural history of DAVFs is further complicated by their dynamic nature and potential for long term changes in the venous drainage [6]. There are reports of low grade DAVFs developing cortical venous drainage during long term follow-up and resulting in new symptoms of intracranial venous hypertension or hemorrhage [2,13]. Three different mechanisms have been observed: stenosis or thrombosis of draining veins, increased arterial flow, or a new fistulous shunt [2,13]. Extrapolating from the series by Satomi et al. [13], it appears that the risk of developing cortical venous drainage

Table 1 Classifications for dural arteriovenous fistulas, all based on venous drainage pattern. Type

Merland and Djindjian 1977

Cognard 1995

Borden 1995

I

䊉 Dural sinus or meningeal vein

䊉 Dural sinus with normal antegrade flow

䊉 Dural sinus with cortical venous reflux

䊉 Dural sinus with reflux

䊉 Antegrade into dural sinus - Single meningeal feeder - Multiple meningeal feeders 䊉 Antegrade into dural sinus and retrograde into cortical vein

III

䊉 Purely into cortical vein

- Retrograde into dural sinus only - Retrograde into cortical veins only - Retrograde into dural sinus + cortical vein 䊉 Cortical vein only without venous ectasia

IV

䊉 Cortical vein with supra or infra-tentorial venous lake

Ia Ib II IIa IIb IIc

V

䊉 Exclusive retrograde drainage into cortical veins which may be dilated

䊉 Cortical vein only with venous ectasia (>5 mm and 3 times size of draining vein) 䊉 Intracranial DAVF drainage into medullary veins


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in low grade DAVFs is approximately 1% per year. Any change in clinical symptoms requires a detailed repeat angiogram [2]. At the other end of the spectrum, spontaneous regression and thrombosis of DAVFs have also been reported [14,15]. 3. Clinical presentation: highly variable DAVFs have a predilection for presenting in adults in the fifth to seventh decades of life [2]. Aggressive neurologic symptoms and associated cortical venous drainage are more common in males [2]. DAVFs in children and neonates are rare [16]. The two main modes of presentation are either intracranial hemorrhage, or non-hemorrhagic neurological manifestations, usually as a consequence of intracranial venous hypertension. In the seminal study by Cognard et al. [2], 18% of DAVFs presented with hemorrhage. A prospective, population study of patients with intracranial vascular malformations presenting with hemorrhage reported an 11:1 ratio in the incidence of hemorrhage caused by arteriovenous malformations compared to DAVFs [17], reflecting the higher prevalence of AVMs in the population. Pulsatile tinnitus is the most common presentation of DAVFs. Tinnitus, defined as experiencing auditory sensation in the absence of external stimuli, is considered pulsatile when it coincides with the patient’s heartbeat. When a bruit heard by the patient is perceptible to auscultation, the tinnitus becomes “objective”. DAVFs are the most common cause of objective pulsatile tinnitus in patients with a normal otoscopic exam [11–14], the most common site being the transverse-sigmoid junction. Other presentations in the absence of hemorrhage and presumably due to intracranial venous hypertension can by highly variable. Progressive dementia (venous hypertensive encephalopathy) has been reported as the mode of presentation in 12% of DAVFs [11], and is reversible after treatment [11]. Seizures [2], focal neurologic deficits [2–11], reversible parkinsonism [18], hydrocephalus due to defective CSF reabsorption [19], are also potential clinical presentations. Neonates typically present with congestive heart failure [16]. Often symptoms depend on the location and the anatomy of the lesion. Cavernous sinus and clival DAVFs most often present with ocular symptoms, i.e. diploplia from abducens or oculomotor nerve palsies and exophtalmos from retrograde drainage to the superior ophthalmic vein [15,16]. Cognard type V fistulas (drainage into perimedullary veins) often present with progressive myelopathy). DAVFs involving Meckel’s cave, or less commonly the transversesigmoid sinus may present with trigeminal neuralgia [20]. DAVFs in the craniocervical junction can present with brainstem ischemia [21]. Hypoglossal canal (anterior condylar) DAVFs can present with hypoglossal nerve palsy [22]. 4. Diagnostic evaluation Patterns of blood distribution in patients with intracranial hemorrhage from ruptured DAVFs are not specific and can be evaluated with noncontrast head CT or MRI. Intraparenchymal hemorrhage is the commonest pattern of intracranial bleeding [17] and is usually lobar. Subarachnoid hemorrhage (SAH) may be relatively more common in DAVFs with leptomeningeal or pure cortical venous drainage, while intraparenchymal hemorrhage may be seen in all forms of DAVFs. Cognard type V DAVFs have a relatively high propensity for presenting with SAH [2]. Intraventricular hemorrhage may result from transependymal extension of intraparenchymal hemorrhage, from ventricular recirculation of blood after SAH, or rarely from transependymal venous congestion [23]. Subdural hematoma is uncommon, but has been reported, especially with anterior cranial fossa (ethmoidal) DAVFs [24].

Fig. 1. Transarterial Onyx obliteration of sigmoid sinus DAVF (Grade I Cognard and Borden) with sinus preservation in a 52 year-old woman with pulsatile tinnitus. A: MRI imaging demonstrates flow voids in the wall of the left sigmoid sinus (arrow). B: Left external carotid artery, lateral view, shows enlarged petrosquamosal branch of middle meningeal artery connecting directly to sigmoid sinus (arrow). C: Left occipital artery, lateral view, shows limited number of transmastoid DAVF feeders connecting to sigmoid sinus wall (arrow). D: Superselective angiogram, anteroposterior view, with microcatheter tip (short arrow) in distal middle meningeal artery petrosquamosal branch shows relatively well defined vascular network surrounding the sinus wall (arrow). E: Anteroposterior view of sigmoid sinus shows cast of Onyx embolic material within DAVF (arrow). F: Left common carotid artery, late venous phase, antero-posterior view, shows preserved patency of left sigmoid sinus (arrow) after DAVF elimination.

In patients with neurological complaints, whether benign or aggressive, a combination of imaging studies is usually necessary to make the diagnosis and properly plan for treatment. Magnetic resonance imaging (MRI) or computed tomography (CT) are commonly the initial studies obtained, which may show dilated arterioles alongside the walls of dural sinuses (Figs. 1 and 2), dilated sinuses and large veins which fill in a retrograde fashion (Figs. 3 and 4 ), or enlarged cortical veins which may culminate in a “pseudophlebitic pattern” consistent with aggressive venous congestion possibly associated with leptomeningeal drainage (Fig. 3) [27,28]. A focused approach in relation to the patient’s symptoms and the possible location of the lesion is required when interpreting cross-sectional studies in patients with suspicion of DAVFs. For example, enlarged superior ophthalmic veins and proptosis can often be appreciated in cases of cavernous sinus or clival DAVFs (Fig. 3), and intra-osseous serpentine flow voids can often


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Fig. 2. Transvenous obliteration of left sigmoid sinus DAVF with retrograde venous drainage (Grade II a+c Cognard/Grade II Borden) causing severe headaches and pulsatile tinnitus in 47 year-old woman. A: Left external carotid artery, lateral view, shows enlarged petrosquamosal branch of middle meningeal artery connecting directly to sigmoid sinus (arrows) via a poorly defined vascular network. B: Left occipital artery, lateral view, shows large number of poorly defined transmastoid DAVF feeders connecting to sigmoid sinus wall (arrow). C: Left occipital artery, lateral view, late venous phase, shows stenosis of sigmoid sinus-jugular junction (arrowhead), and retrograde venous drainage in cavernous sinus and superior ophthalmic vein (long arrow) and vertebral venous plexus (short arrow). D: Left internal carotid artery, lateral view, shows poorly defined marginal tentorial arterial network (arrow) supplying the fistula. E: Left common carotid artery, lateral view, shows total DAVF obliteration and coil mass (thin arrow) in the sigmoid sinus. F: Left common carotid artery, lateral view, late venous phase, shows preserved vein of Labbé (broad arrow) outflow immediately proximal to coil mass (thin arrow).

be appreciated in anterior condylar DAVFs (Figs. 5 and 6) [29,30]. It is critical to remember that a normal MRI, MRA, or CTA does not exclude the presence of a DAVF and catheter angiography is required if there is ongoing clinical suspicion. Of note, MRI can provide complementary information not obtained by conventional catheter angiography. MRI can evaluate for associated hydrocephalus, other possible causes of pulsatile tinnitus, and white matter T2 hyperintensity as evidence for intracranial venous hypertension [31]. Reduction of the apparent diffusion coefficient (ADC) can be seen in patients with cortical venous drainage and neurological symptoms, but not in asymptomatic patients with cortical venous drainage, and hence it can be useful when assessing the severity of cortical venous drainage and resultant venous hypertension [32]. Also helpful in treatment planning, the combination of dynamic susceptibility contrast (DSC) MRI with susceptibility weighted imaging (SWI) [33] allows to evaluate the detailed anatomy of cortical veins. MRA and CTA have both recently undergone a major improvement with time-resolved techniques, which use the first pass effect

Fig. 3. Transvenous treatment of cavernous sinus DAVF (Grade IV Cognard/Grade III Borden) in 63 year-old female with right VIth nerve palsy and headache. A: Coronal T2 MRI shows prominent right cavernous sinus (arrow). B: Contrast-enhanced axial CT shows dilated round and serpiginous structures in the right cerebellum (arrow) suggesting venous ectasia. C: Right internal carotid artery, lateral view, arterial phase, shows early arterial shunting in dilated cavernous sinus (thin arrow), and early opacification of anterior cerebellar vein (broad arrow). D: Right internal carotid artery, lateral view, venous phase, shows dilated cerebellar veins with multiple venous varices (broad arrow). E: Lateral view shows coils within the cavernous sinus and the foot of the superior ophthalmic vein (arrow), obliterating DAVF. F: Right internal carotid artery, lateral view, arterial phase, shows elimination of arteriovenous shunting and coils within cavernous sinus (arrow).

of intravenous contrast to evaluate blood flow dynamics in the intracranial circulation. High-field (3 T) time-resolved MRA was credited in a recent study with a sensitivity and specificity of 100% compared to angiography for the screening, the follow-up and the post-treatment evaluation of intracranial DAVFs [34]. Around the foramen magnum, 4D contrast-enhanced time-resolved MRA has been reported to show great detail, which may facilitate DAVF treatment planning [35]. In addition to time-resolved technology, CTA has recently been enhanced by four-dimensional (4D) rendering with superb volume rendering from cross-sectional images which have higher spatial and temporal resolution. Another recent study found 4D CTA almost equivalent to angiography in diagnosing intracranial DAVFs, and in disclosing major arterial feeders in those deemed suitable for treatment [36]. However, the radiation dose delivered by 4D CTA was found to range between one half and two-thirds that of cerebral angiography [36]. Cerebral angiography remains the gold standard to diagnose DAVFs and for treatment planning, requiring catheterization of all possible arterial feeders and a thorough depiction of normal and




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abnormal veins, including potential access routes to the venous system [37]. The precise assessment of vascular anatomy around the fistulous venous collector is particularly crucial for proper treatment planning, especially in complex anatomical areas such as the anterior and posterior condylar confluences [25,38], the inferior petrosal sinus [29,39] the basal vein of Rosenthal (Fig. 4) [26] and the marginal sinus at the foramen magnum [31]. Superselective three dimensional (3D) angiography or venography have been advocated to help elucidate the vascular anatomy at the foramen magnum [39]. 5. General facts about endovascular therapy

Fig. 4. Transvenous coil obliteration of venous collector resulting in total elimination of extensive tentorial DAVF (Grade IV Cognard/Grade III Borden) in 55 year-old man. A: Axial T2 MRI image shows dilated venous structures adjacent to the right tentorial incisural insertion (arrow). B: Axial T2 MRI image shows dilated basal vein or Rosenthal posterior to the right cerebral peduncle (arrow). C: Axial T2 MRI image shows venous varix in basal vein or Rosenthal which reaches the galenic system (arrow). D: Right external carotid artery, lateral view, arterial phase, shows early arterial shunting in collector (thin arrow) reaching dilated basal vein of Rosenthal harboring venous varix (arrowhead). E: Right external carotid artery, anteroposterior view, arterial phase, shows early arterial shunting in collector (thin arrow) reaching dilated basal vein of Rosenthal harboring venous varix (arrowhead). F: Right internal carotid artery, lateral view, arterial phase, shows marginal tentorial artery with early shunting in collector (arrow) reaching dilated basal vein of Rosenthal. G: Left internal carotid artery, anteroposterior view, arterial phase, shows contralateral marginal tentorial artery with early shunting in collector (arrow) reaching dilated basal vein of Rosenthal. H: Lateral view showing catheter in right sigmoid sinus (arrowhead) and microcatheter in basal vein of Rosenthal (thin arrow) with tip and coil delivered within venous collector (short arrow). I: Right external carotid artery, anteroposterior view, late arterial phase, shows occluded venous collector with coils (arrow) and no residual

Spontaneous regression of DAVFs is possible, and has been reported, mostly in cavernous sinus lesions [40,41] but also in other locations [14,15]. Therefore, a conservative approach should be recommended in low grade asymptomatic DAVFs, or low grade mildly symptomatic DAVFs with symptoms not greatly impacting the quality of life. Digital compression of the carotid artery (using the contralateral hand) may enhance the chances of spontaneous thrombosis. Endovascular therapy is currently considered by many the first line of treatment for ruptured or higher grade DAVFs. Endovascular intervention may be performed transarterially or via the venous route; various embolic agents may be used, each with its own merits. Transvenous obliteration is credited with superior curative value over the transarterial approach whenever the venous collector can be entirely eliminated [42–46], with reported cure rates ranging between 80% and 100% [44]. The transvenous approach is safer when the participating sinus segment has minimal contributions to normal outflow, and hence can be completely occluded [44]. Similarly, it is not uncommon in transverse-sigmoid DAVFs for the arterial feeders to converge on a “parallel venous channel”, which is communicating, but distinct from the sinus, in which case obliteration of this channel results both in complete cure of the fistula and in preservation of the sinus [45]. Transvenous packing of the affected venous collector or dural sinus is most commonly performed with detachable coils. Tight packing must be obtained in order to prevent residual fistula with resultant cortical venous drainage and associated persistent hemorrhagic risk [44–46]. A double microcatheter technique can enhance the density of packed coils. Onyx embolic material (Ev3 Neurovascular, Irvine, CA) may be effectively used as well, usually in combination with coils. Retrograde transvenous catheterization of the fistulous sinus or vein may prove difficult for a variety of reasons [47]. Dural sinus stenosis, possibly severe, may be present, causing venous hypertension, in which case stent placement has been advocated, on the theoretical grounds that the radial force of the stent could result in both restoration of normal sinus venous flow, and occlusion of arterial shunts within the sinus wall [48,49]. However long-term results remain to be seen, and there are significant risks and technical limitations due to the stiffness of current stent delivery systems. Dural sinuses may also contain thrombus, which may still permit retrograde catheterization through the clot by gentle “drilling” with a microwire. Such approach is particularly useful in carotid sinus DAVFs where the often thrombosed inferior petrosal sinus is navigated with a microcatheter in order to access the cavernous sinus [50,51]. When petrosal sinus retrograde catheterization proves impossible, the cavernous sinus may still be approached

shunting. J: Axial T2 MRI image shows dilated metallic artifact from coils in vein in right tentorial incisural region (arrow). K: Axial T2 MRI image does not show anymore dilated basal vein or Rosenthal posterior to the right cerebral peduncle (arrow). L: Axial T2 MRI image shows thrombosed basal vein or Rosenthal venous varix (arrow).




Fig. 5. Left: C1 condylar intraosseous DAVF (Grade V Cognard/Grade III Borden) presenting as severe SAH treated with surgery, followed by transarterial acrylate embolization. A: Axial non contrast CT shows extensive subarachnoid blood in anterior medullary cistern extending into the foramen of Luschka (arrow). B: Left vertebral artery angiogram, anteroposterior view, arterial phase shows small DAVF in left C1 condylar region (broad arrow), draining into perimedullary veins (thin arrow). C: Axial contrast-enhanced CT after partial resection of left posterior arch of C1 shows surgical clip (arrow). D: Left vertebral artery angiogram, anteroposterior view, arterial phase shows small residual DAVF adjacent to left C1 condyle (short arrow), draining into perimedullary veins adjacent to surgical clip (thin arrow). Note microcatheter tip proximal to DAVF (arrowhead). E: Axial CT after shows embolic material in DAVF and proximal perimedullary draining vein (arrow). F: Left vertebral artery angiogram, anteroposterior view, late arterial phase shows no residual DAVF adjacent to surgical clip (arrow).

by catheter a variety of ways, including through the superior ophthalmic vein [52], the superior orbital fissure [53], the pterygoid plexus [54], the facial vein [55] or the superficial temporal vein [40]. Access to the intracranial venous system may be possible in selected cases by direct puncture through the skull to reach emissary foramina [56]. As a last resort, a surgical transphenoidal approach may allow access to the cavernous sinus [57], or similarly a subtemporal approach may allow exposure to the superficial middle cerebral vein [58]. Direct surgical approaches may also be

Fig. 6. Transarterial cyanoacrylate embolization of anterior condylar confluence DAVF causing transient monoparesis and transient global amnesia in 77 year-old man. A: Post-contrast sagittal T1 weighted MRI shows enhancing, dilated curvilinear vein (arrows) wrapping around the brainstem. B: Post-contrast axial T1 weighted MRI shows enhancing, tortuous, dilated vein (arrow) anterior to the medulla. C and D: Selective right ascending pharyngeal artery angiogram, anterior oblique (C) and lateral (D) views, showing anterior condylar confluence (thin arrow) DAVF with small osseous condylar component at shunt site (thick arrow), draining intracranially into both petrosal sinuses (arrowhead). E: Superselective catheterization of neuromeningeal trunk (thin arrow), with introducing catheter wedged into proximal right ascending pharyngeal artery (arrowhead) to provide flow arrest, shows exquisitely area of shunting (thick arrow). F: Selective right ascending pharyngeal artery angiogram, lateral view, obtained immediately after n-BCA embolization shows interruption of arteriovenous shunting (arrow) and contrast stagnation in veins. G and H: Axial T2 MRI images obtained at the level of the medulla and hypoglossal canals before (G) and a few weeks after treatment (H) show interval regression of dilated veins in hypoglossal canal (thick arrow), around right posterolateral medulla (thin arrow) and anterior to medulla (arrowhead).




used to reach the sigmoid sinus [59] or the superior sagittal sinus [60]. The risks associated with transvenous therapy include vascular rupture, intracranial hemorrhage [47], transient or permanent neurologic deficits related to changes in venous drainage course [61], and new, or worsening of pre-existing cranial neuropathies [61]. Transarterial embolization: In situations when transvenous access is not possible because of stenosis, exclusion or compartmentalization of the venous drainage system, transarterial therapy may be performed by accessing distal arterial feeders. This is often the preferred route of embolization with anterior cranial fossa (ethmoidal) DAVFs and tentorial DAVFs, where venous access may not be an option [24].

• Particulate agents may be used as adjunctive therapy, prior to surgery or radiosurgery. Although particles may succeed at reducing shunt flow, cures are uncommon because the occlusion sites are too proximal to the shunt(s), resulting in recanalization from collateral recruitment [24,40]. • The Onyx® liquid embolic material (ev3 Neurovascular, Irvine, CA) has become the transarterial agent of choice for cases where microcatheter position can be achieved within or very close to the point of arteriovenous communication (Fig. 1) [62–71]. Onyx® is a soft, non-adhesive, minimally thrombogenic embolic material which resembles a spongelike mass upon polymerization [62]. The combination of the active agent in Onyx, ethylene vinylalcohol copolymer (EVOH) with its solvent, dimethyl-sulfoxide (DMSO), was first described and used successfully by Taki in Japan [63] who used metrizamide as the opacifying agent instead of micronized tantalum, used in the current Onyx® formula. Onyx® is commercialized in the United States in two concentrations of increasing viscosity, 18 or 34 centipoises. Onyx® 18 contains 6% EVOH and 94% DMSO, and Onyx® 34 has 8% EVOH and 92% DMSO [50]. The lower viscosity of Onyx® 18 makes it the preferred agent for plexiform shunt configurations (Fig. 1), while Onyx® 34 is more suited for large, higher flow fistulas. In order to obtain homogeneous consistency and radiopacity, the Onyx® preparation must be shaken for at least 20 min prior to injection [65]. Although DMSO has potential angiotoxicity, its effect is negligible at usual infusion rates [50]. Reported cure rates for DAVFs treated with Onyx currently range between 60 and 100% [62,69,71]. • The other liquid embolic material currently available in the United States is the liquid polymer n-butyl-cyano-acrylate (nBCA), also referred to as “glue” and marketed as Trufill n-BCATM (Cordis Neurovascular Inc, Miami Lakes, FL). n-BCA is a fast acting liquid adhesive, where a polymer chain is immediately activated upon contact with anions present in blood as it is injected into the artery. Polymerization results in an exothermic reaction which causes irreversible endothelial and tissue injury and coagulation. Once the microcatheter is in the desired position, its lumen must be cleared from ionic material (blood or contrast medium) with a flush of a dextrose solution (usually 5%). n-BCA is commonly mixed with an ethiodized oil, i.e. lipiodol, which confers some degree of radiopacity to the embolic agent, and lengthens the mixture’s polymerization time by acting as a temporary buffer between the monomer and blood. Tantalum powder may be added to the mixture to increase radiopacity. Glacial acetic acid, when added in microliter amounts, may be used to further lengthen polymerization times in high-flow lesions [72]. The injection of lower concentration mixtures allows proximal venous penetration of the liquid adhesive, which maximizes the efficacy of treatment [40,73–74].

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6. Practical aspects of endovascular therapy based on venous collector structure 6.1. Shunting into dural sinus (sinus-type DAVF) Two major shunting configurations may be associated with “sinus-type” DAVFs: “plexiform”, i.e. consistent with a limited number of anatomically definable shunts (Fig. 1), or “diffuse” (Fig. 2). The former pattern may allow distal feeding artery catheterization to the level of arteriovenous communication, in which case transarterial embolization with Onyx material or n-BCA glue may be curative with dural sinus preservation (Fig. 1). On the other hand, if there is a large number of distal arterioles, from multiple sources, in a diffuse pattern, the safest and only effective endovascular option is therapeutic dural sinus occlusion, usually performed with thrombogenic coils (Fig. 2). In Western countries, the transverse-sigmoid sinus location is the most common site for DAVFs, and many present with benign symptoms. Aggressive clinical presentation correlates well with venous drainage pattern, so that the classification system devised by Lalwani et al. [75], may help decide about treatment strategy: Grade 1 transverse-sigmoid sinus DAVFs have antegrade sinus drainage without venous restriction or cortical venous reflux; Grade 2 have both antegrade and retrograde sinus drainage with or without cortical venous reflux; Grade 3 have only retrograde sinus drainage with cortical venous reflux, and Grade 4 lesions have cortical venous reflux only. Spontaneous regression is relatively rare (5%) and usually occurs after hemorrhage [76]. The overall rate of permanent complications for transvenous therapy in direct shunt DAVFs is 4% [46]. For cavernous sinus DAVFs which present with aggressive clinical signs and/or cortical venous drainage, and therefore requiring treatment, transvenous therapy may be the safer option (Fig. 3), as the usual arterial feeders may supply vasa nervorum, including those of the second through seventh cranial nerves. Transvenous sacrifice of one of two paired (such as the sigmoid or transverse) dural sinuses may appear acceptable because the contralateral channel is left in place. In fact, most dural sinuses, including large segments of the superior sagittal sinus, may be obliterated safely [43]. In addition, most DAVFs requiring treatment have been present for some time, allowing the development of effective compensatory transmedullary venous channels. Superior sagittal sinus DAVFs often present with psychiatric disturbances due to bilateral frontal lobe involvement, with retrograde cortical venous drainage, and with sinus thrombosis. Whenever possible, transarterial embolization should be attempted. However, retrograde sinus catheterization may allow shunt elimination, either via access to cortical veins [40], or to feeding arteries [77]. Whenever transvenous sinus interruption is not possible by endovascular means in aggressive lesions, surgery should be considered. 6.2. Shunting into leptomeningeal veins (non-sinus-type DAVF) Non-sinus type DAVFs drain into one or more leptomeningeal veins, which arise from a venous “collector”. Adequate identification of the venous collector may be difficult, particularly in the face of severe venous hypertension. Tentorial DAVFs drain directly into leptomeningeal veins, which is why they often present with higher grades (Cognard III-IV; Borden III), aggressive neurological presentation (10%/year), and with a hemorrhage in 60–74%, often fatal when it involves the posterior fossa [2]. The venous drainage commonly involves the basal vein of Rosenthal, which may be tortuous and harbor venous ectasias (Fig. 4). Transvenous therapy may be curative if a venous collector is clearly identified, and may be reached through retrograde catheterization of intracranial veins (Fig. 4). Whenever those conditions




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are not met, transarterial embolization may be the safer approach, preferably with a low concentration of n-BCA liquid polymer mixture in order to promote passage into the proximal vein. Anterior cranial fossa DAVFs are also associated with higher grades and increased likelihood of aggressive neurological manifestation or hemorrhage. They are often supplied by meningeal branches of the ophthalmic artery, including the anterior falcine branch, and often drain into tortuous, aneurysmal, intracerebral veins. Although surgical access to these lesions is recommended as it relatively straightforward and safe, transarterial embolization may be safely performed by microcatheter positioning distal to the central retinal artery [78]. DAVFs which drain directly into cortical veins [24] are preferably treated with transarterial therapy whenever safe distal arterial catheterization and proximal vein embolic penetration may be achieved. 6.3. Shunting into venous confluence Certain anatomical locations such as the anterior condylar confluence, the marginal sinus, the petrosal sinus or the posterior condylar confluence may rarely harbor DAVFs [23,24,26], in which case a venous drainage pattern may be more difficult to characterize owing to their multiple connections. In anterior condylar confluence DAVFs, the area of arteriovenous shunting is located in the hypoglossal (anterior condylar) canal, and venous drainage may borrow various paths (Fig. 6). Although transvenous therapy is considered the preferred treatment for those lesions [24–26], access to the venous collector, or disconnection of symptomatic intracranial or spinal veins may not be possible. Arterial feeders to these DAVFs usually supply critical structures, cranial nerves or other. Therefore, planning for the treatment of these lesions should include teams of specialized individuals. 6.4. Spinal DAVFs Spinal DAVFs represent 80–85% of spinal cord shunts. Arterial supply is from radiculomeningeal branches of segmental spinal arteries (anterior or posterior radicular arteries) and venous drainage is retrograde toward the spinal cord and into underlying medullary veins (Fig. 7) [79]. The shunt is typically located in the dura mater around the sensory ganglion of the proximal nerve root. As suggested by Aminoff [80], spinal DAVFs become symptomatic from flow reversal in the perimedullary veins causing spinal cord venous hypertension, venous ischemia, eventually resulting in the devastating necrotizing myelopathy described by Foix and Alajouanine [81]. Within the two layers of the dura, a vascular structure resembling a glomerulus has been described [82,83], which role is to maintain intraspinal venous pressure constant, despite frequent and significant changes in intra-abdominal or intra-thoracic pressures. This glomerulus-like structure consists of the terminal portion of radiculo-medullary veins, which, upon entering the arachnoid and the dura, become tortuous and narrow, so as to prevent passage of venous blood from the epidural venous plexus to the intradural space. At some point, the wall of the radiculo-medullary vein is replaced by a meningeal cuff [83], possibly leading to active connections between spinal arteries and perimedullary veins. Because of this anatomical configuration, endovascular treatment should aim at thoroughly obliterating the origin of the proximal draining vein (Fig. 7) to prevent recurrence. 7. Pathophysiology and mechanism of formation 7.1. Molecular factors A clear understanding of the mechanism of development of DAVFs is still lacking. Although occasionally found in the perinatal

Fig. 7. Transarterial cyanoacrylate embolization of spinal DAVF causing paraparesis in 57 year-old man. A: Sagittal T2 thoracic spine MRI shows significantly edematous lower thoracic cord (large arrow) and serpiginous flow voids consistent with dilated vascular structures anterior and posterior to the spinal cord (thin arrows). B: Sagittal T2 lumbar spine MRI shows large serpiginous flow void below the conus medullaris consistent with a dilated vein (arrowhead). C: Right L2 spinal angiogram, anteroposterior view, late arterial phase shows dilated perimedullary veins (arrow). D: Right L2 spinal superselective angiogram, anteroposterior view, unsubtracted view, shows catheter tip in fistula (large arrow) dilated perimedullary veins (small arrow). E: Right L2 spinal superselective angiogram, anteroposterior view, early arterial phase shows catheter tip in fistula (large arrow) dilated perimedullary veins (small arrow). F: Plain X-ray anteroposterior view shows embolic material in fistula (large arrow) and in proximal vein (small arrow).

period, the overwhelming majority of DAVFs appear to be acquired. Venous thrombosis and venous hypertension were the first factors identified as major triggers in DAVF formation [84–86]. Arterial feeder recruitment and DAVF growth appear to be related to angiogenesis, as shown by enhanced dural expression of vascular endothelial growth factor (VEGF) [87,88]. A more comprehensive mechanistic model was then advanced, based on the observation that non-ischemic venous hypertension in the brain results in a pro-angiogenic state resulting in upregulation of hypoxia-inducible factor-1 (HIF-1) expression. HIF-1 directly increases angiogenesis by increasing expression of VEGF in surrounding tissue, and of stroma-cell derived factor alpha (SDF-1 ␣) in macrophages, and indirectly increases neutrophilic activity of MMP-9 matrix metalloproteinase, in a large part via inflammatory cytokines such as interleukin-6 [89,90]. Once arteriovenous shunting is established, VEGF stimulation may be maintained by endothelial shear stress




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Fig. 8. Drawing illustrating the presumed mechanism of formation of dural fistulas (Figure courtesy of AristomenisThanos, MD). A: Coronal view of cerebral convexity at the level of the superior sagittal sinus. B: Close-up of A showing initial event consistent with thrombus in dural sinus (arrow). C: Non-ischemic venous hypertension results in upregulation of hypoxia-inducible factor-1 (HIF-1) expression, which, in turn, initiates an angiogenicresponse. Microscopic fistulas develop within the wall of the thrombosed sinus (arrow) and extend. There is also enlargement of dural arteries within the two layers of the dura (arrowhead). D: Following recanalization of the occluded sinus the fistula becomes active with arteriovenous shunting (arrow).

and nitric oxide (NO) production [89–92]. Whether the cause or the result of hemodynamic disturbance, thrombophilic abnormalities clearly also play a role, as shown by elevated blood D-Dimer levels in active DAVFs, which are consistently reversed after successful treatment [93]. Whichever factors may cause the molecular derangements leading to DAVF formation may also induce multiple, migrating and metachronous DAVFs. The presence of two, three or even four DAVFs in the same patient has been reported and estimated to occur in up to 8% of patients [94,95]. Although the presence of cortical venous drainage has been advanced as a possible causal factor to explain multiplicity of lesions [95], both phenomena may merely be indirect consequences of molecular disturbances affecting venous integrity and coagulation mechanisms. Migration of DAVF from one location to another has also been reported [96] as has been the occurrence of a new DAVF after successful prior elimination of another [97]. Conversely, spontaneous elimination of a DAVF, although uncommon, is a recognized occurrence [14,15]. Why exactly venous hypertension and local thrombophilia occur in specific and predictable locations within the cerebral venous system of some patients, possibly resulting in DAVFs still remains unclear. A three-stage hypothesis for the formation of DAVFs has been proposed [98]. Stage 1 – the initial event is venous sinus thrombosis; Stage 2 – microscopic fistulas develop within the wall of the thrombosed venus sinus connecting vaso vasorum to small venous tributaries. This process is dependent on angiogenic factors; Stage 3 – recanalization of the thrombosed sinus occurs (Fig. 8). 7.2. Anatomical factors A better understanding of DAVF behavior as relates to drainage pathways may be derived from a recent classification based on embryological differences between three distinct epidural venous systems, which all ultimately communicate with major venous collectors, i.e. jugular, azygos and paravertebral veins [99]. The dorsal epidural group results from the merging of calvarial osseous and cerebral leptomeningeal veins and comprises the following dural sinuses: superior sagittal, transverse, sigmoid, medial occipital,

Fig. 9. Illustration of possible emissary vein origin to DAVF in 58 year-old woman presenting with large left occipital lobe hemorrhage. A–C: Non contrast CT shows left occipital pole hemorrhage (arrow) extending to the cortical surface (arrowhead). D: Left occipital artery angiogram, anteroposterior view, shows aneurysmal dilata-tion of left occipital artery (large arrow), and suspicious small arteries (thin arrow). E: Left occipital artery angiogram, lateral view, shows small rami off left occipital artery crossing the diploic space (arrow). F: Axial T2 MRI image obtained at the time of hemorrhage shows left occipital lobe hematoma (large arrow), and linear intradiploic structure at the same level (thin arrow). G: Axial post-contrast T1 MRI image obtained several months after hemorrhagic event shows enhancing left occipital scalp vascular lesion corresponding to aneurysmal occipital artery (arrow). H: Axial post-contrast T1 MRI image obtained several months after hemorrhagic event shows dilated emissary arteries crossing the diploe (thin arrows), and left occipital lobe curvilinear hemosiderin containing area corresponding to prior hemorrhage.

and posterior marginal sinuses and torcular Herophili; this group comprises about 22% of DAVFs (Figs. 1 and 2). The lateral epidural venous space includes all emissary or bridging veins which drain the brain and spine, and which, unlike their corresponding arteries, do not closely follow cranial and peripheral nerves. The lateral epidural venous system includes the marginal sinus at the foramen magnum, emissary veins at the anterior and posterior condylar confluences, the vein of Galen, the petrosal, basitentorial, sphenoparietal, cavernous sinuses, and intraorbital and cribriform plate veins, and gives rise to about 21% of DAVFs (Figs. 3 and 6). Lastly, the ventral epidural space, from which may originate about 50% of all DAVFs, is located within spongious bony structures of the basiocciput, petrous bone, basisphenoid and adjacent sphenoid wings, and related dural structures (Figs. 4 and 5) [99]. The reason why arteriovenous shunting may be present in a variety of venous structures, including within the walls of dural sinuses, cortical veins or emissary veins is still unclear. Miyachi et al. [100], suggest that DAVFs may originate within emissary foramina (within bony or arachnoid structures) as shunting between emissary arteries and veins resulting from inflammation




or microtrauma, and may either involute or secondarily extend to larger venous structures, i.e. dural sinuses or cortical veins, under the influence of cytokines and angiogenic factors (Figs. 8 and 9).

8. Conclusion Dural arteriovenous fistulas remain incompletely characterized lesions despite recent advances in our understanding of the molecular mechanisms of vasculogenesis and angiogenesis. Perhaps the most important factor impacting risk stratification and treatment success is the anatomical configuration of DAVF, and in particular the presence of cortical venous drainage, especially in the conjunction with an aggressive clinical presentation. Careful assessment of the anatomy, multidisciplinary evaluation of treatment options, and a high level of attention to technique are all necessary to obtain the best possible outcomes.

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Endovascular therapy for intracranial dural arteriovenous fistulas.

Endovascular treatment of intracranial dural arteriovenous fistulas.

Surgical management of spinal dural arteriovenous fistulas.

Endovascular Treatment of Dural Arteriovenous Fistulas: Single Center Experience.

Endovascular treatment of intracranial dural arteriovenous fistulas with spinal perimedullary venous drainage.

Spinal dural arteriovenous fistulas: how, when, and why.

Recurrence Rates After Surgical or Endovascular Treatment of Spinal Dural Arteriovenous Fistulas: A Meta-analysis.

Aneurysms, arteriovenous malformations, and dural arteriovenous fistulas: diagnosis and treatment.

Comparison of surgical and endovascular approach in management of spinal dural arteriovenous fistulas: A single center experience of 27 patients.

Endovascular treatment of a spinal dural arteriovenous malformation (DAVF).

Endovascular treatment and computed imaging follow-up of 14 anterior condylar dural arteriovenous fistulas.

A variant of arteriovenous fistulas within the wall of dural sinuses. Results of combined surgical and endovascular therapy.

Treatment of Dural Arteriovenous Fistulas with Cortical Venous Reflux-Endovascular Therapy and Surgery Preferred Modality of Treatment.

Embryological Consideration of Dural Arteriovenous Fistulas.

Bilateral cervical spinal dural arteriovenous fistulas with intracranial venous drainage mimicking a foramen magnum dural arteriovenous fistula.

Treatment options for symptomatic dural arteriovenous fistulas.

Dural arteriovenous fistulas: evaluation with MR imaging.

Dural arteriovenous fistulas supplied by ethmoidal arteries.

Spinal dural arteriovenous fistula.

Spinal dural arteriovenous fistulas--presentation, management and outcome in a single neurosurgical institution.

Diagnosis and management of intracranial dural arteriovenous fistulas.

Multiple dural arteriovenous fistulas causing rapid progressive dementia successfully treated by endovascular surgery: case report.

Long-term outcomes after surgical and endovascular treatment of spinal dural arteriovenous fistulae.

Late diagnosis of spinal dural arteriovenous fistulas resulting in severe lower-extremity weakness: a case series.