Combined Treatment of Brain AVMs with Use of Onyx Embolization followed by Radiosurgery

BACKGROUND AND PURPOSE:The treatment of cerebral AVMs is complex, reliant on interventions such as embolization, surgery, and radiosurgery, or a combination of these modalities. To date, treatment with the embolic agent Onyx, followed by radiosurgery, has not been evaluated. The goal of this study was to evaluate the safety and efficacy of this combination in a homogeneous, monocentric series.MATERIALS AND METHODS:From April 2003 to June 2008, a total of 20 patients (11 women and 9 men; age range, 10–55 years) were treated for AVMs with Onyx embolization followed by radiosurgery. AVM sizes were <3 cm in 7 patients and ≥3 cm in 13 patients. Modalities and complications of the procedure were analyzed as well as the long-term clinical and anatomic outcomes (2–5 years after treatment).RESULTS:Of 17 patients evaluated by DSA after radiosurgery, 10 (58.8%) were observed to have complete occlusion of the AVM nidus. Complete occlusion was observed in 5 (71.4%) of 7 Spetzler-Martin grade I–II AVMs and in 5 (50.0%) of 10 Spetzler-Martin grade III–IV AVMs. Complete occlusion was observed in 4 (80.0%) of 5 AVMs of <3 cm and 6 (50.0%) of 12 AVMs of >3 cm. One of 20 patients had significant worsening of clinical status (mRS ≥2) at long-term follow-up.CONCLUSIONS:In this preliminary series, the safety and efficacy of combined treatment by Onyx embolization followed by radiosurgery are quite satisfactory, with a low rate of clinical complications (5.0%) and a 58.8% rate of complete obliteration of the AVM.

Cerebral AVMs are associated with significant morbidity and mortality related to intracerebral hemorrhage, seizures, and progressive neurologic decline.¹ The treatment of cerebral AVMs can be quite complicated, and indication for treatment in some clinical situations is controversial (eg, for asymptomatic AVMs). Moreover, several modalities of treatment are available (surgery, radiosurgery, and embolization), and these modalities can be used in combination for some AVMs.Several techniques are available for embolization, dependent on the embolization agent used and technique of microcatheterization. For many years, embolization with n-BCA has been standard clinical practice for the treatment of brain AVMs. In the last 10 years, n-BCA has been progressively replaced by Onyx (ev3, Irvine, California), a copolymer that precipitates when coming into contact with blood.^2–5 The progression of Onyx when injected into a brain AVM follows a lavalike flow pattern and is not associated with the risks of gluing the distal portion of the microcatheter as when using n-BCA. Onyx injections can be more prolonged and controlled compared with n-BCA, making it possible to occlude larger portions of the nidus during each injection.The combination of embolization and radiosurgery is often used in the treatment of brain AVMs; however, the effectiveness of this combination remains controversial. Some series have suggested that embolization before radiosurgery was associated with lower obliteration rates and worse outcomes.^6,7 Several mechanisms have been suggested to explain lower obliteration rates, including recanalization of the nidus after embolization, enhanced angiogenesis after embolization (as demonstrated in animal models), difficulty in delineation of the nidus after embolization, and beam attenuation by the liquid embolization material.In most studies dedicated to the combination therapy of embolization followed by radiosurgery for the treatment of brain AVMs, particles or glue were used as the embolization agent.^6,8,9 To our knowledge, no study to date has evaluated embolization with Onyx followed by radiosurgery. To very precisely evaluate the combined therapy of Onyx embolization and radiosurgery, we conducted a monocentric, retrospective study, with all patients having very homogeneous modalities of treatment with embolization and radiosurgery.     

Imaging Artifacts of Liquid Embolic Agents on Conventional CT in an Experimental in Vitro Model

BACKGROUND AND PURPOSE:Endovascular embolization using liquid embolic agents is a safe and effective treatment option for AVMs and dural arteriovenous fistulas. The aim of this study was to assess the degree of artifact inducement by the most frequently used liquid embolic agents in conventional CT in an experimental in vitro model.MATERIALS AND METHODS:Dimethyl-sulfoxide–compatible tubes were filled with the following liquid embolic agents (n = 10, respectively): Onyx 18, all variants of Squid, PHIL 25%, PHIL LV, and n-BCA mixed with iodized oil. After inserting the tubes into a CT imaging phantom, we acquired images. Artifacts were graded quantitatively by the use of Hounsfield units in a donut-shaped ROI using a customized software application that was specifically designed for this study and were graded qualitatively using a 5-point scale.RESULTS:Quantitative and qualitative analyses revealed the most artifacts for Onyx 18 and the least artifacts for n-BCA, PHIL 25%, and PHIL LV. Squid caused more artifacts compared with PHIL, both for the low-viscosity and for the extra-low-viscosity versions (eg, quantitative analysis, Squid 18: mean ± SD, 30.3 ± 9.7 HU versus PHIL 25%: mean ± SD, 10.6 ± 0.8 HU; P < .001). Differences between the standard and low-density variants of Squid were observed only quantitatively for Squid 12. There were no statistical differences between the different concentrations of Squid and PHIL.CONCLUSIONS:In this systematic in vitro analysis investigating the most commonly used liquid embolic agents, relevant differences in CT imaging artifacts could be demonstrated. Ethylene-vinyl alcohol–based liquid embolic agents induced more artifacts compared with liquid embolic agents that use iodine as a radiopaque component.

In addition to microneurosurgery and stereotactic radiation therapy, endovascular embolization using liquid embolic agents (LEAs) is an effective treatment mode for the therapy of cerebral AVMs or cranial dural AVFs. Depending on the type and extension of the vascular malformation, the endovascular treatment can be performed either alone or in combination with one of the other methods.¹For the treatment of such vascular malformations, several LEAs, each with different properties, are currently available on the market. The most commonly used nonadhesive material is Onyx (Medtronic), a LEA consisting of an ethylene-vinyl alcohol (EVOH) copolymer, dimethyl-sulfoxide, and tantalum powder. Numerous studies have demonstrated the effectiveness and safety of Onyx for the treatment of vascular malformations.^2,3 Another LEA, also based on EVOH and tantalum powder is Squid (Balt Extrusion), which has been commercially available since 2012, with its low-viscosity versions, Squid 18 and Squid 18 low density (LD), and its extra-low-viscosity versions, Squid 12 and Squid 12 LD. For adequate visibility during embolization, radiopacity for these 5 nonadhesive agents is induced by the admixed tantalum powder.^4,5 The difference between Onyx and Squid is that for Squid, the tantalum powder consists of a smaller “micronized” grain size, which is aimed at enhancing the homogeneity in radiopacity and improving the visibility during longer injections times.⁵ The aim of the LD variants of Squid is to reduce the radiopacity to improve the differentiation of the embolized and nonembolized parts of the malformation without influencing the embolic properties.A further commercially available LEA, which was introduced recently, is Precipitating Hydrophobic Injectable Liquid (PHIL; MicroVention) with its low-viscosity version PHIL 25% and its extra-low-viscosity version PHIL low viscosity (LV).^6,7 PHIL is a nonadhesive precipitating embolic agent that consists of 2 specific copolymers [poly(lactide-co-glycolide) and polyhydroxyethylmethacrylate] as its active ingredients and triiodophenol (an iodine compound), which is covalently bound to the copolymers, thus enabling the intrinsic radiopacity of PHIL.^8,9Before the introduction of these nonadhesive embolic agents, which are all based on the mechanism of precipitation, liquid embolization was predominantly performed with adhesive cyanoacrylates. The active component of cyanoacrylates is n-butyl cyanoacrylate (n-BCA), which is available in different chemical compositions and is normally mixed with iodized oil for adequate radiopacity. Even though the use of cyanoacrylates has decreased since the introduction of the above-mentioned nonadhesive LEAs,^10,11 n-BCA and its derivates are still used effectively in particular situations, for example, for the treatment of high-flow malformations and for specific techniques such as the pressure cooker technique.¹²A major drawback of LEAs is imaging artifacts, predominantly in CT.^13,14 Because intracranial vascular malformations are associated with an increased risk of peri- and postprocedural hemorrhage, embolization-related artifacts can represent a crucial obstacle in the detection of intracranial blood during or after embolization in CT.¹⁵ Furthermore, some vascular malformations, especially complex AVMs, cannot be completely occluded by endovascular means, requiring subsequent radiation therapy afterward.¹ The corresponding treatment-planning recordings are usually based on conventional CT imaging.¹⁶ Thus, embolization-related artifacts represent another substantial drawback for adequate and safe treatment planning of further radiation projects.^17-19Systematic data for imaging artifacts of LEAs is rare. To our knowledge, to date, only a few reports with low case numbers that investigated the imaging artifacts of the above-mentioned LEAs (Onyx versus PHIL and Onyx versus Squid) are available.^13,14 The differences in CT artifacts between Squid and PHIL, between nonadhesive LEAs and n-BCA, and imaging artifacts of the extra-low viscosity LEAs Squid 12 and PHIL LV were not the focus of research until now.The aim of the present study was the systematic assessment of artifacts of the most commonly used LEAs in conventional CT in an in vitro tube model.     

Dual-Lumen Balloon Catheters May Improve Liquid Embolization of Vascular Malformations: An Experimental Study in Swine

BACKGROUND AND PURPOSE:Liquid embolic agents are increasingly used to treat vascular malformations. We sought to assess embolization with these agents by using a dual-lumen balloon catheter in an experimental setting.MATERIALS AND METHODS:Eighteen injections of liquid embolic agents were performed in the rete mirabile of swine. We used 3 methods to control liquid embolic agent reflux: 1) dual-lumen balloon-catheter (group A, n = 8); 2) injection of liquid embolic agent after proximal n-BCA plug formation through a second microcatheter (group B, n = 4); and 3) standard liquid embolic agent injection (group C, controls, n = 6). The following outcomes were graded by using ordinal scales by angiography, macrophotography, and radiography of retia after euthanasia: 1) angiographic and pathologic extent of liquid embolic agent embolization of the rete, 2) reflux of liquid embolic agents in the parent artery, and 3) density of liquid embolic agents in the proximal rete. Technical complications were also recorded. A successful injection was defined as an embolization that reached the contralateral rete without reflux into proximal external branches. Exact logistic regression analyses were performed to compare groups.RESULTS:There were significant differences among groups for reflux (P = .029) and liquid embolic agent density in the proximal rete (P = .014), while extension to the contralateral rete did not reach statistical significance (P = .07). Injections differed among groups (P = .004), with dual-lumen balloon-catheter injections more frequently successful compared with control injections (P = .019).CONCLUSIONS:Dual-lumen balloon catheters allowed better liquid embolic agent injections than standard injections.

Ethylene-vinyl alcohol copolymer liquid embolic agents (LEAs) have changed the management of vascular malformations such as arteriovenous malformations and dural arteriovenous fistulas.^1–4 LEAs such as Onyx (Covidien, Irvine, California) can be injected through small microcatheters, and on injection, they precipitate out of the dimethyl-sulfoxide solvent and slowly harden after coming in contact with blood. These agents are cohesive rather than adhesive and perhaps better controlled than other agents such as n-BCA. In many cases, these features (of LEAs such as Onyx/Phil) may permit longer injections and possibly more complete embolizations than other LEAs.¹The standard method used to control injections is to slowly inject the LEA, allowing some reflux for a short plug proximal to the catheter tip to form and harden, and to wait for the LEA to preferentially move in an antegrade direction deep into the nidus of the malformation. One factor potentially limiting the efficacy of the injection is excessive reflux of LEA back along the catheter, which can enter and occlude unwanted vessels.⁵ Additionally, if a segment of microcatheter that is too long is left in contact with the LEA for too long, the proximal plug may entrap the catheter tip in place. Removal of entrapped catheters has led to intracranial hemorrhages, leading to an FDA warning regarding this aspect of treatment with Onyx.⁶Several potential solutions to these problems have been proposed. One option is to use 2 microcatheters together: One microcatheter with a detachable tip is used for the injection of the LEA, while the other microcatheter is used to deliver n-BCA quickly, intentionally gluing the detachable portion of the first catheter, forming the proximal plug that will prevent reflux of LEA, and ensuring antegrade embolization of the nidus.^7–9 Another option is to use a dimethyl-sulfoxide–compatible dual-lumen balloon catheter, in which 1 lumen is used to inflate a balloon and prevent reflux, while the second lumen delivers the embolic agent (Scepter; MicroVention, Tustin, California).^5,10Animal models may be useful to inform clinical applications of embolic agents.^11–14 We sought to explore whether using a dual-lumen balloon catheter could improve embolization of the swine rete (a model often used for experimental AVM embolization)^12,15,16 and prevent excessive reflux compared with more traditional techniques. We hypothesized that the use of the balloon would promote more complete nidus filling with less reflux and fewer complications than other methods.     

Embolization of Intracranial Dural Arteriovenous Fistulas Using PHIL Liquid Embolic Agent in 26 Patients: A Multicenter Study

BACKGROUND AND PURPOSE:The introduction of liquid embolic agents has revolutionized endovascular approach to cranial vascular malformations. The aim of the study was to retrospectively assess the efficacy and safety of Precipitating Hydrophobic Injectable Liquid (PHIL), a new nonadhesive liquid embolic agent, in the treatment of patients with cranial dural arteriovenous fistulas. The primary end point was the rate of complete occlusion of dural arteriovenous fistulas. Secondary end points included the incidence of adverse events and clinical status at 3-month follow-up.MATERIALS AND METHODS:This was a retrospective multicenter study. Twenty-six consecutive patients with dural arteriovenous fistulas (de novo or previously treated) treated by injection of PHIL only or with PHIL in combination with other embolization products (such as Onyx or detachable coils) were included in the study. Recruitment started in August 2014 and ended in September 2015.RESULTS:Twenty-two (85%) patients were treated with PHIL only, with 3 patients treated with both PHIL and Onyx, and 1, with both PHIL and coils. Immediate complete angiographic occlusion was achieved in 20 (77%) patients. Of the 6 patients with residual fistulas, 3 were retreated with PHIL and 1 achieved angiographic cure. An adverse event was seen in 1 patient who developed worsening of preexisting ataxia due to acute thrombosis of the draining vein.CONCLUSIONS:PHIL appears to be safe and effective for endovascular treatment of cranial dural arteriovenous fistulas. Short-term angiographic and clinical results are comparable with those of Onyx, with the added advantage of easier preparation and improved homogeneous cast visualization. The use of iodine as a radio-opacifier also produces considerably less artifacts on CT compared with tantalum-based embolic materials.

Dural arteriovenous fistulas (DAVFs) are a rare type of acquired intracranial vascular malformation consisting of a pathologic shunt located within the dura mater of the brain.^1–3 These lesions have been categorized by Awad et al,⁴ Borden et al,⁵ and Cognard et al⁶ according to their locations and patterns of venous drainage. Acute presentation with intracranial hemorrhage occurs in up to 65% of patients,⁶ and patients with a previous intracranial hemorrhage may have up to a 35% risk of another neurologic event within 2 weeks.⁷Endovascular embolization has become the primary treatment approach for DAVFs.^1,8,9 The goal of endovascular therapy is to achieve complete obliteration of the fistulous point between the feeding arteries and the draining veins. This can be safely accomplished by occluding the draining veins, which often results in complete closure of the lesion, unlike in cerebral arteriovenous malformations.The introduction of liquid embolic agents has a significant impact on the endovascular approach to DAVFs. Precipitating Hydrophobic Injectable Liquid (PHIL; MicroVention, Tustin, California) is a new nonadhesive liquid embolic agent comprising a copolymer dissolved in dimethyl-sulfoxide (DMSO). It is delivered by slow and controlled injection through a DMSO-compatible microcatheter under fluoroscopic control. An iodine component is chemically bonded to the copolymer to provide homogeneous radio-opacity during fluoroscopic visualization. When it comes in contact with human blood, the DMSO solvent dissipates, causing the copolymer to precipitate in situ into a coherent embolus. The PHIL liquid embolic system is available in 3 formulations: 25%, 30%, and 35%. PHIL 25% will travel more distally and penetrate deeper into the fistula due to its lower viscosity compared with PHIL 30% or 35%. The latter 2 are more appropriate for use in high-flow arteriovenous shunts with ≥1 direct fistula. Higher strength formulations are also preferred when increased fluoroscopic visibility is desirable.The aim of our study was to assess the efficacy and safety of PHIL in the treatment of patients with cranial DAVFs.     

Hemorrhagic Complications after Endovascular Treatment of Cerebral Arteriovenous Malformations

BACKGROUND AND PURPOSE:Intracranial hemorrhage is the most severe complication of brain arteriovenous malformation treatment. We report our rate of hemorrhagic complications after endovascular treatment and analyze the clinical significance and potential mechanisms, with emphasis on cases of delayed hemorrhage after uneventful embolization.MATERIALS AND METHODS:During a 10-year period, 846 embolization procedures were performed in 408 patients with brain AVMs. Any cases of hemorrhagic complications were identified and divided into those related or unrelated to a periprocedural arterial tear (during catheter navigation or catheter retrieval). We analyzed the following variables: sex, age, hemorrhagic presentation, Spetzler-Martin grade, size of the AVM, number of embolized pedicles, microcatheter used, type and volume of liquid embolic agent injected, and the presence of a premature venous occlusion. Univariate and multivariate multiple regression analyses were performed to identify risk factors for hemorrhagic complications.RESULTS:A hemorrhagic complication occurred in 92 (11%) procedures. Forty-four (48%) complications were related to a periprocedural arterial perforation, and 48 (52%) were not. Hemorrhagic complications unrelated to an arterial perforation were located more commonly in the cerebral parenchyma, caused more neurologic deficits, and were associated with worse prognosis than those in the arterial perforation group. Only premature venous occlusion was identified as an independent predictor of hemorrhagic complication in the nonperforation group. Premature venous occlusion was significantly related to the ratio of Onyx volume to nidus diameter.CONCLUSIONS:Higher injected volume of embolic agent and deposition on the venous outflow before complete occlusion of the AVM may account for severe hemorrhagic complications.

Treatment of cerebral arteriovenous malformation is challenging and requires a multidisciplinary approach involving surgery with AVM removal, endovascular treatment (EVT) with embolization, or radiosurgery. Each technique can be combined and has its own advantages and complications. A conservative approach is an important aspect of the management of AVMs. EVT can be used for presurgical or preradiosurgical treatment of AVMs or as a stand-alone procedure for curative purposes. Onyx (Covidien, Irvine, California) is currently the most commonly used embolic agent; in some instances, cyanoacrylate glue can be used. The most serious complication of AVM embolization is hemorrhage, reported in 4%–15% of patients treated by EVT.^1–3 The group of patients who experience delayed hemorrhage after EVT remains poorly understood, with multiple classifications^4–6 and explanations^7–9 and deserves further study. To investigate the potential mechanisms of hemorrhages following EVT, we report our rate of hemorrhagic complications (HCs) and their clinical significance and focus on those not related to an arterial lesion secondary to navigation or microcatheter retrieval.     

Angioarchitectural Characteristics Associated with Complications of Embolization in Supratentorial Brain Arteriovenous Malformation

BACKGROUND AND PURPOSE:Embolization is an important therapeutic technique in brain arteriovenous malformations; however, little has been reported on the factors contributing to complications. We retrospectively reviewed a large series of supratentorial brain AVMs to identify the angioarchitectural characteristics that might be associated with the complications of embolization and poor clinical outcomes.MATERIALS AND METHODS:The clinical and angiographic features of 130 consecutive patients with supratentorial brain AVMs embolized with ethylene-vinyl alcohol copolymer in our hospital from 2005–2008 were retrospectively reviewed. None of these patients had prior embolization. Complications were classified as transient neurologic deficits, persistent neurologic deficits, and death. Univariate and multivariate analyses were conducted to assess the angiographic features in patients with and without complications.RESULTS:Twenty-three complications occurred in 130 embolization procedures, 13 (10%) were transient neurologic deficits (9 ischemic and 4 hemorrhagic), 9 (6.92%) were persistent neurologic deficits (7 ischemic and 2 hemorrhagic), and 1 death occurred. By univariate analyses, eloquent cortex (OR, 2.57; 95% CI, 1.08–3.42) and exclusive deep venous drainage (OR, 4.56; 95% CI, 1.28–9.67) were correlated with procedural complications. The impaction of eloquent cortical location (P = .001) and exclusive deep venous drainage (P = .035) on complications were also demonstrated by multivariate analysis. Eloquent cortex mainly resulted in permanent ischemic neurologic deficit; occlusion of drainage vein was significantly correlated with periprocedural hemorrhage in supratentorial brain AVMs with subtotal and partial embolization.CONCLUSIONS:In a retrospective study on supratentorial brain AVMs with first-time embolization, 6.92% of patients had permanent neurologic deficit or death. Eloquent cortical location and exclusive deep venous drainage were associated with complications.

Embolization is an important adjunctive therapy to microsurgery and radiosurgery in the multidisciplinary management of arteriovenous malformations.^1–3 Recent advances in endovascular embolization techniques including flow-directed microcatheters and the liquid embolic agents n-butyl-cyanoacrylate and ethylene-vinyl alcohol copolymer (EVOH; Onyx, ev3, Irvine, California)⁴ make it possible to cure AVMs with embolization alone.^5,6Because endovascular treatment might result in hemorrhage and ischemic neurologic dysfunction, embolization of unruptured AVMs remains controversial, particularly in supratentorial brain AVMs (sbAVMs), which have a lower risk of hemorrhage than infratentorial AVMs. The reported complication rates of embolization varied from 3–11%^2,7–10 and were associated with angiographic features.⁷In the present study, we retrospectively reviewed 130 patients with sbAVMs to identify angioarchitectural characteristics that might be associated with the complications of embolization and poor clinical outcomes.     

Application of Time-Resolved 3D Digital Subtraction Angiography to Plan Cerebral Arteriovenous Malformation Radiosurgery

BACKGROUND AND PURPOSE:Time-resolved 3D-DSA (4D-DSA) enables viewing vasculature from any desired angle and time frame. We investigated whether these advantages may facilitate treatment planning and the feasibility of using 4D-DSA as a single imaging technique in AVM/dural arteriovenous fistula radiosurgery.MATERIALS AND METHODS:Twenty consecutive patients (8 dural arteriovenous fistulas and 12 AVMs; 13 men and 7 women; mean age, 45 years; range, 18–64 years) who were scheduled for gamma knife radiosurgery were recruited (November 2014 to October 2015). An optimal volume of reconstructed time-resolved 3D volumes that defines the AVM nidus/dural arteriovenous fistula was sliced into 2D-CT-like images. The original radiosurgery treatment plan was overlaid retrospectively. The registration errors of stereotactic 4D-DSA were compared with those of integrated stereotactic imaging. AVM/dural arteriovenous fistula volumes were contoured, and disjoint and conjoint components were identified. The Wilcoxon signed rank test and the Wilcoxon rank sum test were adopted to evaluate registration errors and contoured volumes of stereotactic 4D-DSA and integration of stereotactic MR imaging and stereotactic 2D-DSA.RESULTS:Sixteen of 20 patients were successfully registered in Advanced Leksell GammaPlan Program. The registration error of stereotactic 4D-DSA was smaller than that of integrated stereotactic imaging (P = .0009). The contoured AVM volume of 4D-DSA was smaller than that contoured on the integration of MR imaging and 2D-DSA, while major inconsistencies existed in cases of dural arteriovenous fistula (P = .042 and 0.039, respectively, for measurements conducted by 2 authors).CONCLUSIONS:Implementation of stereotactic 4D-DSA data for gamma knife radiosurgery for brain AVM/dural arteriovenous fistula is feasible. The ability of 4D-DSA to demonstrate vascular morphology and hemodynamics in 4 dimensions potentially reduces the target volumes of irradiation in vascular radiosurgery.

Radiosurgery is an effective treatment alternative for cerebral arteriovenous malformations^1–4 and intracranial dural arteriovenous fistulas (DAVFs).^5–10 In AVM/DAVF radiosurgery, irradiation is delivered in a single fraction stereotactically to only the nidus of an AVM or fistula of a DAVF.Our current clinical practice of AVM/DAVF radiosurgery, integrated stereotactic imaging (MR imaging/MRA and x-ray digital subtraction angiography) is used for nidus/fistula delineation. The integrated multiple-stop stereotactic imaging is considered the reference imaging for AVM/DAVF radiosurgery. MR imaging is superior in delineating radiosurgical target in 3D, and DSA excels in defining the hemodynamics of AVM/AVF and differentiating the nidus/fistula from feeding arteries and draining veins of AVM/DAVF.¹¹ However, the role of DSA as a projective 2D representation of 3D structures in defining the nidus is limited, especially when the AVM is large and the nidus has an oblique long axis relative to the orthogonal DSA projections.¹² Moreover, for AVMs that undergo partial embolization before radiosurgery, the nidus may become intricate, and it may be difficult to define its morphology on 2D-DSA or MR imaging/MRA.¹³ Recently, it was shown that conebeam CT 3D angiography can generate images of a high spatial resolution that depict low-flow nidal compartments better than both DSA and MR imaging, though it lacks temporal information.¹⁴ While our current practice has achieved high tissue conformity in AVM radiosurgery and good therapeutic results,¹⁵ an alternative technique, if chosen, must be able to provide panoramic morphological and hemodynamic evaluation of nidi/fistulas in 1 stop.In contrast to 2D-DSA, fully time-resolved 3D-DSA, also known as 4D-DSA, provides a series of time-resolved 3D volumes that correspond to contrast dynamics with a C-arm-based imaging system.¹⁶ While the reconstruction of a 4D-DSA image from a single rotational image acquisition has some inherited technical difficulties, as mentioned by Royalty,¹⁷ the volumetric vascular morphology and bolus-arrival patterns reconstructed from 4D-DSA algorithms are validated.¹⁷ An animal study based on a canine model also demonstrated that 4D-DSA is capable of delineating vasculature effectively.¹⁸ Small-series studies also suggested that 4D-DSA enhances the ability to visualize the vascular anatomy of an AVM.^19,20 Accordingly, 4D-DSA enables evaluating feeding arteries, nidi, and draining veins in sequential imaging in 3D and eliminates the issue of overlapped vasculatures.In this study, we compare the registration errors of stereotactic 4D-DSA with those of integrated stereotactic imaging and the vascular anatomy of AVMs and DAVFs depicted by 4D-DSA volumes with the planned dose contours for each recruited patient and evaluate whether 4D-DSA may facilitate the planning of AVM/DAVF radiosurgery by minimizing the irradiation volume as 1-stop imaging.     

Transarterial Onyx Embolization of Cranial Dural Arteriovenous Fistulas: Long-Term Follow-Up

BACKGROUND AND PURPOSE:Endovascular therapy with liquid embolic agents is a common treatment strategy for cranial dural arteriovenous fistulas. This study evaluated the long-term effectiveness of transarterial Onyx as the single embolic agent for curative embolization of noncavernous cranial dural arteriovenous fistulas.MATERIALS AND METHODS:We performed a retrospective review of 40 consecutive patients with 41 cranial dural arteriovenous fistulas treated between March 2006 and June 2012 by using transarterial Onyx embolization with intent to cure. The mean age was 57 years; one-third presented with intracranial hemorrhage. Most (85%) had cortical venous drainage. Once angiographic cure was achieved, long-term treatment effectiveness was assessed with DSA and clinical follow-up.RESULTS:Forty-nine embolization sessions were performed; 85% of cranial dural arteriovenous fistulas were treated in a single session. The immediate angiographic cure rate was 95%. The permanent neurologic complication rate was 2% (mild facial palsy). Thirty-five of the 38 patients with initial cure underwent short-term follow-up DSA (median, 4 months). The short-term recurrence rate was only 6% (2/35). All patients with occlusion at short-term DSA undergoing long-term DSA (median, 28 months) had durable occlusion. No patient with long-term clinical follow-up (total, 117 patient-years; median, 45 months) experienced hemorrhage.CONCLUSIONS:Transarterial embolization with Onyx as the single embolic agent results in durable long-term cure of noncavernous cranial dural arteriovenous fistulas. Recurrence rates are low on short-term follow-up, and all patients with angiographic occlusion on short-term DSA follow-up have experienced a durable long-term cure. Thus, angiographic cure should be defined at short-term follow-up angiography instead of at the end of the final embolization session. Finally, long-term DSA follow-up may not be necessary if occlusion is demonstrated on short-term angiographic follow-up.

Endovascular therapy is commonly used for the treatment of noncavernous cranial dural arteriovenous fistulas (cDAVFs). Cyanoacrylates, ethyl alcohol, coils, and particles can be used alone or in combination via transarterial, transvenous, or occasionally direct percutaneous treatment routes. There is no US Food and Drug Administration–approved liquid embolic agent for the treatment of cDAVFs. The ethylene-vinyl alcohol copolymer liquid embolic system (Onyx; Covidien, Irvine, California) is FDA-approved for the presurgical embolization of brain arteriovenous malformations. Since Onyx has become available, transarterial embolization of cDAVFs by using Onyx as the sole endovascular embolic agent has become our preferred treatment strategy. This endovascular treatment approach represents an “off-label” use of the Onyx liquid embolic system.The immediate occlusion rate in large cohort studies of patients treated with transarterial Onyx embolization ranges from 62% to 92%, and short-term durable occlusion has been demonstrated.^1–4 We have previously reported our short-term experience using Onyx in these patients⁵ and have compared the success of this technique with embolization using n-butyl cyanoacrylate.⁶ However, there currently remain no published data on the long-term effectiveness for embolization of cDAVFs by using Onyx, to our knowledge. Here we report our long-term angiographic occlusion rate and clinical follow-up in a cohort of noncavernous cranial DAVFs that were treated by using transarterial Onyx embolization with the intention of complete cure.     

Evaluation of 4D Vascular Flow and Tissue Perfusion in Cerebral Arteriovenous Malformations: Influence of Spetzler-Martin Grade,Clinical Presentation,and AVM Risk Factors

BACKGROUND AND PURPOSE:The role of intracranial hemodynamics in the pathophysiology and risk stratification of brain AVMs remains poorly understood. The purpose of this study was to assess the influence of Spetzler-Martin grade, clinical history, and risk factors on vascular flow and tissue perfusion in cerebral AVMs.MATERIALS AND METHODS:4D flow and perfusion MR imaging was performed in 17 patients with AVMs. Peak velocity and blood flow were quantified in AVM feeding and contralateral arteries, draining veins, and the straight sinus. Regional perfusion ratios (CBF, CBV, and MTT) were calculated between affected and nonaffected hemispheres.RESULTS:Regarding flow parameters, high-grade AVMs (Spetzler-Martin grade of >2) demonstrated significantly increased peak velocity and blood flow in the major feeding arteries (P < .001 and P = .004) and straight sinus (P = .003 and P = .012) and increased venous draining flow (P = .001). The Spetzler-Martin grade significantly correlated with cumulative feeding artery flow (r = 0.85, P < .001) and draining vein flow (r = 0.80, P < .001). Regarding perfusion parameters, perinidal CBF and CBV ratios were significantly lower (P < .001) compared with the remote ratios and correlated negatively with cumulative feeding artery flow (r = −0.60, P = .014 and r = −0.55, P = .026) and draining vein flow (r = −0.60, P = .013 and r = −0.56, P = .025). Multiple regression analysis revealed no significant association of AVM flow or perfusion parameters with clinical presentation (rupture and seizure history) and AVM risk factors.CONCLUSIONS:Macrovascular flow was significantly associated with increasing Spetzler-Martin grade and correlated with perinidal microvascular perfusion in cerebral AVMs. Future longitudinal studies are needed to evaluate the potential of comprehensive cerebral flow and perfusion MR imaging for AVM risk stratification.

Cerebral arteriovenous malformations are associated with an increased risk of intracranial hemorrhage, accounting for 2%–4% of all hemorrhagic strokes annually.¹ Previous studies have demonstrated the potential risk of hemorrhage following AVM embolization, presumably due to acute alterations in AVM or cerebral hemodynamics.² However, the Spetzler-Martin grade (SMG), widely used for surgical risk stratification in cerebral AVMs, does not provide insight into local or global hemodynamics.³ Quantitative assessment of AVM feeding and draining flow, combined with whole-brain tissue perfusion, can potentially characterize both AVM macro- and microvascular pathophysiology. In addition, the relationships between quantitative AVM hemodynamic parameters and the SMG or clinical history (rupture/seizures) and other risk factors (eg, presence of flow-induced aneurysms or venous stenosis, deep AVM location, and single or deep venous drainage) remain unclear.In this study, a comprehensive MR imaging and analysis protocol based on 4D flow and DSC perfusion MR imaging was applied for the characterization of 3D AVM macrovascular flow and microvascular brain tissue perfusion. 4D flow MR imaging can measure the 3-directional velocity field with full volumetric coverage of the vessels of interest.^4,5 Previous studies have shown that 4D flow MR imaging is highly promising in the evaluation of intracranial hemodynamics in cerebral AVMs.^6–8 To gain additional information on the impact of AVMs on cerebral tissue perfusion, we used DSC PWI based on a fast spin-echo EPI acquisition during the first pass of contrast agent through the brain vasculature to quantify microvascular perfusion biomarkers.^9,10 The AVM nidus has relatively low resistance and thus often causes high-flow transnidal shunts, which may result in hypoperfusion in the cerebral parenchyma immediately adjacent to AVMs. However, this so-called “steal effect” with diversion of blood from the adjacent tissue to the AVM nidus is still controversial, and it is unclear whether it should be considered a mechanism for the clinical presentation of cerebral AVMs.¹¹The purpose of this study was to quantitatively evaluate macrovascular flow in AVM arterial and venous networks and microvascular perfusion of the peripheral cerebral parenchyma. We investigated relationships between these quantitative hemodynamic parameters and SMG classification followed by correlation with various AVM symptomatic and anatomic risk factors.     

Value of 4D MR Angiography at 3T Compared with DSA for the Follow-Up of Treated Brain Arteriovenous Malformation

BACKGROUND AND PURPOSE:Four-dimensional, contrast-enhanced MRA is a useful technique for the diagnosis and classification of brain AVM. The purpose of this study was to evaluate its usefulness in the follow-up of treated brain AVM.MATERIALS AND METHODS:Patients with treated brain AVM (embolization, radiosurgery, and/or surgery) were investigated with both DSA (the “gold standard”) and 4D MRA. Four-dimensional MRA was performed at 3T using a 4D sequence, combining contrast-enhanced timing-robust angiography, keyhole, and sensitivity encoding techniques. Examinations were evaluated by 2 independent readers and disagreements were resolved by a third reader. Interobserver and intermodality agreement with respect to residual nidus, residual venous drainage, and brain AVM patency were determined.RESULTS:Between May 2008 and February 2013, 37 patients with a median age of 45 years (interquartile range = 26–55) were prospectively included. Examinations were acquired 36 months (IQR = 10–45.5) after the last treatment. Interobserver agreement for brain AVM patency was very good for both 4D MRA (κ 0.82, 95% CI .67–.98) and DSA (κ 0.84, 95% CI .69–.98). After consensus reading, intermodality agreement for the evaluation of brain AVM patency was good (κ 0.73, 95% CI .55–.90). Diagnostic accuracy of 4D MRA for residual brain AVM compared with DSA, reached a sensitivity of 73.7%, specificity 100%, positive predictive value 100%, and negative predictive value 78.3%. Agreements by technique of treatment are also detailed.CONCLUSIONS:Four-dimensional MRA is a useful radiation-free technique for the follow-up of patients with treated brain AVM, especially patients treated by radiosurgery. However, given its actual limitations it is not sufficient to assert the cure; DSA remains mandatory for this purpose.

Brain AVMs (bAVMs) are rare developmental disorders (prevalence of 0.01%–0.52%) composed of a network of channels (nidus) interposed between feeding arteries and draining veins.¹ They are often revealed by spontaneous intracranial hemorrhages with high morbidity and mortality.^2,3 They are often diagnosed in young, otherwise healthy patients and carry a life-long bleeding risk ranging between 1.5% and 4.0% per year.^4,5 There are several treatment options, including surgical resection, endovascular embolization, and radiosurgery, that can be attempted to achieve a cure.^6–10 The risk of bleeding persists as long as an anatomic cure is not completely achieved.^5,6 Therefore, it is necessary to confirm an AVM cure after the treatment. When the AVM is treated by surgery and/or embolization, imaging is performed a few weeks or months after the end of the treatment to evaluate the AVM occlusion status (complete occlusion or residual AVM). When AVM is treated with radiosurgery (alone or after embolization and/or surgery), occlusion is usually achieved after a few years, and a regular imaging follow-up is conducted every 6 or 12 months.^5,6Despite several disadvantages, such as radiation exposure, iodinated contrast agent injection risks (including allergy and nephrotoxicity), and neurologic procedural risks (0.30%–2.63%),^11–13 DSA is the reference method to evaluate AVM occlusion status because of posttreatment modifications. Indeed, it has a very good spatial and especially temporal resolution allowing for a precise evaluation of potential residual nidus and residual venous drainage. To reduce these risks, several noninvasive cross-sectional imaging techniques like 3D TOF-MRA and 3D contrast-enhanced MRA were used.^14–16 The diagnostic accuracy of these techniques was quite good, but not enough to replace DSA because they suffered from a poor temporal resolution that limited analysis of the angioarchitecture and hemodynamics.^14–16 Four-dimensional contrast-enhanced MRA (4D-MRA) was conceived to solve this problem and to provide a better temporal resolution while also preserving spatial resolution. However, the first examinations were not efficient enough; by incorporating progressive new technologies such as parallel imaging and intelligent sampling of the k-space, it became an emergent imaging technique with the advantage of a dynamic “DSA-like” evaluation of the AVM that allows for the definition of arterial feeders, nidus, and draining veins in the same examination.¹⁷ Actually, 4D-MRA permits the effective diagnosis and classification of bAVM.^17–20 The value of 4D-MRA for the follow-up of patients with a treated bAVM has been rarely evaluated.^21,22 The purpose of this study was to evaluate the performance of 4D-MRA at 3T for the follow-up of patients with a treated bAVM. In other words, this study will try to answer the 2 following questions: is 4D-MRA enough to assert the cure? Is 4D-MRA useful for the follow-up of treated bAVM?     

The Preventive Effect of Endovascular Treatment for Recurrent Hemorrhage in Patients with Spinal Cord Arteriovenous Malformations

BACKGROUND AND PURPOSE:Spinal cord AVMs represent rare and insufficiently studied pathologic entities. Embolization is thought to play an important role in the management of spinal cord AVMs. Factors for recurrent hemorrhage and the impact of endovascular treatment on prevention of recurrent hemorrhage remain to be confirmed. We aimed to assess recurrent hemorrhagic incidence of spinal cord AVMs and its prevention by endovascular treatment.MATERIALS AND METHODS:We reviewed 80 patients with spinal cord AVMs by spinal cord angiography who had hemorrhage before the first endovascular treatment at New York University Medical Center, Beth Israel Medical Center, or Roosevelt Hospital in New York. We compared the baseline and radiologic characteristics of patients with and without recurrent hemorrhage by the log-rank test and the Cox proportional hazards model.RESULTS:We observed recurrent hemorrhage in 35 (44%) patients (1/41 patients with endovascular treatment and 34/39 patients without endovascular treatment). The median length of total follow-up was 659 days (interquartile range, 129–2640 days), and the median length from first-to-recurrent hemorrhage was 369 days (interquartile range, 30–1596 days). The log-rank test revealed that endovascular treatment and venous thrombosis reduced recurrent hemorrhage, and associated aneurysm was related to recurrent hemorrhage. Even in multivariate analysis, the endovascular treatment reduced (hazard ratio, 0.027; P < .0001) and associated aneurysm increased (hazard ratio, 3.4; P = .044) the risk of recurrent hemorrhage.CONCLUSIONS:Endovascular embolization is the first choice of treatment for spinal cord AVMs and is effective in preventing recurrent hemorrhage.

Spinal cord AVMs (SCAVMs) represent rare and insufficiently studied pathologic entities characterized by considerable variation.¹ Insufficient study of this disease is associated with the rarity and complexity of its diagnosis.^2,3 Spinal cord arteriovenous fistula is a direct communication between arteries and veins, while spinal cord arteriovenous malformation in its narrow denotation has a nidus, an abnormal vascular network interposed between arteries and veins. On some occasions, both AVF and AVM constitute a shunt, which is also called AVM in its broader meaning.⁴ Spinal cord AVFs and AVMs manifest with sudden or gradual deterioration of sensorimotor function in the extremities and/or of micturition, defecation, or sexual function due mainly to venous hypertension/ischemia and, in some cases, arterial steel, hemorrhage, or mass effect.⁴There has been advancement in endovascular treatment of SCAVM, including monitoring systems. Treatment of an SCAVM aims to decrease the risk of hemorrhage and arrest the progression of neurologic deterioration.⁵ Embolization is thought to play an important role in the management of SCAVMs, both as a primary treatment and as an adjunct to surgical excision. However, complete cure of SCAVMs by endovascular embolization is exceptional except for spinal cord AVFs, and endovascular treatment often results in partial obliteration of the lesion by target embolization. Target embolization aims at occluding dangerous structures causing hemorrhage or neurologic symptoms, such as aneurysms, high-flow fistulas, and nerve root lesions for radicular pain. To date, various studies investigated the factors related to initial hemorrhage.^6–10 However, factors for recurrent hemorrhage and the impact of endovascular treatment on prevention of recurrent hemorrhage remain to be confirmed. The purpose of this study was to assess the recurrent hemorrhagic incidence of SCAVMs and its prevention by endovascular treatment.     

Carotid Stenting without Embolic Protection Increases Major Adverse Events: Analysis of the National Surgical Quality Improvement Program

BACKGROUND AND PURPOSE:Published data regarding embolic protection device efficacy is mixed, and its use during carotid artery stent placement remains variable. We, therefore, examined the frequency of embolic protection device use and its association with outcomes after carotid artery stent placement using a national quality improvement data base.MATERIALS AND METHODS:Patients undergoing carotid artery stent placement with or without embolic protection devices were identified in the American College of Surgeons National Surgical Quality Improvement Program data base. The primary outcome was the incidence of major adverse cardiovascular events (defined as death, stroke, or myocardial infarction/arrhythmia) within 30 days. Propensity scoring was used to create 2 matching cohorts of patients using demographic and baseline variables.RESULTS:Between 2011 and 2018, among 1200 adult patients undergoing carotid artery stent placement, 23.8% did not have embolic protection devices. There was no trend toward increased embolic protection device use with time. Patients without embolic protection device use received preoperative antiplatelets less frequently (90.6% versus 94.6%, P = .02), underwent more emergent carotid artery stent placement (7.2% versus 3.6%, P = .01), and had a higher incidence of major adverse cardiovascular events (OR = 1.81; 95% CI, 1.11–2.94) and stroke (OR = 3.31; 95% CI, 1.71–6.39). After compensating for baseline imbalances using propensity-matched cohorts (n = 261 for both), carotid artery stent placement without an embolic protection device remained associated with increased major adverse cardiovascular events (9.2% versus 4.2%; OR = 2.30; 95% CI, 1.10–4.80) and stroke (6.5% versus 1.5%; OR = 4.48; 95% CI, 1.49–13.49).CONCLUSIONS:Lack of embolic protection device use during carotid artery stent placement is associated with a 4-fold increase in the likelihood of perioperative stroke. Nevertheless, nearly one-quarter of patients in the American College of Surgeons National Surgical Quality Improvement Program underwent unprotected carotid artery stent placement. Efforts targeting improved embolic protection device use during carotid artery stent placement are warranted.

Carotid artery stent placement (CAS) has developed rapidly during the past 30 years to become a viable option for carotid revascularization, especially in patients at high-risk for carotid endarterectomy.¹ One of the major remaining concerns about CAS is the risk of embolic stroke caused by mobilization and migration of plaque fragments during stent placement.² Embolic protection devices (EPDs) have been developed to reduce the risk of distal embolization.³ In 2011, guidelines from the American Stroke Association suggested that the use of EPDs during CAS can be beneficial to reduce the risk of stroke when the risk of vascular injury is low.⁴ Nevertheless, randomized trials, systematic reviews, and meta-analyses offer conflicting evidence regarding the frequency and efficacy of EPD use, with some showing diminished rates of postoperative stroke and death when an EPD was used,^5-8 whereas others have not supported the benefit of an EPD during CAS.^9-12 We, therefore, examined the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) data base to determine the frequency of EPD use during CAS and compared preoperative and postoperative characteristics, complications, and outcomes of patients undergoing CAS with and without an EPD.     

Preoperative Embolization of Intracranial Meningiomas: Efficacy,Technical Considerations,and Complications

BACKGROUND AND PURPOSE:Preoperative embolization for intracranial meningiomas offers potential advantages for safer and more effective surgery. However, this treatment strategy has not been examined in a large comparative series. The purpose of this study was to review our experience using preoperative embolization to understand the efficacy, technical considerations and complications of this technique.MATERIALS AND METHODS:We performed a retrospective review of patients undergoing intracranial meningioma resection at our institution (March 2001 to December 2012). Comparisons were made between embolized and nonembolized patients, including patient and tumor characteristics, embolization method, operative blood loss, complications, and extent of resection. Logistic regression analyses were used to identify factors predictive of operative blood loss and extent of resection.RESULTS:Preoperatively, 224 patients were referred for embolization, of which 177 received embolization. No complications were seen in 97.1%. There were no significant differences in operative duration, extent of resection, or complications. Estimated blood loss was higher in the embolized group (410 versus 315 mL, P = .0074), but history of embolization was not a predictor of blood loss in multivariate analysis. Independent predictors of blood loss included decreasing degree of tumor embolization (P = .037), skull base location (P = .005), and male sex (P = .034). Embolization was not an independent predictor of gross total resection.CONCLUSIONS:Preoperative embolization is a safe option for selected meningiomas. In our series, embolization did not alter the operative duration, complications, or degree of resection, but the degree of embolization was an independent predictor of decreased operative blood loss.

Preoperative embolization has been an option for adjunctive treatment of intracranial meningiomas for almost 4 decades, but it remains used in only a minority of cases.¹ Meningiomas are commonly supplied by the middle meningeal, accessory meningeal, ascending pharyngeal, or occipital branches of the external carotid artery (ECA), which are easily accessible by selective microcatheterization.² Branches of the internal carotid artery and pial feeders supplying the tumor may also be embolized,^3–6 though these vessels are typically more difficult to access and are associated with a higher risk of parenchymal infarct. In an attempt to change the tumor characteristics to increase the likelihood of a gross total resection and minimize operative morbidity, a variety of embolization materials have been used, including polyvinyl alcohol (PVA) particles,^7,8 large-caliber microspheres,^8,9 ethylene-vinyl alcohol (Onyx; Covidien, Irvine, California),^10,11 detachable coils,¹² fibrin glue¹³ and hyperosmolar mannitol.¹⁴ The potential advantages of preoperative embolization include decreased operative duration, reduced operative blood loss, and alteration of tumor consistency, all of which decrease the technical difficulty of surgical resection and increase the likelihood of achieving a more complete resection. Embolization likely causes histopathologic changes within the meningioma, including necrosis, ischemic changes, and microvascular fibrinoid changes.¹⁵ Hypoxia caused by disruption of tumoral blood supply also causes changes in protein expression consistent with angiogenesis and promotion of growth,¹⁶ along with cytologic changes, including infiltration of macrophages.¹⁷ The combination of these changes may make histologic examination of embolized meningiomas more difficult because they may histopathologically resemble higher grade tumors.^15,18–20 Embolization also carries with it the risk of procedural complications, including large-vessel dissection, microcatheter fracture, and unintended arterial or venous occlusion resulting in hemorrhagic or ischemic infarct.^1,7,21–28Series of meningiomas that were preoperatively embolized have been recently published,⁷ but the operative findings and postoperative course for embolized tumors have not been compared with nonembolized tumors in a large modern series. In this study, we sought to review our outcomes following preoperative angiography, embolization when possible, and resection of intracranial meningiomas for the following objectives: 1) to assess the effect of preoperative embolization on operative time, surgical blood loss, and extent of resection; 2) to compare outcomes and complications between resection of embolized and nonembolized meningiomas; and 3) to determine predictors of objective utility of meningioma embolization.     

Endovascular Treatment of Dural Arteriovenous Fistulas of the Transverse and Sigmoid Sinuses Using Transarterial Balloon-Assisted Embolization Combined with Transvenous Balloon Protection of the Venous Sinus

BACKGROUND AND PURPOSE:Combined transarterial balloon-assisted endovascular embolization with double-lumen balloon microcatheters and concomitant transvenous balloon protection was described as a promising treatment technique for dural arteriovenous fistulae of the transverse and sigmoid sinus. The purpose of this study was to evaluate the technical efficacy and safety of this combined treatment technique.MATERIALS AND METHODS:Nine consecutive patients presenting with dural arteriovenous fistulas of the transverse and sigmoid sinuses underwent combined transarterial and transvenous balloon-assisted endovascular embolization. Prospectively collected data were reviewed to assess the technical success rate, complication rate, and clinical outcome.RESULTS:Six patients presented with clinically symptomatic Borden type I, and 3 patients, with Borden type II dural arteriovenous fistulas of the transverse and sigmoid sinuses (3 men, 6 women; mean age, 50.4 years). Transarterial embolization was performed with a double-lumen balloon with Onyx and concomitant transvenous sinus protection with a dedicated venous remodeling balloon. Complete angiographic occlusion at the latest follow-up (mean, 4.8 months) was achieved in 6 patients, and near-complete occlusion, in 2 patients. Clinical cure or remission of symptoms was obtained in 6 and 2 patients, respectively. One patient with a residual fistula underwent further treatment in which the dural arteriovenous fistula was cured by sinus occlusion. Complete occlusion of the dural arteriovenous fistula was visible on the follow-up angiography after final treatment in 8 patients. One patient refused follow-up angiography but was free of symptoms. There were no immediate or delayed postinterventional complications.CONCLUSIONS:Transarterial balloon-assisted embolization of dural arteriovenous fistulas of the transverse and sigmoid sinuses with combined transvenous balloon protection is safe and offers a high rate of complete dural arteriovenous fistula occlusion and remission of clinical symptoms.

During the past few decades, endovascular embolization has become the first-line treatment for a wide range of dural arteriovenous fistulas (dAVFs). Several transarterial and transvenous endovascular approaches have been advocated. Preliminary studies on the use of double-lumen balloon microcatheters for transarterial embolization of dAVFs with Onyx (Covidien, Irvine, California) have shown encouraging results. These studies have reported high occlusion rates, reduction of reflux into the feeding artery, a reduced quantity of injected Onyx and peri-interventional time, and low complication rates.^1–9 In addition, transvenous balloon-assisted sinus protection during transarterial embolization has been reported to be another useful adjunct to the endovascular treatment of dAVFs.^10–12 Transvenous balloon protection of the recipient sinus has mainly been associated with a reduction in inadvertent occlusion of the lumen of a functioning sinus, preservation of venous patency, facilitation of occlusion of abnormal arteriovenous connections within the sinus wall and separate venous channels, and increased penetration of embolic material by retrograde reflux into other dural feeders of the fistula network. Techniques aiming to preserve the underlying sinus may have lower complication rates than sinus-occluding embolization techniques, in which the recipient venous sinus has to be sacrificed.¹³ Therefore, transarterial balloon-assisted embolization with a concomitant transvenous balloon protection technique theoretically has the advantages of both techniques combined; this combination leads to increased occlusion and reduced complication rates.The purpose of this study was to report the angiographic and clinical outcomes of patients with dAVFs of the transverse and sigmoid sinuses treated with a combined approach of transarterial balloon-assisted endovascular embolization and double-lumen balloon microcatheters with concomitant transvenous balloon protection.     

Risk Factors of Hematomyelia Recurrence and Clinical Outcome in Children with Intradural Spinal Cord Arteriovenous Malformations

BACKGROUND AND PURPOSE:Few published data are available concerning the risk of re-bleeding of spinal cord AVM after an hematomyelia and concerning the long-term clinical outcome. Our aim was to assess the risk of recurrence and long-term clinical outcome after hematomyelia in children with spinal cord AVMs.MATERIALS AND METHODS:This single-center retrospective study reviewed the clinical and radiologic data of 28 children younger than 18 years of age with arteriovenous malformation who had experienced at least 1 episode of hematomyelia between 1988 and 2012. Long-term clinical outcome was assessed by the American Spinal Injury Association Impairment Scale, and radiologic review included MR imaging and angioarchitecture on angiography (blinded to clinical information) before treatment and at recurrence.RESULTS:Sixteen children (57%) experienced 1 episode of hematomyelia, while 12 children (43%) experienced recurrence. Girls and boys were equally affected (sex ratio, 1:1), and mean clinical follow-up was 5.7 ± 4.4 years. The risk of recurrence was higher for AVMs of the cervical and upper thoracic spine, 12 (100%) versus 11 (69%) (P = .01). A high American Spinal Injury Association scale score at last follow-up was reported for 11 children (39%), and the risk of recurrence tended to be associated with poorer functional prognosis (7 [64%] versus 5 [29%], P = .07). At the time of recurrence, perimedullary venous drainage was the main factor associated with recurrence (P = .002). Occlusion rate ≥50% was associated with a decreased risk of recurrence (P = .047).CONCLUSIONS:In the present series, cervical and upper thoracic spinal cord AVMs and microarchitecture were predictive of the risk of hematomyelia recurrence. Perimedullary venous drainage was one of the main parameters associated with recurrence. Functional prognosis was better in patients with a single episode of hematomyelia.

Spinal cord vascular malformations, particularly arteriovenous malformations, are the most common causes of nontraumatic intraspinal bleeding, called “hematomyelia.”¹ Spinal cord AVMs may present with acute neurologic symptoms or deterioration of pre-existing neurologic deficits after hematomyelia.¹ MR imaging is a useful tool for the diagnosis of hematomyelia and defining the type of vascular injury but may not be sufficient to accurately define the type of injury, the site of the shunt, and the angioarchitecture of the lesion. Angiography is therefore the reference tool for diagnosis, detailed analysis of the angioarchitecture of spinal vascular malformations, and defining the treatment strategy.² Due to the fragility of vascular lesions and their eloquent localization in the spinal cord, partial and targeted treatment can be proposed to avoid deterioration of the neurologic deficit because endovascular treatment is often technically challenging, especially when no specific vascular target is identified. Although a number of angioarchitectural factors associated with an increased risk of bleeding in cerebral AVMs have been described,^3–7 few published data are available concerning the risk of bleeding of spinal AVMs, particularly predictive factors of intraspinal rebleeding after a first episode of hematomyelia and predictive factors of long-term clinical outcome. Moreover, endovascular embolization is considered a good option to prevent rebleeding.^2,8 The primary objective of this study was, therefore, to identify clinical, radiologic, and angiographic factors associated with recurrent hematomyelia in a series of children with hematomyelia. Treatment decisions and targets in the AVM management strategy could be facilitated when only partial removal was acceptable in terms of the risks of treatment, to prevent further bleeding. The secondary objective was to determine the clinical, radiologic, and angiographic factors of clinical severity after a first or subsequent episodes of hematomyelia.     

Autosomal Dominant Polycystic Kidney Disease and Intracranial Aneurysms: Is There an Increased Risk of Treatment?

BACKGROUND AND PURPOSE:Autosomal dominant polycystic kidney disease is associated with an increased risk of intracranial aneurysms. Our purpose was to assess whether there is an increased risk during aneurysm coiling and clipping.MATERIALS AND METHODS:Data were obtained from the National Inpatient Sample (2000–2011). All subjects had an unruptured aneurysm clipped or coiled and were divided into polycystic kidney (n = 189) and control (n = 3555) groups. Primary end points included in-hospital mortality, length of stay, and total hospital charges. Secondary end points included the International Classification of Diseases, Ninth Revision codes for iatrogenic hemorrhage or infarction; intracranial hemorrhage; embolic infarction; and carotid and vertebral artery dissections.RESULTS:There was a significantly greater incidence of iatrogenic hemorrhage or infarction, embolic infarction, and carotid artery dissection in the patients with polycystic kidney disease compared with the control group after endovascular coiling. There was also a significantly greater incidence of iatrogenic hemorrhage or infarction in the polycystic kidney group after surgical clipping. However, the hospital stay was not longer in the polycystic kidney group, and the total hospital charges were not higher. Additional analysis within the polycystic kidney group revealed a significantly shorter length of stay but similar in-hospital costs when subjects underwent coiling versus clipping.CONCLUSIONS:Patients with polycystic kidney disease face an increased risk during intracranial aneurysm treatment, whether by coiling or clipping. This risk, however, does not translate into longer hospital stays or increased hospital costs. Despite the additional catheterization-related risks of dissection and embolization, coiling results in shorter hospital stays and similar mortality compared with clipping.

Autosomal dominant polycystic kidney disease (ADPCKD) is a genetic disorder affecting 1 in 1000 individuals worldwide and is associated with an increased risk of intracranial aneurysms, ranging from 4% to 23%^1–6 compared with the general population risk of 2%–3%.^7–10 Patients with ADPCKD are also at increased risk for aneurysm rupture earlier in life (mean age, 35–45 years),^1,11–13 compared with the general population (mean age, 50–54 years).^14,15There is evidence that the associated vascular defects in ADPCKD may be due to mutations in the PKD1 and PKD2 genes, located on the short arm of chromosomes 16 and 4.^16,17 Abnormalities of these genes in mouse models correspond with increased rates of arterial dissection, arterial rupture, and intracranial vascular abnormalities.¹⁸ To our knowledge, only 1 study to date has investigated whether these issues engender an increased risk when treating intracranial aneurysms (whether by endovascular coiling or surgical clipping).² The purpose of this investigation was to assess whether ADPCKD confers an increased peri- and immediate postprocedural risk of aneurysm coiling and clipping.     

Progressive versus Nonprogressive Intracranial Dural Arteriovenous Fistulas: Characteristics and Outcomes

BACKGROUND AND PURPOSE:A minority of intracranial dural arteriovenous fistulas progress with time. We sought to determine features that predict progression and define outcomes of patients with progressive dural arteriovenous fistulas.MATERIALS AND METHODS:We performed a retrospective imaging and clinical record review of patients with intracranial dural arteriovenous fistula evaluated at our hospital.RESULTS:Of 579 patients with intracranial dural arteriovenous fistulas, 545 had 1 fistula (mean age, 45 ± 23 years) and 34 (5.9%) had enlarging, de novo, multiple, or recurrent fistulas (mean age, 53 ± 20 years; P = .11). Among these 34 patients, 19 had progressive dural arteriovenous fistulas with de novo fistulas or fistula enlargement with time (mean age, 36 ± 25 years; progressive group) and 15 had multiple or recurrent but nonprogressive fistulas (mean age, 57 ± 13 years; P = .0059, nonprogressive group). Whereas all 6 children had fistula progression, only 13/28 adults (P = .020) progressed. Angioarchitectural correlates to chronically elevated intracranial venous pressures, including venous sinus dilation (41% versus 7%, P = .045) and pseudophlebitic cortical venous pattern (P = .048), were more common in patients with progressive disease than in those without progression. Patients with progressive disease received more treatments than those without progression (median, 5 versus 3; P = .0068), but as a group, they did not demonstrate worse clinical outcomes (median mRS, 1 and 1; P = .39). However, 3 young patients died from intracranial venous hypertension and intracranial hemorrhage related to progression of their fistulas despite extensive endovascular, surgical, and radiosurgical treatments.CONCLUSIONS:Few patients with dural arteriovenous fistulas follow an aggressive, progressive clinical course despite treatment. Younger age at initial presentation and angioarchitectural correlates to venous hypertension may help identify these patients prospectively.

Intracranial dural arteriovenous fistulas (DAVFs) are rare arteriovenous shunts involving the epidural space and adjacent dura mater, which receive arterial supply from meningeal vessels and drain directly to dural venous sinuses or cortical veins.¹ In the early days of cerebral angiography, DAVFs were considered a subset of AVMs: Newton and Cronqvist² classified AVMs by arterial supply as pure dural, mixed pial-dural, or pure pial malformations. Unlike brain AVMs, however, DAVFs are most often thought to be acquired (as opposed to congenital), and DAVFs lack a nidus of vessels in the brain parenchyma. DAVF is also distinguished from nongalenic pial arteriovenous fistula by its fistula location in the dura.Management of a DAVF is based on its expected clinical course: Fistulas demonstrating cortical venous drainage (CVD) generally warrant curative therapy to prevent intracranial hemorrhage, and fistulas without CVD are managed for either symptom palliation or cure.^3–6 Treatment modalities include transarterial or transvenous endovascular embolization to occlude the arteriovenous fistula site, microsurgical interruption of the fistula site, stereotactic radiosurgery, or multimodality therapy. Endovascular procedures are used to treat a most DAVFs and are the treatment of choice for lesions accessible to catheterization.^5,6A small number of patients with DAVFs respond poorly to conventional therapies and demonstrate progressive neurologic and angiographic deterioration with enlargement of existing fistulas, formation of de novo fistulas, and development of features that increase the risk of intracranial hemorrhage.⁷ Reports of such rapidly progressive “runaway” DAVFs are scarce. Only a few cases have been published in the past 15 years; therefore, the pathogenesis, presentation, clinical course, and treatment remain unclear.^4,8–12 The purpose of this single-institution retrospective cohort study was to compare the clinical characteristics, angioarchitecture, and treatment outcomes of patients with progressive (enlarging fistulas or developing de novo fistulas) versus nonprogressive (recurrent original fistula or the presence of multiple unchanging fistulas) intracranial DAVFs.     

New ischemic brain lesions on diffusion-weighted MRI after carotid artery stenting with filter protection: frequency and relationship with plaque morphology

BACKGROUND AND PURPOSE:CAS carries an inherent risk of distal cerebral embolization, precipitating new brain ischemic lesions and neurologic symptoms. Our purpose was to evaluate the frequency of new ischemic lesions found on DWI after protected CAS placement and to determine its association with plaque morphology.MATERIALS AND METHODS:Fifty patients (mean age 65.13 ± 7.08 years) with moderate and severe internal carotid artery stenosis underwent CAS with distal filter protection. Fibrolipid and fibrocalcified plaque morphology was determined by sonography according to the relative contribution of echogenic and echolucent material, and by multisection CT using plaque attenuation. There were 46.81% of patients with fibrolipid and 53.19% with fibrocalcified plaques. DWI was performed before and 24 hours after CAS.RESULTS:Seven (14.89%) patients showed new lesions. Four (8.51%) had 6 new lesions inside the treated vascular territory. Three had a single lesion and 1 patient had 3 lesions (mean: 1.5 ± 1). Most lesions (66.66%) were subcortical, with a mean diameter of 9 mm (range 5–15 mm). All lesions occurred in the area supplied by the middle cerebral artery and were clinically silent. A significant relationship was found between plaque morphology and the appearance of new lesions. Patients with fibrolipid plaques had a significantly higher number of new lesions compared with patients with fibrocalcified plaques (P = .041). The absolute risk of new lesions in the fibrolipid group was 18.18%.CONCLUSIONS:New ischemic lesions were observed in the treated vascular territory in 8.51% of patients. The appearance of new ischemic lesions was significantly related to the plaque morphology. Fibrolipid plaques were associated with higher numbers of new lesions.

CAS carries an inherent risk of distal cerebral embolization, precipitating new brain ischemic lesions and neurologic symptoms.^1–4 This has led to the development and widespread application of cerebral protection devices.^5,6 The most widely used devices are those based on distal filter placement that capture emboli dislodged from plaque; however, their application may result in additional complications.^7–12Several reviews have reported contradictory data concerning the rate of stroke and ischemia after protected versus unprotected stent placement.^3,13–15 The frequency of new ischemic lesions after CAS may be associated with numerous factors, such as clinical status, vascular anatomy, plaque morphology, and complexity. Therefore, the need to identify patients at risk for embolic events has become increasingly important. The morphologic characteristics of atherosclerotic carotid plaques may be useful in heralding embolic potential in the carotid arteries. Several authors have reported that plaques in the carotid arteries that are associated with large lipid pools or soft extracellular lipid are more prone to rupture and production of emboli.¹⁶ DWI is the most sensitive tool for the detection of neurologically silent or asymptomatic infarcts at a very early stage.^17–19The aim of this study was to determine the frequency of new ischemic DWI lesions in patients with moderate and severe ICA stenosis after protected CAS using a filter device, and to determine its potential association with plaque morphology.     

Neurologic complications of arteriovenous malformation embolization using liquid embolic agents

BACKGROUND AND PURPOSE: Embolization of arteriovenous malformations (AVMs) is commonly used to achieve nidal volume reduction before microsurgical resection or stereotactic radiosurgery. The purpose of this study was to examine the overall neurologic complication rate in patients undergoing AVM embolization and analyze the factors that may determine increased risk.MATERIALS AND METHODS: We performed a retrospective review of all patients with brain AVMs embolized at 1 center from 1995 through 2005. Demographics, including age, sex, presenting symptoms, and clinical condition, were recorded. Angiographic factors including maximal nidal size, presence of deep venous drainage, and involvement of eloquent cortex were also recorded. For each embolization session, the agent used, number of pedicles embolized, the percentage of nidal obliteration, and any complications were recorded. Complications were classified as the following: none, non-neurologic (mild), transient neurologic deficit, and permanent nondisabling and permanent disabling deficits. The permanent complications were also classified as ischemic or hemorrhagic. Modified Rankin Scale (mRS) scores were collected pre- and postembolization on all patients. Univariate regression analysis of factors associated with the development of any neurologic complication was performed.RESULTS: Four hundred eighty-nine embolization procedures were performed in 192 patients. There were 6 Spetzler-Martin grade I (3.1%), 26 grade II (13.5%), 71 grade III (37.0%), 57 grade IV (29.7%), and 32 grade V (16.7%) AVMs. Permanent nondisabling complications occurred in 5 patients (2.6%) and permanent disabling complications or deaths occurred in 3 (1.6%). In addition, there were non-neurologic complications in 4 patients (2.1%) and transient neurologic deficits in 22 (11.5%). Five of the 8 permanent complications (2.6% overall) were ischemic, and 3 of 8 (1.6% overall) were hemorrhagic. Of the 178 patients who were mRS 0–2 pre-embolization, 4 (2.3%) were dependent or dead (mRS >2) at follow-up. Univariate analysis of risk factors for permanent neurologic deficits following embolization showed that basal ganglia location was weakly associated with a new postembolization neurologic deficit.CONCLUSION: Embolization of brain AVMs can be performed with a high degree of technical success and a low rate of permanent neurologic complications.

The treatment of brain arteriovenous malformations (AVMs) is challenging and often requires the use of all 3 established modalities: superselective embolization, microsurgical resection, and stereotactic radiosurgery. Embolization of AVMs is typically used to reduce nidal size in advance of surgical resection or radiosurgery.^1–8 Embolization can also be used to reduce hemorrhage risk by attempting to eliminate specific areas at high risk for hemorrhage such as intranidal aneurysms,⁹ or less commonly, by attempting to completely obliterate the nidus. Recent advances in the embolization technique during the past decade include the development of softer flow-directed microcatheters and the increased use of liquid embolic agents, including cyanoacrylate derivatives to assure nidal penetration during embolization. In addition, superselective provocative testing with barbiturates has been shown to offer an additional level of safety.^10–13There is a large multicenter ongoing study to examine the natural history of unruptured AVMs and compare outcomes with multimodality therapy in a randomized fashion (ARUBA study, http://www.arubastudy.org; accessed June 12, 2007). Better understanding of treatment-related complications of embolization would be a key component of understanding risks of therapy versus conservative management, especially for unruptured brain AVMs.¹⁴ Several recent series have reported the complication rates with AVM embolization,^{2,5,6,8,15–17} with treatment-related morbidity ranging from 3% to 11%. An embolization protocol using continuous neurophysiologic testing, superselective provocative testing, conscious sedation instead of general anesthesia whenever possible to allow direct clinical examination, staged embolization during several sessions, and strict postprocedure blood pressure control has been adopted at our institution. The purpose of this study was to determine the risk of new neurologic deficits by using this protocol.