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Maksim Shapiro, Tibor Becske, and Peter K. Nelson

OBJECTIVE

A detailed analysis was performed of anterior circulation aneurysms treated with a Pipeline Embolization Device (PED) that did not progress to complete occlusion by 1-year follow-up. Angiography was performed with the purpose of identifying specific factors potentially responsible for these failed outcomes.

METHODS

From among the first 100 patients with anterior circulation aneurysms, 92 underwent 1-year follow-up angiography and were individually studied through review of their pre- and postembolization studies.

RESULTS

Nineteen aneurysms (21%) remained unoccluded at 12 months. Independent predictors of treatment failure, identified by logistic regression analysis, were found to be fusiform aneurysm morphology, decreasing dome-to-neck ratio, and the presence of a preexisting laser-cut stent. Further examination of individual cases identified several common mechanisms—device malapposition, inadequate coverage of the aneurysm neck with persistent exchange across the device, and the incorporation of a branch vessel into the aneurysm fundus—potentially contributing to failed treatment in these settings.

CONCLUSIONS

Attention to specific features of the aneurysm and device construct can frequently identify cases predisposed to treatment failure and suggest strategies to maximize favorable outcomes.

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Jason W. Allen, Anthony J. G. Alastra, and Peter K. Nelson

Object. The aim of this study was to determine the prevalence of angiographically identifiable skull base arterial branches that potentially serve as collateral conduits during a balloon occlusion test (BOT) of the internal carotid artery (ICA). The authors posited that neurological deficits in patients who had previously tolerated the occlusion test may be attributable to an unrecognized collateral support through these channels (operant during proximal ICA BOT) when permanent ICA occlusion was performed more distally.

Methods. In 481 cases (962 ICAs), cerebral angiograms obtained during routine Wada testing were retrospectively reviewed. Two hundred sixty-one patients had at least one angiographically identifiable ICA branch; 109 patients had two or more branches. A meningohypophyseal branch of the cavernous ICA was identified on the right side in 108 patients and on the left in 122. A vidian artery originated from the petrous portion of the ICA on the right side in 58 patients and on the left in 85. The inferolateral trunk revealed itself as a branch of the cavernous ICA on the right side in 17 patients and on the left in 33. A caroticotympanic artery arose from a left cavernous ICA. A persistent trigeminal artery was situated on the right side in two patients and on the left in three. More than half of the patients had angiographically identifiable and perhaps hemodynamically significant skull base branches of the ICA, and approximately one quarter had more than one identifiable branch.

Conclusions. The authors recommend that patients be screened during angiography studies performed prior to BOT in branches of the proximal intracranial ICA and that the site of BOT be moved distally if such branches are identified.

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Daniel H. Sahlein, Paloma Mora, Tibor Becske, and Peter K. Nelson

Object

Nidal embolization of brain arteriovenous malformations (bAVMs) has become an increasingly important component of bAVM treatment. However, controversy exists as to the relative efficacy and safety of single-stage versus multistage approaches to bAVM embolization, with recent literature favoring multistage strategies. The authors present a series of consecutive bAVMs embolized at their institution, demonstrating the safety and efficacy of a predominantly single-stage embolization strategy. The safety and efficacy of embolization are reported in the context of predetermined treatment strategies to provide more generalizable insight into treatment outcome.

Methods

One hundred thirty consecutive patients with 131 bAVMs underwent endovascular embolization at a single center. Diagnostic angiography with superselective microcatheterizations was performed in all patients. Postembolization angiograms were reviewed by 3 neuroradiologists for degree of occlusion and angiographic evidence of procedural complications. Patients were divided into cohorts based on the prospectively determined treatment strategy, which included the following: global devascularization of the bAVM (Devasc); targeting of a focal angioarchitectural weakness (Target), typically as an adjunct to surgery or Gamma Knife treatment; and primary occlusion of the bAVM by embolization alone (Occlude). Safety and efficacy were evaluated in the context of these treatment groups.

Results

The 131 bAVMs were treated over an average of 1.28 embolization sessions per bAVM; 105 bAVMs (80%) were treated in a single stage. The average percentage devascularization in the Devasc arm was 85.3%, which was statistically significantly greater than the 72% aggregate devascularization reported in 8 modern N-butyl cyanoacrylate and Onyx papers based on 1-sample Wilcoxon rank-sum testing (p < 0.001). Focal angioarchitectural weaknesses were successfully embolized for all 24 bAVMs in the Target group, directly with the embolic agent in 23 bAVMs and indirectly in 1 bAVM with a venous aneurysm/pseudoaneurysm by reducing arterial inflow and inducing venous thrombosis. Lesions in all patients in the Occlude arm were 100% occluded with embolization alone. Overall, the bAVMs in the Occlude arm were significantly smaller and required embolization of fewer pedicles than those in the Devasc group. One patient (0.8%) experienced significant morbidity following embolization, and 1 patient in the cohort died (0.8%).

Conclusions

This research communicates the authors' experience in developing a largely single-stage strategy for embolization of bAVMs. The results suggest that an aggressive, single-stage embolization may be implemented with a margin of safety and effectiveness similar to the multistage approaches more commonly reported in the literature. This work additionally introduces the importance of prospective assignment to a treatment strategy in assessing procedural outcome in bAVM embolization, thereby improving generalizability of the results and allowing for more rigorous interpretation of efficacy and safety.

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Gádor Cantón, David I. Levy, Juan C. Lasheras, and Peter K. Nelson

Object. The goal of this study was to quantify the reduction in velocity, vorticity, and shear stresses resulting from the sequential placement of stents across the neck of sidewall cerebral aneurysms.

Methods. A digital particle image velocimetry (DPIV) system was used to measure the pulsatile velocity field within a flexible silicone sidewall intracranial aneurysm model and at the aneurysm neck–parent artery interface in this model. The DPIV system is capable of providing an instantaneous, quantitative two-dimensional measurement of the velocity vector field of “blood” flow inside the aneurysm pouch and the parent vessel, and its changes at varying stages of the cardiac cycle. The corresponding vorticity and shear stress fields are then computed from the velocity field data. Three Neuroform stents (Boston Scientific/Target), each with a strut thickness between 60 and 65 µm, were subsequently placed across the neck of the aneurysm model and measurements were obtained after each stent had been placed.

The authors measured a consistent decrease in the values of the maximal averaged velocity, vorticity, and shear stress after placing one, two, and three stents. Measurements of the circulation inside the sac demonstrated a systematic reduction in the strength of the vortex due to the stent placement. The decrease in the magnitude of the aforementioned quantities after the first stent was placed was remarkable. Placement of two or three stents led to a less significant reduction than placement of the first stent.

Conclusions. The use of multiple flexible intravascular stents effectively reduces the strength of the vortex forming in an aneurysm sac and results in a decrease in the magnitude of stresses acting on the aneurysm wall.

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Matthew B. Potts, Daniel W. Zumofen, Eytan Raz, Peter K. Nelson, and Howard A. Riina

Endovascular embolization is typically reserved as an adjuvant therapy in the management of cerebral arteriovenous malformations (AVMs), either for preoperative devascularization or preradiosurgical volume reduction. Curative embolization plays a limited role in AVM treatment but several studies have shown that it is possible, especially with later-generation liquid embolic agents. Given the complexity of AVM anatomy and the recent controversies over the role of any intervention in AVM management, it is critical that the cerebrovascular community better define the indications of each treatment modality to provide quality AVM management. In this review, the authors evaluate the role of curative AVM embolization. Important considerations in the feasibility of curative AVM embolization include whether it can be performed reliably and safely, and whether it is a durable cure. Studies over the past 20 years have begun to define the anatomical factors that are amenable to complete endovascular occlusion, including size, feeding artery anatomy, AVM morphology, and endovascular accessibility. More recent studies have shown that highly selected patients with AVMs can be treated with curative intent, leading to occlusion rates as high as 100% of such prospectively identified lesions with minimal morbidity. Advances in endovascular technology and techniques that support the efficacy and safety of curative embolization are discussed, as is the importance of superselective diagnostic angiography. Finally, the durability of curative embolization is analyzed. Overall, while still unproven, endovascular embolization has the potential to be a safe, effective, and durable curative treatment for select AVMs, broadening the armamentarium with which one can treat this disease.

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Xiaotong Fan, Brian D. Nelson, Yi Ai, David K. Stiles, Don M. Gash, Peter A. Hardy, and Zhiming Zhang

OBJECT

Assessing the safety and feasibility of chronic delivery of compounds to the brain using convection-enhanced delivery (CED) is important for the further development of this important therapeutic technology. The objective of this study was to follow and model the distribution of a compound delivered by CED into the putamen of rhesus monkeys.

METHODS

The authors sequentially implanted catheters into 4 sites spanning the left and right putamen in each of 6 rhesus monkeys. The catheters were connected to implanted pumps, which were programmed to deliver a 5-mM solution of the MRI contrast agent Gd-DTPA at 0.1 μl/minute for 7 days and 0.3 μl/minute for an additional 7 days. The animals were followed for 28 days per implant cycle during which they were periodically examined with MRI.

RESULTS

All animals survived the 4 surgeries with no deficits in behavior. Compared with acute infusion, the volume of distribution (Vd) increased 2-fold with 7 days of chronic infusion. Increasing the flow rate 3-fold over the next week increased the Vd an additional 3-fold. Following withdrawal of the compound, the half-life of Gd-DTPA in the brain was estimated as 3.1 days based on first-order pharmacokinetics. Histological assessment of the brain showed minimal tissue damage limited to the insertion site.

CONCLUSIONS

These results demonstrate several important features in the development of a chronically implanted pump and catheter system: 1) the ability to place catheters accurately in a predetermined target; 2) the ability to deliver compounds in a chronic fashion to the putamen; and 3) the use of MRI and MR visible tracers to follow the evolution of the infusion volume over time.

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Matthew B. Potts, Maksim Shapiro, Daniel W. Zumofen, Eytan Raz, Erez Nossek, Keith G. DeSousa, Tibor Becske, Howard A. Riina, and Peter K. Nelson

OBJECTIVE

The Pipeline Embolization Device (PED) is now a well-established option for the treatment of giant or complex aneurysms, especially those arising from the anterior circulation. Considering the purpose of such treatment is to maintain patency of the parent vessel, postembolization occlusion of the parent artery can be regarded as an untoward outcome. Antiplatelet therapy in the posttreatment period is therefore required to minimize such events. Here, the authors present a series of patients with anterior circulation aneurysms treated with the PED who subsequently experienced parent vessel occlusion (PVO).

METHODS

The authors performed a retrospective review of all anterior circulation aneurysms consecutively treated at a single institution with the PED through 2014, identifying those with PVO on follow-up imaging. Aneurysm size and location, number of PEDs used, and follow-up digital subtraction angiography results were recorded. When available, pre- and postembolization platelet function testing results were also recorded.

RESULTS

Among 256 patients with anterior circulation aneurysms treated with the PED, the authors identified 8 who developed PVO after embolization. The mean aneurysm size in this cohort was 22.3 mm, and the number of PEDs used per case ranged from 2 to 10. Six patients were found to have asymptomatic PVO discovered incidentally on routine follow-up imaging between 6 months and 3 years postembolization, 3 of whom had documented “delayed” PVO with prior postembolization angiograms confirming aneurysm occlusion and a patent parent vessel at an earlier time. Two additional patients experienced symptomatic PVO, one of which was associated with early discontinuation of antiplatelet therapy.

CONCLUSIONS

In this large series of anterior circulation aneurysms, the authors report a low incidence of symptomatic PVO, complicating premature discontinuation of postembolization antiplatelet or anticoagulation therapy. Beyond the subacute period, asymptomatic PVO was more common, particularly among complex fusiform or very large–necked aneurysms, highlighting an important phenomenon with the use of PED for the treatment of anterior circulation aneurysms, and suggesting that extended periods of antiplatelet coverage may be required in select complex aneurysms.

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Nathan A Shlobin, Eytan Raz, Maksim Shapiro, Luke Moretti, Donald R Cantrell, Sandi K Lam, Michael C Hurley, Sameer A Ansari, Erez Nossek, Howard A Riina, Peter K Nelson, Babak S Jahromi, Ali Shaibani, and Matthew B Potts

OBJECTIVE

Cerebral aneurysms in the pediatric population are rare and optimal treatment strategies are not as well characterized as in adults. The Pipeline embolization device (PED) is an endoluminal flow diverter that is commonly used to treat aneurysms in adults, but experience with this device in children is limited. The authors sought to further characterize PED use and outcomes in this specific population by performing both a systematic review of patient-level data from studies reporting the use of the PED to treat pediatric aneurysms and a retrospective review of their experience.

METHODS

A systematic review of the PubMed, Embase, and Scopus databases was performed to identify studies reporting the use of the PED in pediatric patients (age ≤ 18 years). Disaggregated data regarding demographics, aneurysm characteristics, treatment, and outcomes were collected. Retrospective data from the authors’ two institutions were also included.

RESULTS

Thirty studies comprising patient-level data on 43 pediatric patients with 47 aneurysms were identified. An additional 9 patients with 9 aneurysms were included from the authors' institutions for a total of 52 patients with 56 aneurysms. The mean patient age was 11.1 years. Presentations included aneurysm rupture (17.3%) and symptomatic mass effect (23.1%). Aneurysms were located in the anterior circulation in 55.4% of cases, and 73.2% were described as nonsaccular. Imaging follow-up was available for 89.3% with a mean follow-up of 13.3 months. Aneurysm occlusion was reported in 75%, with 1 case each (1.8%) demonstrating significant in-stent stenosis and parent vessel occlusion. Clinical follow-up was reported in 90.4% with a mean follow-up of 14.7 months. Good functional outcomes (modified Rankin Scale score of 0–1 or Glasgow Outcome Scale score of 5) were reported in 65.4% of the total population. Two major complications were reported, including 1 death.

CONCLUSIONS

Despite substantial differences in aneurysm location and type between published pediatric and adult patient populations treated with the PED, the use of the PED in the pediatric population appears to be safe. While the short-term effectiveness is also similar to that of adults, additional studies are needed to further characterize the long-term outcomes and better define the use of this device in pediatric patients.