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Aneurysmal recurrence after successful flow-diversion embolization is exceptionally rare. The rarity of recurrence has called into question the yield of interval surveillance imaging. Here we report the case of a recurrent intracranial aneurysm despite complete angiographic resolution after flow-diversion therapy with a Pipeline embolization device (PED). Given the absence of poor wall apposition, endoleak, and device migration, how this aneurysm recurred remains unclear, particularly given the recurrence was at a timepoint at which complete reendothelialization of the device would be expected. The patient ultimately underwent interval treatment with a second device placed across the neck of the aneurysm. Although rare, reports of aneurysmal recurrences support the use of interval non-invasive imaging surveillance to ensure successful embolization in this patient population.

Introduction The COVID-19 pandemic has led to excess mortality out of proportion to documented COVID-19 cases while also affecting the care of non-COVID-19 related diseases. No data exist on the effects of the COVID-19 pandemic on the care and outcomes of patients with aneurysmal subarachnoid hemorrhage (aSAH). Here we determine the impact of the COVID-19 pandemic on latency to presentation and clinical outcomes for aneurysmal subarachnoid hemorrhage. Methods We performed a retrospective cohort study of all patients presenting to a single center in Atlanta, Georgia, USA with aSAH between 2012 and 2020. COVID-19 was first reported in Georgia on March 2, 2020. All patients presenting from March 2nd through June 30th of a given calendar year were compared from the pre-COVID-19 era (2012- 2019) to the COVID-19 era (2020). Patient characteristics, latency from ictus to presentation, and clinical outcomes were compared. Every index digital subtraction angiogram was scored for the presence of vasospasm, and all cranial imaging studies were reviewed for infarcts consistent with delayed cerebral ischemia. Results 470 patients presented with aneurysmal subarachnoid hemorrhage during the study period. 433 and 37 presented before and during the COVID-19 era, respectively. Compared to the pre-COVID-19 era patients, patients presenting during the early phase of the pandemic were more likely to delay presentation (2.3 ± 1.3 days vs. 0.9 ± 2.2 days, respectively, p

BackgroundAtrial fibrillation (AF) associated ischemic stroke is associated with worse functional outcomes, less effective recanalization, and increased rates of hemorrhagic complications after intravenous thrombolysis (IVT). Conversely, AF is not associated with hemorrhagic complications or functional outcomes in patients undergoing mechanical thrombectomy (MT). This differential effect of MT and IVT in AF associated stroke raises the question of whether bridging thrombolysis increases hemorrhagic complications in AF patients undergoing MT.MethodsThis international cohort study of 22 comprehensive stroke centers analyzed patients with large vessel occlusion (LVO) undergoing MT between June 1, 2015 and December 31, 2020. Patients were divided into four groups based on comorbid AF and IVT exposure. Baseline patient characteristics, complications, and outcomes were reported and compared.Results6461 patients underwent MT for LVO. 2311 (35.8%) patients had comorbid AF. In non-AF patients, bridging therapy improved the odds of good 90 day functional outcomes (adjusted OR (aOR) 1.29, 95% CI 1.03 to 1.60, p=0.025) and did not increase hemorrhagic complications. In AF patients, bridging therapy led to significant increases in symptomatic intracranial hemorrhage and parenchymal hematoma type 2 (aOR 1.66, 1.07 to 2.57, p=0.024) without any benefit in 90 day functional outcomes. Similar findings were noted in a separate propensity score analysis.ConclusionIn this large thrombectomy registry, AF patients exposed to IVT before MT had increased hemorrhagic complications without improved functional outcomes, in contrast with non-AF patients. Prospective trials are warranted to assess whether AF patients represent a subgroup of LVO patients who may benefit from a direct to thrombectomy approach at thrombectomy capable centers.

The early phase of the COVID-19 pandemic led to significant healthcare avoidance, perhaps explaining some of the excess reported deaths that exceeded known infections. The impact of the early COVID-19 era on aneurysmal subarachnoid hemorrhage (aSAH) care remains unclear.To determine the impact of the early phase of the COVID-19 pandemic on latency to presentation, neurological complications, and clinical outcomes after aSAH.We performed a retrospective cohort study from March 2, 2012, to June 30, 2021, of all patients with aSAH admitted to our center. The early COVID-19 era was defined as March 2, 2020, through June 30, 2020. The pre-COVID-19 era was defined as the same interval in 2012 to 2019.Among 499 patients with aSAH, 37 presented in the early COVID-19 era. Compared with the pre-COVID-19 era patients, patients presenting during this early phase of the pandemic were more likely to delay presentation after ictus (median, interquartile range; 1 [0-4] vs 0 [0-1] days, respectively, P.001). Radiographic-delayed cerebral ischemia (29.7% vs 10.2%, P.001) was more common in the early COVID-19 era. In adjusted analyses, presentation in the early COVID-19 era was independently associated with increased inhospital death or hospice disposition (adjusted odds ratio 3.29 [1.02-10.65], P = .046). Both latency and adverse outcomes returned to baseline in 2021.aSAH in the early COVID-19 era was associated with delayed presentation, neurological complications, and worse outcomes at our center. These data highlight how healthcare avoidance may have increased morbidity and mortality in non-COVID-19-related neurosurgical disease.

Urokinase-type plasminogen activator (uPA) is a serine proteinase that catalyzes the generation of plasmin on the cell surface and activates cell signaling pathways that promote remodeling and repair. Neuronal cadherin (NCAD) is a transmembrane protein that in the mature brain mediates the formation of synaptic contacts in the II/III and V cortical layers. Our studies show that uPA is preferentially found in the II/III and V cortical laminae of the gyrencephalic cortex of the non-human primate. Furthermore, we found that in murine cerebral cortical neurons and induced pluripotent stem cell (iPSC)-derived neurons prepared from healthy human donors, most of this uPA is associated with pre-synaptic vesicles. Our in vivo experiments revealed that in both, the gyrencephalic cortex of the non-human primate and the lissecephalic murine brain, cerebral ischemia decreases the number of intact synaptic contacts and the expression of uPA and NCAD in a band of tissue surrounding the necrotic core. Additionally, our in vitro data show that uPA induces the synthesis of NCAD in cerebral cortical neurons, and in line with these observations, intravenous treatment with recombinant uPA three hours after the onset of cerebral ischemia induces NCAD-mediated repair of synaptic contacts in the area surrounding the necrotic core.

* on behalf of the Stroke Thrombectomy and Aneurysm Registry (STAR) Collaborators Introduction: Intravenous thrombolysis complications are enriched in AF associated stroke, as these patients have worse functional outcomes, less effective recanalization, and increased rates of hemorrhagic complications. These data suggest that AF patients may be at particularly high risk for complications of bridging therapy for large vessel occlusions treated with mechanical thrombectomy (MT). Here we determine whether clinical outcomes differ in AF associated stroke treated with MT and bridging therapy. Methods: We performed a retrospective cohort study of the Stroke and Aneurysm Registry (STAR) from January 2015 to December 2018 and identified 4,169 patients who underwent MT for an anterior circulation stroke, 1,517 (36.4 %) of which had comorbid AF. Prospectively defined baseline characteristics and clinical outcomes were compared. Results: Hemorrhagic complications after MT were similar in patients with or without AF. In patients without AF, bridging therapy improved 90-day outcomes (aOR 1.32, 1.02-1.74, p Conclusions: Bridging therapy in AF patients undergoing thrombectomy independently increased the odds of intracranial hemorrhage and did not improve functional outcomes. AF patients may represent a high-risk subgroup for thrombolytic complications. Randomized trials are warranted to determine whether patients with AF associated stroke may benefit by deferring bridging therapy at thrombectomy-capable centers.

Background The Woven EndoBridge (WEB) device was granted premarket approval in the United States following results of the Woven EndoBridge Intrasaccular Therapy (WEB-IT) study. WEB-IT reported excellent adequate angiographic occlusion of treated aneurysms with a high safety profile. These results were achieved, however, in the context of a prospective study with strict inclusion criteria and rigorous training support. Objective To review early as-practiced clinical experience with the WEB device in the United States. Methods Retrospective review across 6 institutions identified 91 patients undergoing 92 treatment sessions for WEB device placement in treatment of 91 intracranial aneurysms. Details regarding demographics, aneurysm characteristics, treatment considerations, clinical outcomes, and aneurysm occlusion were obtained and analyzed in a multicenter database. Angiograms from the index procedure and follow-up studies were reviewed by a blinded and independent adjudicator. Results The middle cerebral, anterior communicating, and basilar artery complexes were the commonly treated locations. Eight patients presented with ruptured aneurysms. A mean of 1.2 devices were introduced per case. Technical failure without deployment of a WEB device occurred in 2% (2/92) of sessions. Adequate aneurysm occlusion for patients with imaging follow-up was 49% (mean follow-up of 8 mo). Four aneurysms were retreated. 90% of patients had modified Rankin Scale ≤ 2 at last clinical follow-up with no mortalities. Conclusion Immediate postmarket experience with the WEB device, newly introduced at American centers, confirms safe procedural use, but long-term efficacy remains unclear. Early challenges include accurate sizing and device selection.

BackgroundRuptured aneurysms of the intracranial vertebral artery (VA) or posterior inferior cerebellar artery (PICA) are challenging to treat as they are often dissecting aneurysms necessitating direct sacrifice of the diseased segment, which is thought to carry high morbidity due to brainstem and cerebellar stroke. However, relatively few studies evaluating outcomes following VA or proximal PICA sacrifice exist. We sought to determine the efficacy and outcomes of endovascular VA/PICA sacrifice.MethodsA retrospective series of ruptured VA/PICA aneurysms treated by endovascular sacrifice of the VA (including the PICA origin) or proximal PICA is reviewed. Collected data included demographic, radiologic, clinical, and disability information.ResultsTwenty-one patients were identified. Median age was 57 years (IQR 11); 15 were female. The Hunt and Hess grade was mostly 3 and 4 (18/21). Seven cases (33%) involved VA-V4 at the PICA take-off, and 14 cases (67%) involved the PICA exclusively. For VA pathology, V4 was sacrificed in all cases, while for PICA pathology, sacrificed segments included anterior medullary (4/14), lateral medullary (7/14), and tonsillomedullary (3/14) segments. Four patients went to hospice (19%). Twelve patients (57%) had evidence of stroke on follow-up imaging: cerebellar (8), medullary (1), and both (3). One patient required suboccipital decompression for brainstem compression. No aneurysm re-rupture occurred. Median discharge modified Rankin Scale score was 2.0 (IQR 2), which decreased to 1.0 (IQR 1) at median follow-up of 6.5 months (IQR 23).ConclusionsEndovascular sacrifice of V4 or PICA aneurysms may carry less morbidity than previously thought, and is a viable alternative for poor surgical candidates or those with good collateral perfusion.

BackgroundAtrial fibrillation (AF) associated ischemic stroke has worse functional outcomes, less effective recanalization, and increased rates of hemorrhagic complications after intravenous thrombolysis (IVT). Limited data exist about the effect of AF on procedural and clinical outcomes after mechanical thrombectomy (MT).ObjectiveTo determine whether recanalization efficacy, procedural speed, and clinical outcomes differ in AF associated stroke treated with MT.MethodsWe performed a retrospective cohort study of the Stroke Thrombectomy and Aneurysm Registry (STAR) from January 2015 to December 2018 and identified 4169 patients who underwent MT for an anterior circulation stroke, 1517 (36.4 %) of whom had comorbid AF. Prospectively defined baseline characteristics, procedural outcomes, and clinical outcomes were reported and compared.ResultsAF predicted faster procedural times, fewer passes, and higher rates of first pass success on multivariate analysis (pConclusionsIn patients treated with MT, comorbid AF is associated with faster procedural time, fewer passes, and increased rates of first pass success without increased risk of intracranial hemorrhage or worse functional outcomes. These results are in contrast to the increased hemorrhage rates and worse functional outcomes observed in AF associated stroke treated with supportive care and or IVT. These data suggest that MT negates the AF penalty in ischemic stroke.

Background Aneurysms at the origin of the posterior communicating artery (PcommA) have been demonstrated to be effectively treated with the pipeline embolization device (PED). Much less is known about the efficacy of the PED for aneurysms associated with a fetal posterior cerebral artery (fPCA) variant. Objective To study PED treatment efficacy of PcommA aneurysms, including fPCA aneurysms. Methods A prospectively maintained university database of aneurysm patients treated with the PED was retrospectively reviewed. Demographics, treatment details, and imaging were reviewed for all PcommA and fPCA aneurysms. Results Out of a total of 285 patients treated with PED, 50 patients (mean age 57.5 ± 12.2 yr, 42 females) with unruptured PcommA (9 fPCA) aneurysms were identified. Mean follow-up duration was 14.0 ± 11.6 mo (48 patients). Roy-Raymond class I occlusion on follow-up magnetic resonance or catheter angiography (mean time 11.7 ± 6.8 mo) was achieved in 30 patients (62.5%), class II occlusion in 11 patients (22.9%) and class III occlusion in 7 patients (14.5%). The PcommA was occluded in 56% of patients without any clinical symptoms. No deaths or permanent neurological complications occurred. In fPCA aneurysms, class I occlusion was seen in 1 patient, class 2 occlusion in 2 patients, and class III occlusion in 6 patients. Multivariate analysis revealed an independent association between incomplete occlusion and fPCA configuration (OR 73.65; 95% CI: 5.84-929.13; P = .001). Conclusion The PED is a safe and effective treatment for PcommA aneurysms, although fetal anatomy should increase consideration of traditional endovascular techniques or surgical clipping.

BACKGROUND AND PURPOSE: Flow diversion is an established method to treat complex intracranial aneurysms. The natural history of flow-diversion treatment failure resulting in aneurysm remnants is not well-defined. We aimed to delineate the clinical and angiographic features of this entity. MATERIALS AND METHODS: Review of a prospectively maintained Pipeline Embolization Device data base from inception to October 2017 was performed for aneurysms that demonstrated residual filling on follow-up imaging. Procedural and follow-up clinical details were recorded. Independent, blinded, angiographic assessment of occlusion was performed on the basis of the O9Kelly-Marotta scale. Aggregated outcomes were analyzed using the Fisher exact and Mann-Whitney U tests for categoric and continuous variables, respectively (statistical significance, α = .05). RESULTS: During the study period, 283 sequential patients were treated; 87% (246/283) were women. The median patient age was 55 years (interquartile range, 47–65 years). Six-month follow-up imaging was available in 83.7% (237/283) of patients, which showed 62.4% (148/237) complete occlusion (class D, O9Kelly-Marotta grading scale). Adjunctive coiling (P = .06), on-label Pipeline Embolization Device use (P = .04), and multiple device constructs (P = .02) had higher rates of complete occlusion at 6 months. Aneurysm remnants were identified in 25 cases on long-term follow-up imaging (median, 16 months; interquartile range, 12–24 months). No patient with an aneurysm remnant after flow diversion presented with delayed rupture or other clinical sequelae, with a median clinical follow-up of 31 months (interquartile range, 23–33 months). CONCLUSIONS: Aneurysm remnants after flow diversion are infrequent with minimal clinical impact. When appropriate, the presence of overlapping devices and possibly adjunctive coiling may result in higher rates of complete occlusion.

The Pipeline embolization device (PED) is commonly used for the treatment of distal internal carotid artery (ICA) aneurysms, which often require placing the stent across the origin of the precommunicating segment of the anterior cerebral artery (ACA-A1). We sought to characterize the clinical and angiographic consequences of this maneuver.We performed a retrospective review of a prospectively collected database of patients treated with the PED at a single academic center from 2011 to 2017 to find patients for whom the PED was extended across the origin of the ACA-A1. The patient demographic data, pretreatment angiographic imaging findings, sizing of the bilateral A1 and ipsilateral M1 segment of the middle cerebral artery (MCA-M1), and follow-up angiographic and clinical imaging findings were recorded.A total of 27 patients were included in the present study (8 men and 19 women; age, 52 ± 14.9 years). Follow-up angiography was conducted at a median of 9.2 months (interquartile range, 6; range, 5-84). The covered A1 segment was patent in 17 patients (63%). The covered ACA-A1/ipsilateral MCA-M1 ratio was 1.43 times greater for the patent ACA-A1 segments than those that were occluded (P = 0.0006). Similarly, the covered ACA-A1/contralateral ACA-A1 ratio was significantly larger statistically (1.64; P0.0001) for the patent ACA-A1 segments than that for those that were occluded. None of the patients developed clinical or radiographic signs of ACA stroke. The modified Rankin scale worsened for 1 patient during follow-up owing to a further decline of presenting vision loss.The PED can be used to treat aneurysms with deployment from the MCA-M1 to the ICA without resulting in ACA stroke. Ipsilateral A1 segment dominance might be predictive of continued blood flow into the ACA after deployment at this location.

INTRODUCTION: Increasing reports suggest that patients have been reluctant to present for care due to fear of contracting severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), even in the setting of ischemic stroke or myocardial infarction The impact of the ongoing pandemic on patients with aneurysmal subarachnoid hemorrhage (aSAH) remains unknown METHODS: We performed a retrospective cohort study of all patients presenting to a single referral center in Atlanta, Georgia, USA with aSAH between 2012 and 2020 SARSCoV- 2 was first reported in Georgia on March 2, 2020 All patients presenting from March through June of a given calendar year were compared from the pre-SARS-CoV-2 era (2012-2019) to the SARS-CoV-2 era (2020) Patient characteristics, latency from ictus to presentation, and clinical outcomes were compared RESULTS: A total of 472 patients presented with aSAH during the study period, with comparable distribution in the age, sex, and Hunt and Hess grade on presentation The mean latency in days from ictus to presentation was significantly longer in 2020 when compared to the pre- SARS-CoV-2 era (2 3, + 3 0 vs 0 9 + 2 2, respectively, p< 05) Absolute rates of discharge home or in-hospital mortality were not significantly different In binary regression analysis, patients were more likely to present post-bleed day 2 or after (OR 3 9, 1 9-8 1, p< 05) This effect was driven by delays to presentation in low grade aSAH (OR 3 2, 1 1-9 25, p< 05) with no difference to time in presentation in highgrade aSAH (2 3, 0 25 - 21 6) The delay to presentation was persistent on multiple binary regression analysis after controlling for age and grade (aOR 3 7, 1 7-8 0, p< 05) There was a non-significant trend towards increased mortality in the SARS-CoV-2 era on multiple regression analysis (2 78, 0 95-8 16) CONCLUSIONS: Similar to patients with myocardial and cerebral infarctions, patients are presenting for care later after an aSAH This effect is driven by low grade aSAH, as high grade aSAH patients with a more fulminant presentation are still largely presenting within the first day, similar to the pre- SARS-CoV-2 era These data highlight the ongoing collateral damage of the SARS-CoV-2 pandemic and need for vigilant public health efforts to encourage rapid presentation for care

An adult rhesus macaque developed seizures after the induction of ischemic stroke. Initially, on the day of surgery, a focal ischemic lesion was present exclusively in the right caudate nucleus. By 48 h after stroke induction, the lesion had extended into the putamen, when a seizure was observed. Our report highlights the temporal changes in infarction of unilateral basal ganglia after acute stroke and the accompanying clinical symptoms. This unusual case may provide additional information regarding the involvement of the basal ganglia in seizures, given that prior case reports and studies usually have not described the temporal and spatial evolution of the lesion before clinical symptoms emerge.

An adult rhesus macaque developed seizures after the induction of ischemic stroke. Initially, on the day of surgery, a focal ischemic lesion was present exclusively in the right caudate nucleus. By 48 h after stroke induction, the lesion had extended into the putamen, when a seizure was observed. Our report highlights the temporal changes in infarction of unilateral basal ganglia after acute stroke and the accompanying clinical symptoms. This unusual case may provide additional information regarding the involvement of the basal ganglia in seizures, given that prior case reports and studies usually have not described the temporal and spatial evolution of the lesion before clinical symptoms emerge.

The video highlights a challenging case of bilateral vertebral artery dissection presenting with subarachnoid hemorrhage. The patient was found to have a critical flow-limiting stenosis in his dominant right vertebral artery and a ruptured pseudoaneurysm in his left vertebral artery. A single-stage endovascular treatment with stent reconstruction of the right vertebral artery and coil embolization sacrifice of the left side was performed. The case highlights the rationale for treatment and potential alternative strategies.The video can be found here: https://youtu.be/e0U_JE2jISw.

Purpose Intracranial dural arteriovenous fistulas (dAVFs) constitute approximately 10%–15% of all intracranial vascular malformations. More rarely, these lesions can lead to intracranial hemorrhage. Early re-bleeding rates from unsecured, ruptured dAVFs have been reported as high as 50%. Therefore, early intervention is paramount. Our aim of this study was to investigate the angiographic and clinical outcomes of early endovascular intervention in this rare disease presentation. Methods A HIPPA compliant neuroendovascular procedural database was reviewed for all treated dAVFs from 1999 to 2017. Inclusion criteria for the study included: 1) hemorrhagic presentation and 2) early endovascular intervention defined as less than 48 hours from initial ictus. Clinical demographics, angiographic and procedural details (Anatomic location, Borden classification, route of embolization, material used during embolization, number of retreatments, and need for completion microsurgical ligation), as well as clinical and angiographic follow up outcomes (modified Rankin scale and occlusion status on last follow-up imaging) were recorded. Appropriate statistical analyses were performed on parametric and non-parametric variables as applicable (statistical significance, α=0.05). Results A total of 262 dAVFs were identified, of those only 18 patients met inclusion criteria. Overall, the majority of patients were male (12/18; 66%), with a median age of 56 years (IQR 46–68 years). Hemorrhagic presentations included isolated intraparenchymal hemorrhage (IPH) (8/18; 44%), isolated subarachnoid hemorrhage (SAH) (7/18; 39%), SAH with subdural hematoma/intraventricular hemorrhage (IVH) (2/18; 11%), and isolated IVH (1/18; 6%). Almost all the hemorrhagic dAVF were of the aggressive type (Borden type II/III, 17/18; 94%). Anatomically, the most common location was tentorial (8/18; 44%). The anterior fossa, torcula, superior sagittal sinus, and transverse/sigmoid sinus all proportionately were the next common location (2/18; 11%, each respective group). Foramen magnum and straight sinus were the least common locations (1/18; 6%, each respective group). Transarterial embolization was performed most commonly (15/18; 83%), followed by transvenous approach (3/18; 17%). nBCA glue or Onyx embolization was most commonly used (15/18; 83%) with coils used exclusively in all transvenous cases (3/18; 17%). At last clinical follow-up, two patients succumbed to complications related to initial hemorrhage with the majority of patients (14/16; 88%) achieving good clinical outcome (mRS=0–2). On imaging follow-up when residual dAVF or incomplete embolization was noted (5/12; 42%) all cases underwent endovascular retreatment. Overwhelmingly, endovascular re-treatment failed in the majority of the cases (3/5; 60%); requiring microsurgical ligation for completion therapy. In no instance was early or late re-bleeding observed on last clinical follow-up, median 5 months (IQR 2–19 months). Conclusion Early endovascular intervention for ruptured dAVFs is feasible and effectively secures these lesions with no re-bleeding. Attention must be paid to lesions, which are incompletely embolized/show residual filling, as microsurgical ligation is imperative for completion therapy. Disclosures T. Madaelil: None. J. Grossberg: None. M. Cawley: None. F. Tong: None. J. Dion: 5; C; Vice President, Scientific Affairs at MicroVention-Terumo. B. Howard: None.

BackgroundAneurysmal subarachnoid hemorrhage is a potentially devastating condition, and among the first priorities of treatment is aneurysm occlusion to prevent re-hemorrhage. An emerging strategy to treat patients whose aneurysms are not ideal for surgical or endovascular treatment is subtotal coiling followed by flow diversion in the recovery phase or ‘plug and pipe’. However, data regarding the safety and efficacy of this strategy are lacking.MethodsA retrospective cohort study was performed to evaluate the efficacy and safety of ‘plug and pipe’. All patients with a ruptured intracranial aneurysm intentionally, subtotally treated by coiling in the acute stage followed by flow diversion after recovery, were included. The primary outcome was re-hemorrhage. Secondary outcomes included aneurysm occlusion and functional status. Complications were reviewed.Results22 patients were included. No patient suffered a re-hemorrhage, either in the interval between coiling and flow diversion or in follow-up. The median interval between aneurysm rupture and flow diversion was 3.5 months. Roy–Raymond (R-R) class I or II occlusion was achieved in 91% of target aneurysms at the last imaging follow-up (15/22(68%) R-R 1 and 5/22(23%) R-R 2). Complications occurred in 2 (9%) patients, 1 of which was neurological.ConclusionsOverall, these data suggest that subtotal coiling of ruptured intracranial aneurysms followed by planned flow diversion is both safe and effective. Patients who may most benefit from ‘plug and pipe’ are those with aneurysms that confer high operative risk and those whose severity of medical illness increases the risk of microsurgical clip ligation.

BACKGROUND AND PURPOSE: Current nonhuman primate stroke models are limited by either stroke variability or survivability. A new nonhuman primate stroke model was developed by using endovascular trapping techniques to limit collateral vessels with serial MR imaging and neurologic assessments. MATERIALS AND METHODS: Eight adult rhesus monkeys (female, 7–13 years of age) underwent MR imaging and Spetzler neurologic assessment followed by endovascular stroke induction consisting of superselective endovascular placement of surgical silk sutures into the right MCA by using a trapping technique. Two initial subjects were euthanized immediately following postocclusion MR imaging. The subsequent 6 subjects recovered and underwent follow-up MR imaging and Spetzler neurologic assessments at 48 hours, with 4 being followed to 96 hours. Stroke infarct volumes were measured, and the longitudinal Spetzler clinical neurologic scores were assessed. The brain tissues were harvested and prepared with hematoxylin-eosin staining. RESULTS: Focal permanent cerebral ischemia was induced in the targeted right MCA territory in all subjects. The volumes of the ischemic lesions at 6, 48, and 96 hours were 3.18 ± 1.007 mL (standard error of the mean) ( n = 8), 6.70 ± 1.666 mL (standard error of the mean) ( n = 6), and 7.23 ± 1.371 mL (standard error of the mean) ( n = 4). For the survival animals, the immediate postsurgical Spetzler grading score improved from 60.7 at 24 hours to 68.7 at 48 hours. CONCLUSIONS: We report a trapping modification to an established endovascular suture stroke model that yielded reproducible ischemia and clinically quantifiable neurologic deficits with no strokes in nontarget areas. This technique may be useful in evaluating translational stroke and penumbral imaging research in addition to preclinical testing of neuroprotective therapies.

Applications for noninvasive biologic temperature monitoring are widespread in biomedicine and of particular interest in the context of brain temperature regulation, where traditionally costly and invasive monitoring schemes limit their applicability in many settings. Brain thermal regulation, therefore, remains controversial, motivating the development of noninvasive approaches such as temperature-sensitive nuclear MR phenomena. The purpose of this work was to compare the utility of competing approaches to MR thermometry by using proton resonance frequency chemical shift. We tested 3 methodologies, hypothesizing the feasibility of a fast and accurate approach to chemical shift thermometry, in a phantom study at 3T.A conventional, paired approach (difference [DIFF]-1), an accelerated single-scan approach (DIFF-2), and a new, further accelerated strategy (DIFF-3) were tested. Phantom temperatures were modulated during real-time fiber optic temperature monitoring, with MR thermometry derived simultaneously from temperature-sensitive changes in the water proton chemical shift (∼0.01 ppm/°C). MR thermometry was subsequently performed in a series of in vivo nonhuman primate experiments under physiologic and ischemic conditions, testing its reproducibility and overall performance.Chemical shift thermometry demonstrated excellent agreement with phantom temperatures for all 3 approaches (DIFF-1: linear regression R(2) = 0.994; P.001; acquisition time = 4 minutes 40 seconds; DIFF-2: R(2) = 0.996; P.001; acquisition time = 4 minutes; DIFF-3: R(2) = 0.998; P.001; acquisition time = 40 seconds).These findings confirm the comparability in performance of 3 competing approaches to MR thermometry and present in vivo applications under physiologic and ischemic conditions in a primate stroke model.

Background: Previous Diffusion Tensor Imaging (DTI) studies have demonstrated the temporal evolution of stroke injury in grey matter and white matter can be characterized by DTI indices. However, it still remains not fully understood how the DTI indices of white matter are altered progressively during the hyperacute (first 6 hours) and acute stage of stroke (≤ 1 week). In the present study, DTI was employed to characterize the temporal evolution of infarction and white matter injury after stroke insult using a macaque model with permanent ischemic occlusion. Methods and materials: Permanent middle cerebral artery (MCA) occlusion was induced in rhesus monkeys (n=4, 10-21 years old). The brain lesion was examined longitudinally with DTI during the hyperacute phase (2-6 hours, n=4), 48 hours (n=4) and 96 hours (n=3) post-occlusion. Results: Cortical infarction was seen in all animals. The Mean Diffusivity (MD) in lesion regions decreased substantially at the first time point (2 hours post stroke) (35%, p Conclusion: The temporal evolution of ischemic injury to the grey matter and white matter from 2 to 96 hours after stroke onset was characterized using a macaque model and DTI. Progressive MD changes in white matter bundles are seen from hyperacute phase to acute phase after permanent MCA occlusion and temporally correlated with the MD changes in entire infarction regions. MD reduction in white matter bundles is mild in comparison with that in the grey matter but significant and progressive, indicating it may be useful to detect early white matter degeneration after stroke.

BackgroundAdministration of ε-aminocaproic acid (εACA), as adjuvant therapy following incompletely embolized cranial dural arteriovenous (dAVFs) and direct carotid artery to cavernous sinus fistulae (CCFs), is a strategy to promote post-procedural thrombosis. However, the efficacy of εACA to treat incompletely obliterated dAVFs and CCFs has not been published. The purpose of this study was to determine if administration of εACA following incomplete embolization of cranial dAVFs or CCFs was associated with an increased likelihood of cure on follow-up imaging compared with patients not given adjuvant εACA.MethodsA retrospective cohort study was performed. All patients who underwent treatment of a dAVF or CCF at our institution between 1998 and 2016 were reviewed (n=262). Patients with residual shunting following the first attempted endovascular embolization were included in the analysis (n=52). The study groups were those treated with εACA following incomplete obliteration of the fistula and those who were not. The primary outcome was obliteration of the fistula on initial follow-up imaging. Complication rates between cohorts were compared.Results20 (38%) patients with incompletely obliterated fistulae were treated with adjuvant εACA. A trend towards an improved rate of complete obliteration on initial follow-up imaging was observed in the group treated with εACA (55% vs 34% in the group not treated with εACA, p=0.14). No difference in clinical outcomes or thromboembolic complications was observed between the groups.ConclusionsIn summary, these data suggest that administration of εACA is a safe adjuvant therapy in the management of cranial dAVFs and CCFs that are incompletely treated endovascularly.

Introduction Aneurysms at the origin of the posterior communicating artery (PcommA) have been demonstrated to be effectively treated with the Pipeline Embolization Device (PED). Much less is known about the efficacy of the PED for aneurysms associated with a fetal posterior cerebral artery (fPCA) variant. Herein, the largest series of patients with ICA aneurysms at the origin of the PcommA or fPCA treated with the PED is presented. Methods A prospectively maintained university database of aneurysm patients treated with the PED was retrospectively reviewed. Demographics, treatment details, and imaging were reviewed for all PcommA and fPCA aneurysms. Results Out of a total of 285 patients treated with PED, 50 patients (mean age 57.5±12.2 years, 42 females) with unruptured PcommA (9 fPCA) aneurysms were identified. Mean follow-up duration was 14.0±11.6 months (48 patients). Roy-Raymond Class I occlusion on follow up Magnetic Resonance or catheter angiography (mean time 11.7±6.8 months) was achieved in 30 patients (62.5%), Class II occlusion in 11 patients (22.9%) and Class III occlusion in 7 patients (14.5%). The PcommA was occluded in 56% of patients without any clinical symptoms. No deaths or permanent neurological complications occurred. In fPCA aneurysms, Class I occlusion was seen in 1 patient, Class II occlusion in 2 patients, and Class III occlusion in 6 patients (figure 1). Multivariate analysis revealed an independent association between incomplete occlusion and fPCA configuration (OR 73.65; 95% CI [5.84–929.13]; p=0.001). The current literature on flow diversion treatment of fPCA aneurysms was reviewed and added to the current series and found to be associated with a low rate of aneurysm occlusion (5/23 or 22%; table 1). Conclusion PEDs are a safe and effective choice in the treatment of PcommA aneurysms. The presence of fetal anatomy, however, should increase consideration of traditional intra-saccular endovascular techniques or surgical clipping. Longer follow-up is needed to determine the ultimate efficacy of PED treatment for these aneurysms. Disclosures A. Roy: None. B. Howard: None. D. Haussen: None. J. Osbun: None. S. Halani: None. S. Skukalek: None. F. Tong: None. R. Nogueira: None. J. Dion: None. C. Cawley: None. J. Grossberg: None.

BACKGROUND AND PURPOSE: Endovascular reconstruction and flow diversion by using the Pipeline Embolization Device is an effective treatment for complex cerebral aneurysms. Accurate noninvasive alternatives to DSA for follow-up after Pipeline Embolization Device treatment are desirable. This study evaluated the accuracy of contrast-enhanced time-resolved MRA for this purpose, hypothesizing that contrast-enhanced time-resolved MRA will be comparable with DSA and superior to 3D-TOF MRA. MATERIALS AND METHODS: During a 24-month period, 37 Pipeline Embolization Device–treated intracranial aneurysms in 26 patients underwent initial follow-up by using 3D-TOF MRA, contrast-enhanced time-resolved MRA, and DSA. MRA was performed on a 1.5T unit by using 3D-TOF and time-resolved imaging of contrast kinetics. All patients underwent DSA a median of 0 days (range, 0–68) after MRA. Studies were evaluated for aneurysm occlusion, quality of visualization of the reconstructed artery, and measurable luminal diameter of the Pipeline Embolization Device, with DSA used as the reference standard. RESULTS: The sensitivity, specificity, and positive and negative predictive values of contrast-enhanced time-resolved MRA relative to DSA for posttreatment aneurysm occlusion were 96%, 85%, 92%, and 92%. Contrast-enhanced time-resolved MRA demonstrated superior quality of visualization (P = .0001) and a higher measurable luminal diameter (P = .0001) of the reconstructed artery compared with 3D-TOF MRA but no significant difference compared with DSA. Contrast-enhanced time-resolved MRA underestimated the luminal diameter of the reconstructed artery by 0.965 ± 0.497 mm (27% ± 13%) relative to DSA. CONCLUSIONS: Contrast-enhanced time-resolved MRA is a reliable noninvasive method for monitoring intracranial aneurysms following flow diversion and vessel reconstruction by using the Pipeline Embolization Device.

Background Spinal digital subtraction angiography (DSA) is the gold standard for diagnosis of spinal dural arterial venous fistulas (SDAVFs), but can require extensive time, radiation exposure and contrast dose. We hypothesize that contrast-enhanced time-resolved MR angiography (CE-TR MRA) will have utility for the non-invasive diagnosis and pre-angiographic localization of SDAVFs. Methods Eighteen patients underwent both CE-TR MRA and DSA for suspected SDAVFs, with DSA performed a median of 11 days (range 0–41) after MRA. CE-TR MRA was performed on a 1.5 T GE unit using Time Resolved Imaging of Contrast Kinetics (TRICKS). CE-TR MRA and DSA images were evaluated for the presence of SDAVFs and location of the feeding arterial supply, with DSA as the reference standard. DSA was also evaluated for the number of vessels catheterized, contrast volume and fluoroscopic and procedure times. Results Eight of the 18 patients were positive for SDAVF on DSA. Sensitivity, specificity, positive predictive value and negative predictive value for the 18 CE-TR MRAs were 88%, 90%, 88% and 90%, respectively. Localization of the SDAVF arterial supply on CE-TR MRA was within one vertebral level from DSA for 6/7 SDAVFs. Compared with patients with a SDAVF and feeding artery identified on CE-TR MRA, patients with negative or suboptimal CE-TR MRA had a significantly increased number of vessels catheterized (p=0.027) and larger contrast volumes (p=0.022). Conclusions CE-TR MRA is a useful initial examination for the diagnosis and localization of SDAVFs, with a high concordance rate with DSA. When CE-TR MRA demonstrates a SDAVF, the number of catheterized vessels and contrast dose can be decreased during DSA.

Background and Purpose: There are limited data on the optimal duration of dual antiplatelet therapy for secondary stroke prevention in patients with symptomatic intracranial atherosclerotic disease. Methods: Consecutive patients presenting with high-grade (70-99%) symptomatic intracranial stenosis from January 1, 2011, to December 31, 2013, and evaluated within 30 days of the index event were eligible for this analysis. All patients underwent treatment with aspirin plus clopidogrel for a target duration of 12 months along with aggressive medical management based on the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) protocol; all patients were given gastrointestinal prophylaxis for the duration of their aspirin and clopidogrel treatment. Clinical and safety outcomes of our cohort were compared with the medical arm of the SAMMPRIS trial cohort (n = 227). Results: Our cohort included 25 patients that met the inclusion criteria. Achievement of blood pressure and LDL cholesterol targets were similar between our cohort and the SAMMPRIS cohort. At 1 year, the rates of stroke, myocardial infarction or vascular death were 0% in our cohort and 16% in the SAMMPRIS cohort (p = 0.03). At 1 year, major bleeding rates were similar between our cohort and the SAMMPRIS cohort (4 vs. 2.2%, p = 1.0). Conclusion: A prolonged course of dual antiplatelet therapy for symptomatic intracranial atherosclerotic disease may be associated with less vascular events with no increase in hemorrhagic complications.

BACKGROUND AND PURPOSE: Cerebral thermoregulation remains poorly understood. Temperature dysregulation is deeply implicated in the potentiation of cerebrovascular ischemia. We present a multiphasic, MR thermographic study in a nonhuman primate model of MCA infarction, hypothesizing detectable brain temperature disturbances and brain-systemic temperature decoupling. MATERIALS AND METHODS: Three Rhesus Macaque nonhuman primates were sourced for 3-phase MR imaging: 1) baseline MR imaging, 2) 7-hour continuous MR imaging following minimally invasive, endovascular MCA stroke induction, and 3) poststroke day 1 MR imaging follow-up. MR thermometry was achieved by multivoxel spectroscopy (semi-localization by adiabatic selective refocusing) by using the proton resonance frequency chemical shift. The relationship of brain and systemic temperatures with time and infarction volumes was characterized by using a mixed-effects model. RESULTS: Following MCA infarction, progressive cerebral hyperthermia was observed in all 3 subjects, significantly outpacing systemic temperature fluctuations. Highly significant associations were observed for systemic, hemispheric, and global brain temperatures (F-statistic, P = .0005 for all regressions) relative to the time from stroke induction. Significant differences in the relationship between temperature and time following stroke onset were detected when comparing systemic temperatures with ipsilateral (P = .007), contralateral (P = .004), and infarction core (P = .003) temperatures following multiple-comparisons correction. Significant associations were observed between infarction volumes and both systemic (P ≤ .01) and ipsilateral (P = .04) brain temperatures, but not contralateral brain temperature (P = .08). CONCLUSIONS: Successful physiologic and continuous postischemic cerebral MR thermography was conducted and prescribed in a nonhuman primate infarction model to facilitate translatability. The results confirm hypothesized temperature disturbance and decoupling of physiologic brain-systemic temperature gradients. These findings inform a developing paradigm of brain thermoregulation and the applicability of brain temperature as a neuroimaging biomarker in CNS injury.

ObjectiveCarotid cavernous fistula (CCF) development after Pipeline Embolization Device (PED) treatment of cavernous carotid aneurysms (CCA) can be a challenging pathology to treat for the neurointerventionalist.MethodsA database of all patients whose aneurysms were treated with the PED since its approval by the Food and Drug Administration in 2011 was retrospectively reviewed. Demographic information, aneurysm characteristics, treatment technique, antiplatelet regimen, and follow-up data were collected. A literature review of all papers that describe PED treatment of CCA was then completed.ResultsA total of 44 patients with 45 CCAs were identified (38 women, 6 men). The mean age was 59.9±9.0 years. The mean maximal aneurysm diameter was 15.9±6.9 mm (mean neck 7.1±3.6 mm). A single PED was deployed in 32 patients, with two PEDs deployed in 10 patients and three PEDs in 3 patients. Adjunctive coiling was performed in 3 patients. Mean follow-up duration based on final imaging (MR angiography or digital subtraction angiography) was 14.1±12.2 months. Five patients (11.4%) developed CCFs in the post-procedural period after PED treatment, all within 2 weeks of device placement. These CCFs were treated with a balloon test occlusion followed by parent artery sacrifice. Our literature review yielded only three reports of CCFs after PED placement, with the largest series having a CCF rate of 2.3%.ConclusionsCCF formation is a known risk of PED treatment of CCA. Although transvenous embolization can be used for treating CCFs, parent artery sacrifice remains a viable option on the basis of these data. Studies support the view that adjunctive coiling may have a protective effect against post-PED CCF formation. None of the coiled aneurysms in our database or in the literature have ruptured. Follow-up data will lead to a better understanding of the safety profile of the PED for CCA.

BACKGROUND: Intraprocedural rupture is a dangerous complication of endovascular treatment. Small ruptured anterior communicating artery (ACoA) aneurysms and microaneurysms present a challenge for both surgical and endovascular therapies to achieve obliteration. An understanding of the complication rates of treating ruptured ACoA microaneurysms may help guide therapeutic options. OBJECTIVE: To report the largest cohort of ACoA microaneurysms treated with endovascular therapy over the course of the past 10 years. METHODS: We performed a retrospective review of 347 ACoA aneurysms treated in 347 patients at Cleveland Clinic and Emory University over a 10-year period. Patient demographics, aneurysmal rupture, size, use of balloon remodeling, patient outcomes, intraprocedural rupture, and rerupture were reviewed. RESULTS: Rupture rates were examined by size for all patients and subgroups and dichotomized to evaluate for size ranges associated with increased rupture rates. The highest risk of rupture was noted in aneurysms less than 4 mm. Of 347 aneurysms, 74 (21%) were less than 4 mm. The intraprocedural rupture rate was 5% (18/347) for ACoA aneurysms of any size. There was an intraprocedural rupture rate of 2.9% (8/273) among ACoA aneurysms greater than 4 mm compared with 13.5% (10/74) in less than 4-mm aneurysms. Procedural rupture was a statistically significant predictor of modified Rankin score after adjusting for Hunt and Hess grades (HH). CONCLUSION: ACoA aneurysms less than 4 mm have a 5-fold higher incidence of intraprocedural rerupture during coil embolization. Outcome is negatively affected by intraprocedural rerupture after adjusting for HH grade.

BACKGROUND AND PURPOSE: Denser coil packing in intracranial aneurysms is believed to result in lower recanalization rates. Hydrogel-coated expandable coils (HydroCoil) improve volumetric packing of aneurysms in animal models and clinical studies, but data from large clinical series are limited. The objective of this retrospective analysis was to analyze immediate and follow-up angiographic results as well as complications in a large consecutive series of patients treated with HydroCoils at a single institution. MATERIALS AND METHODS: Retrospective analysis was performed of periprocedural complications, immediate and follow-up angiograms, and retreatments of the first 200 consecutive intracranial aneurysms treated at Emory University Hospital. RESULTS: One hundred eighty-seven patients with 200 intracranial aneurysms were treated with HydroCoils during a 3-year period. Immediate angiograms showed complete aneurysmal obliteration in 58.4% of small aneurysms and 42.7% of large aneurysms. Periprocedural complications included early rebleeding and thromboembolic events resulting in permanent neurologic morbidity and mortality in 6% of cases. Follow-up angiography during an average of 16.3 months demonstrated recanalization in 17.7% of small aneurysms and 28.6% of large aneurysms, requiring retreatment in 6.3% and 19.0% of cases, respectively. During the same time period, there was delayed angiographic improvement in aneurysm obliteration in 26.6% of small aneurysms and 26.2% of large aneurysms. CONCLUSIONS: First-generation HydroCoil treatment of intracranial aneurysms has a favorable rate of recanalization compared with most large series of pure platinum coils with similar complication rates.

An intracranial aneurysm can be a serious condition that can go undetected until the aneurysm ruptures, causing hemorrhaging within the subarachnoid space surrounding the brain. The typical treatment for large aneurysms is by embolization using platinum coils. However, in about 15% of the cases treated by platinum coils, the aneurysm eventually re-opens as a result of the bio-inertness of platinum. One solution to this is to develop suitable materials with increased bio-activity to use as coil implants. In this research, a shape memory polymer (SMP), Calomer™, produced by The Polymer Technology Group, Inc., was investigated as a candidate for aneurysm coils. The SMP was tested to determine its thermo-mechanical properties and the strength of the shape recovery force. Composite SMP specimens containing tantalum filler were produced and tested to determine the mechanical effect of adding this radio-opaque metal. Thermo-mechanical testing showed that the material exhibited a shape recovery force a few degrees above the glass transition temperature, T g . The effects of the addition were small and included a decrease in T g and recovery force. SMP coils deployed inside a simulated aneurysm model demonstrate that typical hemodynamic forces do not hinder the shape recovery process. The radio-opacity of the Ta-filled material was characterized with clinical fluoroscopy.

Spines are dendritic protrusions that receive most of the excitatory input in the brain. Early after the onset of cerebral ischemia dendritic spines in the peri-infarct cortex are replaced by areas of focal swelling, and their re-emergence from these varicosities is associated with neurological recovery after acute ischemic stroke (AIS). Urokinase-type plasminogen activator (uPA) is a serine proteinase that plays a central role in tissue remodeling via binding to the urokinase plasminogen activator receptor (uPAR). We report that cerebral cortical neurons release uPA during the recovery phase from ischemic strokein vivoor hypoxiain vitro. Although uPA does not have an effect on ischemia- or hypoxia-induced neuronal death, genetic deficiency of uPA (uPA−/−) or uPAR (uPAR−/−) abrogates functional recovery after AIS. Treatment with recombinant uPA after ischemic stroke induces neurological recovery in wild-type and uPA−/−but not in uPAR−/−mice. Diffusion tensor imaging studies indicate that uPA−/−mice have increased water diffusivity and decreased anisotropy associated with impaired dendritic spine recovery and decreased length of distal neurites in the peri-infarct cortex. We found that the excitotoxic injury induces the clustering of uPAR in dendritic varicosities, and that the binding of uPA to uPAR promotes the reorganization of the actin cytoskeleton and re-emergence of dendritic filopodia from uPAR-enriched varicosities. This effect is independent of uPA's proteolytic properties and instead is mediated by Rac-regulated profilin expression and cofilin phosphorylation. Our data indicate that binding of uPA to uPAR promotes dendritic spine recovery and improves functional outcome following AIS.

PurposeThe pipeline embolization device (PED) necessitates dual antiplatelet therapy (APT) to decrease thrombotic complications while possibly increasing bleeding risks. The role of APT dose, duration, and response in patients with hemorrhagic and thromboembolic events warrants further analysis.MethodsA PubMed and Google Scholar search from 2009 to 2014 was performed using the following search terms individually or in combination: pipeline embolization device, aneurysm(s), and flow diversion, excluding other flow diverters. Review of the bibliographies of the retrieved articles yielded 19 single and multicenter studies. A statistical meta-analysis between aspirin (ASA) dose (low dose ≤160 mg, high dose ≥300 mg), loading doses of APT agents, post-PED APT regimens, and platelet function testing (PFT) with hemorrhagic or thrombotic complications was performed.ResultsASA therapy for ≤6 months post-PED was associated with increased hemorrhagic events. High dose ASA ≤6 months post-PED was associated with fewer thrombotic events compared with low dose ASA. Post-PED clopidogrel for ≤6 months demonstrated an increased incidence of symptomatic thrombotic events. Loading doses of ASA plus clopidogrel demonstrated a decreased incidence of permanent symptomatic hemorrhagic events. PFT did not show a statistically significant relationship with symptomatic hemorrhagic or thrombotic complications.ConclusionsHigh dose ASA >6 months is associated with fewer permanent thrombotic and hemorrhagic events. Clopidogrel therapy ≤6 months is associated with higher rates of thrombotic events. Loading doses of ASA and clopidogrel were associated with a decreased incidence of hemorrhagic events. PFT did not have any significant association with symptomatic events.

Endovascular therapy for intracranial aneurysms has evolved since Serbinenko pioneered embolisation with latex balloons in the 1970s. The focus of modern endovascular therapy has shifted to the use of Guglielmi Detachable Coils (GDC; Boston Scientific Corporation, Natick, MA, USA) which are retrievable until the operator is satisfied with placement and they are detached. GDC therapy has been shown to be most efficacious in smaller aneurysms with relatively large dome:neck ratios which allow maximal coil packing within the aneurysm lumen. Wide neck aneurysms with dome:neck ratios of less than 2.0 and large aneurysms have a significantly lower incidence of complete treatment, with higher rates of repeat rupture following GDC therapy. The geometry of wide neck aneurysms is less favourable for retention of coils within the aneurysm lumen, resulting in greater risk of parent vessel compromise from coil herniation and difficulty obtaining maximal coil packing. This chapter will summarise GDC therapy for intracranial aneurysms including newer techniques designed to address the problem of wide neck aneurysms.

Background Stable access to target lesions is foundational to endovascular therapy, be it in hemorrhagic or ischemic disease. Continued evolution in access technology has resulted in next generation catheters that afford improved trackability and proximal support. Objective Assess safety and patterns of use at two high volume centers, and conceptualize usage patterns. Materials and methods A retrospective review of 608 cases in which a ‘next generation’ catheter was used during 2008–2010 at Cleveland Clinic (Cleveland, Ohio, USA) and throughout 2009–2010 at Emory University Hospital (Atlanta, Georgia, USA) was conducted, and the cases classified by indication. Catheter placement, distal most location, and related complications were recorded and experience summarized. We also reviewed the differences in the catheters and the rationale for catheter selection, as well as relative costs for each approach. Results 311 Neuron 053, 166 Neuron 070, 36 distal access catheter (DAC) 3.9 F, 61 DAC 4.3 F, and 34 DAC 5.2 F catheters were deployed. Of these, 459 placements were in the anterior circulation, 130 in the posterior circulation, 11 in the external carotid artery, and eight were used intravenously. Complication rates were 9/131 (6.9%) for the DAC catheter group, 16/311 (5.1%) for the Neuron 053 group, and 14/166 (8.4%) for the Neuron 070 group (p=0.37, χ2 test). Conclusions Next generation access catheters possess characteristics that blend qualities of traditional microcatheters and stiff guide catheters. There was no statistically significant difference in complication rates between the various catheter families in this small retrospective review, and the complication rates were similar to historical complication rates.

Introduction: The need for therapeutic dual antiplatelet therapy in patients with cerebral aneurysms treated with flow-diverting stents increases the risk of thromboembolic and hemorrhagic complications. To balance these risks, we assessed patients for their responsiveness to dual antiplatelet therapy using a modified platelet aggregation study (PIPA). We hypothesized that double doses of clopidogrel or aspirin in patients with antiplatelet non-responsiveness would reduce the incidence of thromboembolic complications without increasing the incidence of hemorrhage or decreasing the rate of aneurysm occlusion. Methods: 79 patients with 98 cerebral aneurysms were treated with the pipeline embolization device. All patients with a suboptimal PIPA received double doses of clopidogrel or aspirin prior to treatment. Aneurysm occlusion was categorized using the Roy-Raymond Occlusion Classification (RROC). Chi-square or Fisher’s exact tests were used for univariate analyses, and logistic regression was used to identify potential predictors of complications and aneurysm occlusion. Results: Seven patients had a major complication and 7 had a minor complication (8.9%). There were 3 cerebral ischemic strokes (3.8%) and 5 cerebral hemorrhages (6.3%). Thirty-eight patients had angiographic follow-up at 6 months. Of these, 18 patients were resistant to clopidogrel or aspirin, and 19 received double dose therapy prior to treatment. Double dose clopidogrel or aspirin was not associated with major, minor, cerebral ischemic or hemorrhagic complications. Twenty-one patients (55.3%) had complete occlusion of their aneurysms (RROC type 1), and 17 patients were categorized as RROC type 2 or 3 at 6 months. Treatment with double dose clopidogrel or aspirin was not associated with reduced occlusion (RROC type 2 or 3) in a univariate and multivariate analysis. Conclusions: In patients treated with flow-diverting stents, the risk of ischemia must be balanced with the risk of hemorrhage. We found that the use of double dose clopidogrel and aspirin in the setting of antiplatelet non-responsiveness is safe. It is not associated with increased hemorrhagic complications. Patients treated with double dose therapy did not exhibit a reduced aneurysm occlusion rate.

Introduction: Flow-diversion has emerged as a novel treatment for complex cerebral aneurysms. Although preliminary reports suggest flow-diverting devices are safe and effective, the risk of thromboembolic and hemorrhagic complications must be balanced with the added risk of dual antiplatelet therapy. Although the prevalence of antiplatelet therapy non-responsiveness (NR) has been associated with adverse cardiac events in patients with acute coronary syndrome (ACS), it has has not been studied in patients treated with these devices. Methods: All patients received clopidogrel 75mg and aspirin 325mg prior to modified light transmittance platelet aggregometry (LTA) using 4 agonists (ADP 5 and 20 uM, arachidonic acid (ACA), and U46619 ). NR was defined as a maximum amplitude (MA) > 60% with ADP 20uM and 40% with ADP 5uM for clopidogrel and a MA >20% with ACA for aspirin. Patients were also assessed for known drug interactions. Chi-square or Fisher’s exact tests were used for univariate analyses, and logistic regression was used to identify potential predictors of NR. Results: 79 patients with 98 cerebral aneurysms were treated with the pipeline embolization device (PED). The prevalence of clopidogrel and aspirin NR was 27.6% and 30.3%, respectively. In univariate and multivariate analyses, age, gender, race, presence of drug interactions, history of hypertension, diabetes, ischemic stroke, subarachnoid hemorrhage and smoking were not significant predictors of NR. Conclusions: In our cohort, the prevalence of clopidogrel and aspirin NR was high and similar to that reported in ACS patients. As a result of the rate of NR, patients were evaluated by a virtual antiplatelet clinic and patients with suboptimal LTA results underwent modification of a drug interaction, received double doses of clopidogrel and/or aspirin, or were transitioned to an alternative P2Y12 inhibitor (prasugrel or ticagrelor). The mechanisms underlying antiplatelet NR remain to be further explored to minimize the risk of hemorrhagic complications if more potent antiplatelet therapy is required.

Intracranial aneurysms affect thousands of people every year, therefore the ability to monitor their growth or predict their rupture would be invaluable for planning treatment. One proposed method to address this issue of predicting rupture is to use computational fluid dynamics (CFD) based on phase contrast magnetic resonance (PC-MR). CFD and PCMR have been used to understand some of the fundamental conditions of cerebrovascular flow. While there has been general acceptance of the validity of CFD, some research suggests that there can be poor correlation between CFD flow calculations and directly measured flow (1). Previous research has qualitatively compared CFD to PC-MR and demonstrated similar pathlines (2). To the authors’ knowledge a systematic quantitative comparison has not been preformed. Therefore the purpose of this work is to quantitatively compare velocity data from phase-contrast MRI measurements and from a CFD model derived from MRI geometry and flow boundary conditions in an in-vitro aneurysm model.

Gadolinium chelates can be utilized as a fluoroscopic contrast agent when iodinated contrast is contraindicated. However, the nephrotoxicity of gadolinium at radiographic doses limits its role as fluoroscopic contrast. Gadolinium chelate-enhanced digital subtraction angiography (DSA) is particularly limited by the kV of DSA, where gadolinium chelates are relatively more radiolucent. Flat panel detectors improve conspicuity of gadolinium chelates during DSA and should be employed where possible.

Geometric indices defined on intracranial aneurysms have been widely used in rupture risk assessment and surgical planning. However, most indices employed in clinical settings are currently evaluated based on two-dimensional images that inevitably fail to capture the three-dimensional nature of complex aneurysmal shapes. In addition, since measurements are performed manually, they can suffer from poor inter and intra operator repeatability. The purpose of the current work is to introduce objective and robust techniques for the 3D characterization of intracranial aneurysms, while preserving a close connection to the way aneurysms are currently characterized in clinical settings. Techniques for automatically identifying the neck plane, key aneurysm dimensions, shape factors, and orientations relative to the parent vessel are demonstrated in a population of 15 sidewall and 15 terminal aneurysms whose surface has been obtained by two trained operators using both level-set segmentation and thresholding, the latter reflecting typical clinical practice. Automatically-identified neck planes are shown to be in concordance with those manually positioned by an expert neurosurgeon, and automatically-derived geometric indices are shown to be largely insensitive to segmentation method or operator. By capturing the 3D nature of aneurysmal sacs and by minimizing observer variability, our approach allows large retrospective and prospective studies on aneurysm geometric risk factors to be performed using routinely acquired clinical images.

Background: There are limited data on the effect of an early aggressive risk factor modification program to achieve risk factor targets and its impact on clinical outcomes among patients with symptomatic intracranial stenosis. Methods: We prospectively identified patients with symptomatic intracranial stenosis of 50% to 99% (using computed tomographic angiography or cerebral angiography) who failed to qualify for or declined to participate in the Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis trial but elected to receive aggressive medical management. Aggressive medical management was defined as aspirin plus clopidogrel therapy for a minimum of 3 months, blood pressure control, statin use with a low-density lipoprotein (LDL) goal of ,70 mg/dL, smoking cessation, and body mass index ,25 kg/m 2 . Results: Of 22 patients, the mean age was 65.6 6 7.7 years, 82% were male, 59% were white, and mean percent stenosis was 71.5 6 9.5% (55% with 70% to 99% stenosis). Median time from symptomatic event to first evaluation was 3 days. All patients completed 3 months of dual antiplatelet therapy, and at last follow-up, 86% had met their blood pressure goal, all were on statin therapy although only 73% had met their LDL goal, 96% reported no active tobacco use, and 36% had lost weight, but only 23% had achieved the BMI target. Over a mean follow-up of 1.2 years, there was no ischemic stroke, brain hemorrhage, or death from other vascular causes. Conclusions: An early aggressive risk factor modification program achieved high levels of blood pressure and cholesterol targetsforpatients withsymptomatic intracranial stenosis and when combinedwith dual antiplatelet therapy was effective for the prevention of recurrent vascular

Computational fluid dynamic simulation (CFD) is a valuable tool that has been used to understand some of the fundamental conditions of cerebrovascular flow. Current methods include anatomic modeling of cerebral aneurysms derived from vascular imaging such as MRA, CTA, and three-dimensional angiography. The input blood flow waveforms can be represented from either mathematical models or physiologic sampling of flow with phase contrast MR techniques or particle image velocimetry (1). While there has been general acceptance of the validity of computational fluid dynamics, some research suggests that there can be poor correlation between CFD flow calculations and directly measured flow (2). Therefore, the purpose of this study is to qualitatively compare flow patterns in a cerebral aneurysm model using data derived from three sources: (i) direct phase contrast MRA measurement in the model; (ii) CFD simulation using computer models created from three dimensional angiography, and (iii) previously published high speed injection dye studies.Copyright © 2010 by ASME

Object The introduction of the Neuroform microstent has facilitated the embolization of complex cerebral aneurysms, which were previously not amenable to endovascular therapy. Typically, the use of this stent necessitates the administration of dual antiplatelet therapy to minimize thromboembolic complications. Such therapy may increase the risk of hemorrhage in patients who require concurrent external ventricular drainage and/or subsequent permanent cerebrospinal fluid diversion. Methods The authors' neurosurgical database was queried for all patients who underwent stent-assisted coil embolization for cerebral aneurysms and who required an external ventricular drain (EVD) or ventriculoperitoneal (VP) shunt placement for management of hydrocephalus. Results Thirty-seven patients underwent stent-assisted coil embolization for intracranial aneurysms at the authors' institution over a recent 2-year period. Seven of these patients required placement of an EVD and/or a VP shunt. Three of the 7 patients suffered an immediate intraventricular hemorrhage (IVH) associated with placement or manipulation of an EVD; 1 experienced a delayed intraparenchymal hemorrhage and an IVH; 1 suffered an aneurysmal rehemorrhage; and the last patient had a subdural hematoma (SDH) that resulted from placement of a VP shunt. This patient required drainage of the SDH and exchange of the valve. Conclusions The necessity of dual antiplatelet therapy in the use of stent-assisted coil embolization increases the risk of intracranial hemorrhage and possibly rebleeding from a ruptured aneurysm. This heightened risk must be recognized when contemplating the appropriate therapy for a cerebral aneurysm and when considering the placement or manipulation of a ventricular catheter in a patient receiving dual antiplatelet therapy. Further study of intracranial procedures in patients receiving dual antiplatelet therapy is indicated.

Background and Purpose Diffusion-weighted imaging (DWI) and perfusion MRI were used to examine the spatiotemporal evolution of stroke lesions in adult macaques with ischemic occlusion. Methods Permanent MCA occlusion was induced with silk sutures through an interventional approach via the femoral artery in adult rhesus monkeys (n = 8, 10–21 years old). The stroke lesions were examined with high-resolution DWI and perfusion MRI, and T2-weighted imaging (T2W) on a clinical 3T scanner at 1–6, 48, and 96 hours post occlusion and validated with H&E staining. Results The stroke infarct evolved via a natural logarithmic pattern with the mean infarct growth rate = 1.38 ± 1.32 ml per logarithmic time scale (hours) (n = 7) in the hyperacute phase (1–6 hours). The mean infarct volume after 6 hours post occlusion was 3.6±2.8 ml (n = 7, by DWI) and increased to 3.9±2.9 ml (n = 5, by T2W) after 48 hours, and to 4.7±2.2ml (n = 3, by T2W) after 96 hours post occlusion. The infarct volumes predicted by the natural logarithmic function were correlated significantly with the T2W-derived lesion volumes (n = 5, r = 0.92, p = 0.01) at 48 hours post occlusion. The final infarct volumes derived from T2W were correlated significantly with those from H&E staining (r = 0.999, p < 0.0001, n = 4). In addition, the diffusion-perfusion mismatch was visible generally at 6 hours but nearly diminished at 48 hours post occlusion. Conclusion The infarct evolution follows a natural logarithmic pattern in the hyperacute phase of stroke. The logarithmic pattern of evolution could last up to 48 hours after stroke onset and may be used to predict the infarct volume growth during the acute phase of ischemic stroke. The nonhuman primate model, MRI protocols, and post data processing strategy may provide an excellent platform for characterizing the evolution of acute stroke lesion in mechanistic studies and therapeutic interventions of stroke disease.

Introduction/Purpose MRI fusion is a recently developed image targeting technique that volumetrically overlays an MRI sequence onto a live fluoroscopic image updated in real time. The ability to utilize the superior soft tissue resolution of MRI for interventional lesion targeting without the practical constraints of an interventional MRI suite is potentially a powerful tool. Lesions that are well-visualized under MRI but possessing little fluoroscopic contrast are otherwise untreatable in the angio suite and ideally suited to this new technique. We present four consecutive cases involving small intraorbital masses in children where MRI-fusion volumetric overlay techniques were used to precisely target the lesions for the purposes of both percutaneous biopsy and venolymphatic malformation sclerotherapy. Materials/Methods Four pediatric patients were referred for percutaneous biopsy (n=1) and sclerotherapy (n=3) for small intraorbital masses. The DICOM MRI data sequences that best demonstrated the target lesions were imported to a Philips Allura fluoroscopy system. General anesthesia was administered and an XperCT scan of the head was obtained in the angiography suite. A multimodality matching overlay of the imported MRI data with the obtained XperCT data was performed to facilitate procedure planning with the MRI target superimposed over the live fluoroscopic images. Direct puncture of the target lesion was performed with a 23- or 25-gauge needle. Percutaneous sclerotherapy intralesional needle tip confirmation was assessed with aspiration and contrast injection. The targeted sclerotherapy lesions were then slowly injected manually with a mixture of Bleomycin and contrast with intermittent fluoroscopic evaluation to ensure intralesional placement. The biopsy case specimen was aspirated with a 23 gauge needle and a cell smear and core sample were submitted to Pathology. Results The treatment/biopsy needles were successfully placed in all four lesions in the angiographic suite using this technique. The needle was placed intralesional on the first pass in all four cases without complication with needle repositioning in the treatment cases as necessary for aspiration. No contrast extravasation or venous drainage was identified in the treatment group with intralesional contrast and Bleomycin/contrast injection. The biopsy patient had a diagnostic sample obtained while the sclerotherapy lesions were all decreased in size on follow-up imaging with resolution of their clinical symptoms. No sclerotherapy patient has required additional treatment. Conclusion MRI fusion with real-time fluoroscopic imaging allows for treatment of previously non-visualized lesions in the angiographic suite with sufficient soft tissue detail to perform precise percutaneous orbital interventions in a safe and therapeutic manner. Competing interests None.

Introduction Stable access to target lesions is foundational to endovascular therapy, be it in hemorrhagic or ischemic disease. Continued evolution in access technology has resulted in next generation catheters that afford improved trackability, as well as distal and proximal support. Neuron guide catheter family and the Concentric Outreach Distal Access Catheter fall into this category of hybrid catheters. Both families of devices possess overlapping characteristics allowing operators to achieve a more stable proximal access complex. Methods A retrospective review of 608 cases in which an intermediate catheter was used during 2008–2010 at Cleveland Clinic (Cleveland, OH) and throughout 2010 at Emory University Hospital (Atlanta, GA) was conducted, and the cases classified by indication. Catheter placement, distal most location and related complications were recorded and experience summarized. We also review the differences in the catheters and the rationale for catheter selection, as well as relative costs for each approach. Results A total of 311 Neuron 053, 166 Neuron 070, 36 DAC 3.9 Fr, 61 DAC 4.3 Fr, and 34 DAC 5.2 Fr catheters were deployed. Of these, 459 placements were in the anterior circulation, 130 in the posterior circulation, 11 in the external carotid artery, and eight were used intravenously. Abstract P-017 table 1 summarizes the clinical scenarios where the catheters were used, Abstract P-017 table 2 the distal most placements, Abstract P-017 table 3 the complications and Abstract P-017 table 4 the estimated costs for a typical catheter selection. Complication rates were 9/131 (6.9%) for the DAC catheter group, 16/311 (5.1%) for the Neuron 053 group, and 14/166 (8.4%) for the Neuron 070 group with p=0.37, χ2 test Abstract P-017 table 5. Conclusion Next generation access catheters possess characteristics that blend qualities of traditional microcatheters and guide catheters. These “intermediate catheters” represent a class of access devices that allow for better catheter support, and allow for multi-axial access techniques. The utility of these catheters must be balanced against costs. The increased procedural complexity involved in using multi-axial techniques should also be a consideration, but judicious application should prove beneficial to patients. There is no statistically significant difference in complication rates when using these catheters as well as comparable complication rates when compared to historical complication rates quoted to patients.

Introduction/purpose The purpose of this study was to determine the efficacy and safety of flow diversion technology in the treatment of aneurysms of carotid-ophthalmic aneurysms. Materials and methods This study retrospectively reviewed outcomes in 45 consecutive patients with carotid-ophthalmic aneurysms who were treated with Pipeline Embolization Device (PED) by three separate neuro-interventionalists. A chart review was performed to collect information on demographics, aneurysm size, treatment outcomes, and procedure-related complications. The primary end-points were rate of aneurysm occlusion and ophthalmic artery patency, as assessed by angiographic images. The secondary end point was peri- and post-procedural complications were evaluated. Descriptive statistical analysis was performed. Results There were 39 females and 6 males in the study. The average age was 56.4 (range 31–81). Thirty-two patients had a single aneurysm treated during the PED procedure; multiple aneurysms were treated in 13 cases. All of the aneurysms treated were unruptured. Seven aneurysms were recurrences of prior coil embolization procedures. The average aneurysm size was 8.9 mm (range 2.1–26). The treated aneurysm measured The PED was successfully deployed in 44 of 45 cases. There were two mortalities (4.4%) within 30 days of treatment-one from a large intraparenchymal haemorrhage and one from unknown causes. Other 30-day complications included capture coil fracture (2), reversible intra-procedural thrombosis (2), small contralateral convexity subarachnoid haemorrhage (1), and symptomatic embolic infarcts (1). There were no complications seen after 30 days. Six month angiographic follow-up was available in 37. There was complete aneurysm occlusion in 27 patients (73%). There was minimal residual aneurysm filling in eight patients (22%) and only slightly decreased aneurysm filling in two patients (5%). There was only one instance (3%) of ophthalmic artery occlusion noted, and this was asymptomatic. Conclusion Flow diversion treatment for carotid-ophthalmic aneurysms has a high rate of aneurysm occlusion, while maintaining a low complication rate. Disclosures J. Grossberg: None. F. Tong: None. C. Cawley: None. J. Dion: None.