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The interval appearance of cerebral microbleeds (CMBs) after endovascular treatment has never been described. We investigated the frequency and predictors of new CMBs that developed shortly after mechanical thrombectomy for acute ischemic stroke, and its impact on clinical outcome.We retrospectively analyzed patients with large-vessel occlusion strokes treated with Merci Retriever, Penumbra System, or stent-retriever devices. Serial T2*-weighted gradient-recall echo (GRE) magnetic resonance imaging (MRI) before and 48 h after endovascular thrombectomy were assessed to identify new CMBs. We examined independent factors associated with new CMBs after mechanical thrombectomy. We analyzed the association of the presence, burden, and distribution of new CMBs with clinical outcome.A total of 187 consecutive patients with serial GRE were enrolled in this study. CMBs were evident in 36 (19.3%) patients before mechanical thrombectomy. New CMBs occurred in 41 (21.9%) patients after mechanical thrombectomy. Of the 68 new CMBs, 45 appeared in the lobar location, 18 in the deep location and 5 in the infratentorial location. The presence of baseline CMBs was associated with new CMBs after mechanical thrombectomy (OR 5.38; 95% CI 2.13-13.59; P < 0.001), no matter whether the patients were treated primarily with mechanical thrombectomy or with intravenous thrombolysis followed by mechanical thrombectomy. Patients with new CMBs did not have increased rates of hemorrhagic transformation, in-hospital mortality, and modified Rankin Scale score 4 to 6 at discharge.New CMBs are common after mechanical thrombectomy in one-fifth of patients with acute ischemic stroke. Baseline CMBs before mechanical thrombectomy predicts the development of new CMBs. New CMBs after mechanical thrombectomy do not influence clinical outcome., Competing Interests: The authors have no conflicts of interest to disclose.

Object: Encephaloduroarteriosynangiosis (EDAS) is a form of revascularization that has shown promising early results in the treatment of adult patients with moyamoya disease (MMD) and more recently in patients with intracranial atherosclerotic steno-occlusive disease (ICASD). Herein the authors present the long-term results of a single-center experience with EDAS for adult MMD and ICASD., Methods: Patients with ischemic symptoms despite intensive medical therapy were considered for EDAS. All patients undergoing EDAS were included. Clinical data, including recurrence of transient ischemic attack (TIA) and/or stroke, functional status, and death, were collected from a retrospective data set and a prospective cohort. Perren revascularization and American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) collateral grades were recorded from angiograms., Results: A total of 107 EDAS procedures were performed in 82 adults (36 with ICASD and 46 with MMD). During a median follow-up of 22 months, 2 (2.4%) patients had strokes; both patients were in the ICASD group. TIA-free survival and stroke-free survival analyses were performed using the product limit estimator (Kaplan-Meier) method. The probability of stroke-free survival at 2 years in the ICASD group was 94.3% (95% CI 80%-98.6%). No patient in the MMD group suffered a stroke. The probability of TIA-free survival at 2 years was 89.4% (95% CI 74.7%-96%) in ICASD and 99.7% (95% CI 87.5%-99.9%) in MMD. There were no hemorrhages or stroke-related deaths. Angiograms in 85.7% of ICASD and 92% of MMD patients demonstrated Perren Grade 3 and improvement in ASITN/SIR grade in all cases., Conclusions: EDAS is well tolerated in adults with MMD and ICASD and improves collateral circulation to territories at risk. The rates of stroke after EDAS are lower than those reported with other treatments, including intensive medical therapy in patients with ICASD.

Background and Purpose: Remote ischemic conditioning (RIC) is a phenomenon in which short periods of nonfatal ischemia in 1 tissue confers protection to distant tissues. Here we performed a longitudinal human pilot study in patients with aneurysmal subarachnoid hemorrhage undergoing RIC by limb ischemia to compare changes in DNA methylation and transcriptome profiles before and after RIC., Methods: Thirteen patients underwent 4 RIC sessions over 2 to 12 days after rupture of an intracranial aneurysm. We analyzed whole blood transcriptomes using RNA sequencing and genome-wide DNA methylomes using reduced representation bisulfite sequencing, both before and after RIC. We tested differential expression and differential methylation using an intraindividual paired study design and then overlapped the differential expression and differential methylation results for analyses of functional categories and protein-protein interactions., Results: We observed 164 differential expression genes and 3493 differential methylation CpG sites after RIC, of which 204 CpG sites overlapped with 103 genes, enriched for pathways of cell cycle (P<3.8×10(-4)) and inflammatory responses (P<1.4×10(-4)). The cell cycle pathway genes form a significant protein-protein interaction network of tightly coexpressed genes (P<0.00001)., Conclusions: Gene expression and DNA methylation changes in aneurysmal subarachnoid hemorrhage patients undergoing RIC are involved in coordinated cell cycle and inflammatory responses., (© 2015 American Heart Association, Inc.)

Background: The ideal population of patients for endovascular therapy (ET) in acute ischemic stroke remains undefined. Recent ET trials have moved towards selecting patients with proximal middle cerebral artery (MCA) or internal carotid artery occlusions, which will likely leave a gap in our understanding of the treatment outcomes of M2 occlusions., Objective and Methods: To examine the presentation, treatment, and outcomes of M2 compared with M1 MCA occlusions in patients undergoing ET by assessing comprehensive MRI, angiography, and clinical data., Results: We found that M2 occlusions can lead to massive strokes defined by hypoperfused and infarcted volumes as well as death or moderate to severe disability in nearly 50% of patients at discharge. Compared with M1 occlusions, M2 occlusions achieved similar Thrombolysis in Cerebral Infarction (TICI) 2b/3 recanalization rates, with significantly less hemorrhage. M2 occlusions presented with smaller infarct and hypoperfused volumes and had smaller final infarct volumes regardless of recanalization. TICI 2b/3 recanalization of M2 occlusions was associated with smaller infarct volumes compared with TICI 0-2a recanalization, as well as less infarct expansion, in patients who received IV tissue plasminogen activator as well as those that did not. Successful reperfusion of M2 occlusions was associated with improved discharge modified Rankin scale., Conclusions: If suitable as targets of ET, M2 occlusions should be given the same consideration as M1 occlusions., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The electronic health record (EHR) contains a diverse set of clinical observations that are captured as part of routine care, but the incomplete, inconsistent, and sometimes incorrect nature of clinical data poses significant impediments for its secondary use in retrospective studies or comparative effectiveness research. In this work, we describe an ontology-driven approach for extracting and analyzing data from the patient record in a longitudinal and continuous manner. We demonstrate how the ontology helps enforce consistent data representation, integrates phenotypes generated through analyses of available clinical data sources, and facilitates subsequent studies to identify clinical predictors for an outcome of interest. Development and evaluation of our approach are described in the context of studying factors that influence intracranial aneurysm (ICA) growth and rupture. We report our experiences in capturing information on 78 individuals with a total of 120 aneurysms. Two example applications related to assessing the relationship between aneurysm size, growth, gene expression modules, and rupture are described. Our work highlights the challenges with respect to data quality, workflow, and analysis of data and its implications toward a learning health system paradigm., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The authors report the treatment of a rare type of dural arteriovenous fistula of the paracavernous venous plexus. These fistulas can mimic carotid-cavernous fistulas in both imaging characteristics and clinical presentation, but the anatomical differences require differences in management. The authors describe an integrated open surgical and direct endovascular embolization approach and review of the literature pertaining to the anatomy of and treatment options for paracavernous fistulas.

Stroke is the third leading cause of death in developed nations. Up to 88% of strokes are ischemic in nature. Extracranial carotid artery atherosclerotic disease is the third leading cause of ischemic stroke in the general population and the second most common nontraumatic cause among adults younger than 45 years. This article provides comprehensive, evidence-based recommendations for the management of extracranial atherosclerotic disease, including imaging for screening and diagnosis, medical management, and interventional management., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Remote ischemic conditioning (RIC) is a powerful endogenous mechanism whereby a sublethal ischemic stimulus confers a protective benefit against a subsequent severe ischemic insult. RIC has significant potential clinical implications for the prevention of delayed ischemic neurological deficit after aneurysmal subarachnoid hemorrhage (aSAH). Although RIC has been extensively investigated in animal models, it has not been fully evaluated in humans., Objective: To assess the feasibility and safety of RIC for aSAH in a phase I clinical trial., Methods: Consecutive patients hospitalized for treatment of an aSAH who met the inclusion/exclusion criteria were approached for consent. Enrolled patients received up to 4 RIC sessions on nonconsecutive days. Primary end points were the development of a symptomatic deep venous thrombosis, bruising, or injury to the limb and request to stop by the patient or surrogate. The secondary end points were the development of new neurological deficits or cerebral infarct, demonstrated by brain imaging after enrollment, and neurological deficit and condition at follow-up., Results: Twenty patients were enrolled and underwent 76 RIC sessions, 75 of which were completed successfully. One session was discontinued when the patient became confused. No patient developed a deep venous thrombosis or injury to the preconditioned limb. No patient developed delayed ischemic neurological deficit during enrollment. At follow-up, median modified Rankin Scale score was 1 and Glasgow Outcome Scale score was 5., Conclusion: The RIC procedure was well tolerated and did not cause any injury. RIC for aSAH warrants investigation in a subsequent pivotal clinical trial.

Background: Animal studies suggest that ischemic preconditioning prolongs coagulation times., Objective: Because coagulation changes could hinder the translation of preconditioning into clinical settings where hemorrhage may be an issue, such as ischemic or hemorrhagic stroke, we evaluated the effects of remote ischemic preconditioning (RIPC) on coagulation in patients undergoing RIPC after aneurysmal subarachnoid hemorrhage (SAH)., Methods: Twenty-one patients with SAH (mean age, 56.3 years) underwent 137 RIPC sessions 2 to 12 days after SAH, each consisting of 3 to 4 cycles of 5 to 10 minutes of lower limb ischemia followed by reperfusion. Partial thromboplastin time (PTT), prothrombin time (PT), and international normalized ratio (INR) were analyzed before and after sessions. Patients were followed for hemorrhagic complications., Results: No immediate effect was identified on PTT (mean pre-RIPC, 27.62 s; post-RIPC, 27.54 s; P = .82), PT (pre-RIPC, 10.77 s; post-RIPC, 10.81 s; P = .59), or INR (pre-RIPC, 1.030; post-RIPC, 1.034; P = .57) after each session. However, statistically significant increases in PT and INR were identified after exposure to at least 4 sessions (mean PT pre-RIPC, 11.33 s; post-RIPC, 12.1 s; P = .01; INR pre-RIPC, 1.02; post-RIPC, 1.09; P = .014, PTT pre-RIPC, 27.4 s; post-RIPC, 27.85 s; P = .092) with a direct correlation between the number of sessions and the degree of increase in PT (Pearson correlation coefficient = 0.59, P = .007) and INR (Pearson correlation coefficient = 0.57, P = .010). Prolonged coagulation times were not observed in controls. No hemorrhagic complications were associated with the procedure., Conclusion: RIPC by limb ischemia appears to prolong the PT and INR in human subjects with SAH after at least 4 sessions, correlating with the number of sessions. However, values remained within normal range and there were no hemorrhagic complications.

Despite recent advances, cerebral vasospasm and delayed cerebral ischemia (DCI) still represent a major cause of morbidity and mortality following aneurysmal subarachnoid hemorrhage (aSAH). Although a significant portion of the morbidity and mortality associated with aSAH is related to the initial hemorrhagic ictus, cerebral vasospasm and DCI are still the leading cause of poor outcomes and death in the acute posthemorrhage period, causing long-term disability or death in more than one in five of all patients who have suffered aSAH and initially survived.Management of patients following aSAH includes four major considerations: (1) prediction of patients at highest risk for development of DCI, (2) prophylactic measures to reduce its occurrence, (3) monitoring to detect early signs of cerebral ischemia, and (4) treatments to correct vasospasm and cerebral ischemia once it occurs. The authors review the pertinent literature related to each, including both the current management guidelines supported by the literature as well as novel management strategies that are currently being investigated., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Purpose: To characterize the relationship between aneurysm size and epidemiologic risk factors with growth and rupture by using computed tomographic (CT) angiography., Materials and Methods: In this HIPAA-compliant, institutional review board approved study, patients with known asymptomatic unruptured intracerebral aneurysms were followed up longitudinally with CT angiographic examinations. Growth was defined as an increase in one or more dimensions above the measurement error, and at least 5% volume by using the ABC/2 method. Associations of epidemiologic factors with aneurysm growth and rupture were analyzed by using logistic regression analysis. Intra- and interobserver agreement coefficients for dimension, volume, and growth were evaluated by using the Pearson correlation coefficient and difference of means with 95% confidence intervals, the agreement statistic, and the McNemar χ(2)., Results: Patients (n = 165) with aneurysms (n = 258) had a mean follow-up time of 2.24 years from time of diagnosis. Forty-six of 258 (18%) aneurysms in 38 patients grew larger. Spontaneous rupture occurred in four of 228 (1.8%) intradural aneurysms of average size (6.2 mm). Risk of aneurysm rupture per patient-year was 2.4% (95% CI: 0.5%, 7.12%) with growth and 0.2% (95% CI: 0.006%, 1.22%) without growth (P = .034). There was a 12-fold higher risk of rupture for growing aneurysms (P < .002), with high intra- and interobserver correlation coefficients for size, volume, and growth. Tobacco smoking (3.806, one degree of freedom; P < .015,) and initial size (5.895, two degrees of freedom; P < .051) were independent covariates, predicting 78.4% of growing aneurysms., Conclusion: These results support imaging follow-up of all patients with aneurysms, including those whose aneurysms are smaller than the current 7-mm treatment threshold. Aneurysm growth, size, and smoking were associated with increased rupture risk., (© RSNA, 2013.)

Objectives: Remote ischemic preconditioning (RIPC) is a powerful endogenous mechanism whereby a brief period of ischemia is capable of protecting remote tissues from subsequent ischemic insult. While this phenomenon has been extensively studied in the heart and brain in animal models, little work has been done to explore the effects of RIPC in human patients with acute cerebral ischemia. This study investigates whether chronic peripheral hypoperfusion, in the form of pre-existing arterial peripheral vascular disease (PVD) that has not been surgically treated, is capable of inducing neuroprotective effects for acute ischemic stroke., Methods: Individuals with PVD who had not undergone prior surgical treatment were identified from a registry of stroke patients. A control group within the same database was identified by matching patient's demographics and risk factors. The two groups were compared in terms of outcome by NIH Stroke Scale (NIHSS), modified Rankin scale (mRS), mortality, and volume of infarcted tissue at presentation and at discharge., Results: The matching algorithm identified 26 pairs of PVD-control patients (9 pairs were female and 17 pairs were male). Age range was 20-93 years (mean 73). The PVD group was found to have significantly lower NIHSS scores at admission (NIHSS≤4: PVD 47.1%, control 4.35%, p<0.003), significantly more favorable outcomes at discharge (mRS≤2: PVD 30.8%, control 3.84%, p<0.012), and a significantly lower mortality rate (PVD 26.9%, control 57.7%, p=0.024). Mean acute stroke volume at admission and at discharge were significantly lower for the PVD group (admission: PVD 39.6 mL, control 148.3 mL, p<0.005 and discharge: PVD 111.7 mL, control 275 mL, p<0.001)., Conclusion: Chronic limb hypoperfusion induced by PVD can potentially produce a neuroprotective effect in acute ischemic stroke. This effect resembles the neuroprotection induced by RIPC in preclinical models., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Ten percent of all strokes occurring in the USA are caused by intracranial arterial stenosis (IAS). Symptomatic IAS carries one of the highest rates of recurrent stroke despite intensive medical therapy (25 % in high-risk groups). Clinical results for endovascular angioplasty and stenting have been disappointing. The objectives of this study were to review the contemporary understanding of symptomatic IAS and present potential alternative treatments to resolve factors not addressed by current therapies. We performed a literature review on IAS pathophysiology, natural history, and current treatment. We present an evaluation of the currently deficient aspects in its treatment and explore the role of alternative surgical approaches. There is a well-documented interrelation between hemodynamic and embolic factors in cerebral ischemia caused by IAS. Despite the effectiveness of medical therapy, hemodynamic factors are not addressed satisfactorily by medications alone. Collateral circulation and severity of stenosis are the strongest predictors of risk for stroke and death. Indirect revascularization techniques, such as encephaloduroarteriosynangiosis, offer an alternative treatment to enhance collateral circulation while minimizing risk of hemorrhage associated with hyperemia and endovascular manipulation, with promising results in preliminary studies on chronic cerebrovascular occlusive disease. Despite improvements in medical management for IAS, relevant aspects of its pathophysiology are not resolved by medical treatment alone, such as poor collateral circulation. Surgical indirect revascularization can improve collateral circulation and play a role in the treatment of this condition. Further formal evaluation of indirect revascularization for IAS is a logical and worthy step in the development of intracranial atherosclerosis treatment strategies.

Background and Purpose: DAVFs rarely involve the sphenoid wings and middle cranial fossa. We characterize the angiographic findings, treatment, and outcome of DAVFs within the sphenoid wings., Materials and Methods: We reviewed the clinical and radiologic data of 11 patients with DAVFs within the sphenoid wing that were treated with an endovascular or with a combined endovascular and surgical approach., Results: Nine patients presented with ocular symptoms and 1 patient had a temporal parenchymal hematoma. Angiograms showed that 5 DAVFs were located on the lesser wing of sphenoid bone, whereas the other 6 were on the greater wing of the sphenoid bone. Multiple branches of the ICA and ECA supplied the lesions in 7 patients. Four patients had cortical venous reflux and 7 patients had varices. Eight patients were treated with transarterial embolization using liquid embolic agents, while 3 patients were treated with transvenous embolization with coils or in combination with Onyx. Surgical disconnection of the cortical veins was performed in 2 patients with incompletely occluded DAVFs. Anatomic cure was achieved in all patients. Eight patients had angiographic and clinical follow-up and none had recurrence of their lesions., Conclusions: DAVFs may occur within the dura of the sphenoid wings and may often have a presentation similar to cavernous sinus DAVFs, but because of potential associations with the cerebral venous system, may pose a risk for intracranial hemorrhage. Curative embolization through a transarterial or transvenous approach is the primary therapeutic strategy for these lesions. In incompletely embolized patients, exclusion of any refluxing cortical veins is necessary.

Ischemic conditioning is a form of endogenous protection induced by transient, subcritical ischemia in a tissue. Organs with high sensitivity to ischemia, such as the heart, the brain, and spinal cord, represent the most critical and potentially promising targets for potential therapeutic applications of ischemic conditioning. Numerous preclinical investigations have systematically studied the molecular pathways and potential benefits of both pre- and postconditioning with promising results. The purpose of this review is to summarize the present knowledge on cerebral pre- and postconditioning, with an emphasis in the clinical application of these forms of neuroprotection. A systematic MEDLINE search for the terms preconditioning and postconditioning was performed. Publications related to the nervous system and to human applications were selected and analyzed. Pre- and postconditioning appear to provide similar levels of neuroprotection. The preconditioning window of benefit can be subdivided into early and late effects, depending on whether the effect appears immediately after the sublethal stress or with a delay of days. In general, early effects have been associated posttranslational modification of critical proteins (membrane receptors, mitochondrial respiratory chain) while late effects are the result of gene up- or downregulation. Transient ischemic attacks appear to represent a form of clinically relevant preconditioning by inducing ischemic tolerance in the brain and reducing the severity of subsequent strokes. Remote forms of ischemic pre- and postconditioning have been more commonly used in clinical studies, as the remote application reduces the risk of injuring the target tissue for which protection is pursued. Limb transient ischemia is the preferred method of induction of remote conditioning with evidence supporting its safety. Clinical studies in a variety of populations at risk of central nervous damage including carotid disease, cervical myelopathy, and subarachnoid hemorrhage have shown improvement in surrogate markers of injury. Promising preclinical and early clinical studies noting improvement in surrogate markers of central nervous injury after the use of remote pre- and postconditioning treatments demand follow-up systematic investigations to address effectiveness. Challenges in the application of these techniques to pressing clinical cerebrovascular disease ought to be overcome through careful, well-designed, translational investigations.

Background: Remote ischemic preconditioning (RIPC) is a form of endogenous neuroprotection induced by transient, subcritical ischemia in a distant tissue. RIPC effects on cerebral hemodynamics and metabolism have not been explored in humans. This study evaluates hemodynamic and metabolic changes induced by RIPC in patients with aneurysmal subarachnoid hemorrhage (SAH)., Methods: Patients underwent three or four RIPC sessions 2-12 days following SAH. Continuous vitals, intracranial pressure (ICP), and transcranial Doppler (TCD) data were collected. Brain microdialysis metabolic changes were monitored. ICP and TCD morphological clustering and analysis of intracranial pulse (MOCAIP) metrics were compared to positive and negative control groups for cerebral vasodilation., Results: Seven ICP and six TCD recordings from four patients demonstrated an increase in mean ICP (8-14.57 mmHg, p < 0.05). There was a reduction in middle cerebral artery (MCA) mean velocities (111-87 cm/s, p = 0.039). ICP and TCD MOCAIP metrics demonstrated variances consistent with vasodilation that returned to baseline following the RIPC. Over the duration of the RIPC, microdialysis showed reduction in the lactate/pyruvate (L/P) ratio (42.37-33.77, p = 0.005) and glycerol (174.04-126 μg/l, p < 0.005), which persisted for 25-54 h after the last RIPC., Conclusions: This study demonstrated cerebrovascular effects induced by RIPC consistent with transient vasodilation. Cerebral metabolic effects suggest protection from ischemia and cell membrane preservation lasting up to 2 days following RIPC.

Object: Surgical evacuation of spontaneous intracerebral hemorrhage (sICH) remains a subject of controversy. Minimally invasive techniques for hematoma evacuation have shown a trend toward improved outcomes. The aim of the present study is to describe a minimally invasive alternative for the evacuation of sICH and evaluate its feasibility., Methods: The authors reviewed records of all patients who underwent endoscopic evacuation of an sICH at the UCLA Medical Center between March 2002 and March 2011. All patients in whom the described technique was used for evacuation of an sICH were included in this series. In this approach an incision is made at the superior margin of the eyebrow, and a bur hole is made in the supraorbital bone lateral to the frontal sinus. Using stereotactic guidance, the surgeon advanced the endoscopic sheath along the long axis of the hematoma and fixed it in place at two specific depths where suction was then applied until 75%-85% of the preoperatively determined hematoma volume was removed. An endoscope's camera, then introduced through the sheath, was used to assist in hemostasis. Preoperative and postoperative hematoma volumes and reduction in midline shift were calculated and recorded. Admission Glasgow Coma Scale and modified Rankin Scale (mRS) scores were compared with postoperative scores., Results: Six patients underwent evacuation of an sICH using the eyebrow/bur hole technique. The mean preoperative hematoma volume was 68.9 ml (range 30.2-153.9 ml), whereas the mean postoperative residual hematoma volume was 11.9 ml (range 5.1-24.1 ml) (p = 0.02). The mean percentage of hematoma evacuated was 79.2% (range 49%-92.7%). The mean reduction in midline shift was 57.8% (p < 0.01). The Glasgow Coma Scale score improved in each patient between admission and discharge examination. In 5 of the 6 patients the mRS score improved from admission exam to last follow-up. None of the patients experienced rebleeding., Conclusions: This minimally invasive technique is a feasible alternative to other means of evacuating sICHs. It is intended for anterior basal ganglia hematomas, which usually have an elongated, ovoid shape. The approach allows for an optimal trajectory to the long axis of the hematoma, making it possible to evacuate the vast majority of the clot with only one pass of the endoscopic sheath, theoretically minimizing the amount of damage to normal brain.

Aims: To investigate the frequency and predictors of Merci device fracture in patients with acute ischemic stroke treated with mechanical thrombectomy and its impact on clinical outcome., Methods: We retrospectively analyzed patients with acute ischemic stroke treated by thrombectomy with the Merci Retriever and identified the presence of device fracture. The predictors of device fracture were assessed. We evaluated the impact of device fracture on hemorrhage and clinical outcome., Results: Of 136 patients treated by thrombectomy, 6 (4.4%) experienced intraprocedural Merci device fracture. Internal carotid artery occlusion was associated with device fracture. The fractured X and L series Merci Retrievers were successfully ensnared in four patients. Patients with fractured devices had similar rates of successful revascularization with those without. In patients with fractured devices, no parenchymal hematomas were found, while hemorrhagic infarction and subarachnoid hemorrhage were found in three and two patients, respectively. Patients with fractured devices tended to be more dependent (modified Rankin Scale ≥ 3) at discharge, but had similar rates of in-hospital mortality., Conclusions: Merci device fracture is relatively infrequent in patients with acute ischemic stroke treated with thrombectomy. This complication may not increase the risk of parenchymal hematoma but tends to be associated with poor outcome., (© 2012 Blackwell Publishing Ltd.)

Background and Purpose: The purpose of this study was to determine whether leukoaraiosis (LA) predicts hemorrhagic transformation and poor outcome in patients with acute ischemic stroke treated by mechanical thrombectomy., Methods: We retrospectively analyzed patients with anterior circulation stroke treated with Merci devices and identified LA in the deep white matter (DWM) and periventricular white matter on the preintervention MR images. We dichotomized patients into those with moderate or severe LA in the DWM versus those without. Hemorrhage rates and outcomes were evaluated between 2 groups. We analyzed the association of moderate or severe LA with hemorrhagic transformation and poor outcome., Results: Twenty-six of 105 patients had moderate or severe LA in the DWM. Patients with moderate or severe LA in the DWM were older, had more severe neurological deficits and worse outcome, had higher rates of hemorrhagic transformation and parenchymal hematoma, but had equivalent rates of hemorrhagic infarct and subarachnoid hemorrhage when compared with those without. Patients with only periventricular LA did not have a higher rate of parenchymal hematoma. Moderate or severe LA in the DWM was an independent predictor of hemorrhagic transformation (OR, 3.4; P=0.019) and parenchymal hematoma (OR, 6.3; P=0.005). Patients with parenchymal hematoma were less often independent (modified Rankin Scale≤2, 3.8% versus 32.5%; P=0.003) and had greater in-hospital mortality (50% versus 10.4%; P<0.001)., Conclusions: Moderate or severe LA in the DWM increases the risk of parenchymal hematoma after Merci thrombectomy for patients with acute stroke. These findings require validation in a larger prospective study.

Background: Changes in neurosurgical practice and graduate medical education impose new challenges for training programs., Objective: We present our experience providing neurosurgical residents with digital and mobile educational resources in support of the departmental academic activities., Methods: A weekly mandatory conference program for all clinical residents based on the Accreditation Council for Graduate Medical Education competencies, held in protected time, was introduced. Topics were taught through didactic sessions and case discussions. Faculty and residents prepare high-quality presentations, equivalent to peer-review leading papers or case reports. Presentations are videorecorded, stored in a digital library, and broadcasted through our Website and iTunes U. Residents received mobile tablet devices with remote access to the digital library, applications for document/video management, and interactive teaching tools., Results: Residents responded to an anonymous survey, and performances on the Self-Assessment in Neurological Surgery examination before and after the intervention were compared. Ninety-two percent reported increased time used to study outside the hospital and attributed the habit change to the introduction of mobile devices; 67% used the electronic tablets as the primary tool to access the digital library, followed by 17% hospital computers, 8% home computers, and 8% personal laptops. Forty-two percent have submitted operative videos, cases, and documents to the library. One year after introducing the program, results of the Congress of Neurological Surgeons-Self-Assessment in Neurological Surgery examination showed a statistically significant improvement in global scoring and improvement in 16 of the 18 individual areas evaluated, 6 of which reached statistical significance., Conclusion: A structured, competency-based neurosurgical education program supported with digital and mobile resources improved reading habits among residents and performance on the Congress of Neurological Surgeons-Self-Assessment in Neurological Surgery examination.

Object: Symptomatic intracranial arterial stenoses have a high rate of recurrent stroke despite medical and endovascular treatments. The authors present clinical and angiographic quantitative outcomes of indirect revascularization for patients with symptomatic intracranial stenosis., Methods: Patients treated for symptomatic intracranial arterial stenosis by indirect revascularization were included. The patient population comprised those in whom medical management had failed and for whom endovascular therapy was unsuitable or had failed. Patients underwent encephaloduroarteriosynangiosis (EDAS) with or without bur holes. Preoperative and postoperative angiograms were evaluated for change in caliber of extracranial blood vessels (superficial temporal artery [STA] and middle meningeal artery [MMA]) and for evidence of neovascularization., Results: Thirteen patients underwent EDAS. Ischemic symptoms ceased within the follow-up period in all patients, returning in a delayed fashion in only 2. No other patients had recurrent TIAs or strokes after the initial postoperative period. Donor blood vessels increased in size relative to preoperative sizes in all but 1 case (average increase of 52% for proximal STA [p=0.01], 74% for midpoint of STA [p=0.01], and 84% for the MMA [p=0.02]). In addition, 8 of 11 patients demonstrated direct spontaneous anastomoses from extracranial to middle cerebral artery branches, and all patients demonstrated angiographic evidence of vascular blush and/or new branches from the STA and/or MMA., Conclusions: Indirect revascularization appears to be a safe and effective method to improve blood flow to ischemic brain due to intracranial arterial stenosis. Neovascularization and enlargement of the branches of the ECA were observed in all patients and correlated with improvement in ischemic symptoms. Indirect revascularization is an option for patients in whom medical therapy has failed and who are not suitable for endovascular treatment.

Exposure of one tissue to ischemia-reperfusion confers a systemic protective effect, referred to as remote ischemic preconditioning (RIPC). Confirmation that the desired effect of ischemia is occurring in tissues used to induce RIPC requires an objective demonstration before this technique can be used consistently in the clinical practice. Enrolled patients underwent three to four RIPC sessions on non-consecutive days. Sessions consisted of 4 cycles of 5 min of leg cuff inflation to 30 mmHg above the systolic blood pressure followed by reperfusion. Absence of leg pulse was confirmed by Doppler evaluation. To evaluate limb transient ischemia, patients were monitored with muscle microdialysis. Glucose, lactate, lactate/pyruvate ratio, and glycerol levels were measured. Fourteen microdialysis sessions were performed in seven patients undergoing RIPC (42.8 % male; mean age, 51.8; Fisher grade 4 in all seven patients, Hunt and Hess grade 5 in five patients, four in one patient and one in one patient). An average follow-up of 29 days demonstrated no complications associated with the procedure. Muscle microdialysis during RIPC sessions showed a significant increase in lactate/pyruvate ratio (21.2 to 26.8, p = 0.001) and lactate (3.0 to 3.9 mmol/L, p = 0.002), indicating muscle ischemia. There was no significant variation in glycerol (234 to 204 μg/L, p = 0.43), indicating no permanent cell damage. The RIPC protocol used in this study is safe, well tolerated, and induces transient metabolic changes consistent with sublethal ischemia. Muscle microdialysis can be used safely as a confirmatory tool in the induction of RIPC.

Background: While stroke is the second leading cause of death worldwide, little work has been done to quantify the growth and progress of stroke publications. The purpose of this study is to quantitatively analyze trends in the stroke literature over the past 12 years, specifically examining changes in worldwide productivity and study methodology., Methods: The study was a retrospective bibliometric analysis of all stroke articles published between 1996 and 2008 indexed in MEDLINE. Country of origin, MEDLINE-defined methodology, specialty of the first author, and funding sources (for US articles) were recorded. Growth was analyzed by using linear and nonlinear regression., Results: Total articles numbered 32,309 during the study period, with leading global contributors including the United States with 8795 (27.2%) articles, Japan with 2757 (8.5%) articles, and the United Kingdom with 2629 (8.1%) articles. Growth globally and in the United States followed a linear pattern at 209.9 and 56.2 articles per year, respectively (both P < 0.001). Review articles and clinical trials numbered 5932 (18.4%) and 2934 (9.1%), respectively. Clinical trials followed an exponential growth pattern of 7.7% per year (P < 0.001). Regarding specialty influence, pain management and rehabilitation had the largest proportional growth in clinical trials from 4 to 51 articles., Conclusions: Within the stroke literature, we observed continued growth worldwide, sustained growth in the United States, and a steady increase in the number of clinical trials, especially by pain management and rehabilitation.

Dural arteriovenous fistulas (dAVFs) of the anterior cranial fossa have traditionally been treated by open surgical disconnection. Safe navigation through the ophthalmic artery or fragile cortical veins has historically provided a barrier to effective endovascular occlusion of these lesions. Using current microcatheter technology and embolic materials, safe positioning within the distal ophthalmic artery, beyond the origin of the central retinal artery, is achievable. We describe two cases in which anterior cranial fossa dAVFs were treated by exclusively endovascular strategies, and highlight the pertinent technical and anatomic considerations. We discuss the clinical symptoms resulting from the differing venous drainage patterns.

Objectives: Acute, simultaneous, concomitant internal carotid artery (ICA) and middle cerebral arteries (MCA) occlusions almost invariably lead to significant neurological disability if left untreated. Endovascular therapy is frequently the method of treatment in such situations but there remains a chance of incomplete recanalization. Successful recanalization of the proximal aspect of the occlusion may allow for endogenous thrombolysis and facilitate further endogenous recanalization of any residual MCA occlusion., Methods: Consecutive patients with acute ischemic stroke undergoing endovascular therapy for tandem extracranial ICA-MCA or contiguous intracranial ICA-MCA occlusions were retrospectively analyzed. Rates of facilitated endogenous recanalization at 24 h (FER(24)) were compared by imaging within the immediate post-intervention 5-24 h period in those with proximal recanalization and in those without., Results: 17 patients were included in the analysis. 12 patients had good initial proximal recanalization but a residual partial or total occlusion of the MCA while five patients failed any recanalization. Seven patients (58.3%) in the first group and none in the second had FER(24) on interval imaging after intervention (p=0.04). The probability of death and disability at discharge was less in patients with FER(24) than those without (p=0.05)., Conclusions: More than half of all patients who present with both ICA and MCA occlusions who are only partially recanalized will undergo facilitated endogenous recanalization within the subsequent 24 h following intervention.

Background: Double-injection models of subarachnoid hemorrhage (SAH) in rats are the most effective in producing vasospasm, delayed neurological deficits and infarctions. However, they require two large surgeries to expose the femoral artery and the atlanto-occipital membrane. We have developed a minimally-invasive modification that prevents confounding effects of surgical procedures, leakage of blood from the subarachnoid space and minimizes risk of infection., Methods: Rats are anesthetized and the ventral tail artery is exposed through a small (5 mm), midline incision, 0.2 mL of blood is taken from the artery and gentle pressure is applied for hemostasis. The rat is flipped prone, and with the head flexed to 90 degrees in a stereotactic frame, a 27G angiocath is advanced in a vertical trajectory, level with the external auditory canals. Upon puncturing the atlanto-occipital membrane, the needle is slowly advanced and observed for cerebrospinal fluid (CSF). A syringe withdraws 0.1 mL of CSF and the blood is injected into the subarachnoid space. The procedure is repeated 24 hours later by re-opening the tail incision. At 8 days, the rats are euthanized and their brains harvested, sectioned, and incubated with triphenyltetrazolium chloride (TTC)., Results: Rats develop neurological deficits consistent with vasospasm and infarction as previously described in double-injection models. Cortical and deep infarctions were demonstrated by TTC staining and on histopathology., Conclusions: A minimally invasive, double-injection rat model of SAH and vasospasm is feasible and produces neurological deficits and infarction. This model can be used to study neuroprotective treatments for vasospasm and delayed neurological deficits following SAH, reducing the confounding effects of surgical interventions.

Background: Several forms of indirect cerebral revascularization have been proposed to promote neovascularity to the ischemic brain., Objective: To present clinical and angiographic outcomes of indirect revascularization by encephaloduroarteriosynangiosis and burr holes for the treatment of Moyamoya disease in adults and children., Methods: Data from 63 hemispheres treated in 42 patients (average age, 30 years; 33 adults; 30 female patients; median follow-up, 14 months) were reviewed. In hemispheres with preoperative and postoperative (6- to 12-month) angiograms available, superficial temporal artery (STA) and middle meningeal artery (MMA) diameters were measured. Preoperative and postoperative corrected arterial sizes were compared., Results: Seven patients (17%) had transient ischemic attacks that resolved within 1 month of surgery. No patients suffered moyamoya-related hemorrhage after treatment. Two patients developed additional symptoms many years after surgery. In 18 hemispheres with preoperative and postoperative angiograms, there was an average postoperative increase in STA and MMA diameters of 51% (P = .003) and 49% (P = .002), respectively. Both children and adults displayed revascularization. Two patients did not demonstrate increased vessel size. STA blush and new branches and MMA blush and new branches were identified in 12, 14, 14, and 16 hemispheres, respectively. Angiographic blush was identified in 59% of frontal and 19% of parietal burr holes (P = .03). Surgical complications included 2 subdural hemorrhages requiring evacuation and 2 new ischemic deficits (1 transient)., Conclusion: Indirect revascularization by encephaloduroarteriosynangiosis and burr holes for moyamoya results in long-term resolution of ischemic and hemorrhagic manifestations in 95% of adults and children. The MMA appears to contribute significantly to the revascularization on follow-up angiograms with increased size and neovascularity comparable to that of the STA. Angiographically, parietal burr holes do not contribute as significantly as frontal burr holes.

Objective: We recently demonstrated that the preprocedural magnetic resonance imaging (MRI) pattern of deep middle cerebral artery (MCA) territory injury predicts poor prognosis. We postulate that the structures of the deep MCA field are particularly vulnerable to hemorrhagic transformation (HT) following reperfusion., Methods: We reviewed all cases of acute occlusions involving the M1 segment of the MCA with diffusion restriction of at least 50% of the deep MCA field on MRI (M1a pattern) that underwent endovascular therapy. We compared those with and without recanalization in regards to HT and disability on discharge., Results: Thirty-five patients met inclusion criteria. The recanalized M1a group (n=27) had higher rates of HT (67% vs. 25%, P=0.05) and a trend toward more parenchymal HT (37% vs. 0%, P=0.07) and symptomatic HT (22% vs. 0%, P=0.12) than those M1a patients who failed to recanalize (n=8). Clinical improvement in the National Institutes of Health Stroke Scale by discharge was better in the survivors of the recanalized group., Conclusions: Among patients with the preintervention M1a MRI pattern of advanced basal ganglionic injury, successful recanalization predicts a higher risk of HT but better outcome., (Published by Elsevier Inc.)

Background and Purpose: Subarachnoid hemorrhage (SAH) is a potential hemorrhagic complication after endovascular intracranial recanalization. The purpose of this study was to describe the frequency and predictors of SAH in acute ischemic stroke patients treated endovascularly and its impact on clinical outcome., Methods: Acute ischemic stroke patients treated with primary mechanical thrombectomy, intra-arterial thrombolysis, or both were analyzed. Postprocedural computed tomography and magnetic resonance images were reviewed to identify the presence of SAH. We assessed any decline in the National Institutes of Health Stroke Scale score 3 hours after intervention and in the outcomes at discharge., Results: One hundred twenty-eight patients were treated by primary thrombectomy with MERCI Retriever devices, whereas 31 were treated by primary intra-arterial thrombolysis. Twenty patients experienced SAH, 8 with pure SAH and 12 with coexisting parenchymal hemorrhages. SAH was numerically more frequent with primary thrombectomy than in the intra-arterial thrombolysis groups (14.1% vs 6.5%, P = 0.37). On multivariate analysis, independent predictors of SAH were hypertension (odds ratio = 5.39, P = 0.035), distal middle cerebral artery occlusion (odds ratio = 3.53, P = 0.027), use of rescue angioplasty after thrombectomy (odds ratio = 12.49, P = 0.004), and procedure-related vessel perforation (odds ratio = 30.72, P < 0.001). Patients with extensive SAH or coexisting parenchymal hematomas tended to have more neurologic deterioration at 3 hours (28.6% vs 0%, P = 0.11), to be less independent at discharge (modified Rankin Scale ≤ 2; 0% vs 15.4%, P = 0.5), and to experience higher mortality during hospitalization (42.9% vs 15.4%, P = 0.29)., Conclusions: Procedure-related vessel perforation, rescue angioplasty after thrombectomy with MERCI devices, distal middle cerebral artery occlusion, and hypertension were independent predictors of SAH after endovascular therapy for acute ischemic stroke. Only extensive SAH or SAH accompanied by severe parenchymal hematomas may worsen clinical outcome at discharge.

Background and Purpose: Endovascular therapy is an alternative for the treatment of AIS resulting from large intracranial arterial occlusions that depends on the use of iodinated RCM. The risk of RCM-mediated AKI following endovascular therapy for AIS may be different from that following coronary interventions because patients may not have identical risk factors., Materials and Methods: All consecutive patients with large-vessel AIS undergoing endovascular therapy were prospectively recorded. We recorded the baseline kidney function, and RCM-AKI was assessed according to the AKIN criteria at 48 hours after RCM administration. We compared the rate of RCM-AKI 48 hours after the procedure and sought to determine whether any preexisting factors increased the risk of RCM-AKI., Results: We identified 99 patients meeting inclusion criteria. The average volume of contrast was 189 ± 71 mL, and the average creatinine change was -4.6% at 48 hours postangiography. There were 3 patients with RCM-AKI. Although all 3 patients died as a result of their strokes, return to baseline creatinine levels occurred before death. There was a trend toward higher rates of premorbid diabetes mellitus, chronic renal insufficiency, preadmission statin and NSAID use, and a higher serum creatinine level on admission for the RCM-AKI group. The volume of procedural contrast was similar between groups (those with and those without RCM-AKI) (P = .5)., Conclusions: In this small study, the rate of RCM-AKI following endovascular intervention for AIS was very low. A much larger study is required to determine its true incidence.

Background and Purpose: Mechanical thrombectomy is a promising means of recanalizing acute cerebrovascular occlusions in certain situations. We sought to determine if increasing age adversely affects prognosis., Materials and Methods: We reviewed all Merci thrombectomy cases and compared patients younger than 80 years of age with older individuals. We compared these 2 age groups with respect to recanalization rates, hospital LOS, hemorrhagic transformation, and death and disability on discharge., Results: Elderly patients were more likely to die from their stroke than those younger than 80 years of age, regardless of recanalization success (48% versus 15%; OR, 5.5; 95% CI, 2.1-14.1). Among survivors, there was no difference in the probability of having a good functional outcome (mRS,

Background and Purpose: Use of the Merci retriever is increasing as a means to reopen large intracranial arterial occlusions. We sought to determine whether there is an optimum number of retrieval attempts that yields the highest recanalization rates and after which the probability of success decreases., Materials and Methods: All consecutive patients undergoing Merci retrieval for large cerebral artery occlusions were prospectively tracked at a comprehensive stroke center. We analyzed ICA, M1 segment of the MCA, and vertebrobasilar occlusions. We compared the revascularization of the primary AOL with the number of documented retrieval attempts used to achieve that AOL score. For tandem lesions, each target lesion was compared separately on the basis of where the device was deployed., Results: We identified a total of 97 patients with 115 arterial occlusions. The median number of attempts per target vessel was 3, while the median final AOL score was 2. Up to 3 retrieval attempts correlated with good revascularization (AOL 2 or 3). When >or=4 attempts were performed, the end result was more often failed revascularization (AOL 0 or 1) and procedural complications (P = .006)., Conclusions: In our experience, 3 may be the optimum number of Merci retrieval attempts per target vessel occlusion. Four or more attempts may not improve the chances of recanalization, while increasing the risk of complications.

Background: More elderly patients are presenting with intracranial aneurysms. Many are poor surgical candidates and often undergo endovascular treatment., Objective: We present our experience with embolization in elderly patients., Methods: We performed a retrospective review of a prospective database of elderly patients treated with coil embolization for intracranial aneurysms., Results: In a period of 16 years, 205 aneurysms were treated in 196 individuals (age range, 70-96 years; mean age, 77.3 years), including 159 females (average follow-up, 16.2 months). Ninety-seven patients presented with unruptured aneurysms, and 99 patients presented after subarachnoid hemorrhage; the diagnosis was confirmed by computed tomographic scan or lumbar puncture. Complete occlusion was achieved in 53 aneurysms (26%), with a neck remnant in 127 (62%), incomplete occlusion in 13 (6%), and 12 unsuccessful attempts. Postembolization, 89.3% of patients were neurologically intact or unchanged, whereas 8.7% had new deficits. Four patients died. By modified Rankin Scale score, at last clinical evaluation, 128 patients (65%) had a good outcome. Follow-up angiograms were available for 113 aneurysms; they revealed that 62% were unchanged, 21% were further thrombosed, and 17% had recanalized. Three aneurysms ruptured after treatment during follow-up. Rupture was not associated with incomplete occlusion or neck remnant results (P = .6). Twenty-five aneurysms required reembolization. Reembolization was not associated with new deficits or death (odds ratio, 0.56; 95% confidence interval, 0.19-1.58; P = .27)., Conclusion: Coil embolization of intracranial aneurysms is safe and effective in the elderly. Preembolization clinical condition strongly correlates with clinical outcome. Incomplete embolizations are not associated with a higher rerupture risk. Additional embolization does not affect the clinical results.

Background: Complex DAVFs involving both the clivus and cavernous sinus are rare, especially when associated with brainstem compression from a large varix. In this report, we describe the use of a covered stent in combination with a liquid embolic agent to cure a complex clival-cavernous DAVF., Methods: A 46-year-old man presented with 6 months of dizziness, dysphagia, and progressive dysarthria. Magnetic resonance imaging showed tortuous and enlarged right cavernous and preclival flow voids. There were also bilateral prepontine varices compressing the ventral pons, which led to marked dorsal pontine edema. A cerebral angiogram revealed a clival DAVF supplied by multiple branches of the right ECA, as well as the MHT of the right ICA., Results: An endovascular cure was achieved by deploying a covered stent in the right cavernous ICA, followed by transarterial embolization of the feeding arteries originating from the ECA with Onyx (ev3, Irvine, Calif). This combined approach resulted in complete occlusion of the fistula. His 1-month follow-up angiogram confirmed persistent occlusion of the fistula and preserved patency of the right ICA. The patient made a full recovery without any new symptoms, and he remained neurologically intact at 18-month follow-up., Conclusion: The combined technique of covered stent placement and Onyx transarterial embolization is valuable for the management of complex DAVFs supplied by branches of both the external and internal carotid arteries.

Objective: Because of their anatomic configuration, middle cerebral artery (MCA) aneurysms are most often treated with surgical clipping. However, endovascular coil embolization of these aneurysms is an increasingly used alternative. We retrospectively reviewed the anatomic and clinical outcomes of patients with MCA aneurysms who underwent endovascular treatment at our institution., Methods: One hundred fifteen MCA aneurysms in 115 patients (mean age, 55.1 years) were treated by an endovascular technique from April 1990 to March 2007. Forty-eight patients (42%) presented with acute subarachnoid hemorrhage, and 67 patients (58%) had unruptured aneurysms. Fifty-three aneurysms (46%) were small with a small neck, 28 (24%) were small with a wide neck, 22 (19%) were large, and 12 (11%) were giant., Results: Angiographic results immediately after embolization showed complete occlusion in 53 aneurysms (46%), a neck remnant in 51 (44%), and incomplete occlusion in 3 (3%). Because of anatomic difficulties, we could not embolize 8 aneurysms (7%). Thirteen patients underwent combined treatment that included endovascular and extracranial-intracranial bypass surgery. Morbidity and mortality rates were 6.9% (8 patients) and 3% (3 patients), respectively. Procedure-related complications were encountered in 10 patients (9%). Seventy patients had long-term follow- up angiograms. Seven aneurysms (10%) were recanalized; all were large or giant. One partially embolized large aneurysm ruptured 13 months after embolization., Conclusion: In this series, endovascular coil embolization of MCA aneurysms has morbidity and mortality rates comparable to those of conventional surgical clipping. Combined treatment of endovascular and bypass surgery can successfully treat large or giant complex fusiform MCA aneurysms.

Objective: Giant intracranial aneurysms present unique therapeutic intricacies. The purpose of this study was to evaluate the anatomic and hemodynamic characteristics of these lesions and the current endovascular and combined surgical and endovascular techniques available for their treatment., Methods: A review of the literature and the personal experiences of the authors with endovascular treatment of giant aneurysms are presented. This review included anatomic and hemodynamic features and analysis of the diverse endovascular techniques that have been reported for the management of these aneurysms., Results: Anatomic features that create particular challenges in the therapeutic approach of giant aneurysms include size, shape (saccular, fusiform, serpentine), neck dimensions, branch involvement, intraluminal thrombosis, and location. Hemodynamic characteristics that affect endovascular treatment are lateral or terminal aneurysm type of flow and embolic material placement (inflow versus outflow aneurysmal region). The current endovascular therapeutic approaches include parent artery occlusion, trapping, endosaccular embolization with or without adjunctive techniques such as balloon-assisted or stent placement, and combined surgical and endovascular approaches, mainly with surgical revascularization and endovascular occlusion., Conclusion: Although there are a wide variety of endovascular therapeutic options for the treatment of giant intracranial aneurysms, none of the current techniques is completely successful and free of complications in the management of these complex lesions. A detailed and individualized analysis of each case in conjunction with sufficient understanding of the anatomy and hemodynamics of a particular aneurysm should guide the therapeutic decision. Further research advances will assist in elucidating the factors predisposing to genesis, progression, and aggressive clinical manifestations of these giant lesions.

Background: One of the limiting factors of C1-C2 fixation is the location of the vertebral artery (VA). The authors sought to assess the potential variations in atlanto-axial VA anatomy using computed tomography angiography (CTA)., Methods: Detailed measurements were made on digital images of 106 patients undergoing CTA at our institution (54 males, 52 females; mean age 56, range 20-86). Distances, diameters and angles of osseous and vascular elements of the atlanto-axial complex were measured., Results: Optimal C1 and C2 screw trajectories demonstrated wide variations among patients. The size of the VA groove or foramen was not predictive of exact arterial location or size., Conclusions: The size, location and path of the VA cannot be precisely predicted by the appearance of osseous structures such as the transverse foramina and/or the VA groove. CTA provides additional information regarding the atlanto-axial complex, and should be considered as a useful adjunct in the preoperative evaluation of select patients., ((c) 2008 John Wiley & Sons, Ltd.)

Objective: Dural arteriovenous fistulae (DAVFs) rarely involve the clivus. This report examines the clinical presentation, angiographic findings, endovascular management, and outcome of clival DAVFs. Particular attention was given to safety and efficacy of transarterial embolization using liquid embolic agents., Methods: We reviewed the clinical and radiological data of 10 patients with spontaneous clival DAVFs who were treated endovascularly at the University of California at Los Angeles Medical Center between 1992 and 2006., Results: Nine patients presented with ocular symptoms and one patient experienced pulsatile tinnitus. Cerebral angiograms showed that these clival DAVFs were supplied by multiple branches of the internal and external carotid arteries. The patterns of venous drainage were from the clival veins to the cavernous sinus and superior ophthalmic vein in nine patients and to the inferior petrosal sinus in two patients. Six clival DAVFs were embolized transarterially through the clival branches of the ascending pharyngeal artery. Onyx 18 (Micro Therapeutics Inc., Irvine, CA) was used in three patients and n-butyl cyanoacrylate was used in three patients. Immediate complete angiographic obliteration was achieved in three patients. All six patients experienced an angiographic and clinical cure without any complications at 3 months. Two patients were incompletely treated using particles and coils for the relief of the symptoms. Two other patients were completely treated after the recipient clival venous structures were occluded transvenously with coils., Conclusion: Clival DAVFs can be misdiagnosed as dural cavernous sinus fistulae. The best treatment is transarterial embolization of the dural feeders using liquid embolic agents. Transvenous occlusion of the cavernous sinus is unnecessary in most cases.

Object: The goal in this study was to create an index (vasospasm probability index [VPI]) to improve diagnostic accuracy for vasospasm after subarachnoid hemorrhage (SAH)., Methods: Seven hundred ninety-five patients in whom aneurysmal SAH was demonstrated by computed tomography, and in whom one or more intracranial aneurysms had been diagnosed, underwent transcranial Doppler (TCD) studies between April 1998 and January 2000. In 154 patients angiography was performed within 24 hours of the TCD examination, and in 75 133Xe cerebral blood flow (CBF) studies were obtained the same day. Seven cases were excluded because of a limited sonographic window. Forty-one women (60.3%) and 27 men (39.7%) between the ages of 35 and 84 years (58.0 +/- 13.2 years [mean +/- standard deviation]) were included. Clinical characteristics analyzed included age, sex, Hunt and Hess grade, Fisher grade, days after SAH, day of treatment, type of treatment (coil embolization, surgical clip occlusion, or conservative treatment), smoking history, and hypertension history. Lindegaard ratios and spasm indexes (TCD velocities/hemispheric CBF) were calculated bilaterally. Digital subtraction angiography images were measured at specific points of interest. Sensitivity, specificity, predictive values, and global accuracy of the different tests were calculated. Logistic regression was used to evaluate the possible predictive factors, and the coefficients of the logistic regression were integrated to create the VPI., Results: In 18 patients (26.5%) symptomatic vasospasm was diagnosed, and 33 (48.5%) had angiographic evidence of vasospasm. For TCD velocities above 120 cm/second at the middle cerebral artery, the global accuracy was 81.1% for the diagnosis of clinical vasospasm and 77.2% for angiographic vasospasm. For a Lindegaard ratio higher than 3.0, the accuracy was 85% for clinical vasospasm and 83.2% for angiographic vasospasm. A spasm index higher than 3.5 had an accuracy of 82.0% for the diagnosis of clinical vasospasm and 81.6% for angiographic vasospasm. The selected model for estimation of clinical vasospasm included Fisher grade, Hunt and Hess grade, and spasm index. The VPI had a global accuracy of 92.9% for clinical vasospasm detection. For diagnosis of angiographic vasospasm, the model included Fisher grade, Hunt and Hess grade, and Lindegaard ratio. The VPI achieved a global accuracy of 89.9% for angiographic vasospasm detection., Conclusions: The use of TCD velocities, Lindegaard ratio, and spasm index independently is of limited value for the diagnosis of clinical and angiographic vasospasm. The combination of predictive factors associated with the development of vasospasm in the new index reported here has a significantly superior accuracy compared with the independent tests and may become a valuable tool for the clinician to evaluate the individual probability of cerebral vasospasm after aneurysmal SAH.

Objective: Giant intracranial aneurysms present unique therapeutic intricacies. The purpose of this study was to evaluate the anatomic and hemodynamic characteristics of these lesions and the current endovascular and combined surgical and endovascular techniques available for their treatment., Methods: A review of the literature and the personal experiences of the authors with endovascular treatment of giant aneurysms are presented. This review included anatomic and hemodynamic features and analysis of the diverse endovascular techniques that have been reported for the management of these aneurysms., Results: Anatomic features that create particular challenges in the therapeutic approach of giant aneurysms include size, shape (saccular, fusiform, serpentine), neck dimensions, branch involvement, intraluminal thrombosis, and location. Hemodynamic characteristics that affect endovascular treatment are lateral or terminal aneurysm type of flow and embolic material placement (inflow versus outflow aneurysmal region). The current endovascular therapeutic approaches include parent artery occlusion, trapping, endosaccular embolization with or without adjunctive techniques such as balloon-assisted or stent placement, and combined surgical and endovascular approaches, mainly with surgical revascularization and endovascular occlusion., Conclusion: Although there are a wide variety of endovascular therapeutic options for the treatment of giant intracranial aneurysms, none of the current techniques is completely successful and free of complications in the management of these complex lesions. A detailed and individualized analysis of each case in conjunction with sufficient understanding of the anatomy and hemodynamics of a particular aneurysm should guide the therapeutic decision. Further research advances will assist in elucidating the factors predisposing to genesis, progression, and aggressive clinical manifestations of these giant lesions.

A new angiographic finding in intracranial aneurysms embolized with Matrix coils is described. Two illustrative cases with a well-defined radiolucent separation between the coil mass and the parent artery are presented. To the best of our knowledge, this is the first report in humans of this finding. On the basis of prior histopathologic studies, this finding, which we call the "white-collar sign," may indicate the formation of a thick connective tissue barrier between aneurysm and artery that prevents any further aneurysmal filling.

Background and Purpose: Acceleration of intra-aneurysmal clot organization and fibrosis may be a solution to preventing aneurysm recanalization after endovascular treatment. The purpose of this study was to evaluate the short-term efficacy and long-term safety of the new Matrix coil system., Methods: Matrix coils consist of thin platinum coils covered with a bioabsorbable, polymeric material (polyglycolic acid/lactide). Fifty-two experimental aneurysms were created in 26 swine. All of the aneurysms were tightly packed with Matrix or Guglielmi detachable coils (GDC). Comparative angiographic and histopathologic data were analyzed at 2 weeks (n=14), 3 months (n=6), and 6 months (n=6) after embolization., Results: Three aneurysms treated with GDC ruptured despite tight packing. No recanalization or rupturing was observed in the aneurysms embolized with Matrix coils. At 14 days after embolization, the aneurysms treated with Matrix coils exhibited a more extensive area of organized thrombus when compared with the aneurysms treated with GDC (87% versus 75%, P=0.008, n=11). At 3 months, both Matrix and GDC-treated aneurysms demonstrated complete clot organization. Neck tissue thickness was higher in Matrix-treated aneurysms at 14 days and 3 months, but not at 6 months. No untoward parent artery stenosis was observed in aneurysms treated with Matrix during follow-up. The angiographic cross-sectional area of the Matrix-treated aneurysms was smaller than those treated with GDC at the 3 months., Conclusions: Matrix accelerated aneurysm fibrosis and neointima formation without parent artery stenosis. The Matrix system might prevent aneurysmal recanalization after endovascular treatment of cerebral aneurysms.

Objective: The goal of this study was to quantify the effects of endovascular therapy on vasospastic cerebral vessels., Methods: We reviewed the medical records for 387 patients with ruptured intracranial aneurysms who were treated at a single institution (University of California, Los Angeles) between May 1, 1993, and March 31, 2001. Patients who developed cerebral vasospasm and underwent cerebral arteriographic, transcranial Doppler ultrasonographic, and cerebral blood flow (CBF) studies before and after endovascular therapy for cerebral arterial spasm (vasospasm) were included in this study., Results: Forty-five patients fulfilled the aforementioned criteria and were treated with either papaverine infusion, papaverine infusion with angioplasty, or angioplasty alone. After balloon angioplasty (12 patients), CBF increased from 27.8 +/- 2.8 ml/100 g/min to 28.4 +/- 3.0 ml/100 g/min (P = 0.87); the middle cerebral artery blood flow velocity was 1 57.6 +/- 9.4 cm/s and decreased to 76.3 +/- 9.3 cm/s (P < 0.05), with a mean increase in cerebral artery diameters of 24.4%. Papaverine infusion (20 patients) transiently increased the CBF from 27.5 +/- 2.1 ml/100 g/min to 38.7 +/- 2.8 ml/100 g/min (P < 0.05) and decreased the middle cerebral artery blood flow velocity from 109.9 +/- 9.1 cm/s to 82.8 +/- 8.6 cm/s (P < 0.05). There was a mean increase in vessel diameters of 30.1% after papaverine infusion. Combined treatment (13 patients) significantly increased the CBF from 33.3 +/- 3.2 ml/100 g/min to 41.7 +/- 2.8 ml/100 g/min (P< 0.05) and decreased the transcranial Doppler velocities from 148.9 +/- 12.7 cm/s to 111.4 +/- 10.6 cm/s (P < 0.05), with a mean increase in vessel diameters of 42.2%., Conclusion: Balloon angioplasty increased proximal vessel diameters, whereas papaverine treatment effectively dilated distal cerebral vessels. In our small series, we observed no correlation between early clinical improvement or clinical outcomes and any of our quantitative or physiological data (CBF, transcranial Doppler velocities, or vessel diameters).

Background and Purpose: Acceleration of healing mechanisms is a promising approach to improve current limitations of endovascular aneurysm therapy with the use of platinum coils. We evaluated a new endovascular therapeutic, bioabsorbable polymeric material (BPM), which may promote cellular reaction in the aneurysms., Methods: Four different concentrations of lactide/glycolic acid copolymer [poly(D-L-lactic-co-glycolic acid)] (PLGA), 85/15, 75/25, 65/35, and 50/50, were used as BPMs. Sixteen experimental aneurysms were created in 8 swine. Eight-millimeter-long spiral-shaped BPMs were surgically implanted in the aneurysms without tight packing (n=3 for each BPM). Guglielmi detachable coils (GDCs) were used as control (n=4). The animals were killed 14 days after embolization, and angiographic, histological, and immunohistochemical analyses were performed., Results: Despite loose packing of aneurysms with BPMs, faster BPMs such as 50/50 or 65/35 PLGA demonstrated more mature collagen formation and fibrosis in the sac and neck of the aneurysm. One aneurysm treated with 65/35 PLGA, 1 treated with 75/25 PLGA, and all 3 treated with 85/15 PLGA showed a neck remnant on angiography. There was a linear relationship between collagen levels and polymer degradation properties (r=-0.9513)., Conclusions: This preliminary animal study indicates that acceleration of aneurysm healing with the use of BPM is feasible. This concept can be applied to decrease and perhaps prevent aneurysmal recanalization after endovascular treatment of cerebral aneurysms.

Purpose: (a) To assess in swine long-term (12-month) histopathologic changes, particularly, those related to recanalization and angiotoxicity after endovascular delivery of ethylene vinyl alcohol copolymer (EVAC), and (b) to evaluate initial clinical experience in 18 patients with head and neck tumors and arteriovenous malformations., Materials and Methods: Embolization with EVAC was performed in one rete each in five swine. After 12 months, an angiogram was obtained, and the contralateral rete was also embolized (acute). Swine were sacrificed and the retia harvested for pathologic examination. In the clinical study, 18 patients with tumors (n = 14), facial arteriovenous malformations (n = 3), and vertebral arteriovenous fistula (n = 1) underwent therapeutic embolization. The technical aspects of EVAC embolization, percentage of occlusion, and clinical complications were evaluated., Results: Angiographic 12-month follow-up in swine revealed persistent occlusion of the embolized rete or retia. Histologic examination of the same rete showed vascular occlusion and moderate intraluminal foreign body giant cell reaction; the acutely embolized rete showed no endothelial denudation or angionecrosis. Clinical evaluation in patients revealed satisfactory penetration of lesion vasculature with EVAC when the microcatheter was advanced within 2 cm of a lesion or when percutaneous puncture was performed. There were two transient complications: one increase in a preexisting fifth nerve palsy and one increase in preexisting hemiparesis., Conclusion: EVAC is a promising liquid embolic material providing long-term occlusion of blood vessels.

Object: A new embolic agent, bioabsorbable polymeric material (BPM), was incorporated into Guglielmi detachable coils (GDCs) to improve long-term anatomical results in the endovascular treatment of intracranial aneurysms. The authors investigated whether BPM-mounted GDCs (BPM/GDCs) accelerated the histopathological transformation of unorganized blood clot into fibrous connective tissue in experimental aneurysms created in swine., Methods: Twenty-four experimental aneurysms were created in 12 swine. In each animal, one aneurysm was embolized using BPM/GDCs and the other aneurysm was embolized using standard GDCs. Comparative angiographic and histopathological data were analyzed at 2 weeks and 3 months postembolization. At 14 days postembolization, angiograms revealed evidence of neck neointima in six of eight aneurysms treated with BPM/GDCs compared with zero of eight aneurysms treated with standard GDCs (p < 0.05). At 3 months postembolization, angiograms demonstrated that four of four aneurysms treated with BPM/GDC were smaller and had neck neointima compared with zero of four aneurysms treated with standard GDCs (p = 0.05). At 14 days, histological analysis of aneurysm healing favored BPM/GDC treatment (all p < 0.05): the grade of cellular reaction around the coils was 3 +/- 0.9 (mean +/- standard deviation) for aneurysms treated using BPM/GDCs compared with 1.6 +/- 0.7 for aneurysms treated using GDCs alone; the percentage of unorganized thrombus was 16 +/- 12% compared with 37 +/- 15%, and the neck neointima thickness was 0.65 +/- 0.26 mm compared with 0.24 +/- 0.21 mm, respectively. At 3 months postembolization, only neck neointima thickness was significantly different (p < 0.05): 0.73 +/- 0.37 mm in aneurysms filled with BPM/GDCs compared with 0.16 +/- 0.14 mm in aneurysms filled with standard GDCs., Conclusions: In experimental aneurysms in swine, BPM/GDCs accelerated aneurysm fibrosis and intensified neck neointima formation without causing parent artery stenosis or thrombosis. The use of BPM/GDCs may improve long-term anatomical outcomes by decreasing aneurysm recanalization due to stronger in situ anchoring of coils by organized fibrous tissue. The retraction of this scar tissue may also decrease the size of aneurysms and clinical manifestations of mass effect observed in large or giant aneurysms.