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Background and Purpose— Stroke is a leading cause of disability, cognitive impairment, and death in the United States and accounts for 1.7% of national health expenditures. Because the population is aging and the risk of stroke more than doubles for each successive decade after the age of 55 years, these costs are anticipated to rise dramatically. The objective of this report was to project future annual costs of care for stroke from 2012 to 2030 and discuss potential cost reduction strategies. Methods and Results— The American Heart Association/American Stroke Association developed methodology to project the future costs of stroke-related care. Estimates excluded costs associated with other cardiovascular diseases (hypertension, coronary heart disease, and congestive heart failure). By 2030, 3.88% of the US population >18 years of age is projected to have had a stroke. Between 2012 and 2030, real (2010$) total direct annual stroke-related medical costs are expected to increase from $71.55 billion to $184.13 billion. Real indirect annual costs (attributable to lost productivity) are projected to rise from $33.65 billion to $56.54 billion over the same period. Overall, total annual costs of stroke are projected to increase to $240.67 billion by 2030, an increase of 129%. Conclusions— These projections suggest that the annual costs of stroke will increase substantially over the next 2 decades. Greater emphasis on implementing effective preventive, acute care, and rehabilitative services will have both medical and societal benefits. (Stroke. 2013;44:2361-2375.)

Despite the global impact and advances in understanding the pathophysiology of cerebrovascular diseases, the term “stroke” is not consistently defined in clinical practice, in clinical research, or in assessments of the public health. The classic definition is mainly clinical and does not account for advances in science and technology. The Stroke Council of the American Heart Association/American Stroke Association convened a writing group to develop an expert consensus document for an updated definition of stroke for the 21st century. Central nervous system infarction is defined as brain, spinal cord, or retinal cell death attributable to ischemia, based on neuropathological, neuroimaging, and/or clinical evidence of permanent injury. Central nervous system infarction occurs over a clinical spectrum: Ischemic stroke specifically refers to central nervous system infarction accompanied by overt symptoms, while silent infarction by definition causes no known symptoms. Stroke also broadly includes intracerebral hemorrhage and subarachnoid hemorrhage. The updated definition of stroke incorporates clinical and tissue criteria and can be incorporated into practice, research, and assessments of the public health.

Introduction/Purpose To achieve aneurysm occlusion, flow diverters (FDs) must be accurately sized to maximize coverage over the neck and induce thrombosis. Catheterization for diagnostic angiography can cause vasospasm that may affect vessel measurements. This study evaluates impacts of intra-arterial infusion of a calcium channel blocker (CCB) on angiographic measurements in patients treated with FDs to determine effects on final diameter of the FD and subsequent occlusion. Materials and methods Pre-treatment measurements were recorded for diameter of the distal and proximal landing zones and maximum and minimum diameters between these segments. Post-treatment measurements of the stent following deployment were recorded at these locations. When CCB was infused, post-infusion pre-treatment measurements were recorded. Rates of occlusion were noted for all patients. T-tests were performed to assess for differences in pre- and post-treatment measurements and rates of occlusion between groups with and without CCB infusion. Results Twenty-eight FDs were deployed to treat 25 aneurysms in 24 patients. CCB infusion was performed prior to deployment of 12 (42.9%) devices. No significant difference was noted between groups for pre- and post-treatment measurement changes. Confirmed aneurysm occlusion was more likely to occur in the CCB infusion group (88.9% vs. 36.4%, p = 0.009). Conclusion Optimization of device sizing is important to increase FD density over the aneurysm neck and promote thrombosis. To improve measurement accuracy, CCB infusion can reduce effects of mild vasospasm. Subsequent aneurysm occlusion was more likely to occur following FD treatment when device size selection was based on measurements performed following CCB infusion.

OBJECT Large arteriovenous malformations (AVMs) remain difficult to treat, and ideal treatment parameters for volume-staged stereotactic radiosurgery (VS-SRS) are still unknown. The object of this study was to compare VS-SRS treatment outcomes for AVMs larger than 10 ml during 2 eras; Era 1 was 1992-March 2004, and Era 2 was May 2004–2008. In Era 2 the authors prospectively decreased the AVM treatment volume, increased the radiation dose per stage, and shortened the interval between stages. METHODS All cases of VS-SRS treatment for AVM performed at a single institution were retrospectively reviewed. RESULTS Of 69 patients intended for VS-SRS, 63 completed all stages. The median patient age at the first stage of VS-SRS was 34 years (range 9–68 years). The median modified radiosurgery-based AVM score (mRBAS), total AVM volume, and volume per stage in Era 1 versus Era 2 were 3.6 versus 2.7, 27.3 ml versus 18.9 ml, and 15.0 ml versus 6.8 ml, respectively. The median radiation dose per stage was 15.5 Gy in Era 1 and 17.0 Gy in Era 2, and the median clinical follow-up period in living patients was 8.6 years in Era 1 and 4.8 years in Era 2. All outcomes were measured from the first stage of VS-SRS. Near or complete obliteration was more common in Era 2 (log-rank test, p = 0.0003), with 3- and 5-year probabilities of 5% and 21%, respectively, in Era 1 compared with 24% and 68% in Era 2. Radiosurgical dose, AVM volume per stage, total AVM volume, era, compact nidus, Spetzler-Martin grade, and mRBAS were significantly associated with near or complete obliteration on univariate analysis. Dose was a strong predictor of response (Cox proportional hazards, p < 0.001, HR 6.99), with 3- and 5-year probabilities of near or complete obliteration of 5% and 16%, respectively, at a dose < 17 Gy versus 23% and 74% at a dose ≥ 17 Gy. Dose per stage, compact nidus, and total AVM volume remained significant predictors of near or complete obliteration on multivariate analysis. Seventeen patients (25%) had salvage surgery, SRS, and/or embolization. Allowing for salvage therapy, the probability of cure was more common in Era 2 (log-rank test, p = 0.0007) with 5-year probabilities of 0% in Era 1 versus 41% in Era 2. The strong trend toward improved cure in Era 2 persisted on multivariate analysis even when considering mRBAS (Cox proportional hazards, p = 0.055, HR 4.01, 95% CI 0.97–16.59). The complication rate was 29% in Era 1 compared with 13% in Era 2 (Cox proportional hazards, not significant). CONCLUSIONS VS-SRS is an option to obliterate or downsize large AVMs. Decreasing the AVM treatment volume per stage to ≤ 8 ml with this technique allowed a higher dose per fraction and decreased time to response, as well as improved rates of near obliteration and cure without increasing complications. Reducing the volume of these very large lesions can facilitate a surgical approach for cure.

Background and Purpose— Current US guideline statements regarding primary and secondary cardiovascular risk prediction and prevention use absolute risk estimates to identify patients who are at high risk for vascular disease events and who may benefit from specific preventive interventions. These guidelines do not explicitly include patients with stroke, however. This statement provides an overview of evidence and arguments supporting (1) the inclusion of patients with stroke, and atherosclerotic stroke in particular, among those considered to be at high absolute risk of cardiovascular disease and (2) the inclusion of stroke as part of the outcome cluster in risk prediction instruments for vascular disease. Methods and Results— Writing group members were nominated by the committee co-chairs on the basis of their previous work in relevant topic areas and were approved by the American Heart Association (AHA) Stroke Council's Scientific Statements Oversight Committee and the AHA Manuscript Oversight Committee. The writers used systematic literature reviews (covering the period from January 1980 to March 2010), reference to previously published guidelines, personal files, and expert opinion to summarize existing evidence, indicate gaps in current knowledge, and, when appropriate, formulate recommendations using standard AHA criteria. All members of the writing group had the opportunity to comment on the recommendations and approved the final version of this document. The guideline underwent extensive AHA internal peer review, Stroke Council leadership review, and Scientific Statements Oversight Committee review before consideration and approval by the AHA Science Advisory and Coordinating Committee. There are several reasons to consider stroke patients, and particularly patients with atherosclerotic stroke, among the groups of patients at high absolute risk of coronary and cardiovascular disease. First, evidence suggests that patients with ischemic stroke are at high absolute risk of fatal or nonfatal myocardial infarction or sudden death, approximating the ≥20% absolute risk over 10 years that has been used in some guidelines to define coronary risk equivalents. Second, inclusion of atherosclerotic stroke would be consistent with the reasons for inclusion of diabetes mellitus, peripheral vascular disease, chronic kidney disease, and other atherosclerotic disorders despite an absence of uniformity of evidence of elevated risks across all populations or patients. Third, the large-vessel atherosclerotic subtype of ischemic stroke shares pathophysiological mechanisms with these other disorders. Inclusion of stroke as a high-risk condition could result in an expansion of ≈10% in the number of patients considered to be at high risk. However, because of the heterogeneity of stroke, it is uncertain whether other stroke subtypes, including hemorrhagic and nonatherosclerotic ischemic stroke subtypes, should be considered to be at the same high levels of risk, and further research is needed. Inclusion of stroke with myocardial infarction and sudden death among the outcome cluster of cardiovascular events in risk prediction instruments, moreover, is appropriate because of the impact of stroke on morbidity and mortality, the similarity of many approaches to prevention of stroke and these other forms of vascular disease, and the importance of stroke relative to coronary disease in some subpopulations. Non-US guidelines often include stroke patients among others at high cardiovascular risk and include stroke as a relevant outcome along with cardiac end points. Conclusions— Patients with atherosclerotic stroke should be included among those deemed to be at high risk (≥20% over 10 years) of further atherosclerotic coronary events. Inclusion of nonatherosclerotic stroke subtypes remains less certain. For the purposes of primary prevention, ischemic stroke should be included among cardiovascular disease outcomes in absolute risk assessment algorithms. The inclusion of atherosclerotic ischemic stroke as a high-risk condition and the inclusion of ischemic stroke more broadly as an outcome will likely have important implications for prevention of cardiovascular disease, because the number of patients considered to be at high risk would grow substantially.

Segmental arterial mediolysis (SAM) is a rare, non-inflammatory, non-atherosclerotic vasculopathy typically affecting the abdominal arteries although it may also affect the great vessels and cerebral vasculature. Diseased vessels manifest with aneurysms and/or dissections, often presenting clinically with catastrophic thromboembolic injury and less frequently with subarachnoid hemorrhage (SAH). The etiology of SAM remains indeterminate although there is evidence it may be an endogenous pathological response to vasospasm. The SAM literature is reviewed and a case of SAH related to a ruptured dissecting-type vertebral artery aneurysm is described. In addition to furthering awareness of SAM, this unique case offers insight into the acute phase of the disease and the potential role of vasospastic induction.

Purpose— The aim of this guideline is to present current and comprehensive recommendations for the diagnosis and treatment of aneurysmal subarachnoid hemorrhage (aSAH). Methods— A formal literature search of MEDLINE (November 1, 2006, through May 1, 2010) was performed. Data were synthesized with the use of evidence tables. Writing group members met by teleconference to discuss data-derived recommendations. The American Heart Association Stroke Council's Levels of Evidence grading algorithm was used to grade each recommendation. The guideline draft was reviewed by 7 expert peer reviewers and by the members of the Stroke Council Leadership and Manuscript Oversight Committees. It is intended that this guideline be fully updated every 3 years. Results— Evidence-based guidelines are presented for the care of patients presenting with aSAH. The focus of the guideline was subdivided into incidence, risk factors, prevention, natural history and outcome, diagnosis, prevention of rebleeding, surgical and endovascular repair of ruptured aneurysms, systems of care, anesthetic management during repair, management of vasospasm and delayed cerebral ischemia, management of hydrocephalus, management of seizures, and management of medical complications. Conclusions— aSAH is a serious medical condition in which outcome can be dramatically impacted by early, aggressive, expert care. The guidelines offer a framework for goal-directed treatment of the patient with aSAH.

Object Spinal dural arteriovenous fistulas (SDAVFs) cause myelopathy through arterialization of the perimedullary venous plexus and venous congestion of the spinal cord. The authors hypothesized that the craniocaudal extent of engorgement of intrathecal draining veins between the fistula site and the point of drainage out of the thecal sac correlates with the degree of myelopathy. Methods A retrospective review of the authors' institution's radiology databases identified 31 patients with SDAVFs who had undergone digital subtraction angiography (DSA) and MRI examinations of the spine. The authors counted the number of vertebral body levels of spinal cord enhancement and intrathecal vessel enhancement on T1-weighted postcontrast MRI studies. They also counted the number of levels of cord hyperintensity and intrathecal flow voids on T2-weighted MRI studies. On DSA, the authors identified the number of vertebral body levels of dilated intrathecal draining veins and outflow points from intrathecal veins to epidural veins. Functional status of the patients at the time of diagnosis was assessed using the Aminoff-Logue scale (ALS). Results Enlargement of the intrathecal draining veins averaged 10 ± 7.7 spinal levels on DSA. Patients with enlarged draining veins extending 10 or more spinal levels on DSA had worse ALS scores (mean gait 3.4, mean micturition 1.5) than patients with draining veins extending fewer than 10 levels (mean gait 1.8, mean micturition 0.6; p = 0.009 and 0.02, respectively). The number of vertebral body levels of enlarged draining veins correlated with the ALS score (gait r = 0.42, p = 0.009; and micturition r = 0.55, p = 0.0006). More extensive enlarged draining veins were associated with more spinal cord T2 hyperintensity, T2 intrathecal flow voids, and T1 vessel enhancement but not cord enhancement. Conclusions The craniocaudal extent of enlarged intrathecal veins draining SDAVF correlates with patient functional status, providing further insight into the pathophysiology of venous hypertensive myelopathy.

Background and Purpose— We investigated whether brain arteriovenous malformation silent intralesional microhemorrhage, that is, asymptomatic bleeding in the nidal compartment, might serve as a marker for increased risk of symptomatic intracranial hemorrhage (ICH). We evaluated 2 markers to assess the occurrence of silent intralesional microhemorrhage: neuroradiological assessment of evidence of old hemorrhage—imaging evidence of bleeding before the outcome events–and hemosiderin positivity in hematoxylin and eosin-stained paraffin block sections. Methods— We identified cases from our brain arteriovenous malformation database with recorded neuroradiological data or available surgical paraffin blocks. Using 2 end points, index ICH or new ICH after diagnosis (censored at treatment, loss to follow-up, or death), we performed logistic or Cox regression to assess evidence of old hemorrhage and hemosiderin positivity adjusting for age, sex, deep-only venous drainage, maximal brain arteriovenous malformation size, deep location, and associated arterial aneurysms. Results— Evidence of old hemorrhage was present in 6.5% (n=975) of patients and highly predictive of index ICH ( P P =0.010). Hemosiderin positivity was found in 36.2% (29.6% in unruptured; 47.8% in ruptured; P =0.04) and associated with index ICH in univariate (OR, 2.18; 95% CI, 1.03–4.61; P =0.042; n=127) and multivariable models (OR, 3.64; 95% CI, 1.11–12.00; P =0.034; n=79). Conclusions— The prevalence of silent intralesional microhemorrhage is high and there is evidence for an association with both index and subsequent ICH. Further development of means to detect silent intralesional microhemorrhage during brain arteriovenous malformation evaluation may present an opportunity to improve risk stratification, especially for unruptured brain arteriovenous malformations.

The limitations of intravenous thrombolysis therapy have paved the way for the development of novel endovascular technologies for use in the setting of acute stroke. These technologies range from direct intraarterial thrombolysis to various thrombus disruption or retrieval devices to angioplasty and stenting. The tools in the armamentarium of the neuroendovascular interventionalist enable fast, effective revascularization to be offered to a wider population of patients that may otherwise have few therapeutic options available to them. In this paper, we review the current state-of-the-art in neuroendovascular intervention for acute ischemic stroke. Particular emphasis is placed on delineating the indications and outcomes for use of these various technologies.

BACKGROUND AND PURPOSE: Children with brain aneurysms may be at higher risk than adults to develop new or enlarging aneurysms in a relatively short time. We sought to identify comorbidities and angiographic features in children that predict new aneurysm formation or enlargement of untreated aneurysms. MATERIALS AND METHODS: Retrospective analysis of the University of California–San Francisco Pediatric Aneurysm Cohort data base including medical records and imaging studies was performed. RESULTS: Of 83 patients harboring 114 intracranial aneurysms not associated with brain arteriovenous malformations or intracranial arteriovenous fistulas, 9 (8.4%) developed new or enlarging brain aneurysms an average of 4.2 years after initial presentation. Comorbidities that may be related to aneurysm formation were significantly higher in patients who developed new aneurysms (89%) as opposed to patients who did not develop new or enlarging aneurysms (41%; RR, 9.5; 95% CI, 1.9%–48%; P = .0099). Patients with multiple aneurysms at initial presentation were more likely than patients with a single aneurysm at presentation to develop a new or enlarging aneurysm (RR, 6.2; 95% CI, 2.1%–185; P = .0058). Patients who initially presented with at least 1 fusiform aneurysm were more likely to develop a new or enlarging aneurysm than patients who did not present with a fusiform aneurysm (RR, 22; 95% CI, 3.6%–68%; P = .00050). Index aneurysm treatment with parent artery occlusion also was associated with higher risk of new aneurysm formation (RR, 4.2; 95% CI, 1.3%–13%; P = .024). New aneurysms did not necessarily arise near index aneurysms. The only fatality in the series was due to subarachnoid hemorrhage from a new posterior circulation aneurysm arising 20 months after index anterior circulation aneurysm treatment in an immunosuppressed patient. CONCLUSIONS: Patients who presented with a fusiform aneurysm had a significantly greater incidence of developing a new aneurysm or enlargement of an index aneurysm than did those who presented with a saccular aneurysm. In our patient cohort, 8 of the 9 children who eventually developed new or enlarging brain aneurysms initially presented with fusiform aneurysm morphology. Other comorbidities or multiple aneurysms were also common in these patients at initial presentation.

Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) is the established treatment for acute ischemic stroke patients presenting within 4.5 h of stroke onset based on the results of the National Institute of Neurological Disorders and Stroke Study Group trial and European Cooperative Acute Stroke Study III. In a significant number of patients, however, intravenous thrombolysis with rt-PA remains ineffective, with lower rates of recanalization, especially for proximal occlusions and a large thrombus burden. Newer thrombolytic agents, such as reteplase, tenecteplase or desmoteplase, offer pharmacokinetic and hemodynamic advantages over rt-PA and have been, or are currently being, tested for safety and efficacy in clinical trials. Agents such as direct fibrinolytics that do not depend on the availability of plasminogen are also being studied in ongoing trials. Endovascular revascularization is an evolving treatment option enabling mechanical clot disruption or extraction in combination with local directed pharmacological thrombolysis. Several new endovascular devices have been successfully tested for safety in acute ischemic stroke patients and are now being tested for efficacy in larger clinical trials. Continued innovation and refinement of endovascular technology and techniques, including combination therapy such as bridging therapy and the use of stent-like devices, is expected to increase technical success and improve overall efficacy and time to recanalization with minimal procedure-related morbidity in the treatment of acute ischemic stroke.

Background and Purpose— Intracranial cerebral atherosclerosis causes ischemic stroke in a significant number of patients. Technological advances over the past 10 years have enabled endovascular treatment of intracranial atherosclerotic stenosis. The number of patients treated with angioplasty or stent-assisted angioplasty for this condition is increasing. Given the lack of universally accepted definitions, the goal of this document is to provide consensus recommendations for reporting standards, terminology, and written definitions when reporting clinical and radiological evaluation, technique, and outcome of endovascular treatment using angioplasty or stent-assisted angioplasty for stenotic and occlusive intracranial atherosclerosis. Summary of Report— This article was written under the auspices of Joint Writing Group of the Technology Assessment Committee, Society of NeuroInterventional Surgery, Society of Interventional Radiology; Joint Section on Cerebrovascular Neurosurgery of the American Association of Neurological Surgeons and Congress of Neurological Surgeons; and the Section of Stroke and Interventional Neurology of the American Academy of Neurology. A computerized search of the National Library of Medicine database of literature (PubMed) from January 1997 to December 2007 was conducted with the goal to identify published endovascular cerebrovascular interventional data in stenotic intracranial atherosclerosis that could be used as benchmarks for quality assessment. We sought to identify those risk adjustment variables that affect the likelihood of success and complications. This document offers the rationale for different clinical and technical considerations that may be important during the design of clinical trials for endovascular treatment of intracranial stenotic and occlusive atherosclerosis. Included in this guidance document are suggestions for uniform reporting standards for such trials. These definitions and standards are primarily intended for research purposes; however, they should also be helpful in clinical practice and applicable to all publications. Conclusion— In summary, the definitions proposed represent recommendations for constructing useful research data sets. The intent is to facilitate production of scientifically rigorous results capable of reliable comparisons between and among similar studies. In some cases, the definitions contained here are recommended by consensus of a panel of experts in this writing group for consistency in reporting and publication. These definitions should allow different groups to publish results that are directly comparable.

BACKGROUND AND PURPOSE: The natural history of PMAVFs, also known as type IV spinal cord AVFs, is incompletely understood. Both open surgical and endovascular approaches have been described as treatment modalities for this disease. The goal of this study was to evaluate the long-term outcome of patients with PMAVFs treated at a single tertiary care institution. MATERIALS AND METHODS: We conducted a retrospective study of 32 patients with PMAVFs, evaluated between 1983 and 2009. Data were gathered by reviewing outpatient clinic notes, operative and radiologic reports, and spinal angiograms. The PMAVFs were categorized into 1 of 3 types based on the angiographic imaging criteria. Pretreatment and posttreatment ambulation and micturition symptoms were quantified by using the ALS. RESULTS: Thirty patients underwent corrective procedures, 4 by embolization alone, 11 by surgery alone, and 15 with a combination of the 2. Twenty-eight patients underwent follow-up spinal angiography, with residual shunt noted in 6 patients. The mean follow-up period was 54 months (range, 1–228 months). Analysis of the ALS scores revealed that treatment of PMAVFs, independent of technique, resulted in significant improvement in ambulation but inconsistent changes in micturition. In addition, residual fistula at the time of the follow-up angiogram was associated with worsened neurologic status or lack of improvement. Outcome analysis based on fistula type showed dramatic improvement in ALS ambulation scores (62%) for type 3 fistulas, compared with types 1 and 2 (26% and 27%, respectively). CONCLUSIONS: Significant improvement in ambulation but in not micturition was observed following treatment. Residual fistula on follow-up angiography was associated with progressive worsening or lack of improvement in neurologic function. Patients with type 3 fistulas were shown to benefit most from treatment, with marked improvement in posttreatment ambulation scores. As endovascular and surgical techniques continue to evolve, further studies are warranted.

BACKGROUND AND PURPOSE: CV following aneurysmal SAH is a significant cause of morbidity and mortality. We review our experiences using PTA and IA verapamil infusion for treating medically refractory cases. MATERIALS AND METHODS: We performed a retrospective review of patients with SAH admitted from July 2003 to January 2008. RESULTS: Of 546 patients admitted within 72 hours of symptom onset, 231 patients (42%) developed symptomatic CV and 189 patients (35%) required endovascular therapy. A total of 346 endovascular sessions were performed consisting of 1 single angioplasty, 286 IA verapamil infusions, and 59 combined treatments. PTA was performed on 151 vessel segments, and IA verapamil was infused in 720 vessel segments. IA verapamil doses ranged from 2.0 to 30.0 mg per vessel segment and from 3.0 to 55.0 mg per treatment session. Repeat treatments were necessary in 102 patients (54%) for persistent, recurrent, or worsening CV. There were 6 treatment-related complications, of which 2 resulted in clinical worsening. No deaths were attributable to endovascular therapy. At follow-up, 115 patients (61%) had a good outcome and 55 patients (29%) had a poor outcome. Sixteen patients died from causes related to SAH, while 3 died from other medical complications. CONCLUSIONS: Endovascular treatments are an integral part of managing patients with medically refractory CV. In our experience, PTA and IA verapamil are safe, with a low complication rate, but further studies are required to determine appropriate patient selection and treatment efficacy.

Stroke is the third leading cause of death in the USA, Canada, Europe, and Japan. According to the American Heart Association and the American Stroke Association, there are now 750,000 new strokes that occur each year, resulting in 200,000 deaths, or 1 of every 16 deaths, per year in the USA alone. Endovascular therapy for patients with acute ischemic stroke is an area of intense investigation. The American Stroke Association has given a qualified endorsement of intraarterial thrombolysis in selected patients. Intraarterial thrombolysis has been studied in two randomized trials and numerous case series. Although two devices have been granted FDA approval with an indication for mechanical stroke thrombectomy, none of these thrombectomy devices has demonstrated efficacy for the improvement of patient outcomes. The purpose of the present document is to define what constitutes adequate training to perform neuroendovascular procedures in patients with acute ischemic stroke and what performance standards should be adopted to assess outcomes. These guidelines have been written and approved by multiple neuroscience societies which historically have been directly involved in the medical, surgical and endovascular care of patients with acute stroke. The participating member organizations of the Neurovascular Coalition involved in the writing and endorsement of this document are the Society of NeuroInterventional Surgery, the American Academy of Neurology, the American Association of Neurological Surgeons/Congress of Neurological Surgeons Cerebrovascular Section, and the Society of Vascular & Interventional Neurology.

Ischemic stroke remains one of the leading cause of adult death and disability in the United States. Reperfusion of the occluded vessel is the standard of care in the setting of acute ischemic stroke according to established guidelines. Since the introduction of intravenous (IV) recombinant tissue plasminogen activator (rt-PA) in the late 1990s, significant advances have been made in methods to deliver thrombolytic agents and in devices for mechanical recanalization of occluded vessels. Furthermore, improvements in patient selection contribute to achievement of good clinical outcomes after endovascular therapy. This article summarizes findings from recent clinical trials and presents evidence-based guidelines for endovascular interventions in the treatment of ischemic stroke.

BACKGROUND AND PURPOSE: Pediatric aneurysms are rare and, thus, relatively poorly understood as compared to those in adults. Our aim was to characterize the clinical, imaging, treatment, and outcome data of patients younger than 19 years diagnosed with intracranial aneurysms at a tertiary care institution. MATERIALS AND METHODS: We performed a retrospective medical record review of pediatric patients examined at our university hospital between 1981 and 2008. RESULTS: We evaluated 77 patients (mean age, 12 years; 40 female, 37 male) with 103 intracranial aneurysms. Patients presented with headache (45%), cranial neuropathies (16%), nausea/vomiting (15%), vision changes (13%), trauma (13%), seizure (4%), or sensory changes (3%). Subarachnoid hemorrhage occurred in 25 patients. Thirty-one fusiform aneurysms occurred in 25 patients. Forty-seven saccular aneurysms occurred in 35 patients. Twelve infectious aneurysms occurred in 6 patients. Fifteen traumatic aneurysms occurred in 12 patients. Fifty-nine patients underwent treatment of their aneurysms; 18 patients’ conditions were managed conservatively. Nineteen patients underwent primary endovascular coiling, 1 patient had endovascular stent-assisted coiling, 11 patients underwent endovascular parent artery occlusion, 19 patients underwent surgical clipping, and 10 patients had aneurysms trapped and bypassed. Mortality was 1.3%. Morbidity included 8% infarction and 4% new-onset seizures. Six patients developed new aneurysms or had enlargement of untreated aneurysms. CONCLUSIONS: In our experience, intracranial aneurysms of childhood show a female predilection and predominantly saccular morphology. In neurovascular centers where microneurosurgical and endovascular options are available, most children with intracranial aneurysms can be successfully treated with low morbidity and mortality. Fusiform aneurysms require a combined microneurosurgical and endovascular approach more often than saccular aneurysms. The development of new aneurysms in pediatric patients during limited follow-up warrants further investigation.

MRI in catheterized patients is considered unsafe due to the potential for focal heating. This concern arises from the continuous metallic braid that is incorporated into catheters to provide their desired physical properties. The potential for catheter heating during MR scanning was assessed in an in vitro model simulating a patient undergoing a neurovascular procedure in which MR scans of the brain will be performed. Heating adjacent to endovascular devices was assessed with fluoroptic temperature probes in a polyacrylamide gel. The effect of variable immersion lengths, lateral and longitudinal offsets, position along the endovascular device, physical MR system, and specific absorption rate (SAR) level were studied to determine their effect on catheter heating. A rapid temperature rise was evident next to endovascular devices during MR scanning and varied moderately with immersed length, position within the bore, measurement point on the device, and MR system used. Peak heating rates were less than 1°C/min with maximal SAR exposure and anatomically realistic geometries. Heating scaled linearly with SAR and SAR values below 0.2 W/kg produced negligible heating near catheters. For the evaluated application, substantial SAR restrictions, coupled with limited imaging durations, are proposed as sufficient to permit MRI without concern for thermal injury. Magn Reson Med 61:45–53, 2009. © 2008 Wiley-Liss, Inc.

The deposition of intralumenal thrombus in intracranial aneurysms adds a risk of thrombo-embolism over and above that posed by mass-effect and rupture. In addition to biochemical factors, hemodynamic factors that are governed by lumenal geometry and blood flow rates likely play an important role in the thrombus formation and deposition process. In this study, patient-specific computational fluid dynamics (CFD) models of blood flow were constructed from MRA data for three patients who had fusiform basilar aneurysms that were thrombus-free and then proceeded to develop intra-lumenal thrombus. In order to determine whether features of the flow fields could suggest which regions had an elevated potential for thrombus deposition, the flow was modeled in the baseline, thrombus-free geometries. Pulsatile flow simulations were carried out using patient-specific inlet flow conditions measured with MR velocimetry. Newtonian and non-Newtonian blood behavior was considered. A strong similarity was found between the intra-aneurysmal regions with CFD-predicted slow, recirculating flows and the regions of thrombus deposition observed in vivo in the follow-up MR studies. In two cases with larger aneurysms, the agreement between the low velocity zones and clotted off regions improved when non-Newtonian blood behavior was taken into account. A similarity was also found between the calculated low shear stress regions and the regions that were later observed to clot.

Background and Purpose— Intraprocedural rupture (IPR) is a well known complication of intracranial aneurysm treatment. Risks and predictors of IPR and its impact on outcome have not been clearly established. Methods— Potential predictors of IPR were evaluated in patients treated in the Cerebral Aneurysm Rerupture After Treatment (CARAT) study using multivariate logistic regression with stepwise elimination stratified by treatment modality. Periprocedural death or disability was defined as death or a change of ≥2 points on the Modified Rankin Scale at discharge compared to before treatment. Results— IPR occurred in 14.6% of 1010 patients (299 coiled, 711 clipped): 19% with clipping and 5% with coiling ( P P =0.001); among those coiled, 63% with IPR had periprocedural death or disability compared to 15% without IPR ( P Conclusions— IPR was common in patients undergoing treatment of ruptured aneurysms, particularly with surgical clipping. The frequency of IPR with new disability was similar in the surgical and endovascular treatment groups. Coronary artery disease, hyperlipidemia, race, COPD, and lower Hunt and Hess Grade were associated with greater risk of IPR, which may reflect differences in vessel fragility but requires further confirmation.

Background and Purpose— Vasospasm after aneurysmal subarachnoid hemorrhage (SAH) remains a leading cause of death and disability after aneurysm rupture. Decreased availability of nitric oxide (NO) may be crucial in its pathogenesis. We hypothesized that endothelial NO synthase ( eNOS ) polymorphisms may determine susceptibility to vasospasm in SAH patients. Methods— We conducted a prospective cohort study of SAH patients and determined vasospasm by cerebral angiography. We genotyped 3 eNOS polymorphisms: an intron 4 variable-number tandem-repeat, a promoter single-nucleotide polymorphism (−786T→C SNP), and a coding SNP in exon 7 (894G→T encoding E298D). Using multivariable logistic regression, we quantified the association of eNOS polymorphisms in patients with vasospasm confirmed by cerebral angiography. Results— For the eNOS promoter −786T→C SNP, the presence of the CC genotype compared with any T genotype ( CT or TT ) was associated with increased odds of vasospasm (odds ratio=2.97, 95% CI=1.32 to 6.67, P =0.008). No association with vasospasm was observed for the eNOS 894G→T or variable-number tandem-repeat polymorphisms. Conclusions— These findings suggest that genetic variation influencing NO regulation contributes to the risk of angiographic vasospasm in patients with SAH. The specific role of the promoter SNP (−786T→C) may determine the effect of NO regulated by this pathway, distinct from other known eNOS polymorphisms.

Background and Purpose— Endovascular mechanical thrombectomy may be used during acute ischemic stroke due to large vessel intracranial occlusion. First-generation MERCI devices achieved recanalization rates of 48% and, when coupled with intraarterial thrombolytic drugs, recanalization rates of 60% have been reported. Enhancements in embolectomy device design may improve recanalization rates. Methods— Multi MERCI was an international, multicenter, prospective, single-arm trial of thrombectomy in patients with large vessel stroke treated within 8 hours of symptom onset. Patients with persistent large vessel occlusion after IV tissue plasminogen activator treatment were included. Once the newer generation (L5 Retriever) device became available, investigators were instructed to use the L5 Retriever to open vessels and could subsequently use older generation devices and/or intraarterial tissue plasminogen activator. Primary outcome was recanalization of the target vessel. Results— One hundred sixty-four patients received thrombectomy and 131 were initially treated with the L5 Retriever. Mean age±SD was 68±16 years, and baseline median (interquartile range) National Institutes of Health Stroke Scale score was 19 (15 to 23). Treatment with the L5 Retriever resulted in successful recanalization in 75 of 131 (57.3%) treatable vessels and in 91 of 131 (69.5%) after adjunctive therapy (intraarterial tissue plasminogen activator, mechanical). Overall, favorable clinical outcomes (modified Rankin Scale 0 to 2) occurred in 36% and mortality was 34%; both outcomes were significantly related to vascular recanalization. Symptomatic intracerebral hemorrhage occurred in 16 patients (9.8%); 4 (2.4%) of these were parenchymal hematoma type II. Clinically significant procedural complications occurred in 9 (5.5%) patients. Conclusions— Higher rates of recanalization were associated with a newer generation thrombectomy device compared with first-generation devices, but these differences did not achieve statistical significance. Mortality trended lower and the proportion of good clinical outcomes trended higher, consistent with better recanalization.

Background: The purpose of this study was to compare simple visual grading of perfusion CT (PCT) maps to a more quantitative, threshold-based interpretation of PCT parameters in the characterization of presence and severity of vasospasm. Methods: Thirty-three patients with acute subarachnoid hemorrhage were enrolled in a prospective study and underwent a total of 40 paired PCT and digital subtraction angiography (DSA) examinations. A neuroradiologist and a neurologist reviewed the PCT mean transit time (MTT), cerebral blood flow (CBF), and cerebral blood volume maps independently; they evaluated five anatomical regions (frontal, temporal, parietal, occipital/thalami, and basal ganglia/insula) and graded them for abnormality (0 if normal, 1 if abnormal in Results: MTT (R2 = 0.939) and CBF (R2 = 0.907) scores correlated best with DSA scores (p < 0.001). MTT scoring had a sensitivity of 92% and a specificity of 86% compared to DSA; CBF scoring had a sensitivity of 75% and a specificity of 95%. The interobserver agreement between neuroradiologist and neurologist was found to have kappa = 0.789 for MTT and 0.658 for CBF. Conclusion: We propose a user-friendly visual grading system for PCT maps in patients with suspected vasospasm. This visual approach compares favorably to the results of DSA. Sensitive MTT maps should be used for screening, and specific CBF maps for confirmation of vasospasm.

OBJECTIVE: The goals of this study were to characterize the clinical, radiological, treatment, and outcome data associated with patients diagnosed with spinal dural arteriovenous fistulae (SDAVFs) at a single tertiary care institution over a 20-year period. METHODS: A 20-year retrospective study was undertaken at our university hospital. Patients with mixed intracranial and spinal dural fistulas were excluded. A literature review of articles reporting endovascular or combined treatment of SDAVFs was performed. RESULTS: Between 1984 and 2005, our institution diagnosed and treated 63 patients (mean age, 62; 13 women, 50 men) with SDAVFs. The presenting symptoms were consistent with progressive myelopathy, and included lower extremity weakness (33 patients, 52%), parasthesias (19 patients, 30%), back pain (15 patients, 24%), and urinary symptoms (four patients, 6%). Thirty-nine patients underwent an initial endovascular embolization with 27 requiring only this first procedure for complete obliteration. On the other hand, 24 patients underwent an initial surgical procedure with 20 of them treated successfully with a single operation. Endovascular patients presented at mean age 62.3 years (standard deviation [SD], 10.6), were hospitalized for an average of 3.1 days (SD, 2.6), and were followed-up for 39 months (SD, 33). Surgical patients presented at mean age of 65.8 years (SD, 10.3), were hospitalized for 9.8 days (SD, 2.7), and were followed-up for 35 months (SD, 44). A significant improvement in Aminoff-Logue scores was found in both the endovascular and surgery groups (gait, P < 0.001; micturition, P = 0.005). The endovascular group had reduced hospitalization (P = 0.0001). No differences were found in the magnitude of clinical response to treatment. CONCLUSION: SDAVFs most commonly present with progressive myelopathy, yet often remain undiagnosed for months or years. Endovascular therapies and surgical therapies are associated with significantly improved symptoms once the definitive diagnosis of SDAVF is made.

Purpose: To evaluate the accuracy of multidetector-row CT angiography (CTA) for the diagnosis of large-vessel vasospasm following subarachnoid hemorrhage by comparison to digital subtraction angiography (DSA). Methods: Thirty-three patients with acute subarachnoid hemorrhage were enrolled in a prospective study and underwent a total of 40 CTA and DSA examinations within 24 h of each other. Two neuroradiologists reviewed the CTA examinations independently. A third neuroradiologist blinded to the CTA results reviewed the DSA examinations. In each patient, for both techniques, 23 arterial segments were evaluated for their degree of narrowing; the reviewers were asked to attribute every narrowing to ‘vasospasm’ or ‘hypoplasia’. Agreement between CTA and DSA for the degree of narrowing, and agreement between the two CTA readers, were calculated using weighted ĸ-coefficients. Sensitivity, specificity, accuracy, positive and negative predictive value (NPV) of CTA to detect large-vessel vasospasm were calculated considering DSA as the gold standard. Results: Substantial correlation (ĸ = 0.638) was found between CTA and DSA for the detection of arterial narrowing. Interobserver agreement between the two CTA reviewers for the degree of luminal narrowing was substantial (ĸ = 0.712).CTA was 87% accurate for the diagnosis of large-vessel vasospasm; the NPV of CTA was 95%. CTA was more accurate, and interobserver agreement higher, for the proximal arterial segments (basilar and vertebral arteries) than for the distal ones (P2 segments). Using CTA as a screening modality, 83% of unnecessary DSA would have been avoided. Conclusion: Compared to the gold standard of DSA, CTA is accurate for the detection of large-vessel vasospasm, and has a very high NPV.

Purpose— Our goal is to provide an overview of the current evidence about components of the evaluation and treatment of adults with acute ischemic stroke. The intended audience is physicians and other emergency healthcare providers who treat patients within the first 48 hours after stroke. In addition, information for healthcare policy makers is included. Methods— Members of the panel were appointed by the American Heart Association Stroke Council’s Scientific Statement Oversight Committee and represented different areas of expertise. The panel reviewed the relevant literature with an emphasis on reports published since 2003 and used the American Heart Association Stroke Council’s Levels of Evidence grading algorithm to rate the evidence and to make recommendations. After approval of the statement by the panel, it underwent peer review and approval by the American Heart Association Science Advisory and Coordinating Committee. It is intended that this guideline be fully updated in 3 years. Results— Management of patients with acute ischemic stroke remains multifaceted and includes several aspects of care that have not been tested in clinical trials. This statement includes recommendations for management from the first contact by emergency medical services personnel through initial admission to the hospital. Intravenous administration of recombinant tissue plasminogen activator remains the most beneficial proven intervention for emergency treatment of stroke. Several interventions, including intra-arterial administration of thrombolytic agents and mechanical interventions, show promise. Because many of the recommendations are based on limited data, additional research on treatment of acute ischemic stroke is needed.

Purpose: Intracranial aneurysm (IA) growth is associated with increased morbidity. We sought to establish a quantitative computational method based on contrast-enhanced MR angiography (CE-MRA) for estimating aneurysmal volume changes over time. Materials and Methods: Computational volume calculations were tested against a distensible phantom. Untreated patients with IA were followed longitudinally with annual MRI. Maximal linear dimensions along the longitudinal axis and two transverse axes were determined by visual review of maximum intensity projection (MIP) data, and aneurysm volume was approximated as (length x width x height)/2. Averages of the visual approximations were compared to the lumenal volume as determined with a computational algorithm using the MRI data. Results: MRI-based measurements accurately represented volume changes in the phantom (R-2 = 0.97, Y = 1.06x + 271 CM3). In the clinical study there were a total of 11 intervals of one-year follow-up in six patients (mean +/- SD age = 53 +/- 20 years). The raw one-year growth using the computational volume was 9% +/- 17%. The corresponding value for the averaged measurement of the reviewers was 8% +/- 14%. Neither the mean values nor the SDs were different (P = .51). Conclusion: MRI-based measurement of aneurysm volume appears feasible for longitudinal studies of aneurysm natural history.

The approach to stroke therapy has historically been limited due to the existence of relatively few treatment options and the necessity for action within 3 hours of symptom onset. As neuroimaging technology advances, fertile new ground is revealed for novel therapies. Recently, a number of exciting mechanical systems have been developed with potential efficacy even hours after cerebrovascular occlusion: endovascular clot disruption, endovascular clot extraction, and angioplasty with stenting are currently under study, with promising initial results. With more options, each with greater effectiveness in a particular clinical scenario, the physician is now better equipped than ever to treat acute ischemic stroke successfully.

A 13-year-old boy with meningiomatosis, McCune-Albright syndrome, and gray platelet syndrome presented with an enlarging “lump” on his right forehead. A head CT scan revealed a polyostotic fibrous dysplasia involving the entire skull. A 3.4-cm right frontal osseous cavity and an overlying right forehead subcutaneous soft-tissue mass were seen, measuring 5.2 cm in diameter and 1.6 cm thick. Ultrasound of the cavity and overlying mass showed swirling of blood and an arterialized waveform. MRI revealed an en plaque meningioma underlying the cavity. An intraosseous pseudoaneurysm fed by 3 distal anterior division branches of the right middle meningeal artery (MMA) with contrast extravasation was found on angiography. Two MMA feeders were embolized with Onyx, with anterograde filling of the intraosseous cavity with Onyx. A small pocket of residual intracavity contrast filling postembolization from a smaller third MMA feeder eventually thrombosed and the forehead lump regressed.

Background and Purpose To evaluate the ability of IA MR perfusion to characterize meningioma blood supply. Methods Studies were performed in a suite comprised of an x-ray angiography unit and 1.5T MR scanner that permitted intraprocedural patient movement between the imaging modalities. Patients underwent intra-arterial (IA) and intravenous (IV) T2* dynamic susceptibility MR perfusion immediately prior to meningioma embolization. Regional tumor arterial supply was characterized by digital subtraction angiography and classified as external carotid artery (ECA) dural, internal carotid artery (ICA) dural, or pial. MR perfusion data regions of interest (ROIs) were analyzed in regions with different vascular supply to extract peak height, full-width at half-maximum (FWHM), relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), and mean transit time (MTT). Linear mixed modeling was used to identify perfusion curve parameter differences for each ROI for IA and IV MR imaging techniques. IA vs. IV perfusion parameters were also directly compared for each ROI using linear mixed modeling. Results 18 ROIs were analyzed in 12 patients. Arterial supply was identified as ECA dural (n = 11), ICA dural (n = 4), or pial (n = 3). FWHM, rCBV, and rCBF showed statistically significant differences between ROIs for IA MR perfusion. Peak Height and FWHM showed statistically significant differences between ROIs for IV MR perfusion. RCBV and MTT were significantly lower for IA perfusion in the Dural ECA compared to IV perfusion. Relative CBF in IA MR was found to be significantly higher in the Dural ICA region and MTT significantly lower compared to IV perfusion.

Cerebral vasospasm is a devastating complication after subarachnoid hemorrhage. The use of cerebral tissue oxygen saturation (SctO2) to non-invasively assess changes in cerebral tissue perfusion induced by intra-arterial (IA) verapamil treatment has not been described to our knowledge. A total of 21 consecutive post-craniotomy patients scheduled for possible IA verapamil treatment of cerebral vasospasm were recruited. The effect of IA verapamil injection on SctO2 being continuously monitored on both the left and right forehead was investigated. Comparisons between changes in SctO2 monitored on the ipsilateral and contralateral forehead in relationship to the side of internal carotid artery (ICA) injection were performed. A total of 47 IA verapamil injections (15 left ICA, 18 right ICA, and 14 vertebral artery injections) during 18 neurointerventional procedures in 13 patients were analyzed. IA verapamil administration led to both increases and decreases in SctO2. Changes in SctO2 ipsilateral to the ICA injection side were more pronounced (p=0.02 and 0.07 for left and right ICA injections, respectively) and favored compared to contralateral SctO2 changes. We were unable to obtain reliable measurements on the side ipsilateral to the craniotomy during four procedures in three patients, presumably secondary to pneumocephalus. The local cerebral vasodilating effect of IA verapamil injection is suggested by the differential changes in SctO2 ipsilateral and contralateral to the ICA injection side. The inconsistent changes in SctO2 and the limitations of applying cerebral oximetry in this patient population needs to be recognized.

Cerebral oximetry is normally placed on the upper forehead to monitor the frontal lobe cerebral tissue oxygen saturation (SctO2). We present a case in which the SctO2 was simultaneously monitored at both frontal and parietal regions during internal carotid artery (ICA) stenting. Our case involves a 79-year-old man who presented after a sudden fall and was later diagnosed with a watershed ischemic stroke in the distal fields perfused by the left middle cerebral artery. He had diffuse atherosclerotic occlusive lesions in the carotid and cerebral arterial systems including an 85 % stenotic lesion in the left distal cervical ICA. The brain territory perfused by the left ICA was devoid of collateral flow from anterior and posterior communicating arteries due to an abnormal circle of Willis. During stenting, the SctO2 monitored at both frontal and parietal regions tracked the procedure-induced acute flow change. However, the baseline SctO2 values of frontal and parietal regions differed. The SctO2–MAP correlation was more consistent on the stroked hemisphere than the non-stroked hemisphere. This case showed that SctO2 can be reliably monitored at the parietal region, which is primarily perfused by the ICA. SctO2 of the stroked brain is more pressure dependent than the non-stroked brain.

OBJECT Retroclival hematomas are rare, appearing mostly as posttraumatic phenomena in children. Spontaneous retroclival hematoma (SRH) in the absence of trauma also has few descriptions in the literature. None of the reported clinical cases features the combination of an SRH and intraventricular hemorrhage (IVH). Nevertheless, despite extensive cases of idiopathic or angiographically negative subarachnoid hemorrhage (SAH) of the posterior fossa, only a single case report of a patient with a unique spontaneous retroclival hematoma has been identified. In this study, the authors reviewed the presentation, management, and clinical outcome of this rare entity. METHODS The authors performed a retrospective analysis of all patients with diagnosed SRH at their institution over a 3-year period. Collected data included clinical history, laboratory results, treatment, and review of all imaging studies performed. RESULTS Four patients had SRH. All were appropriately evaluated for coagulopathic and/or traumatic etiologies of hemorrhage, though no etiology could be found. Moreover, all of the patients demonstrated SRH that both clearly crossed the basioccipital synchondrosis and was contained within a nondependent configuration along the retroclival dura mater. CONCLUSIONS Spontaneous retroclival hematoma, often associated with IVH, is a rare subtype of intracranial hemorrhage frequently recognized only when MRI demonstrates compartmentalization of the posterior fossa hemorrhage. When angiography fails to reveal an underlying lesion, SRH patients, like patients with traditional angiographically negative SAH, enjoy a remarkably good prognosis.

BackgroundVein of Galen malformations (VOGMs) are rare and complex congenital arteriovenous fistulas. The clinical and radiological features of VOGMs and their relation to clinical outcomes are not fully characterized.ObjectiveTo examine the clinical and radiological features of VOGMs and the predictors of outcome in patients.MethodsWe retrospectively reviewed the available imaging and medical records of all patients with VOGMs treated at the University of California, San Francisco between 1986 and 2013. Radiological and clinical features were identified. We applied the modified Rankin Scale to determine functional outcome by chart review. Predictors of outcome were assessed by χ(2) analyses.ResultsForty-one cases were confirmed as VOGM. Most patients (78%) had been diagnosed with VOGM in the first year of life. Age at treatment was bimodally distributed, with predominantly urgent embolization at

The lack of safe and reliable methods to sample vascular tissue in situ limits discovery of the underlying genetic and pathophysiological mechanisms of many vascular disorders, including aneurysms. We investigated the feasibility and comparable efficacy of in vivo vascular endothelial cell sampling using a spectrum of endovascular devices. Using the rabbit elastase carotid aneurysm model we evaluated the performance of existing aneurysmal coils, intracranial stents, and stent-like devices to collect vascular endothelial cells. Additionally, we modified a subset of devices to assess the effects of alterations to coil pitch, coil wire contour, and stent surface finishing. Device performance was evaluated by (1) the number of viable endothelial cells harvested, (2) the degree of vascular wall damage analyzed using digital subtraction angiography and histopathological analysis, and (3) the ease of device navigability and retrieval. Isolated cells underwent immunohistochemical analysis to confirm cell type and viability. Coil and stent specifications, technique, and endothelial cell counts were tabulated and statistical analysis performed. Using conventional detachable-type and modified aneurysm coils 11 of 14 (78.6%) harvested endothelial cells with a mean of 7.93 (±8.33) cells/coil, while 15 of 15 (100%) conventional stents, stent-like devices and modified stents harvested endothelial cells with a mean of 831.33 (±887.73) cells/device. Coil stiffness was significantly associated with endothelial cell count in univariate analysis (p = 0.044). For stents and stent-like devices univariate analysis demonstrated stent-to-aorta diameter ratios (p = 0.001), stent length (p = 0.049), and the use of a pulling retrieval technique (p = 0.019) significantly predictive of endothelial cell counts, though a multivariate model using these variables demonstrated only the stent-to-aorta diameter ratio (p = 0.029) predictive of endothelial cell counts. Modified devices did not significantly impact harvesting. The efficacy and safety of existing aneurysm coils, intracranial stents and stent-like devices in collecting viable endothelial cells was confirmed. The technique is reproducible and the quantity and quality of collected endothelial cells is adequate for targeted genetic analysis.

Background and Purpose— Sex influences outcome after intravenous thrombolysis. In a combined analysis of the tissue plasminogen activator clinical trials, a sex-by-treatment interaction was observed. We sought to confirm that observation in an independent data set. Methods— Data were from the Pro-Urokinase for Acute Cerebral Thromboembolism-2 (PROACT-2) trial. Baseline factors were compared by sex. The primary outcome was an assessment of a sex-by-treatment interaction term within a logistic regression model, using a modified Rankin Scale score ≤2 at 90 days as the binary outcome. We also assessed whether there were differences in CT-scan appearance and recanalization at 2 hours post-treatment. Results— In the PROACT-2 study of intra-arterial stroke thrombolysis, in both women and men, prourokinase resulted in better outcomes than control. A sex by prourokinase treatment interaction was observed, with women showing a larger treatment effect (20% absolute benefit) compared with men (10% absolute benefit). The reason for this interaction is that thrombolytic treatment nullifies the worse outcome for untreated women compared with men. The reasons for effect modification do not include improved recanalization at 2 hours among women. Conclusions— Women with middle cerebral artery ischemic stroke benefit more from intra-arterial therapy. Further study of how sex affects stroke outcome is needed.

Background and purposeThe proper role of endovascular treatment of cervicocerebral atherosclerosis is unclear. Posterior circulation disease has not been investigated as extensively as disease in the anterior circulation. In this study, we characterized the rates of technical success, transient ischemic attack, stroke, and death or disability, for both acute and elective endovascular treatment of atherosclerosis in the vertebrobasilar system.MethodsWe identified patients with atherosclerosis of the vertebrobasilar circulation who underwent endovascular intervention at our hospital through retrospective medical record review, and evaluated the association between lesion and treatment features and subsequent stroke, death, or disability at 30 days and 1 year.ResultsWe identified 136 lesions in 122 patients, including 13 interventions for acute strokes. Technical success was achieved in 123 of 136 cases (90.4%). Elective procedures had higher rates of technical success (6.5% vs 15.4%, p=0.21) and better clinical outcomes. In multivariate analysis, intracranial lesions were associated with more disability (modified Rankin Scale score >2) at 30 days (OR 7.1, p=0.01) and 1 year (OR 10, p=0.03). Patients with non-hypoperfusion related symptoms had fewer strokes at follow-up at 1 year when treated after an asymptomatic interval of >10 days compared with those treated within 10 days of the presenting symptoms (OR 0.2, p=0.03). Statin treatment prior to intervention was associated with favorable outcomes across several examined endpoints. Preoperative antiplatelet treatment was associated with lower rates of disability at 30 days and 1 year (OR 0.1, pConclusionsEndovascular treatment of symptomatic vertebrobasilar atherosclerosis can be performed safely and with good outcomes. Technical results were better for those with extracranial disease while clinical outcomes were more favorable in those patients with non-progressive symptoms in the subacute period and those receiving statin therapy.

Background and purposeEndovascular sampling and characterization from patients can provide very useful information about the pathogenesis of different vascular diseases, but it has been limited by the lack of an effective method of endothelial cell (EC) enrichment. We optimized the EC yield and enrichment from conventional guide wires by laser capture microdissection (LCM) and fluorescence activated cell sorting (FACS) technique, and addressed the feasibility of using these enriched ECs for downstream gene expression detection.MethodsIliac artery endovascular samples from 10 patients undergoing routine catheter angiography were collected using conventional 0.038 in. J-shape guide wires. Each of these samples was equally divided into two parts, which were respectively used for EC enrichment by immunocytochemistry-coupled LCM or multiple color FACS. After RNA extraction and reverse transcription, the amplified cDNA was used for quantitative polymerase chain reaction (qPCR).ResultsFixed ECs, with positive CD31 or vWF fluorescent signal and endothelial like nucleus, were successfully separated by LCM and live single ECs were sorted on FACS by a seven color staining panel. EC yields by LCM and FACS were 51 ± 22 and 149 ± 56 respectively (P < 0.001). The minimum number of fixed ECs from ICC-coupled LCM for acceptable qPCR results of endothelial marker genes was 30, while acceptable qPCR results as enriched by FACS were attainable from a single live EC.ConclusionBoth LCM and FACS can be used to enrich ECs from conventional guide wires and the enriched ECs can be used for downstream gene expression detection. FACS generated a higher EC yield and the sorted live ECs may be used for single cell gene expression detection.

Depending on the population studied, intracranial atherosclerosis accounts for 10% to 29% of ischemic brain events. A significant number of patients with intracranial atherosclerosis continue to suffer from repeated strokes or transient ischemic attacks despite optimal medical management. In selected patients, intracranial angioplasty with or without stenting is a promising treatment option. Patient selection, careful periprocedural medical management, and a highly skilled neuroendovascular interventionalist are required in order to perform the procedure with an acceptable risk.

Beginning with simple balloon angioplasty, minimally invasive revascularization techniques have progressed to the use of metallic stents for improved immediate and long-term results. Stent-supported angioplasty now offers a therapeutic option for those individuals ineligible for surgical revascularization of stenotic atherosclerotic lesions and who have failed maximal medical therapy. However, the clinical equivalence, or possibly even superiority, of angioplasty of the extracranial carotid and vertebral arteries in atheromatous occlusive disease over surgical revascularization has yet to be determined in ongoing randomized controlled trials. Additionally, endovascular techniques offer treatment for a variety of nonatherosclerotic disease affecting the extracranial arteries, such as inflammatory, radiation-induced, and postsurgical strictures; acute intimal dissection; traumatic and spontaneous arteriovenous fistulas; and aneurysms or pseudoaneurysms. For certain disease entities at high risk for surgical complications, endovascular procedures have gained preference as the therapeutic modality of choice, yet lacking controlled trials providing evidence for noninferiority against surgical approach. Continued innovation and refinement of endovascular technology and techniques will further improve technical success, reduce procedure-related morbidity, and broaden the endovascular therapeutic spectrum for extracranial and intracranial cerebrovascular disease.

Background and Purpose. Aneurysm geometry often dictates the success of coil embolization. A strong hemodynamic force or high intra-aneurysmal flow may indicate a high probability of recanalization. It is necessary to develop a tool that can predict and estimate the level of hemodynamic forces that coils are subject to during the procedure. Methods. A compartment model is developed to estimate the intra-aneurysmal flow after coil embolization from digital fluoroscopy. The model is based on the measured signal intensity curves for the aneurysm and adjacent artery and derives the amount of intra-aneurysmal flow reduction. A clinical case of a carotid aneurysm was used for demonstration of its ability. Results. Intra-aneurysmal flow was reduced by 70% after coil embolization, and the estimated porosity was 60%. Flow reduction was confirmed by computational fluid dynamics simulations that modeled the coiled aneurysm as a porous medium. Conclusion. Intra-aneurysmal flow reduction may be used to predict the outcome of coil embolization or possible aneurysm recurrence. A sustained high intra-aneurysmal flow prohibits complete embolization and allows recanalization of the aneurysm. The compartment model provides a reasonable estimate of intra-aneurysmal flow and hemodynamic forces on the coils.

OBJECTIVE The results of clinical trials affect the practice of surgery and endovascular therapy for cerebrovascular diseases. The purpose of this report is to review the basic components of the designs and methods for randomized clinical trials and to describe the influence of those components on the interpretation of trial results. METHODS The goal of an optimal clinical trial of a new procedure is to provide the most objective and rigorous evaluation of the safety and effectiveness of that procedure. Anything in the design, performance, or analysis that impairs such an assessment decreases the ability of the trial to achieve its goal and answer the research question. To highlight the components of a clinical trial, this report uses examples of Phase III clinical trials that have influenced the practice of cerebrovascular surgery and endovascular therapy in the past three decades, including the International Cooperative Study of Extracranial/Intracranial Arterial Anastomosis, the North American Symptomatic Carotid Endarterectomy Trial, the Asymptomatic Carotid Atherosclerosis Study, the Prolyse in Acute Cerebral Thromboembolism II study, and the International Subarachnoid Aneurysm Trial. RESULTS The research question (objective) of the trial must be clearly defined, with an objective measure of efficacy and a specified quantitative difference to define the superiority of one intervention over another, in a relatively homogeneous patient population. Allocation concealment, randomization with or without stratification, and blinding (or masking) are important strategies to prevent differences in the study populations that could adversely affect the conclusions of the study. The primary end point must correspond to the specific aims of the trial. It should be objectively defined, quantifiable, reliable, and reproducible. Commonly defined end points in surgical trials include changes from baseline illness or disease severity scores, morbidity and mortality rates, and relative risks of reaching an end point with time. The statistical methods used for interim and final analyses are important. The effects of dropouts, crossovers, and missing data should be understood in the context of the final analysis. Additional concepts, such as intention-to-treat analysis and use of actual versus predicted outcomes, are important with respect to interpretation of the final results of the study. CONCLUSION The neurosurgical and neuroendovascular communities are currently planning or conducting several clinical trials to evaluate new procedures for the treatment of cerebrovascular diseases. It is hoped that a better understanding of the components of clinical trials will facilitate the design and implementation of effective studies.

Stroke is a common cause of death and disability in industrialized nations. Technical advances and the increased availability of noninvasive brain imaging techniques have permitted precise and early diagnosis of acute cerebral ischemia. This has made emergent thrombolytic therapy for rapid restoration of cerebral perfusion increasingly possible. Herein, the authors present a review of the clinical trials investigating acute stroke treatment with intraarterial thrombolysis.

Introduction/purpose To best achieve complete occlusion of aneurysms treated with flow diverters (FDs), devices must be accurately sized to precisely match the parent vessel diameter. Appropriately sized FDs will have maximal coverage over the aneurysm neck and will be more likely to induce thrombosis. Catheterization for diagnostic angiography can cause vasospasm that may affect vessel measurements. This study evaluates the effects of intra-arterial infusion of a calcium channel blocker (CCB) on angiographic measurements in patients treated with FDs, investigating the impact on the final diameter of the expanded stent following deployment and subsequent occlusion. Materials and methods Retrospective analysis was performed of prospectively maintained procedure records to identify patients with aneurysms treated with FDs. In all patients, pre-treatment measurements were recorded for vessel diameter of the distal and proximal landing zones, as well as maximum and minimum diameters between these segments. Post-treatment measurements of the stent itself following deployment were recorded at the distal and proximal ends in addition to maximum and minimum diameters. When CCB was infused prior to treatment, post-infusion pre-treatment measurements were recorded. All measurements were performed after calibrating to a catheter included on the image. Rates of occlusion and time to confirmed occlusion were noted for all patients. Independent-sample 2 tailed T-tests were performed to assess for differences in pre- and post-treatment measurements, rates of occlusion, and time to confirmed occlusion between groups with and without CCB infusion. Results 21 FDs were deployed to treat 19 aneurysms in 18 patients. CCB infusion was performed prior to deployment of 9 devices. The change in measurements noted after CCB infusion are summarized in Table 1. No significant difference was noted between groups for pre- and post-treatment measurement changes. Subsequent aneurysm occlusion was more likely to occur in the CCB infusion group (100% vs. 44.4%, p Conclusion Optimization of device sizing is important to increase FD density over the aneurysm neck and promote thrombosis. To improve accuracy of measurements of parent vessels prior to device selection, CCB infusion can reduce the effects of mild vasospasm. In this study, subsequent aneurysm occlusion was more likely to occur following FD treatment when device size selection was based on measurements performed following CCB infusion. Disclosures M. Alexander: None. R. Darflinger: None. F. Settecase: None. A. Nicholson: None. D. Cooke: None. M. Amans: None. S. Hetts: None. C. Dowd: None. R. Higashida: None. V. Halbach: None.

OBJECTIVE The most common location for dural arteriovenous fistulae (AVFs) is the transverse/sigmoid sinus. We describe our prospective analysis of data for 10 patients with recipient fistulae parallel to the transverse/sigmoid sinus. Recognition of this entity allows embolization of the fistula with preservation of the parent sinus. This report reviews the presentation and angiographic characteristics of the “parallel venous channel” and the treatment results for this series of patients. METHODS Between 1995 and June 2002, at the medical center of the University of California, San Francisco, we identified 10 patients with a parallel venous channel as the recipient pouch for all arterial input into a transverse/sigmoid sinus AVF. The clinical presentations, angiographic features, endovascular treatments, and outcomes are described. Angiographic follow-up monitoring was performed for 1 to 6 years for all patients with cortical venous drainage (5 of 10 patients). Clinical follow-up periods ranged from 1 to 7 years. RESULTS All patients presented with pulsatile tinnitus disruptive to sleep. Other symptoms included severe headaches, papilledema and visual disturbances, hemiparesis, and mastoid pain. All 10 parallel venous channels communicated with the transverse or sigmoid sinus. Cortical venous drainage was present in 50% of cases. Endovascular ablative procedures, using either coils or ethanol, were performed for all patients. The parallel venous channel was successfully embolized, with preservation of the transverse/sigmoid sinus, for all 10 patients. There were no major complications. All patients experienced resolution of their symptoms, with no recurrence. CONCLUSION The existence of a parallel venous channel as the recipient pouch for all arterial inflow in a series of 10 transverse/sigmoid sinus AVFs is described. Endovascular obliteration of the parallel channel, with preservation of the parent sinus, was successfully performed for all 10 patients. Recognition of the parallel venous channel is clinically important for the treatment of transverse/sigmoid AVFs.