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Background: Prompt diagnosis and revascularization of large vessel occlusion ischemic stroke is associated with better functional outcome. While both MRI and CT modalities are current standard of care options for initial imaging, and MR imaging provides greater lesion conspicuity and spatial resolution to inform management, few series have yet demonstrated that multimodal MR may be performed speedily and efficiently in AIS-LVO patients. Methods: In a prospectively maintained Comprehensive Stroke Center Registry, we analyzed all anterior circulation LVO thrombectomy patients: 1) arriving directly by EMS transport from the field, 2) with initial NIHSS ≥6, between 2012-2017. Throughout this period, imaging policy was multimodal MRI (including DWI/GRE/MRA w/wo PWI) as the initial evaluation in all patients without contraindications, and multimodal CT (including CT with CTA, w/wo CTP) in the remainder. Achieved process times were compared with national recommendations for door-to-needle (45m, AHA/ASA Target Stroke) and door-to-puncture (90m, SVIN). Results: Among 106 LVO thrombectomy patients, MRI was used in 62.3% and CT in 37.7%. MRI and CT patients were similar in age, 72.5 v 71.3y; severity (NIHSS) 16.4 v 18.2); and IV tPA door-to-needle times, median 45 vs 46 mins. However, MRI patients had longer onset-to-door times, median 100 vs 50 mins. From Jan 2012-Dec2014, in MRI vs CT groups, median door-to-imaging times were 20 min vs 18 min, p=0.88 and door-to-puncture times 102 vs 93 min, p=0.39. From Jan 2015-Dec2017, after the publication of the positive thrombectomy trials and endorsement of endovascular stroke treatment in US guidelines, in MRI vs CT groups, median door-to-imaging times were 17 min vs 17 min (p=0.93) and door-to-groin puncture 86 vs 71 min (p=0.02). There was no difference in functional outcome (mRS 0-2) between groups. Conclusions: Optimized imaging processes enable acute AIS-LVO patients to be evaluated by multimodal MR with care speeds faster than national recommendations for door-to-needle and door-to-puncture times. While some patients have absolute contraindications to high magnetic fields, MRI, with its greater pathophysiologic insight, remains a highly viable primary imaging strategy in acute ischemic stroke patients.

Introduction: Interhospital transfer for endovascular treatment of large vessel occlusion (LVO) stroke results in significant delays and worse outcomes. We hypothesized that interhospital patient transfer using air transport would result in shorter transit times compared to ground ambulance. Methods: Subjects from the STRATIS registry that underwent interhospital transfer for endovascular treatment were separated by air transport vs. ground ambulance transport and analyzed by transfer distance. The primary endpoint was transfer-time, calculated as the time from imaging at the initial hospital to arrival at the treating hospital. Also assessed was travel-time, calculated as time of departure from the initial hospital to arrival at the treating hospital. Results: There were 232 subjects from 41 sites. Mean transfer-time for all air subjects (n=118) was 147.1 min, and for all ground subjects (n=114) was 130.0 min (p=0.019). Mean travel-time was 45.0 min for air transport and 40.2 min for ground transport (p=0.239); though the average travel distance was longer for air (65.5 miles) vs. ground (27.6 miles; p Conclusions: In this large, real-world study, interhospital transfer via air transport did not result in faster transfer times compared to ground ambulance. In fact, there was an advantage to ground transportation for distances of less than 20 miles. These results suggest that ground ambulance should routinely be used for interhospital transfer of stroke patients for travel less than 20 miles.

Background: Randomized trials have shown the benefit of endovascular reperfusion therapy (ERT) in acute ischemic stroke (AIS) is time dependent. However, generalizability to routine practice is uncertain; and modest sample sizes have limited characterization of the degree to which onset to treatment time influences outcome from ERT. Methods: We analyzed data of 6756 AIS patients treated with ERT at 231 hospitals between January 2015 to December 2016. Multivariable logistic regression modeling was conducted to evaluate the independent impact of onset to puncture (OTP) and door to puncture (DTP) time on efficacy and safety outcomes. Results: Among the 6756 patients, median age was 71, 51.2% were female, and NIHSS was 17 (IQR 12-22). Median OTP was 230m (IQR 170-305) and DTP 87m (IQR 62-116). Substantial reperfusion (TICI 2b-3) was in 85.9%. At discharge, 36.9% had independent ambulation, 27.8% were discharged to home, and 23.0% were functionally independent (mRS 0-2). Symptomatic intracranial hemorrhage (sICH) occurred in 6.7% and in-hospital mortality/hospice in 19.6%. For OTP, time-outcome relationships were nonlinear, with steeper slope in 0-270m than 271-480m (see Table and Figure). DTP showed a similar nonlinear time-outcome relationship, with steeper benefit decline in the 30-120m than 121-180m period. Conclusions: In this national registry, faster endovascular therapy start, after onset and after arrival, was associated with better ambulation and functional independence at discharge, and reduced sICH and mortality/hospice. These findings support intensive efforts to accelerate hospital presentation and endovascular treatment in patients with stroke.

Background and Purpose— We determined the effect of sex on outcome after endovascular stroke thrombectomy in acute ischemic stroke, including lifelong disability outcomes. Methods— We analyzed patients treated with the Solitaire stent retriever in the combined SWIFT (Solitaire FR With the Intention for Thrombectomy), STAR (Solitaire FR Thrombectomy for Acute Revascularization), and SWIFT PRIME (Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment) cohorts. Ordinal and logistic regression were used to examine known factors influencing outcome after endovascular stroke thrombectomy and study the effect of sex on the association between these factors and outcomes, including age and time to reperfusion. Years of optimal life after thrombectomy were defined as disability-adjusted life years and calculated by projecting disability through adjusted poststroke life expectancy by sex. Results— Among 389 patients treated with endovascular stroke thrombectomy, 55% were females, and median National Institutes of Health Stroke Scale was 17 (interquartile range, 8–28). There were no differences between females versus males in presenting deficit severity (National Institutes of Health Stroke Scale score, 17 versus 17, P =0.21), occlusion location (69% versus 64% M1, P =0.62), presenting infarct extent (Alberta Stroke Program Early CT Score 8 versus 8, P =0.24), rate of substantial reperfusion (Thrombolysis in Cerebral Infarction 2b/3, 87% versus 83%, P =0.37), onset to reperfusion time (294 versus 302 minutes, P =0.46). Despite older ages (69 versus 64, P P =0.002) for females compared with males, adjusted rates of functional independence at 90 days were similar (odds ratio, 1.0; 95% CI, 0.6–1.6). After adjusting for age at presentation and stroke severity, females had more years of optimal life (disability-adjusted life year) after endovascular stroke thrombectomy, 10.6 versus 8.5 years ( P Conclusions— Despite greater age and higher rate of atrial fibrillation, females experienced comparable functional outcomes and greater years of optimal life after intervention compared with males.

Background CT perfusion (CTP) and diffusion or perfusion MRI might assist patient selection for endovascular thrombectomy. We aimed to establish whether imaging assessments of irreversibly injured ischaemic core and potentially salvageable penumbra volumes were associated with functional outcome and whether they interacted with the treatment effect of endovascular thrombectomy on functional outcome.Methods In this systematic review and meta-analysis, the HERMES collaboration pooled patient-level data from all randomised controlled trials that compared endovascular thrombectomy (predominantly using stent retrievers) with standard medical therapy in patients with anterior circulation ischaemic stroke, published in PubMed from Jan 1,2010, to May 31, 2017. The primary endpoint was functional outcome, assessed by the modified Rankin Scale (mRS) at 90 days after stroke. Ischaemic core was estimated, before treatment with either endovascular thrombectomy or standard medical therapy, by CTP as relative cerebral blood flow less than 30% of normal brain blood flow or by MRI as an apparent diffusion coefficient less than 620 mu m(2)/s. Critically hypoperfused tissue was estimated as the volume of tissue with a CTP time to maximum longer than 6 s. Mismatch volume (ie, the estimated penumbral volume) was calculated as critically hypoperfused tissue volume minus ischaemic core volume. The association of ischaemic core and penumbral volumes with 90-day mRS score was analysed with multivariable logistic regression (functional independence, defined as mRS score 0-2) and ordinal logistic regression (functional improvement by at least one mRS category) in all patients and in a subset of those with more than 50% endovascular reperfusion, adjusted for baseline prognostic variables. The meta-analysis was prospectively designed by the HERMES executive committee, but not registered.Findings We identified seven studies with 1764 patients, all of which were included in the meta-analysis. CTP was available and assessable for 591 (34%) patients and diffusion MRI for 309 (18%) patients. Functional independence was worse in patients who had CTP versus those who had diffusion MRI, after adjustment for ischaemic core volume (odds ratio [OR] 0.47 [95% CI 0.30-0.72], p=0.0007), so the imaging modalities were not pooled. Increasing ischaemic core volume was associated with reduced likelihood of functional independence (CTP OR 0.77 [0.69-0.86] per 10 mL, p(interaction)=0.29; diffusion MRI OR 0.87 [0.81-0.94] per 10 mL, p(interaction)=0.94). Mismatch volume, examined only in the CTP group because of the small numbers of patients who had perfusion MRI, was not associated with either functional independence or functional improvement. In patients with CTP with more than 50% endovascular reperfusion (n=186), age, ischaemic core volume, and imaging-to-reperfusion time were independently associated with functional improvement. Risk of bias between studies was generally low.Interpretation Estimated ischaemic core volume was independently associated with functional independence and functional improvement but did not modify the treatment benefit of endovascular thrombectomy over standard medical therapy for improved functional outcome. Combining ischaemic core volume with age and expected imagingto-reperfusion time will improve assessment of prognosis and might inform endovascular thrombectomy treatment decisions. Copyright (C) 2018 Elsevier Ltd. All rights reserved.

IMPORTANCE Reperfusion is a key factor for clinical outcome in patients with acute ischemic stroke (AIS) treated with endovascular thrombectomy (EVT) for large-vessel intracranial occlusion. However, data are scarce on the association between the time from onset and reperfusion results.OBJECTIVE To analyze the rate of reperfusion after EVT started at different intervals after symptom onset in patients with AIS.DESIGN, SETTING, AND PARTICIPANTS We conducted a meta-analysis of individual patient data from 7 randomized trials of the Highly Effective Reperfusion Using Multiple Endovascular Devices (HERMES) group. This is a multicenter cohort study of the intervention arm of randomized clinical trials included in the HERMES group. Patients with anterior circulation AIS who underwent EVT for M1/M2 or intracranial carotid artery occlusion were included. Each trial enrolled patients according to its specific inclusion and exclusion criteria. Data on patients eligible but not enrolled (eg, refusals or exclusions) were not available. All analyses were performed by the HERMES biostatistical core laboratory using the pooled database. Data were analyzed between December 2010 and April 2015.MAIN OUTCOMES AND MEASURES Successful reperfusion was defined as a modified thrombolysis in cerebral infarction score of 2b/3 at the end of the EVT procedure adjusted for age, occlusion location, pretreatment intravenous thrombolysis, and clot burden score and was analyzed in relation to different intervals (onset, emergency department arrival, imaging, and puncture) using mixed-methods logistic regression.RESULTS Among the 728 included patients, with a mean (SD) age of 65.4 (13.5) years and of whom 345 were female (47.4%), decreases in rates of successful reperfusion defined as a thrombolysis in cerebral infarction score of 2b/3 were observed with increasing time from admission or first imaging to groin puncture. The magnitude of effect was a 22% relative reduction (odds ratio. 0.78; 95% CI, 0.64-0.95) per additional hour between admission and puncture and a 26% relative reduction (odds ratio, 0.74; 95% CI, 0.59-0.93) per additional hour between imaging and puncture.CONCLUSIONS AND RELEVANCE Because the probability of reperfusion declined significantly with time between hospital arrival and groin puncture, we provide additional arguments for minimizing the intervals after symptom onset in anterior circulation acute ischemic stroke.

Background and Purpose- Although intracranial thrombectomy represents the standard treatment approach for anterior circulation tandem occlusions, whether the extracranial lesion requires acute stenting remains unclear. Our aim was to investigate differences in clinical and procedural outcomes related to stenting extracranial lesions in a registry of patients undergoing thrombectomy for acute stroke. Methods- Data were analyzed from the STRATIS registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke)-a prospective, nonrandomized study of patients undergoing neurothrombectomy with the Solitaire device. A total of 984 patients treated at 55 sites were analyzed. Univariate and multivariable logistic regression was used to assess relationship between outcome and procedural technique. Results- Of 147 (14.9%) patients with tandem lesions treated, stenting of the extracranial lesion during thrombectomy was performed in 80 patients and withheld in 67 patients. There were no differences between groups with respect to age, ASPECTS (Alberta Stroke Program Early CT Score), or intravenous-tPA (tissue-type plasminogen activator) use. However, the patients in the stenting group had lower baseline National Institutes of Health Stroke Scale (16 versus 17.9; P=0.07), shorter onset to arterial puncture time (133.6 versus 163.4 minutes; P=0.04), and lower rates of atrial fibrillation (6.3% versus 25.4%) as compared to the nonstenting group. Good outcomes (modified Rankin Scale, 0-2 at 90 days) were higher in the stenting group (68.5% versus 42.2%; P=0.003) with no difference in mortality or symptomatic hemorrhage. After adjustment for covariates, stenting continued to be associated with superior outcomes. Conclusions- Acute stenting of an extracranial carotid stenosis during neurothrombectomy can be achieved with equal safety compared with no stenting. Carotid stenting in the acute phase may lead to better outcomes; this should ideally be confirmed by randomized trials.

Particle image velocimetry (PIV) is used in a wide variety of fields, due to the opportunity it provides for precisely visualizing and quantifying flows across a large spatiotemporal range. However, its implementation typically requires the use of expensive and specialized instrumentation, which limits its broader utility. Moreover, within the field of bioengineering, in vitro flow visualization studies are also often further limited by the high cost of commercially sourced tissue phantoms that recapitulate desired anatomical structures, particularly for those that span the mesoscale regime (i.e., submillimeter to millimeter length scales). Herein, we present a simplified experimental protocol developed to address these limitations, the key elements of which include 1) a relatively low-cost method for fabricating mesoscale tissue phantoms using 3-D printing and silicone casting, and 2) an open-source image analysis and processing framework that reduces the demand upon the instrumentation for measuring mesoscale flows (i.e., velocities up to tens of millimeters/second). Collectively, this lowers the barrier to entry for nonexperts, by leveraging resources already at the disposal of many bioengineering researchers. We demonstratethe applicability of this protocol within the context of neurovascular flow characterization; however, it is expected to be relevant to a broader range of mesoscale applications in bioengineering and beyond.

Background and purpose: The optimal anesthetic management of acute ischemic stroke patients during mechanical thrombectomy (MT) remains controversial. In this post-hoc analysis, we investigated the impact of anesthesia type on clinical outcomes in patients included in SWIFT PRIME trial. Methods: Ninety-seven patients treated with MT were included. Patients treated in centers with general anesthesia (GA) policy (n = 32) were compared with those treated in centers with conscious sedation (CS) policy (n = 65). Primary outcomes studied included times to treatment initiation (TTI), rates of successful recanalization (TICI 2b/3), and functional independence (mRS 0-2 at 90 days). Secondary outcomes were adverse events, lowest systolic and diastolic blood pressures (LSBP and LDBP) during MT. Univariate analysis and multivariate regression logistic modeling were conducted. Results: The GA-policy and CS-policy groups presented comparable TTI (94 ± 36 min vs. 102 ± 48 min; p = 0.44), rates of TICI 2b/3 recanalization (22/32 [68.8%] vs. 51/65 [78.5%]; p = 0.32). CS-policy was associated to higher rate of functional independence than GA-policy, but the difference was not significant (43/65 [66.2%] vs. 16/32 [50.0%]; p = 0.18). GA-policy patients had a higher rate of postoperative pneumonia (11/32 [34.4%] vs. 8/65 [12.3%]; p = 0.02) and lower LSBP (110 [30,160] mmHg vs. 119 [77,170] mmHg; p = 0.03) and LDBP (55 (15,75) mmHg vs. 67 [40,121]; p < 0.001). When corrected for differences in baseline characteristics, GA-policy was associated with lower rate of functional independence (OR 0.32; p = 0.05). A 10-point increase in perprocedural LDBP was associated with an increased likelihood of favorable outcome (OR 1.51; p = 0.01). Conclusions: GA-policy for MT presented comparable TTI and rates of successful revascularization to CS-policy. However, GA-policy was associated with lower rates of functional independence and with higher incidence of perprocedural hypotension and postoperative pneumonia. Clinical Trial Registration: URL-http://www.clinicaltrials.gov. Unique identifier: NCT01657461.

Objective The therapeutic challenge of cavernous sinus dural arteriovenous fistula (CSDAVF) is the anatomy of the CS, which consists of a network of interconnected venous pockets, one or many of which may receive shunt arteries. Although the standard treatment of CSDAVF is coil packing, a substantial number of platinum coils are required to treat the fistulas in most cases, and the treatments may result in incomplete occlusion because of complicating venous structures. Onyx (ethylene-vinyl alcohol copolymer) can be penetrated and might be able to reduce the number of platinum coils. Despite inherent advantages of the liquid embolic material, the neuro- and angiotoxic effects of DMSO and clinical outcomes are still not well documented. The purpose of this study is to evaluate the single-center experience of transvenous treatment of CSDAVFs with the DMSO-based liquid embolic material, ONYX. Methods We retrospectively reviewed 52 cases whose CSDAVFs were treated in our hospital between 2005 and 2016. Four patients treated with transarterial embolization and 2 patients with transorbital embolization were excluded from this study. Their hospital records, angiograms and operation reports were reviewed. Results There were total of 46 patients (13 male and 37 female, age 32–89 years) treated transvenously using Onyx. Thirty patients had a combination of coils and Onyx and 16 patients had Onyx embolization used for treatment. Complete obliteration immediately after the treatment was achieved in 42 patients (91%). There were 5 (11%) periprocedural complications including transient worsening of cranial nerve palsy (n=2, 4%), transient worsening of eye symptoms (n=1, 2%) a transient thromboembolic event (n=1, 2%) and alopecia (n=1, 2%). No patients developed a bradycardia during DMSO injection. Conclusion In our case series, transvenous embolization of CSDAVFs using Onyx has favorable long-term clinical outcomes with low complication rates. Cranial nerve palsy and bradycardia caused by DMSO were uncommon, but should be carefully monitored. Disclosures N. Kaneko: None. S. Tateshima: 1; C; Medtronic. 2; C; Medtronic. V. Szeder: 1; C; Medtronic. F. Liang: None. A. Mowla: None. R. Jahan: 1; C; Medtronic. 2; C; Medtronic. F. Vinuela: None. G. Duckwiler: 1; C; Medtronic.

Background An extensive body of evidence supports mechanical thrombectomy using stentrievers (SR) for acute large vessel occlusion (LVO). Aspiration is also utilized as a first pass technique (ADAPT) and as an adjunct technique during clot removal with a stentriever. Here we report technical results from mechanical thrombectomy cases using SR alone, aspiration alone (ADAPT), or a combination of SR plus aspiration (SA) as a first pass technique for mechanical thrombectomy for acute LVO. Methods An institutional stroke database was reviewed for patients presenting to a single academic hospital with acute LVO and who were treated with mechanical thrombectomy from 2011 to 2017. Patients managed with stentrievers using Solitaire and Trevo (SR) alone, aspiration alone (ADAPT), or a combination of these two techniques (SA) were identified. The rate of successful recanalization, defined as TICI score 2b or greater, following the first pass thrombectomy attempt was compared between the three groups. Results Two hundred thirty-three patients were analyzed in the study, including 135 in SR, 37 in ADAPT, and 61 in SA groups. Mean age of patients were 71±17 years for SR, 70±16 years for ADAPT, and 72±15 years for SA groups. Admission NIHSS were 17±8 for SR, 16±8 for ADAPT, and 15±6 for SA. There was no significant difference for age and admission NIHSS between the groups. Anterior circulation was involved in 207 cases (89%) and posterior circulation in 26 (11%). ADAT was utilized significantly more in posterior circulation LVO compared to the other techniques (35% in ADAPT group versus 6% and 8% in SR and SA groups respectively, p=0.000). Successful recanalization rates after first pass were 35% in SR group, 43% in ADAPT, and 61% in SA, with a statistically significant higher rate of first pass success in the SA group (p=0.003). Conclusion The combination of stentriever and catheter aspiration can increase the rate of successful single pass recanalization compared to these techniques individually. Disclosures G. Colby: 2; C; Stryker Neurovascular, Medtronic. H. Baharvahdat: None. R. Jahan: None. S. Tateshima: None. V. Szeder: None. M. Nour: None. F. Vinuela: None. G. Duckwiler: 2; C; Neurvana Medical, Microvention.

Background and purpose A reliable animal model of ischemic stroke is vital for pre-clinical evaluation of stroke therapies. We describe a reproducible middle cerebral artery (MCA) embolic occlusion in the French Lop rabbit characterized with multimodal MRI and histopathologic tissue analysis. Methods Fluoroscopic-guided microcatheter placement was performed in five consecutive subjects with angiographic confirmation of MCA occlusion with autologous clot. Multimodal MRI was obtained prior to occlusion and up to six hours post after which repeat angiography confirmed sustained occlusion. The brain was harvested for histopathologic examination. Results Angiography confirmed successful MCA catheterization and durable (>6 hour) MCA occlusion in all animals. There was increase of ADC volume over time and variable final core volume presumably related to individual variation in collateral flow. FLAIR hyperintensity indicative of cytotoxic edema and parenchymal contrast enhancement reflective of blood brain barrier disruption was observed over time. Tissue staining of the ischemic brain showed edema and structural alterations consistent with infarction. Conclusions We demonstrate the feasibility of a rabbit model of embolic MCA occlusion with angiographic documentation. Serial MR imaging demonstrated changes comparable to those observed in human ischemic stroke, confirmed histopathologically. Disclosures R. Jahan: None. P. Villablanca: None. R. Harris: None. S. Duarte-Vogel: None. C. Williams: None. H. Vinters: None. N. Rao: None. D. Enzmann: None. B. Ellingson: None.

Background Cerebral vasospasm (CVS) is a major cause of morbidity and mortality after aneurysmal subarachanoid hemorrhage (aSAH). During medically refractory symptomatic CVS targeted intra-arterial (IA) vasodilators, such as verapamil, are routinely used. Despite evidence of radiographic improvement of vessel caliber, there is limited evidence of clinically substantial and persistent improved perfusion subsequent to IA verapamil. Objective To evaluate effect of IA verapamil on down-stream brain tissue oxygen tension (PbTO2) in patients with angiographic vasospasm. Methods All patients with poor grade aSAH who had a PbTO2 monitor and underwent digital subtraction angiography (DSA) for the evaluation of and treatment of CVS with IA-verapamil between 2013 and 2015 at UCLA. All patients that were found to have any extent of angiographic vasospasm were treated with IA verapamil to the corresponding internal carotid artery (ICA) or vertebral artery (VA). PbTO2 over the 24 hour epochs before and after each angiogram in the group with angiographic vasospasm was compared to group without vasospasm using a Student T-test. Results We identified seven patients with aSAH who had PbTO2 monitoring during intervals before and after DSA for the evaluation and treatment of CVS. We found six distinct epochs with and six additional epochs without angiographic vasospasm. The average PbTO2 during a 24 hour epoch prior to DSA with spasm was significantly lower than the ones prior to DSA without vasospasm (18.4 vs 25.4, p=0.04). The average PbtO2 during a 24 hour epoch after DSA with evidence of angiographic vasospasm and treatment with IA verapamil normalized to the distribution of 24 epochs after DSA with no spasm who did not receive any treatment (23.2 vs 24.6, p=0.66). Conclusion Intra-arterial verapamil could be used in normalizing pathologically low brain tissue oxygen tension in the setting of angiographic vasospasm. Further research is needed to understand appropriate dosing of IA verapamil by vasospasm severity. Disclosures K. Khatibi: None. V. Szeder: None. M. Buitrago Blanco: None. S. Tateshima: None. R. Jahan: None. G. Duckwiler: None. P. Vespa: None.

Background A reliable animal model of ischemic stroke is vital for pre-clinical evaluation of stroke therapies. We describe a reproducible middle cerebral artery (MCA) embolic occlusion in the French Lop rabbit characterized with multimodal MRI and histopathologic tissue analysis. New method Fluoroscopic-guided microcatheter placement was performed in five consecutive subjects with angiographic confirmation of MCA occlusion with autologous clot. Multimodal MRI was obtained prior to occlusion and up to six hours post after which repeat angiography confirmed sustained occlusion. The brain was harvested for histopathologic examination. Results Angiography confirmed successful MCA catheterization and durable (>6 h) MCA occlusion in all animals. There was increase of ADC volume over time and variable final core volume presumably related to individual variation in collateral flow. FLAIR hyperintensity indicative of cytotoxic edema and parenchymal contrast enhancement reflective of blood brain barrier disruption was observed over time. Tissue staining of the ischemic brain showed edema and structural alterations consistent with infarction. Comparison with existing methods This study describes a technique of selective catheterization and embolic occlusion of the MCA in the rabbit with MRI characterization of evolution of ischemia in the model. Conclusions We demonstrate the feasibility of a rabbit model of embolic MCA occlusion with angiographic documentation. Serial MR imaging demonstrated changes comparable to those observed in human ischemic stroke, confirmed histopathologically.

OBJECTIVEAs imaging technology has improved, more unruptured intracranial aneurysms (UIAs) are detected incidentally. However, there is limited information regarding how UIAs change over time to provide stratified, patient-specific UIA follow-up management. The authors sought to enrich understanding of the natural history of UIAs and identify basic UIA growth trajectories, that is, the speed at which various UIAs increase in size.METHODSFrom January 2005 to December 2015, 382 patients diagnosed with UIAs (n = 520) were followed up at UCLA Medical Center through serial imaging. UIA characteristics and patient-specific variables were studied to identify risk factors associated with aneurysm growth and create a predicted aneurysm trajectory (PAT) model to differentiate aneurysm growth behavior.RESULTSThe PAT model indicated that smoking and hypothyroidism had a large effect on the growth rate of large UIAs (≥ 7 mm), while UIAs < 7 mm were less influenced by smoking and hypothyroidism. Analysis of risk factors related to growth showed that initial size and multiplicity were significant factors related to aneurysm growth and were consistent across different definitions of growth. A 1.09-fold increase in risk of growth was found for every 1-mm increase in initial size (95% CI 1.04–1.15; p = 0.001). Aneurysms in patients with multiple aneurysms were 2.43-fold more likely to grow than those in patients with single aneurysms (95% CI 1.36–4.35; p = 0.003). The growth rate (speed) for large UIAs (≥ 7 mm; 0.085 mm/month) was significantly faster than that for UIAs < 3 mm (0.030 mm/month) and for males than for females (0.089 and 0.045 mm/month, respectively; p = 0.048).CONCLUSIONSAnalyzing longitudinal UIA data as continuous data points can be useful to study the risk of growth and predict the aneurysm growth trajectory. Individual patient characteristics (demographics, behavior, medical history) may have a significant effect on the speed of UIA growth, and predictive models such as PAT may help optimize follow-up frequency for UIA management.

Endovascular therapy (ET) has become the standard of care for selected patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). However, many LVO or medium vessel occlusion (MVO) patients are ineligible for ET, including some who harbor salvageable tissues. To develop complementary therapies for these patients, it is important to delineate their prevalence, clinical features, and outcomes.In a prospectively maintained database, we reviewed consecutive AIS patients between December 2015 and September 2016. Based on the first multimodal computed tomography or magnetic resonance imaging, patients were categorized as having substantial penumbra if perfusion lesion volume (Tmax 6 seconds) exceeded ischemic core volume (relative cerebral blood flow 30% on CT perfusion or apparent diffusion coefficient 620 on diffusion weighted image) by ≥20%.Among 174 consecutive AIS patients presenting within 24 hours of last known well time, 29 (17%) had LVO or MVO and substantial penumbra, but were deemed ET ineligible. Among these patients, mean age was 81 (±13), 45% were female, and median National Institute of Health Stroke Scale score was 11 (interquartile range [IQR]: 5-19). The most common reasons for not pursuing ET were: distal occlusion (28%), mild neurologic deficit (16%), and temporally advanced core injury (16%). Ischemic core volume was 20 mL (±31), penumbral volume was 54 mL (±63), and mismatch ratio median was 5.6 (IQR: 2-infinite). Severe disability or death at discharge (modified Rankin scale: 4-6) occurred in 72% of the patients.Even in the modern stent retriever era, 1 in 6 AIS patients presents with substantial penumbra judged not appropriate for ET. This population may benefit from the development of alternative therapies, including collateral enhancement, neuroprotection, and thrombectomy devices deployable in distal arteries.

Background and Purpose— Sparse data are available regarding the association between hyperglycemia and outcomes in acute ischemic stroke patients receiving mechanical thrombectomy (MT). We investigated whether hyperglycemia affected the outcomes of subjects treated with MT in the Solitaire Flow Restoration With the Intention for Thrombectomy (SWIFT) multicenter randomized trial, overall and according to reperfusion status after MT. Methods— We analyzed the relationships between the presenting glucose level as a continuous variable and presenting hyperglycemia (>140 mg/dL glucose) as a binary variable and several outcomes of interest. Subjects were stratified according to the completeness of reperfusion (Thrombolysis In Myocardial Ischemia scale 3 versus 0–2) after MT. Excellent outcome at 3 months was defined as a modified Rankin scale score of 0–1. Results— Among all patients undergoing MT, patients with hyperglycemia less frequently exhibited an excellent outcome at 3 months than patients without hyperglycemia, 13% versus 34%; P =0.01. Presenting glucose levels did not differ among patients achieving complete reperfusion and incomplete reperfusion. Among patients with incomplete reperfusion, after adjustment for covariates, higher glucose levels were independently associated with worse outcome at 3 months (per 10 mg/dL increase in glucose: odds ratio for modified Rankin scale score 0–1 at 3 months 0.58, 95% confidence interval 0.34–0.99; P =0.047). In contrast, among patients with complete reperfusion, differences in presenting glucose levels by final outcome did not reach statistical significance. Conclusions— In patients treated with MT, hyperglycemia was independently associated with worse outcome at 3 months, and the negative effects of hyperglycemia may have been exacerbated in patients with incomplete reperfusion after MT. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01054560.

OBJECTIVE Within the context of a prospective randomized trial (SWIFT PRIME), we assessed whether early imaging of stroke patients, primarily with computed tomography (CT) perfusion, can estimate the size of the irreversibly injured ischemic core and the volume of critically hypoperfused tissue. We also evaluated the accuracy of ischemic core and hypoperfusion volumes for predicting infarct volume in patients with the target mismatch profile. METHODS Baseline ischemic core and hypoperfusion volumes were assessed prior to randomized treatment with intravenous (IV) tissue plasminogen activator (tPA) alone versus IV tPA + endovascular therapy (Solitaire stent-retriever) using RAPID automated postprocessing software. Reperfusion was assessed with angiographic Thrombolysis in Cerebral Infarction scores at the end of the procedure (endovascular group) and Tmax > 6-second volumes at 27 hours (both groups). Infarct volume was assessed at 27 hours on noncontrast CT or magnetic resonance imaging (MRI). RESULTS A total of 151 patients with baseline imaging with CT perfusion (79%) or multimodal MRI (21%) were included. The median baseline ischemic core volume was 6 ml (interquartile range= 0-16). Ischemic core volumes correlated with 27-hour infarct volumes in patients who achieved reperfusion (r = 0.58, p 6-second lesion volumes correlated with 27-hour infarct volume (r = 0.78, p = 0.005). In target mismatch patients, the union of baseline core and early follow-up Tmax > 6-second volume (ie, predicted infarct volume) correlated with the 27-hour infarct volume (r = 0.73, p < 0.0001); the median absolute difference between the observed and predicted volume was 13 ml. INTERPRETATION Ischemic core and hypoperfusion volumes, obtained primarily from CT perfusion scans, predict 27-hour infarct volume in acute stroke patients who were treated with reperfusion therapies.

Background The mechanisms leading to delayed rupture, distal emboli and intraparenchymal hemorrhage in relation to pipeline embolization device (PED) placement remain debatable and poorly understood. The aim of this study was to identify clinical and procedural predictors of these perioperative complications. Methods We conducted a retrospective review of consecutive patients who underwent PED placement. We utilized a non-commercial platelet aggregation method measuring adenosine diphosphate (ADP)% inhibition for evaluation of clopidogrel response. To our knowledge, this is the first study to test ADP in neurovascular procedures. Multivariable regression analysis was used to identify the strongest predictor of three separate outcomes: (1) thrombotic complications, (2) hemorrhagic complications, and (3) aneurysm mass effect exacerbation Results Permanent complication-related morbidity and mortality at 3 months was 6% (3/48). No specific predictors of hemorrhagic complications were identified. In the univariate analysis, the strongest predictors of thrombotic complications were: ADP % inhibition Conclusions Procedural complexity, reflected by fluoroscopy time, is the strongest predictor of thrombotic complications in this study. ADP% inhibition is a reliable method of testing clopidogrel response in neurovascular procedures and values of

Background and Purpose— Degree of stent retriever engagement with target thrombi may be reflected by (1) immediate reperfusion (IR) on first deployment, indicating displacement of clot toward the vessel wall, and (2) by early loss of IR (ELOIR), indicating penetration of retriever struts through the thrombus. The relation of these early findings to final reperfusion and clinical outcomes has not been well delineated. Methods— We investigated IR and ELOIR in patients undergoing stent retriever mechanical thrombectomy at an academic medical center between March 2012 and June 2014. Results— Among 56 patients, IR itself was not associated with final successful reperfusion, which occurred in 66.7% of IR patients and 71.4% of non-IR patients ( P =0.999). However, ELOIR was associated with a higher rate of final successful reperfusion (92% versus 44%; P =0.046). Patients with ELOIR had a higher nominal rate of final favorable outcome (42% versus 22%; P =0.64). Conclusions— ELOIR during the embedding period after deployment of stent retrievers is associated with successful final reperfusion, likely because of greater thrombus engagement with the stent retriever. ELOIR may be a useful finding to guide duration of embedding time in clinical practice and design of novel stent retrievers.

Background and Purpose— Imaging findings can predict outcomes in patients with acute stroke. Relationships between imaging findings and clinical and imaging outcomes in patients randomized to intravenous tissue-type plasminogen activator–alone versus tissue-type plasminogen activator plus endovascular therapy (Solitaire device) in the Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke (SWIFT PRIME) study were assessed. Methods— We evaluated associations between imaging assessments (baseline mismatch profiles/ischemic core volumes and successful reperfusion) with imaging outcomes (27-hour infarct volume/growth) and clinical outcomes (modified Rankin Scale scores at 90 days). Imaging variables that predict favorable clinical outcomes were assessed in both univariate and multivariate models. Results— One hundred and ninety-five patients were included. Successful reperfusion and infarct volume (assessed at 27 hours) were powerful independent predictors of favorable clinical outcomes (modified Rankin Scale score of 0–2 at 90 days). Patients with the target mismatch profile at baseline had a higher rate of reperfusion, lesser infarct growth, smaller infarct volumes, and better clinical outcomes in the Solitaire plus tissue-type plasminogen activator (intervention) group than those in the tissue-type plasminogen activator–alone (control) group. Patients with larger mismatch volumes at baseline had a trend toward better treatment response in the intervention group than patients who had smaller ( Conclusions— Patients who achieved reperfusion had substantially more favorable clinical and imaging outcomes in both the intervention and the control groups. Infarct volume at 27 hours strongly correlated with clinical outcome at 90 days in both treatment groups. SWIFT PRIME patients with the target mismatch profile had a highly favorable response to endovascular therapy on both clinical and imaging outcomes. Both reperfusion and infarct volumes at 27 hours were powerful and independent predictors of 90-day clinical outcomes. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01657461.

Rationale Endovascular treatment has been shown to restore blood flow effectively. Second-generation medical devices such as stent retrievers are now showing overwhelming efficacy in clinical trials, particularly in conjunction with intravenous recombinant tissue plasminogen activator. Aims and Design This statistical analysis plan utilizing a novel, sequential approach describes a prospective, individual patient data analysis of endovascular therapy in conjunction with intravenous recombinant tissue plasminogen activator agreed upon by the Thrombectomy and Tissue Plasminogen Activator Collaborative Group. Study outcomes This protocol will specify the primary outcome for efficacy, as ‘favorable’ outcome defined by the ordinal distribution of the modified Rankin Scale measured at three-months poststroke, but with modified Rankin Scales 5 and 6 collapsed into a single category. The primary analysis will aim to answer the questions: ‘what is the treatment effect of endovascular therapy with intravenous recombinant tissue plasminogen activator compared to intravenous tissue plasmi-nogen activator alone on full scale modified Rankin Scale at 3 months?’ and ‘to what extent do key patient characteristics influence the treatment effect of endovascular therapy?’. Key secondary outcomes include effect of endovascular therapy on death within 90 days; analyses of modified Rankin Scale using dichotomized methods; and effects of endovascular therapy on symptomatic intracranial hemorrhage. Several secondary analyses will be considered as well as expanding patient cohorts to intravenous recombinant tissue plasminogen activator-ineligible patients, should data allow. Discussion This collaborative meta-analysis of individual participant data from randomized trials of endovascular therapy vs. control in conjunction with intravenous thrombolysis will demonstrate the efficacy and generalizability of endovascular therapy with intravenous thrombolysis as a concomitant medication.

BACKGROUND AND PURPOSE: Intracranial hemorrhage is the most dreaded complication of neurothrombectomy therapy for acute ischemic stroke. The determinants of intracranial hemorrhage and its impact on clinical course remain incompletely delineated. The purpose of this study is to further investigate the clinical and procedural factors leading to intracranial hemorrhage and to define the clinical impact of different hemorrhagic subtypes. MATERIALS AND METHODS: We analyzed data prospectively collected in the Solitaire FR With Intention for Thrombectomy randomized clinical trial. A multivariable logistic regression model was used to identify independent clinical, imaging, and procedural predictors of any intracranial hemorrhage and of 7 intracranial hemorrhage subtypes. Univariate analysis was used to determine the impact of each of the intracranial hemorrhage subtypes on clinical outcome. RESULTS: Among the 144 enrolled patients, any radiologic intracranial hemorrhage (21.3% versus 38.2%, P = .035), symptomatic intracranial hemorrhage (1.1% versus 10.9%, P = .012), and subarachnoid hemorrhage (2.2% versus 12.7%, P = .027) occurred less frequently in the Solitaire FR than in the Merci retriever arms. The most common independent determinant of hemorrhage occurrence was rescue therapy with intra-arterial rtPA, which was associated with any intracranial hemorrhage and 4 subtypes and tended to be used more frequently in the Merci group (10.9% versus 3.4%; P = .09). Among the hemorrhage subtypes, basal ganglionic hemorrhage had the strongest impact on good clinical outcome at 90 days (OR, 0.30; P = .025) and was associated with higher reperfusion, prolonged time to treatment, and rescue therapy with intra-arterial rtPA. CONCLUSIONS: Intracranial hemorrhage, especially subarachnoid and symptomatic intracerebral hemorrhage, occurs less frequently with the Solitaire FR than the Merci retriever, in part due to less frequent use of rescue therapy with intra-arterial rtPA. Basal ganglionic hemorrhage strongly affects clinical outcome and is distinctively related to late reperfusion.

OBJECTIVE Faster time from onset to recanalization (OTR) in acute ischemic stroke using endovascular therapy (ET) has been associated with better outcome. However, previous studies were based on less-effective first-generation devices, and analyzed only dichotomized disability outcomes, which may underestimate the full effect of treatment. METHODS In the combined databases of the SWIFT and STAR trials, we identified patients treated with the Solitaire stent retriever with achievement of substantial reperfusion (Thrombolysis in Cerebral Infarction [TICI] 2b-3). Ordinal numbers needed to treat values were derived by populating joint outcome tables. RESULTS Among 202 patients treated with ET with TICI 2b to 3 reperfusion, mean age was 68 (±13), 62% were female, and median National Institutes of Health Stroke Scale (NIHSS) score was 17 (interquartile range [IQR]: 14-20). Day 90 modified Rankin Scale (mRS) outcomes for OTR time intervals ranging from 180 to 480 minutes showed substantial time-related reductions in disability across the entire outcome range. Shorter OTR was associated with improved mean 90-day mRS (1.4 vs. 2.4 vs. 3.3, for OTR groups of 124-240 vs. 241-360 vs. 361-660 minutes; p < 0.001). The number of patients identified as benefitting from therapy with shorter OTR were 3-fold (range, 1.5-4.7) higher on ordinal, compared with dichotomized analysis. For every 15-minute acceleration of OTR, 34 per 1,000 treated patients had improved disability outcome. INTERPRETATION Analysis of disability over the entire outcome range demonstrates a marked effect of shorter time to reperfusion upon improved clinical outcome, substantially higher than binary metrics. For every 5-minute delay in endovascular reperfusion, 1 of 100 patients has a worse disability outcome. Ann Neurol 2015;78:584-593.

Background and purposeIncreasing time from symptom onset to emergency department arrival may incur greater ischemic injury and decreased likelihood of good outcomes after acute stroke therapy. The impact of time may be assessed bythe extent of acute CT changes, status of collateral vessels, and clinical outcomes.MethodsThe SOLITAIRE FR With the Intention For Thrombectomy (SWIFT) trial comparing two neurothrombectomy treatments was analyzed by time, Alberta Stroke Program Early CT Scores (ASPECTS), angiographic collaterals, and 90-day modified Rankin Scale outcomes. We determined the interaction of time with ASPECTS, collateral grade, reperfusion, and clinical outcomes, with established determinants of angiographic and clinical outcomes as covariates.Results137 patients (52% female) of mean age 67±12 years and median pretreatment NIH Stroke Scale score 18 (range 8–28) were enrolled. Median onset to door (OTD) time was 180 min (IQR 95–250). Presentation within 3 h of last known well was associated with absence of any prestroke disability and presence of atrial fibrillation but was unrelated to age, sex, other vascular risk factors, deficit severity, glucose level, or blood pressure. Worse collaterals were noted with longer OTD intervals: collateral grade 0–1 (n=32): mean 232±84 min; grade 2 (n=48): 164±99 min; grade 3 (n=35): 155±104 min; grade 4 (n=4): 54±16 min (p3 h vs 9 (IQR 8–10) 3 h as the only predictor of extensive infarct on imaging (ASPECTS ≤7), p=0.003. Earlier presentation was strongly associated with better 90-day modified Rankin Scale outcomes (pConclusionsTime was a critical factor in successful clinical outcomes for neurothrombectomy in the SWIFT trial. Shorter times to presentation were associated with better collaterals, smaller established infarcts, and better clinical outcome after revascularization.

Endovascular therapy for acute stroke has evolved with the use of intra-arterial thrombolytics, intravenous/intra-arterial bridging strategies, and mechanical thrombectomy/aspiration devices. Despite widespread use in clinical practice, randomized trials of first-generation devices failed to demonstrate improved outcomes compared with standard care. New-generation stent retriever devices demonstrate higher rates of revascularization and clinical outcomes compared with first-generation devices. Additional randomized trials are underway and have the potential to confirm clinical efficacy of new-generation devices compared with standard care. The role of additional advanced imaging for patient selection remains unclear, and further trials are needed to demonstrate the role of these techniques for patient selection.

Perimesencephalic subarachnoid hemorrhage (PM-SAH) refers to intracranial hemorrhage located in the perimesencephalic cistern. The etiology remains mainly unclear, although venous leakage or rupture has been postulated. We report an interesting case of a 57-year-old healthy man who presented initially with PM-SAH with worsening of subcortical lesions on follow-up neuroimaging. Histopathological examination demonstrated cerebral amyloid angiopathy with perivascular inflammation.

Introduction: Clot fragmentation and distal embolization is a feared complication of mechanical thrombectomy treatment for acute ischemic stroke, but the frequency, determinants, and outcomes of distal emboli (DE) with modern endovascular reperfusion techniques is poorly characterized. Gradient refocused echo (GRE) MRI, performed before and after intervention, is a novel technique to directly visualize distal emboli and characterize their causes and consequences. Methods: We analyzed consecutive acute ischemic stroke thrombectomy patients who had MR imaging pre- and post-intervention. Distal emboli were defined as new post-procedure susceptibility vessel signs on GRE, within arteries distal to the target occlusion or within new territories. Results: Among 50 consecutive patients, age was 70.4 (±15.8), 44% were female, and NIHSS was 15 (IQR 8-19). Thrombectomy techniques include retrievers alone in 42%, aspiration alone in 8%, both retriever and aspiration in 50%, and other (e.g. angioplasty, wire maceration) in 22%. The rate of substantial reperfusion (mTICI 2b-3) was 84%. New distal emboli downstream in the territory of the target occlusion were noted in 22% of patients (single in 91% and multiple in 9%), while no emboli in a new territory were observed. Predictors of distal emboli were: pretreatment with IV tPA (present in 64% of patients with DE vs 26% without, p=0.03); and ICA target occlusion location (64% vs 28%, p=0.04). Nominal differences in the 3-month rate of severely disabled or dead outcome (mRS 5-6) did not reach statistical significance (44% vs 24%, p=0.40). Conclusions: In the modern neurothrombectomy era, distal emboli within the territory of the target occlusion occur in more than 1 in 5 patients, but embolization to new territories is very uncommon. Predictors of distal emboli are prior intravenous thrombolytic therapy (increasing clot friability) and ICA occlusion location (requiring manipulation of larger thrombi).

Background: Collateral circulation to the ischemic territory is a pivotal factor in outcomes after acute ischemic stroke. Extent of angiographic collaterals prior to endovascular therapy has been linked with reperfusion in previous trials, yet the mechanism remains unclear. We analyzed whether downstream collateral grade influences the pace and degree of ultimate reperfusion. Methods: The angiography dataset collated by the STRATIS Core Lab was analyzed to relate the grade of collateral circulation (ASITN) with adjudicated procedural time metrics to exact time of first TICI ≥ 2A and with the final eTICI score, delineating reperfusion into 7 distinct categories. Results: Collateral grade on routine angiography injections was available in 574/984 (58%) of STRATIS subjects (age 67.5 ± 15.1, 47% women, baseline NIHSS 16.8 ± 5.5). Collaterals included 203/574 (35.4%) with ASITN 3-4, 291/574 (50.7%) ASITN 2 and 80/574 (13.9%) ASITN 0-1. TICI ≥ 2A was achieved at 32.4 ± 23.5 minutes from angiography start and 26.4 ± 18.6 minutes from visualization of the arterial occlusion. The eTICI included 78 TICI 3 (13.6%), 140 TICI 2C (24.4%), 226 TICI o2B (39.3%), 68 TICI m2B (11.8%), 44 TICI 2A (7.7%), 4 TICI 1 (0.7%) and 14 TICI 0 (2.4%). More robust collateral grade was strongly associated with lower NIHSS (15.9 ± 5.4 (ASITN 3-4); 16.7 ± 5.5 (ASITN 2); 19.6 ± 5.1 (ASITN 0-1); p Collaterals and reperfusion were linked at all occlusion sites (ICA, M1, M2, BA). Conclusions: Collaterals on routinely available angiography prior to thrombectomy in STRATIS were strikingly tied to both the speed and degree of final reperfusion, across every site of arterial occlusion.

Background and Purpose— Understanding the influence of hyperglycemia on outcomes in terms of the pretreatment collateral status might contribute to the achievement of case-specific glucose management in acute ischemic stroke. We sought to investigate whether the glucose level can influence the pretreatment collateral status and functional outcomes of endovascular thrombectomy in acute ischemic stroke and whether the impact of hyperglycemia on outcomes can be modified by the pretreatment collateral status. Methods— We analyzed the Triple-S database, which includes individual patient data pooled from 3 prospective Solitaire stent retriever studies (SWIFT [Solitaire With the Intention for Thrombectomy], SWIFT PRIME [SWIFT as Primary Endovascular Treatment], and STAR [Solitaire Flow Restoration Thrombectomy for Acute Revascularization]). Patients were eligible if they had acute ischemic stroke with moderate to severe neurological deficits, harbored angiographically confirmed large vessel occlusion, and were treatable by endovascular thrombectomy within 8 hours of onset. Pretreatment catheter angiograms were scored for collateral grades by a core imaging laboratory. The main outcome was 3-month good outcome (modified Rankin Scale score of 0–2). Results— Angiographic data on collaterals were available in 309 patients (age, 67±12 years; glucose, 131±55 mg/dL). Overall, the glucose level at presentation was not associated with pretreatment collateral status but was significantly lower in patients with a good outcome at 90 days (124 versus 140 mg/dL). Collateral grades modified the effect of glucose on good outcomes at 90 days ( P int =0.03). Among patients with poor collaterals (collateral grades, 0–2), higher glucose levels did not alter the outcome, whereas among patients with good collaterals (3–4), higher glucose levels reduced the likelihood of a good outcome at 90 days (per 10 mg/dL increase: odds ratio, 0.81; 95% CI, 0.69–0.95). Conclusions— Our study revealed that higher glucose levels reduce the likelihood of a good outcome among patients with good collaterals, but their effects on the outcome are less significant for patients with poor collaterals. The results suggest that good collaterals at presentation may be targets for more intensive glucose control and future studies relating to glucose management.

BACKGROUND: General anaesthesia (GA) during endovascular thrombectomy has been associated with worse patient outcomes in observational studies compared with patients treated without GA. We assessed functional outcome in ischaemic stroke patients with large vessel anterior circulation occlusion undergoing endovascular thrombectomy under GA, versus thrombectomy not under GA (with or without sedation) versus standard care (ie, no thrombectomy), stratified by the use of GA versus standard care.METHODS: For this meta-analysis, patient-level data were pooled from all patients included in randomised trials in PuMed published between Jan 1, 2010, and May 31, 2017, that compared endovascular thrombectomy predominantly done with stent retrievers with standard care in anterior circulation ischaemic stroke patients (HERMES Collaboration). The primary outcome was functional outcome assessed by ordinal analysis of the modified Rankin scale (mRS) at 90 days in the GA and non-GA subgroups of patients treated with endovascular therapy versus those patients treated with standard care, adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modelling with a random effect for trials incorporated in all models. Bias was assessed using the Cochrane method. The meta-analysis was prospectively designed, but not registered.FINDINGS: Seven trials were identified by our search; of 1764 patients included in these trials, 871 were allocated to endovascular thrombectomy and 893 were assigned standard care. After exclusion of 74 patients (72 did not undergo the procedure and two had missing data on anaesthetic strategy), 236 (30%) of 797 patients who had endovascular procedures were treated under GA. At baseline, patients receiving GA were younger and had a shorter delay between stroke onset and randomisation but they had similar pre-treatment clinical severity compared with patients who did not have GA. Endovascular thrombectomy improved functional outcome at 3 months both in patients who had GA (adjusted common odds ratio (cOR) 1·52, 95% CI 1·09-2·11, p=0·014) and in those who did not have GA (adjusted cOR 2·33, 95% CI 1·75-3·10, pINTERPRETATION: Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons.FUNDING: Medtronic.

We aimed to evaluate how predefined candidate cerebral perfusion parameters correlate with collateral circulation status and to assess their capacity to predict infarct growth in patients with acute ischemic stroke (AIS) eligible for endovascular therapy. Patients enrolled in the SWIFT PRIME trial with baseline computed tomography perfusion (CTP) scans were included. RAPID software was used to calculate mean relative cerebral blood volume (rCBV) in hypoperfused regions, and hypoperfusion index ratio (HIR). Blind assessments of collaterals were performed using CT angiography in the whole sample and cerebral angiogram in the endovascular group. Reperfusion was assessed on 27-h CTP; infarct volume was assessed on 27-h magnetic resonance imaging/CT scans. Logistic and rank linear regression models were conducted. We included 158 patients. High rCBV ( p = 0.03) and low HIR ( p = 0.03) were associated with good collaterals. A positive association was found between rCBV and better collateral grades on cerebral angiography ( p = 0.01). Baseline and 27-h follow-up CTP were available for 115 patients, of whom 74 (64%) achieved successful reperfusion. Lower rCBV predicted a higher infarct growth in successfully reperfused patients ( p = 0.038) and in the endovascular treatment group ( p = 0.049). Finally, rCBV and HIR may serve as markers of collateral circulation in AIS patients prior to endovascular therapy.

We have reviewed the English literature published in the last 70 years on Diseases of the Vertebral Basilar Circulation, or Posterior Circulation Disease (PCD). We have found that errors have been made in the conduct and interpretation of these studies that have led to incorrect approaches to the management of PCD. Because of the difficulty in evaluating the PC, the management of PCD has been incorrectly applied from anterior circulation disease (ACD) experience to PCD. PCD is a common form of stroke affecting 20-40% patients with stroke. Yet, the evidence is strong that the Anterior Circulation (AC) and Posterior Circulations (PC) differ in their pathology, in their clinical presentations, in the rapidity of development of symptoms, in optimal imaging methods, and in available treatments. There appears to be two categories of patients who present with PCD. The first, acute basilar artery occlusion has a more rapid onset. The diagnosis must be made quickly and if imaging proves a diagnosis of Basilar Artery Occlusion (BAO), the treatment of choice is Interventional removal of the basilar artery thrombosis or embolus. The second category of PCD and the most commonly seen PCD disease process presents with non-specific symptoms and early warnings of PCD that now can be related to ischemic events in the entire PC vessels. These warning symptoms and signs occur much earlier than those in the AC. IA angiography is still the gold standard of diagnosis and is superior in definition to MR and CT angiography which are commonly used as a convenient screening imaging tool to evaluate PCD but are both inferior to IA angiography in definition for lesions below 3-4 mm. In at least two reported studies 7T MR angiography appears superior to other imaging modalities and will become the gold standard of imaging of PCD in the future. Medical treatments applied to the ACD have not been proven of value in specific forms of PCD. Interventional therapy was promising but of unproven value in Randomized Controlled Trials (RCT) except for the treatment of Basilar Artery Occlusion (BAO). Surgical revascularization has been proved to be highly successful in patients, who are refractory to medical therapy. These studies have been ignored by the scientific community basically because of an incorrect interpretation of the flawed EC-IC Bypass Trial in 1985 as applying to all stroke patients. Moreover, the EC-IC Bypass Study did not include PCD patients in their study population, but the study results were extrapolated to patients with PCD without any scientific basis. This experience led clinicians to an incorrect bias that surgical treatments are of no value in PCD. Thus, incorrectly, surgical treatments of PCD have not been considered among the therapeutic possibilities for PCD. QMRA is a new quantitative MR technique that measures specific blood flow in extra and intracranial vessels. QMRA has been used to select those patients who may benefit from medical, or interventional, or surgical treatment for PCD based on flow determinations with a high success rate. QMRA accurately predicts the flows in many large and small vessels in the PC and AC and clearly indicates that both circulations are intimately related. From medical and surgical studies, the longer one waits for surgical treatment the higher the risk of a poor outcome results. This observation becomes obvious when the rapidity of development of PCD is compared with ACD. Recent advances in endovascular therapy in the treatment of acute basilar thrombosis is a clear sign that early diagnosis and treatment of PCD will reduce the morbidity and mortality of these diseases. In this review it is evident that there are multiple medical and surgical treatments for PCD depending upon the location of the lesion(s) and the collateral circulation demonstrated. It is clear that the AC and PC have significant differences. With the exception of the large population studies from Oxford England, the reported studies on the management of PCD in the literature represent small selected subsets of the universe of PC diseases, the information from which is not generalizable to the universe of PCD patients. At this point in the history of PCD, there are not large enough databases of similar patients to provide a basis for valid randomized studies, with the exception of the surgical studies. Thus, a high index of suspicion of the early warning symptoms of PCD should lead to a rapid individual clinical assessment of patients selecting those with PCD. Medical, interventional, and/or surgical treatments should be chosen based on knowledge presented in this review. Recording the results in a national Registry on a continuing basis will provide the data that may help advance the management of PCD based on larger data bases of well documented patient information to guide the selection of future therapies for PCD treatments. It is also clear that the management of patients within the complex of diseases that comprise PCD should be performed in centers with expertise in the imaging, medical, interventional and surgical approaches to diseases of the PCD.

Microcatheter contrast injection (MCI) prior to stent retriever deployment for the treatment of acute ischemic stroke may be useful for evaluation of distal anatomy and flow patterns beyond the occlusion. However, prior data from intra-arterialthrombolysis suggested that MCI increases the risk of intracranial hemorrhage (ICH). The safety and utility of MCI has not been investigated in the setting of thrombectomy.MethodsWe analyzed the Solitaire With the Intention For Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME) trial to correlate pre-intervention MCI flow with collateral flow, and to investigate its impact on ICH and clinical outcome after thrombectomy with the Solitaire device.ResultsMCI was noted in 52% (n=51) of patients with a prevalence for the M2 location of 71% (n=36). Dichotomized correlation demonstrated a strong inverse relationship for partial collaterals with good MCI flow (p=0.004; OR 8.25). None of the MCI variables (presence, number, or grades) correlated with ICH and clinical outcome. The most significant predictors of non-disabled outcome were higher Alberta Stroke Program early CT Score (ASPECTS) (OR 1.61; p=0.0361) and younger age (OR 0.922; p = 0.0109). Higher ASPECTS was also a strong predictor of lower ICH risk (OR 0.501, p=0.0078).ConclusionsCollateral flow inversely correlated with MCI flow in the endovascular arm of the SWIFT PRIME trial. This finding warrants further validation in larger cohorts as MCI may be influenced by individual operator’s technique and choice of syringe size. Evaluation of flow and distal anatomy with MCI prior to stent retriever deployment is safe with no evidence of an impact on ICH or clinical outcome.Clinical trial registrationNCT01657461: Post- results

Background and Purpose— Rapid decision making optimizes outcomes from endovascular thrombectomy for acute cerebral ischemia. Visual displays facilitate swift review of potential outcomes and can accelerate decision processes. Methods— From patient-level, pooled randomized trial data, 100 person-icon arrays (Kuiper–Marshall personographs) were generated showing beneficial and adverse effects of endovascular thrombectomy for patients with acute cerebral ischemia and large vessel occlusion using (1) automated (algorithmic) and (2) expert-guided joint outcome table specification. Results— For the full 7-category modified Rankin Scale, thrombectomy added to IV tPA (intravenous tissue-type plasminogen activator) alone had number needed to treat to benefit 2.9 (95% confidence interval, 2.6–3.3) and number needed to harm 68.9 (95% confidence interval, 40–250); thrombectomy for patients ineligible for IV tPA had number needed to treat to benefit 2.3 (95% confidence interval, 2.1–2.5) and number needed to harm 100 (95% confidence interval, 62.5–250). Visual displays of treatment effects on 100 patients showed: with thrombectomy added to IV tPA alone, 34 patients have better disability outcome, including 14 more normal or near normal (modified Rankin Scale, 0–1); with thrombectomy for patients ineligible for IV tPA, 44 patients have a better disability outcome, including 16 more normal or nearly normal. Displays also showed that harm (increased modified Rankin Scale final disability) occurred in 1 of 100 patients in both populations, mediated by increased new territory infarcts. The person-icon figures integrated these outcomes, and early side-effects, in a single display. Conclusions— Visual decision aids are now available to rapidly educate healthcare providers, patients, and families about benefits and risks of endovascular thrombectomy, both when added to IV tPA in tPA-eligible patients and as the sole reperfusion treatment in tPA-ineligible patients.

Background Endovascular treatment for large-vessel acute ischemic stroke (AIS) has rapidly emerged. However, the understanding of the complex biology involving endothelial cells (ECs) remains scarce. Methods Using stent retrievers during endovascular thrombectomy (ET) in patients with AIS, ECs were segregated, centrifuged in a dissociation buffer, and suspended in endothelial specific antibody solution. Subsequently, fluorescence-activated cell sorting (FACS) and microscopic analyses were performed. Results Three stent-retriever devices (2 Solitaire, 1 Trevo) were collected as separate deployments. Of 5.0% (±.48%) total events using FACS, 6.8% (±.68%) of cells were specific for ECs using fluorescent markers and were further visualized on fluorescence microscopy for consistence with the positive controls. Conclusions We describe a novel, minimally invasive biopsy technique to collect and harvest ECs from stent retrievers during ET and validate the approach in the treatment of AIS. Further work for detailed characterization and viability assessment of ECs is needed to compare their biology with in vitro and animal models.

The purpose of this study was to develop and evaluate a scoring system for assessing reperfusion status based on arterial spin labeled (ASL) perfusion MRI in acute ischemic stroke (AIS) patients receiving thrombolysis and/or endovascular treatment. Pseudo-continuous ASL with background suppressed 3D GRASE was acquired along with DWI in 90 patients within 24 h post-treatment. An automatic reperfusion scoring system (auto-RPS) was devised based on the Alberta Stroke Program Early CT Score (ASPECTS) template, and compared with manual RPS and DWI-ASPECTS. TICI (thrombolysis in cerebral infarction) scores were graded in 48 patients who received endovascular treatment. Favorable outcomes were defined by a modified Rankin Scale score of 0–2 at three months. Auto-RPS was positively correlated with DWI-ASPECTS (ρ = 0.6, P

Background and purpose Cerebral vasospasm following aneurysmal subarachnoid hemorrhage (aSAH) results in significant morbidity due to ischemia. Subarachnoid hematoma evacuation during aneurysm clipping reduces the incidence of vasospasm. However, studies comparing endovascular coiling with open clipping have reported similar rates of spasm. We addressed the question of how coiling produces similar (if not less) vasospasm without the benefit of clot evacuation by evaluating vasospasm patterns among patients with aSAH. We hypothesize that cerebrospinal fluid (CSF) circulation plays a major role in clearing blood breakdown products, and that coiling may preserve CSF flow in the subarachnoid space. Methods A retrospective chart review identified 36 (18 coiled/18 clipped) patients with aSAH who developed angiographic vasospasm. The degree of spasm was quantified using an ordinal scale from 0 (none) to 5 (severe) for 26 anatomic vessel segments evaluated on 164 successive angiograms. Statistical analysis was performed using the Fisher exact test for proportions and the Wilcoxon and Student t tests on ordinal/continuous measures. Quadratic regression was also used as a model for spasm activity versus post-bleed days. Results In both the coiling and clipping groups the most severely spastic vessels were located adjacent to aneurysm rupture. Perianeurysmal spasm affected all subjects. However, whereas spasm remained largely confined in patients treated by clipping, those who underwent coiling developed stepwise progression distally over time. The distal vasospasm severity scores were higher among subjects treated by coiling, particularly in the most dependent regions of the subarachnoid space. Conclusions Patients with aSAH treated by endovascular coiling and surgical clipping demonstrate distinct vasospasm patterns. While both initially exhibit perianeurysmal spasm, patients treated by coiling go on to develop stepwise progression distally over time. This finding may reflect dispersion of blood breakdown products along preserved CSF egress pathways in patients treated by endovascular coiling.

Background and Purpose— The Alberta Stroke Program Early CT Score (ASPECTS) on baseline imaging is an established predictor of acute ischemic stroke outcomes. We analyzed change on serial ASPECTS at baseline and 24-hour imaging in the Solitaire Flow Restoration with the Intention for Thrombectomy (SWIFT) study to determine prognostic value and to identify subgroups with extensive injury after intervention. Methods— ASPECTS at baseline and 24 hours was independently scored in all anterior circulation SWIFT cases, blinded to all other trial data. ASPECTS at baseline, at 24 hours, and serial changes were analyzed with univariate and multivariate approaches. Results— One hundred thirty-nine patients (mean age, 67 [SD, 12] years; 52% women; median National Institutes of Health Stroke Scale, 18 [interquartile range, 8–28]) with complete data at both time points were studied. Multivariate analyses showed that higher 24-hour ASPECTS predicted good clinical outcome (day 90 modified Rankin Scale, 0–2; odds ratio, 1.67; P P =0.019), higher baseline blood glucose ( P =0.133), and failure to achieve Thrombolysis in Cerebral Infarction score of 2b/3 reperfusion ( P P Conclusions— Twenty-four-hour ASPECTS provides better prognostic information compared with baseline ASPECTS. Predictors of dramatic infarct progression on ASPECTS are hyperglycemia, hypertension, and nonreperfusion. Serial ASPECTS change from baseline to 24 hours predicts clinical outcome, providing an early surrogate end point for thrombectomy trials. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01054560.

Importance Randomized clinical trials suggest benefit of endovascular-reperfusion therapy for large vessel occlusion in acute ischemic stroke (AIS) is time dependent, but the extent to which it influences outcome and generalizability to routine clinical practice remains uncertain. Objective To characterize the association of speed of treatment with outcome among patients with AIS undergoing endovascular-reperfusion therapy. Design, Setting, and Participants Retrospective cohort study using data prospectively collected from January 2015 to December 2016 in the Get With The Guidelines-Stroke nationwide US quality registry, with final follow-up through April 15, 2017. Participants were 6756 patients with anterior circulation large vessel occlusion AIS treated with endovascular-reperfusion therapy with onset-to-puncture time of 8 hours or less. Exposures Onset (last-known well time) to arterial puncture, and hospital arrival to arterial puncture (door-to-puncture time). Main Outcomes and Measures Substantial reperfusion (modified Thrombolysis in Cerebral Infarction score 2b-3), ambulatory status, global disability (modified Rankin Scale [mRS]) and destination at discharge, symptomatic intracranial hemorrhage (sICH), and in-hospital mortality/hospice discharge. Results Among 6756 patients, the mean (SD) age was 69.5 (14.8) years, 51.2% (3460/6756) were women, and median pretreatment score on the National Institutes of Health Stroke Scale was 17 (IQR, 12-22). Median onset-to-puncture time was 230 minutes (IQR, 170-305) and median door-to-puncture time was 87 minutes (IQR, 62-116), with substantial reperfusion in 85.9% (5433/6324) of patients. Adverse events were sICH in 6.7% (449/6693) of patients and in-hospital mortality/hospice discharge in 19.6% (1326/6756) of patients. At discharge, 36.9% (2132/5783) ambulated independently and 23.0% (1225/5334) had functional independence (mRS 0-2). In onset-to-puncture adjusted analysis, time-outcome relationships were nonlinear with steeper slopes between 30 to 270 minutes than 271 to 480 minutes. In the 30- to 270-minute time frame, faster onset to puncture in 15-minute increments was associated with higher likelihood of achieving independent ambulation at discharge (absolute increase, 1.14% [95% CI, 0.75%-1.53%]), lower in-hospital mortality/hospice discharge (absolute decrease, −0.77% [95% CI, −1.07% to −0.47%]), and lower risk of sICH (absolute decrease, −0.22% [95% CI, −0.40% to −0.03%]). Faster door-to-puncture times were similarly associated with improved outcomes, including in the 30- to 120-minute window, higher likelihood of achieving discharge to home (absolute increase, 2.13% [95% CI, 0.81%-3.44%]) and lower in-hospital mortality/hospice discharge (absolute decrease, −1.48% [95% CI, −2.60% to −0.36%]) for each 15-minute increment. Conclusions and Relevance Among patients with AIS due to large vessel occlusion treated in routine clinical practice, shorter time to endovascular-reperfusion therapy was significantly associated with better outcomes. These findings support efforts to reduce time to hospital and endovascular treatment in patients with stroke.

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 χ2. Results: Patients (n = 165) with aneurysms (n = 258) had a mean fol-low- 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.

Pediatric intracranial aneurysms are rare and not well characterized in comparison with those in adults.To analyze our institution's longitudinal experience of endovascular treatment for pediatric aneurysms to better understand this rare condition.A retrospective record review was performed of patients aged20 years treated with endovascular methods for intracranial aneurysms between 1995 and 2012. There were 31 patients (average 14.4±4.2 years; 20 male, 11 female) with 35 intracranial aneurysms.The rate of subarachnoid hemorrhage as the initial presentation was 48% and the rates of multiple and giant aneurysms were 13% and 31%, respectively; 28.5% of the cases were posterior circulation aneurysms. Fifteen saccular aneurysms occurred in 14 patients and 17 fusiform aneurysms were noted in 14 patients. Two infectious aneurysms were diagnosed in two patients and one traumatic aneurysm occurred in another patient. Thirty-four aneurysms were treated endovascularly and one had thrombosed spontaneously on a follow-up angiogram. Of the 15 saccular aneurysms, 11 were treated with conventional coiling, one was treated with stent-assisted coiling, one was treated with a flow-diverting stent and two were treated with parent vessel occlusion (PVO). Of the 17 fusiform aneurysms, 15 were treated with PVO with or without prior bypass surgery and one was treated with a flow-diverting stent. The rate of permanent complications and a favorable outcome were 2.9% and 87%, respectively.Endovascular treatment of pediatric aneurysms is technically feasible with an acceptable complication rate despite the high incidence of fusiform aneurysms.

BackgroundWhether brain imaging can identify patients who are most likely to benefit from therapies for acute ischemic stroke and whether endovascular thrombectomy improves clinical outcomes in such patients remains unclear. MethodsIn this study, we randomly assigned patients within 8 hours after the onset of large-vessel, anterior-circulation strokes to undergo mechanical embolectomy (Merci Retriever or Penumbra System) or receive standard care. All patients underwent pretreatment computed tomography or magnetic resonance imaging of the brain. Randomization was stratified according to whether the patient had a favorable penumbral pattern (substantial salvageable tissue and small infarct core) or a nonpenumbral pattern (large core or small or absent penumbra). We assessed outcomes using the 90-day modified Rankin scale, ranging from 0 (no symptoms) to 6 (dead). ResultsAmong 118 eligible patients, the mean age was 65.5 years, the mean time to enrollment was 5.5 hours, and 58% had a favorable penumbral patt...