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BackgroundTargeted eloquence-based tissue reperfusion within the primary motor cortex may have a differential effect on disability as compared with traditional volume-based (thrombolysis in cerebral infarction, TICI) reperfusion after endovascular thrombectomy (EVT) in the setting of acute ischemic stroke (AIS).MethodsWe explored the impact of eloquent reperfusion (ER) within primary motor cortex (PMC) on clinical outcome (modified Rankin Scale, mRS) in AIS patients undergoing EVT. ER-PMC was defined as presence of flow on final digital subtraction angiography (DSA) within four main cortical branches, supplying the PMC (middle cerebral artery (MCA) – precentral, central, postcentral; anterior cerebral artery (ACA) – medial frontal branch arising from callosomarginal or pericallosal arteries) and graded as absent (0), partial (1), and complete (2). Prospectively collected data from two centers were analyzed. Multivariate analysis was conducted to assess the impact of ER-PMC on 90-day disability (mRS) among patients with anterior circulation occlusion who achieved partial reperfusion (TICI 2a and 2b).ResultsAmong the 125 patients who met the study criteria, ER-PMC distribution was: absent (0) in 19/125 (15.2%); partial (1) in 52/125 (41.6%), and complete (2) in 54/125 (43.2%). TICI 2b was achieved in 102/125 (81.6%) and ER-PMC was substantially higher in those patients (PConclusionsEloquent PMC-tissue reperfusion is a key determinant of functional outcome, with a greater impact than volume-based (TICI) degree of partial reperfusion alone. PMC-targeted revascularization among patients with partial reperfusion may further diminish post-stroke disability after EVT.

BACKGROUND AND PURPOSE: Acute leptomeningeal collateral flow is vital for maintaining perfusion to penumbral tissue in acute ischemic stroke caused by large-vessel occlusion. In this study, we aimed to investigate the clinically available indicators of leptomeningeal collateral variability in embolic large-vessel occlusion. MATERIALS AND METHODS: Among prospectively registered consecutive patients with acute embolic anterior circulation large-vessel occlusion treated with thrombectomy, we analyzed 108 patients admitted from January 2015 to December 2019 who underwent evaluation of leptomeningeal collateral status on pretreatment CTA. Clinical characteristics, extent of leukoaraiosis on MR imaging, embolic stroke subtype, time of imaging, occlusive thrombus characteristics, presenting stroke severity, and clinical outcome were collected. The clinical indicators of good collateral status (>50% collateral filling of the occluded territory) were analyzed using multivariate logistic regression analysis. RESULTS: Good collateral status was present in 67 patients (62%) and associated with independent functional outcomes at 3 months. Reduced leukoaraiosis (total Fazekas score, 0–2) was positively related to good collateral status (OR, 9.57; 95% CI, 2.49–47.75), while the cardioembolic stroke mechanism was inversely related to good collateral status (OR, 0.17; 95% CI, 0.02–0.87). In 82 patients with cardioembolic stroke, shorter thrombus length (OR, 0.91 per millimeter increase; 95% CI, 0.82–0.99) and reduced leukoaraiosis (OR, 5.79; 95% CI, 1.40–29.61) were independently related to good collateral status. CONCLUSIONS: Among patients with embolic large-vessel occlusion, reduced leukoaraiosis, noncardiac embolism mechanisms including embolisms of arterial or undetermined origin, and shorter thrombus length in cardioembolism are indicators of good collateral flow.

Background and Purpose— In acute arterial occlusion, fluid-attenuated inversion recovery vascular hyperintensity (FVH) has been linked to slow flow in leptomeningeal collaterals and cerebral hypoperfusion, but the impact on clinical outcome is still controversial. In this study, we aimed to investigate the association between FVH topography or FVH-Alberta Stroke Program Early CT Score (ASPECTS) pattern and outcome in acute M1-middle cerebral artery occlusion patients with endovascular treatment. Methods— We included acute M1-middle cerebral artery occlusion patients treated with endovascular therapy (ET). All patients had diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery before ET. Distal FVH-ASPECTS was evaluated according to distal middle cerebral artery-ASPECT area (M1–M6) and acute DWI lesion was also reviewed. The presence of FVH inside and outside DWI-positive lesions was separately analyzed. Clinical outcome after ET was analyzed with respect to different distal FVH-ASPECTS topography. Results— Among 101 patients who met inclusion criteria for the study, mean age was 66.2±17.8 years and median National Institutes of Health Stroke Scale was 17.0 (interquartile range, 12.0–21.0). FVH-ASPECTS measured outside of the DWI lesion was significantly higher in patients with good outcome (modified Rankin Scale [mRS] score of 0–2; 8.0 versus 4.0, P P =0.013). FVH-ASPECTS inside the DWI lesion was associated with hemorrhagic transformation (odds ratio, 1.3; 95% confidence interval, 1.04–1.51; P =0.019). Conclusions— Higher FVH-ASPECTS measured outside the DWI lesion is associated with good clinical outcomes in patients undergoing ET. FVH-ASPECTS measured inside the DWI lesion was predictive of hemorrhagic transformation. The FVH pattern, not number, can serve as an imaging selection marker for ET in acute middle cerebral artery occlusion.

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.

The recent development of revascularization devices, including stent retrievers, has enabled increasingly higher revascularization rates for arterial occlusions in acute ischemic stroke. Patient-specific factors such as anatomy, however, may occasionally limit endovascular deployment of these new devices via the conventional transfemoral approach. We report three cases of acute ischemic stroke where a transbrachial endovascular approach to revascularization was used, resulting in successful recanalization. These examples suggest that a transbrachial approach may be considered as an alternative in the endovascular treatment of acute ischemic stroke.

// Xin Lou 1 , Songlin Yu 2 , Fabien Scalzo 2 , Sidney Starkman 2 , Latisha K. Ali 2 , Doojin Kim 2 , Neal M. Rao 2 , Jason D. Hinman 2 , Paul M. Vespa 2 , Reza Jahan 3 , Satoshi Tateshima 4 , Nestor R. Gonzalez 5 , Gary R. Duckwiler 6 , Jeffrey L. Saver 2 , Bryan Yoo 3 , Noriko Salamon 3 , Jinhao Lyu 1 , Lin Ma 1 , Danny JJ Wang 2 and David S. Liebeskind 2 1 Department of Radiology, Chinese PLA General Hospital, Beijing, China 2 Department of Neurology, UCLA Stroke Center, Los Angeles, California, USA 3 Department of Radiology, UCLA Stroke Center, Los Angeles, California, USA 4 Department of Medical Center, UCLA Stroke Center, Los Angeles, California, USA 5 Department of Neurosurgery/Interventional Neuroradiology, UCLA Stroke Center, Los Angeles, California, USA 6 Department of Radiology and Neurosurgery, UCLA Stroke Center, Los Angeles, California, USA Correspondence to: David S Liebeskind, email: // Keywords : collateral circulation; stroke; perfusion imaging; arterial spin-labeling; cerebral blood flow Received : October 21, 2016 Accepted : November 24, 2016 Published : December 10, 2016 Abstract Background and Purpose: Multi-delay arterial spin-labeling (ASL) perfusion imaging has been used as a promising modality to evaluate cerebral perfusion. Our aim was to assess the association of leptomeningeal collateral perfusion scores based on ASL parameters with outcome of endovascular treatment in patients with acute ischemic stroke (AIS) in the middle cerebral artery (MCA) territory. Materials and Methods: ASL data at 4 post-labeling delay (PLD) times (PLD = 1.5, 2, 2.5, 3 s) were acquired during routine clinical magnetic resonance examination on AIS patients prior to endovascular treatment. A 3-point scale of leptomeningeal collateral perfusion grade on 10 anatomic regions was determined based on arterial transit times (ATT), cerebral blood flow (CBF), and arterial cerebral blood volume (CBV), estimated by the multi-delay ASL protocol. Based on a 90-day modified Rankin Scale (mRS), the patients were dichotomized to moderate/good (mRS 0–3) and poor outcome (mRS 4–6) and the regional collateral flow scores were compared. Results: Fifty-five AIS patients with unilateral MCA stroke (mean 73.95±14.82 years) including 23 males were enrolled. Compared with poor outcome patients, patients with moderate to good outcomes had a significantly higher leptomeningeal collateral perfusion scores on CBV (3.01±2.11 vs. 1.82±1.51, p =0.024) but no differences on scores on CBF (2.31±1.61 vs. 1.66±1.32, p =0.231) and ATT (2.67±2.33 vs. 3.42±3.37, p =0.593). Conclusions: Higher leptomeningeal collateral perfusion scores on CBV images by ASL may be a specific marker of clinical outcome after endovascular treatment in patients with acute MCA ischemic stroke. Further study with larger sample size is warranted.

BackgroundThe influence of cerebral microbleeds (CMBs) on post-thrombolytic hemorrhagic transformation (HT) in patients with acute ischemic stroke remains controversial.ObjectiveTo investigate the association of CMBs with HT and clinical outcomes among patients with large-vessel occlusion strokes treated with mechanical thrombectomy.MethodsWe analyzed patients with acute stroke treated with Merci Retriever, Penumbra system or stent-retriever devices. CMBs were identified on pretreatment T2-weighted, gradient-recall echo MRI. We analyzed the association of the presence, burden, and distribution of CMBs with HT, procedural complications, in-hospital mortality, and clinical outcome.ResultsCMBs were detected in 37 (18.0%) of 206 patients. Seventy-three foci of microbleeds were identified. Fourteen patients (6.8%) had ≥2 CMBs, only 1 patient had ≥5 CMBs. Strictly lobar CMBs were found in 12 patients, strictly deep CMBs in 12 patients, strictly infratentorial CMBs in 2 patients, and mixed CMBs in 11 patients. There were no significant differences between patients with CMBs and those without CMBs in the rates of overall HT (37.8% vs 45.6%), parenchymal hematoma (16.2% vs 19.5%), procedure-related vessel perforation (5.4% vs 7.1%), in-hospital mortality (16.2% vs 18.3%), and modified Rankin Scale score 0–3 at discharge. CMBs were not independently associated with HT or in-hospital mortality in patients treated with either thrombectomy or intravenous thrombolysis followed by thrombectomy.ConclusionsPatients with CMBs are not at increased risk for HT and mortality following mechanical thrombectomy for acute stroke. Excluding such patients from mechanical thrombectomy is unwarranted. The risk of HT in patients with ≥5 CMBs requires further study.

BackgroundSelection bias may have affected enrollment in first generation endovascular stroke trials. We investigate, evaluate, and quantify such bias for these trials at our institution.MethodsDemographic, clinical, imaging, and angiographic data were prospectively collected on a consecutive cohort of patients with acute ischemic stroke who were enrolled in formal trials of endovascular stroke therapy (EST) or received EST in clinical practice outside of a randomized trial for acute cerebral ischemia at a single tertiary referral center from September 2004 to December 2012.ResultsAmong patients considered appropriate for EST in practice, 47% were eligible for trials, with rates for individual trials ranging from 17% to 70%. Compared with trial ineligible patients treated with EST, trial eligible patients were younger (67 vs 74 years; pConclusionsThe majority of patients felt suitable for EST at our institution were excluded from recent trials. Formal entry criteria succeeded in selecting patients with better prognostic features, although many of these patients were treated outside of trials. Acknowledging and mitigating these biases will be crucial to ongoing investigations.

Background and Purpose— Few studies have addressed outcomes among patients ≥80 years treated with acute stroke therapy. In this study, we outline in-hospital outcomes in (1) patients ≥80 years compared with their younger counterparts; and (2) those over >80 years receiving intra-arterial therapy (IAT) compared with those treated with intravenous recombinant tissue-type plasminogen activator (IV rtPA). Methods— Stroke centers within the Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) prospectively collected data on all patients treated with IV rtPA or IAT from January 1, 2005, to December 31, 2010. IAT was defined as receiving any endovascular therapy; IAT was further divided into bridging therapy when the patient received both IAT and IV rtPA and endovascular therapy alone. In-hospital mortality was compared in (1) all patients aged ≥80 years versus younger counterparts; and (2) IAT, bridging therapy, and endovascular therapy alone versus IV rtPA only among those age ≥80 years using multivariable logistic regression. An age-stratified analysis was also performed. Results— A total of 3768 patients were included in the study; 3378 were treated with IV rtPA alone and 808 with IAT (383 with endovascular therapy alone and 425 with bridging therapy). Patients ≥80 years (n=1182) had a higher risk of in-hospital mortality compared with younger counterparts regardless of treatment modality (OR, 2.13; 95% CI, 1.60–2.84). When limited to those aged ≥80 years, IAT (OR, 0.95; 95% CI, 0.60–1.49), bridging therapy (OR, 0.82; 95% CI, 0.47–1.45), or endovascular therapy alone (OR, 1.15; 95% CI, 0.64–2.08) versus IV rtPA were not associated with increased in-hospital mortality. Conclusions— IAT does not appear to increase the risk of in-hospital mortality among those aged >80 years compared with IV thrombolysis alone.

Objective To investigate whether anterior choroidal artery (AChA) territory sparing or AChA infarction restricted to the medial temporal lobe (MT), implying good collateral status, predicts good outcome, defined as modified Rankin Scale 0–2, at discharge in acute internal carotid artery (ICA) occlusion. Methods The authors studied consecutive patients with acute ICA occlusion admitted to an academic medical centre between January 2002 and August 2010, who underwent MRI followed by conventional angiography. The pattern of AChA involvement on initial diffusion-weighted imaging was dichotomised as spared or MT only versus other partial or full. The association of AChA infarct patterns and good outcome at discharge was calculated by multivariate logistic regression with adjustment. Results For the 60 patients meeting entry criteria, mean age was 68.3 years and median admission NIH Stroke Scale score was 19. AChA territory was spared or restricted to the MT in 27 patients and other partially involved or fully involved in 33 patients. AChA territory spared or ischaemia restricted to MT only, compared with other partial infarct patterns or full infarct, was independently associated with good discharge outcome (44.4% vs 12.1%, OR 7.24, 95% CI 1.32 to 39.89, p=0.023). Conclusion In acute ICA occlusion, the absence of AChA infarction or restriction to the MT is an independent predictor of good discharge outcome. Analysis of AChA infarct patterns may improve early prognostication and decision-making.

Background and Purpose— Determinants of successful recanalization likely differ for Merci thrombectomy and intra-arterial pharmacological fibrinolysis interventions. Although the amount of thrombotic material to be digested is an important consideration for chemical lysis, mechanical debulking may be more greatly influenced by other target lesion characteristics. Methods— In consecutive patients with acute ischemic stroke treated with Merci thrombectomy for middle cerebral artery M1 occlusions, we analyzed the influence on recanalization success and clinical outcome of target thrombus size (length) and shape (curvature and branching) on pretreatment T2* gradient echo MRI. Results— Among 65 patients, pretreatment MRI showed susceptibility vessel signs in 45 (69%). Thrombus length averaged 13.03 mm (range, 5.56–34.91) and irregular shape (curvature or branching) was present in 17 of 45 (38%). Presence and length of susceptibility vessel signs did not predict recanalization or good clinical outcome. Substantial recanalization (Thrombolysis In Cerebral Infarction 2b or 3) and good clinical outcome (modified Rankin Scale score ≤2) were more frequent with regular than irregular susceptibility vessel signs shape (57% versus 18%, P =0.013; 39% versus 6%, P =0.017). On multiple regression analysis, the only independent predictor of substantial recanalization was irregular susceptibility vessel signs (OR, 0.16; 95% CI, 0.04–0.69; P =0.014); and leading predictors of good clinical outcome were baseline National Institutes of Health Stroke Scale (OR, 1.20; 95% CI, 1.03–1.40; P = 0.019) and irregular susceptibility vessel signs (OR, 9.36; 95% CI, 0.98–89.4; P =0.052). Conclusions— Extension of thrombus into middle cerebral artery division branches and curving shape of the middle cerebral artery stem, but not thrombus length, decrease technical and clinical success of Merci thrombectomy in M1 occlusions.

article i nfo Background: Early disruption of the blood-brain barrier (BBB) due to severe ischemia can be detected by MRI T2* permeability imaging. In middle cerebral artery (MCA) infarction, pretreatment T2* permeability de- rangements have been found in 22% of patients and are powerful predictors of hemorrhagic transformation after revascularization therapy. The frequency, clinical correlates, and relation to hemorrhagic transformation of permeability derangements in posterior circulation have not been previously explored, and may differ as ischemia volume and collateral status are different between vertebrobasilar and MCA infarcts. Methods: We analyzed clinical and pretreatment MRI data on consecutive patients undergoing recanalization therapy for acute vertebrobasilar ischemia at a medical center November 2001 through September 2009. Pre- treatment MRI permeability images were derived from perfusion source imaging acquisitions. Permeability abnormality was detected as persisting increased signal intensity at later time points in perfusion MRI acqui- sition, indicating local accumulation of contrast caused by BBB leakage. Results: Among the 14 patients meeting study entry criteria, mean age was 71.1 years and median pretreat- ment NIHSS was 20.5. Permeability imaging abnormality was present in 1 of the 14 patients (7%). Among 14 patients, post-treatment parenchymal hematoma occurred in one and more minor degrees of hemorrhagic transformation in four. The one patient with pretreatment permeability abnormality was the patient to de- velop post-treatment parenchymal hematoma (Fisher's exact test, P=0.07). Conclusion: Pretreatment permeability abnormality, an indicator of BBB derangements, is an infrequent finding in acute posterior circulation ischemic stroke and may be associated with an increased risk of parenchymal hematoma development undergoing recanalization therapy.

Background and Purpose— Conventional analysis of vascular prevention trials assigns equal weight to disparate vascular events in a composite end point at variance with the public's perception of their differential impact on health outcome. This study sought to apply the disability-adjusted life-year (DALY) metric to differential weighting individual vascular end points in trial analyses. Methods— DALY values for the most common major end points in vascular prevention trials (nonfatal myocardial infarction, nonfatal stroke, and vascular death), were derived by using World Health Organization Global Burden of Disease Project methodology. The standardized DALYs for each event were applied to recent major primary and secondary vascular prevention trials and to hypothetical model trials. Results— Standardized DALYs lost were 7.63 for nonfatal stroke, 5.14 for nonfatal myocardial infarction, and 11.59 for vascular death. In the published trials analyses, the direction of treatment effects was consistent between DALY and standard event analysis, but the rank order of treatment effect changed for 10 of 18 trials. The DALY analysis also permitted derivation of number-needed-to-treat values to gain 1 DALY: 2.1 for anticoagulation in atrial fibrillation, 2.7 for carotid endarterectomy in symptomatic stenosis, and 4.7 for clopidogrel added to aspirin in acute coronary syndrome. Hypothetical trial analyses demonstrated that the DALY metric more finely discriminates treatment effects. Conclusions— Compared with a nonfatal myocardial infarction, a nonfatal stroke causes a 1.48-fold greater loss and vascular death a 2.25-fold greater loss of DALY. DALY analysis integrates these valuations in a summary metric reflecting the net impact of therapy on patient and societal health, complementing conventional end point analyses.

The Framingham Coronary Risk Score (FCRS) is based on several factors, including age, sex, total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure, presence of diabetes, and cigarette smoking. Some of these factors are individually linked with acute stroke outcomes. We explored whether FCRS could predict outcome in patients hospitalized with recent stroke. We collected data on consecutive patients hospitalized for ischemic stroke over a 3-year period. Patients with known coronary artery disease were excluded. Discharge outcomes assessed were neurologic deficit (National Institutes of Health Stroke Scale [NIHSS] score), death or disability (modified Rankin Scale [mRS] score ≥2), and discharge to home directly from the hospital. The independent effect of FCRS on these outcomes was evaluated using multivariate regression analysis. During the study period, 434 patients with ischemic stroke met entry criteria (mean age, 64.5 years; 54% females). Median FCRS score was 8%. After adjusting for confounders, higher FCRS score was associated with an increased likelihood of death or being disabled at discharge (odds ratio [OR] = 4.9; 95% confidence interval [CI] = 0.98-24.1; P = .05), and a decreased likelihood of being discharged directly to home (OR = 0.18; 95% CI = 0.04-0.86; P = .032), but not with discharge NIHSS score. Higher FCRS in hospitalized ischemic stroke patients is associated with death or disability at discharge and a lower likelihood of being discharged directly to home. Along with indexing the long-term risk of cardiovascular events, this widely known, easily calculable score provides clinically relevant short-term prognostic information following ischemic stroke.

BACKGROUND We examined the correlation of angiographic collaterals in acute stroke with the presence, extent, and distribution of white matter changes, so-called Leukoaraiosis, in an effort to determine if Leukoaraiosis indicates chronic cerebral hypoperfusion and/or is associated with the development of cerebral collateral circulation. METHODS Consecutive acute strokes due to large-vessel occlusion on angiography had preprocedure CT or MRI white matter changes graded utilizing the Fazekas scale incorporating deep and periventricular components. Angiographic collaterals evaluated with a 5-point scale were correlated with leukoaraiosis. RESULTS Collaterals were evaluated in 102 cases (51 men, 51 women; mean age 66 (SD 18) years with acute occlusions of the proximal middle cerebral artery (MCA) (47%), distal internal carotid artery (ICA) (28%), distal MCA (9%), basilar (7%), proximal ICA (7%), vertebral (1%), posterior cerebral artery (PCA) (1%), and common carotid artery (CCA) (1%). Collateral grade was well distributed across the scale. Periventricular and deep white matter changes were evident in 34% and 51% of cases, respectively. Collateral grade exhibited no relationship with either the presence or extent of periventricular disease (P= .772, r= .029) or deep white matter changes (P= .559, r=−.059). CONCLUSIONS Leukoaraisosis exhibits no overt relationship with the extent of collaterals measured at angiography in acute ischemic stroke. Chronic small-vessel disease may be a distinct pathophysiologic entity unrelated to arteriogenesis and compensatory aspects of collateral flow.

Background and Purpose— Deciding whether to use intravenous fibrinolytic therapy for acute cerebral ischemia within 3 hours of onset is challenging for patients, family members, and health care providers. Visual displays can permit individuals to rapidly understand response patterns to therapy. This study sought to evaluate, refine, and improve existing visual aids for stroke fibrinolytic decision-making. Methods— Existing visual aids were identified by Medline search and querying of national guideline organizations, pharmaceutical manufacturers, and stroke specialists, and were rated on a formal 8-point quality rating scale (0, lowest; 8, highest). Based on available instruments, new visual displays were developed to improve informed decision-making in routine practice. Results— Two existing visual aids were identified, one from an emergency medicine society and one from a pharmaceutical company. Both were comparison visual displays of outcomes with and without treatment; no decision matrix visual aid was found. Both scored 4.0 on the quality scale, showing defects of effect size distortion, privileging less salient outcomes, dissimilar representation by treatment group, and limited stakeholder participation in generation. Revised versions of these graphics were developed with higher quality scores (6.75 and 7.75). In addition, a new decision matrix display with quality score 8.0 was developed that complements the numeric text of a national patient education tool developed jointly by US neurology, emergency medicine, and stroke patient organizations. Conclusion— Existing visual aids for stroke fibrinolysis decision-making have deficiencies. New visual displays are now available to convey the health benefits and risks of fibrinolytic stroke therapy efficiently and informatively to patients and family members.

Background: Endovascular recanalization therapies are an increasingly employed treatment strategy in acute cerebral ischemia. The determinants of the final clinical outcome after endovascular treatment have been understudied. We investigated the effects of hyperlipidemia and statins on acute ischemic stroke outcomes after endovascular procedures. Methods: An inquiry of a prospectively maintained stroke registry was conducted. Endovascular procedures were performed using recombinant tissue plasminogen activator, prourokinase or the Merci device within 12 hours after symptom onset. The analyzed outcomes were revascularization, hemorrhage and excellent functional outcome (Rankin score of 0–1 at 3 months). The analyses included χ2 and Wilcoxon rank sum, logistic regression (for multivariate analyses with binary outcomes) and linear regression (for continuous outcomes). Significance was set at p < 0.05. Results: We included 142 patients, 80% treated with intra-arterial fibrinolysis, 22% with percutaneous mechanical embolectomy and 27% treated with intravenous fibrinolysis prior to endovascular intervention. Age (OR = 0.956, 95% CI = 0.927–0.986, p = 0.0041), National Institutes of Health Stroke Scale (NIHSS) score on admission (OR = 0.881, 95% CI = 0.812–0.957, p = 0.0025) and history of hyperlipidemia (OR = 0.284, 95% CI = 0.08–0.99, p = 0.0478) were negatively associated with excellent functional outcome at 3 months. Every 50 mg/dl increment in the total cholesterol level resulted in 64% decrease in the odds of excellent functional outcome (OR = 0.36, 95% CI = 0.447–0.882, p = 0.0253). History of hyperlipidemia decreased the likelihood of neurological improvement (p = 0.0462) and was associated with a higher NIHSS score at 7 days or discharge. Statin use was related to an average 6.5-unit NIHSS decrease at discharge (p = 0.0168). Statins were not associated with increased frequency of recanalization or symptomatic intracerebral hemorrhage. Conclusions: History of hyperlipidemia may have a negative impact on the outcomes of acute ischemic stroke treated with intra-arterial fibrinolysis or percutaneous mechanical embolectomy. Statin use before and after these procedures may be related to better neurological outcomes. Larger prospective studies are needed to endorse these findings.

Background & Purpose: Children were excluded from the recent positive mechanical thrombectomy trials and the literature on endovascular therapy in this population needs to be built. We report here case series of pediatric patients who received mechanical thrombectomy at our institution. Methodology: Our prospectively collected UCLA acute stroke database from 2000 to present was retrospectively reviewed. Only patients Results: All five patients (ages 2-15) suffered an embolic stroke. Three of them had congenital heart disease and one had repeated episodes of syncope and bradycardia. No risk factors other than PFO were identified in the fifth patient. Occlusion sites were ICA-M1 (n=2), M1 (n=2), and M1-M2 (n=1). IV tPA was used in one case. Time from last known well to reperfusion ranged from 3h to 9h 28min and the patients’ initial collaterals were scored between grades 2 - 3. AOL score of 3 was achieved in all cases, TICI 2a in two and TICI 2b in three cases. Merci was used in two cases, Penumbra, Solitaire and Mindframe Capture were used each in one case. One patient developed intracerebral hemorrhage that required hemicraniectomy. The PedNIHSS score at discharge ranged from 0 to 8 and the Ped-mRS score up-to 90 days ranged from 0 to 4, with 80% of children having Ped-mRS ≤ 3. Conclusion: Mechanical thrombectomy may be a safe and feasible treatment option in pediatric stroke patients with large vessel occlusion.

Introduction: In acute arterial occlusion, the FLAIR vascular hyperintensity (FVH) sign have been linked to slow flow in leptomeningeal collaterals and cerebral hypoperfusion, but the impact on clinical outcome is still controversial. In this study, we aimed to investigate the association between FVH-ASPECTS pattern and outcome in acute M1-MCA occlusion patients with endovascular treatment. Methods: We included acute M1-MCA occlusion patients treated with endovascular therapy. All patients had DWI and FLAIR before endovascular therapy. Distal FVH ASPECT score was evaluated according to distal MCA-ASPECT area (M1-M6) and acute DWI lesion was also reviewed. Presence of FVH inside DWI positive lesion and outside DWI positive lesion was separately analyzed. We analyzed clinical outcome after endovascular therapy based on these different FVH-ASPECTS patterns. Results: Among 101 patients that met inclusion criteria for the study, mean age was 66.2±17.8 and median NIHSS was 17.0 (IQR 12.0-21.0). FVH-ASPECTS measured outside of the DWI lesion was significantly higher in patients with good outcome (mRS 0-2), (8.0 vs 4.0, p Conclusion: Higher FVH-ASPECTS measured outside the DWI lesion is associated with good clinical outcomes in patients undergoing endovascular therapy. FVH-ASPECTS measured inside the DWI lesion was predictive of hemorrhage transformation. FVH pattern, not number, can predict outcome of acute M1-MCA occlusion patients after endovascular therapy.

Objective: To evaluate the levels of circulating angiogenic factors in patients with moyamoya disease (MMD), intracranial atherosclerosis (ICAS), and controls, and the effects of EDAS in their levels. Methods: Prospective longitudinal study of angiogenic factors in 22 patients with MMD, ICAS, and controls. Patients with MMD and ICAS underwent EDAS surgery. Control cases had cranial surgery for non-vascular or tumor pathology. Angiogenic factors were measured at baseline and 7 days after surgery. Log-corrected levels were compared between groups. Multivariate analysis of variance (MANOVA) was used to examine differences within pairs and between groups. Regression mixed models were built to account for intrasubject correlation and evaluate the association of angiogenic levels with group and treatment. Results: Mean age was 41 ± 11 in MMD, 65 ± 16 in ICAS, and 51 ± 19 in controls. There were 83% females in the MMD group, 44% in ICAS, and 43% in controls. Patients with MMD had significantly higher levels of PDGFAA (568.8 pg/ml), vs ICAS (165.9pg/mL), and controls (38.4 pg/mL) p=0.007; PDGFBB (1449.7 pg/mL), vs. ICAS (141.2 pg/mL), and controls (65.2 pg/mL) p=0.03; TGFB1 (24.5 ng/mL), vs. ICAS (13.8 ng/mL), and controls (6.2 ng/mL) p=0.006; TSP1 (128.5 ng/mL), vs. ICAS (91.7 ng/mL), and controls (9 ng/mL) p=0.0007. After surgery (EDAS for MMD and ICAS vs. cranial surgery for controls) levels of PDGFAA, PDGFBB, and TGFB1 increased on the ICAS and control groups eliminating the baseline differences. EDAS, independently from etiology, affected the levels of pro-angiogenic TGFB2 (EDAS: 290 pg/mL, controls: 161 pg/mL), and BMP2 (EDAS: 153 pg/mL, controls: 109 pg/mL) p Conclusion: Patients with MMD have baseline higher levels of pro-angiogenic factors PDGFAA, PDGFBB, and TGFB1, involved in vessel maturation. EDAS, independent from etiology, affected the levels of TGFB2, BMP2 and TSP2, cytokines involved in vessel maturation, increased vascular permeability, and modulation of cell migration, respectively.

Introduction: Speed is critical in fibrinolytic therapy for acute ischemic stroke (AIS), but rapid decision-making may increase tPA use in stroke mimics. Complications from lytics in mimic patients, though uncommon, can be severe. Mimic treatment rates when using non-contrast CT as the only initial imaging modality have increased to as high as 34% with intensified efforts to reduce door to needle (DTN) times. Efficient imaging with MRI or multimodal CT may potentially avoid high mimic treatment rates without prolonging treatment. Methods: In a prospectively maintained registry, we examined all patients treated with IV tPA from January 2010 to June 2015. Institutional policy was to perform MRI first in AIS patients and start tPA on the MR table after DWI showed ischemia and GRE excluded hemorrhage; if MRI could not be performed, multimodal CT with CTA and CTP was performed. Results: Among 319 IV tPA treated patients, age was 71 (±15), 50% were female, and NIHSS was 13.3 (±8.0). Imaging modality before tPA was MR in 193 (61%) and CT in 126 (39%). In the entire population, the DTN time was 54 (IRQ 42-73) mins and the proportion of mimic patients was 3.1%. DTN times decreased steadily throughout the 5.5 year study period, and did not differ among patients imaged with MR vs CT (Figure). The reduction in DTN times was not associated with an increase in mimic-treated rates (Figure). Among the mimic patients, final diagnoses were migraine - 4, seizure - 3, meningitis - 1, PE - 1, and cardiac dysrhythmia - 1. Imaging modalities in mimic patients were MRI in 5 and CT in 5. Preliminary imaging reads suggested abnormality in 2/10, but final reads were normal in all. In 3/10 mimic patients, tPA infusions were stopped before full dose when ongoing imaging further clarified diagnosis. Conclusion: A rapid stroke assessment protocol using MRI or multimodal CT permits swift start of thrombolytic therapy and low rates of stroke mimic treatment. Figure. Door-to-needle time and percent stroke mimics by year.

BackgroundEndovascular reperfusion techniques are a promising intervention for acute ischemic stroke (AIS). Prior studies have identified markers of initial injury (arrival NIH stroke scale (NIHSS) or infarct volume) as predictive of outcome after these procedures. We sought to define the role of collateral flow at the time of presentation in determining the extent of initial ischemic injury and its influence on final outcome.MethodsDemographic, clinical, laboratory, and radiographic data were prospectively collected on a consecutive cohort of patients who received endovascular therapy for acute cerebral ischemia at a single tertiary referral center from September 2004 to August 2010.ResultsHigher collateral grade as assessed by the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) grading scheme on angiography at the time of presentation was associated with improved reperfusion rates after endovascular intervention, decreased post-procedural hemorrhage, smaller infarcts on presentation and discharge, as well as improved neurological function on arrival to the hospital, discharge, and 90 days later. Patients matched by vessel occlusion, age, and time of onset demonstrated smaller strokes on presentation and better functional and radiographic outcome if found to have superior collateral flow. In multivariate analysis, lower collateral grade independently predicted higher NIHSS on arrival.ConclusionsImproved collateral flow in patients with AIS undergoing endovascular therapy was associated with improved radiographic and clinical outcomes. Independent of age, vessel occlusion and time, in patients with comparable ischemic burdens, changes in collateral grade alone led to significant differences in initial stroke severity as well as ultimate clinical outcome.

The interval appearance of cerebral microbleeds (CMBs) after endovascular treatment has never been described. We investigated the frequency and predictors of new CMBs that developed shortly after mechanical thrombectomy for acute ischemic stroke, and its impact on clinical outcome. We retrospectively analyzed patients with large-vessel occlusion strokes treated with Merci Retriever, Penumbra System, or stent-retriever devices. Serial T2∗-weighted gradient-recall echo (GRE) magnetic resonance imaging (MRI) before and 48 h after endovascular thrombectomy were assessed to identify new CMBs. We examined independent factors associated with new CMBs after mechanical thrombectomy. We analyzed the association of the presence, burden, and distribution of new CMBs with clinical outcome. A total of 187 consecutive patients with serial GRE were enrolled in this study. CMBs were evident in 36 (19.3%) patients before mechanical thrombectomy. New CMBs occurred in 41 (21.9%) patients after mechanical thrombectomy. Of the 68 new CMBs, 45 appeared in the lobar location, 18 in the deep location and 5 in the infratentorial location. The presence of baseline CMBs was associated with new CMBs after mechanical thrombectomy (OR 5.38; 95% CI 2.13–13.59; P

Background and Purpose— The enrollment yield and reasons for screen failure in prehospital stroke trials have not been well delineated. Methods— The Field Administration of Stroke Therapy–Magnesium (FAST-MAG) trial identified patients for enrollment using a 2 stage screening process—paramedics in person followed by physician-investigators by cell phone. Outcomes of consecutive screening calls from paramedics to enrolling physician-investigators were prospectively recorded. Results— From 2005 to 2012, 4458 phone calls were made by paramedics to physician-investigators, an average of 1 call per vehicle every 135.7 days. A total of 1700 (38.1%) calls resulted in enrollments. The rate of enrollment of stroke mimics was 3.9%. Among the 2758 patients not enrolled, 3140 reasons for screen failure were documented. The most common reasons for nonenrollment were >2 hours from last known well (17.2%), having a prestroke condition causing disability (16.1%), and absence of a consent provider (9.5%). Novel barriers for phone informed consent specific to the prehospital setting were infrequent, but included: cell phone connection difficulties (3.2%), patient being hard of hearing (1.4%), insufficient time to complete consent (1.3%), or severely dysarthric (1.3%). Conclusions— In this large, multicenter prehospital trial, nearly 40% of every calls from the field to physician-investigators resulted in trial enrollments. The most common reasons for nonenrollment were out of window last known well time, prestroke confounding medical condition, and absence of a consent provider. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00059332.

Background: Prestroke statin use may improve ischemic stroke outcomes, yet there is also evidence that statins and extremely low cholesterol levels may increase the risk of intracranial hemorrhage. We evaluated the independent effect of statin use and admission cholesterol level on risk of symptomatic hemorrhagic transformation (sHT) after recanalization therapy for acute ischemic stroke. Methods: We analyzed ischemic stroke patients recorded in a prospectively maintained registry that received recanalization therapies (IV or intra-arterial fibrinolysis or endovascular embolectomy) at a university medical center from September 2002 to May 2006. The independent effect of premorbid statin use on sHT post intervention was evaluated by logistic regression, adjusting for prognostic and treatment variables known to predict increased HT risk after ischemic stroke. Results: Among 104 patients, mean age was 70 years, and 49% were men. Male sex, hypertension, statin use, low total cholesterol and low-density lipoprotein (LDL) cholesterol, current smoking, elevated glucose levels, and higher admission NIH Stroke Scale (NIHSS) score were all associated with a greater risk of sHT in univariate analysis. After adjusting for covariates, low LDL cholesterol (odds ratio [OR], 0.968 per 1-mg/dL increase; 95% CI, 0.941 to 0.995), current smoking (OR, 14.568; 95% CI, 1.590 to 133.493), and higher NIHSS score (OR, 1.265 per 1-point increase; 95% CI, 1.047 to 1.529) were independently associated with sHT risk. Conclusions: Lower admission low-density lipoprotein cholesterol level with or without statin use, current smoking, and greater stroke severity are associated with greater risk for symptomatic hemorrhagic transformation after recanalization therapy for ischemic stroke.

Background: In acute cerebral ischemia, there is an imbalance between oxygen tissue consumption and delivery and oxygen extraction fraction (OEF) from the circulation increases to maintain normal oxygen metabolism and neuronal function. Detecting such metabolic changes may provide important data to inform decisions on therapeutic interventions such as patient selection for reperfusion or identification of futile therapeutic situations. We used serial OEF MRI to assess metabolic changes in brain tissue associated with reperfusion interventions. Methods: Serial OEF acquired in 10 consecutive cases of acute anterior circulation ischemic stroke at a single center during a 12 month period. Transverse relaxation and static magnetic field inhomogeneity driven relaxation was mapped using multislice gradient echo planar imaging. Data are fitted on a voxel-by-voxel basis to the Yablonskiy and Haacke model to map deoxyhemoglobin concentration and cerebral blood volume. Results: 10 cases (median age 72 years (IQR 62-77), 5 women) were studied. Median NIHSS score 15.5 (IQR 9-25). 3 patients received no intervention as last known well time exceeded a treatment window. 3 patients received intravenous thrombolysis (IV), 3 patients received IV and mechanical thrombectomy (MT), and 1 patient received MT only. In the IV treated patients, median time to therapy 110. 5 minutes (IQR 80-132). In the MT treated patients, median time to therapy 257 minutes (IQR 234-331). In the untreated patients, the OEF was elevated in the ischemic territory and this appeared to persist at 24 hours. In the treated patients, those who had at least partial recanalization, demonstrated improved OEF in the ischemic territory at 24 hours. Conclusions: OEF provides a novel method for non-invasive detection of tissue with impaired oxygen delivery in acute stroke patients and is a novel tool for imaging metabolic changes in pathophysiology and disclosing therapeutic opportunities.

Background: In clinical practice, when no consent provider is immediately available to authorize start of thrombolytic stroke therapy, acute stroke physicians face a fundamental conflict between the ethical principles of autonomy (respect for persons) and beneficence (maximizing benefit). Delaying therapy to reach a consent provider maximizes autonomy but reduces benefit. Physician attitudes toward resolving this conflict have not previously been delineated. Methods: A 6 item internet-based survey was administered to US academic stroke neurologists. Respondents were asked to indicate how much time (minutes), patients (number who fail to benefit due to delay), and brain (neurons lost due to delay) they would spend trying to reach consent provider for an aphasic acute stroke patient before proceeding with treatment under the doctrine of presumed consent. Results: Survey responses were received from 103 of 332 academic stroke neurologists. All respondents were engaged in stroke clinical care, with cerebrovascular disease accounting for more than half of practice time in over 70%. Career duration was substantial, with over 72% having been in practice for more than 5 years. In the time tradeoff framework, respondents indicated they would spend a median of 1.75 minutes (interquartile range, IQR, 0 - 10.0 minutes) trying to contact a consent provider before proceeding with thrombolysis. In the patient tradeoff framework, they would accept a median of 0 (IQR 0-0) per 1000 treated patients failing to benefit from therapy before proceeding. In the brain tradeoff scenario, they would accept a median of 0 (IQR 0-1) neurons lost before proceeding. Converting all choices to time, respondents indicated they would trade off shorter times in the patient framework (0 minutes) and the neuron framework (0 minutes) than in the time framework (1.75 minutes). Conclusion: Vascular neurologists indicate they emphasize beneficence over autonomy in deciding when to forego further attempts to reach consent providers to proceed with thrombolytic therapy under the doctrine of presumed consent. Their preference for rapid intervention is magnified when decisions are framed in person failure to benefit and neuron loss, compared with simple chronologic time.

Introduction: Thrombolytic treatment within 4.5 hours saves ischemic tissue at risk and is associated with improved clinical outcomes in patients with acute middle cerebral artery (MCA) ischemic stroke. Lesion pattern is one of the most important predictors for acute stroke patients’ outcome. However, the efficacy of thrombolysis in acute MCA stroke patients with different lesion patterns remains unclear. In this study, we aimed to compare response to intravenous tPA in patients with different infarction patterns. Methods: We included acute MCA ischemic stroke patients treated with intravenous tPA. All patients had DWI within 24 hours of symptom onset with 6 lesion patterns categorized as territorial, other cortical, small superficial, internal border zone, small deep, and other deep infarcts. We classified territorial infarcts and internal borderzone into Group 1 and the other four lesion patterns as Group 2. We analyzed clinical outcome after tPA based on these distinct DWI lesion patterns. Results: A total of 203 patients were included in our study. Mean age was 66.2±18.1.The percent of patients with hypertension at presentation is higher in Group 1 than in Group 2(100% VS 93.8%, p=0.049). The presenting NIHSS of Group 1 is higher than Group 2 (18.0 vs 12.0, p Conclusion: Good response to intravenous tPA was more frequent in patients with territorial infarcts and internal border zone infarcts, indicating that particular DWI infarction patterns can predict good outcome of acute MCA patients after thrombolysis.

© 2015 International Society for Cerebral Blood Flow & Metabolism, Inc. The purpose of this study was to investigate the relationship between hyperperfusion and hemorrhagic transformation (HT) in acute ischemic stroke (AIS). Pseudo-continuous arterial spin labeling (ASL) with background suppressed 3D GRASE was performed during routine clinical magnetic resonance imaging (MRI) on AIS patients at various time points. Arterial spin labeling cerebral blood flow (CBF) maps were visually inspected for the presence of hyperperfusion. Hemorrhagic transformation was followed during hospitalization and was graded on gradient recalled echo (GRE) scans into hemorrhagic infarction (HI) and parenchymal hematoma (PH). A total of 361 ASL scans were collected from 221 consecutive patients with middle cerebral artery stroke from May 2010 to September 2013. Hyperperfusion was more frequently detected posttreatment (odds ratio (OR)=4.8, 95% confidence interval (CI) 2.5 to 8.9, P

Background: Lesion patterns may predict prognosis after acute ischemic stroke within the middle cerebral artery (MCA) territory; yet it remains unclear whether such imaging prognostic factors are related to patient outcome after intravenous thrombolysis. Aims: The aim of this study is to investigate the clinical outcome after intravenous thrombolysis in acute MCA ischemic strokes with respect to diffusion-weighted imaging (DWI) lesion patterns. Methods: Consecutive acute ischemic stroke cases of the MCA territory treated over a 7-year period were retrospectively analyzed. All acute MCA stroke patients underwent a MRI scan before intravenous thrombolytic therapy was included. DWI lesions were divided into 6 patterns (territorial, other cortical, small superficial, internal border zone, small deep, and other deep infarcts). Lesion volumes were measured by dedicated imaging processing software. Favorable outcome was defined as modified Rankin scale (mRS) of 0-2 at 90 days. Results: Among the 172 patients included in our study, 75 (43.6%) were observed to have territorial infarct patterns or other deep infarct patterns. These patients also had higher baseline NIHSS score (p < 0.001), a higher proportion of large cerebral artery occlusions (p < 0.001) and larger infarct volume (p < 0.001). Favorable outcome (mRS 0-2) was achieved in 89 patients (51.7%). After multivariable analysis, groups with specific lesion patterns, including territorial infarct and other deep infarct pattern, were independently associated with favorable outcome (OR 0.40; 95% CI 0.16-0.99; p = 0.047). Conclusions: Specific lesion patterns predict differential outcome after intravenous thrombolysis therapy in acute MCA stroke patients.

Neurosyphilis is caused by the spirochete Treponema pallidum. These organisms divide slowly, requiring long exposure to antibacterials for treatment success. In order for an antibacterial to be effective in the therapy of neurosyphilis, it must achieve treponemicidal concentrations in the CSF, have a long half-life and be given in a treatment regimen that favours compliance. Penicillin was first introduced for the treatment of syphilis in 1943, and despite interest in the use of amoxicillin, erythromycin, tetracycline, doxycycline, ceftriaxone and azithromycin, penicillin remains the only recommended antibacterial agent for neurosyphilis.

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

Background: Combined IV TPA and catheter-based reperfusion is an emerging treatment strategy for acute ischemic stroke. Both patient care and clinical trial design would be enhanced by delineation of which patients rapidly respond to IV TPA alone, before endovascular therapy can be initiated. Methods: In a prospectively maintained registry of patients treated under a general policy of combined IV TPA and endovascular therapy, we analyzed subjects with MRA/CTA-confirmed anterior circulation occlusions prior to IV TPA start. Results: Among 118 patients meeting study entry criteria, age was mean 71.5 (SD 14.5), 53.0% were female, and baseline NIHSS was 14.4 (SD 7.1). Confirmed sites of occlusion prior to IV TPA were internal cerebral artery (ICA) in 22.9%, M1 segment of middle cerebral artery (MCA) in 50.0%, and M2-3 in 27.1%. Among patients undergoing catheter cerebral angiography, median time from start of IV TPA to diagnostic catheter angiogram was 75 mins (IQR 50-113). A total of 48 (40.7%) patients achieved partial or complete recanalization (AOL 2-3) of the initial target artery with IV TPA alone (partial in 22 (18.6%) and complete in 26 (22.2%)); an additional 44 (37.3%) achieved partial or complete recanalization after endovascular therapy. Recanalization rates after IV TPA alone varied by target occlusion site: ICA - 22.2%, M1 - 40.7%, and M2-3 - 56.2%. In multivariate logistic regression analysis, independent predictors of recanalization with IV TPA alone were: M2-3 clot location, OR 3.04 (95% CI 1.20-7.73, p=0.019) and TOAST etiology large-artery atherosclerosis, OR 0.14 (CI 0.04-0.50, p = 0.003). Good outcome (mRS ≤ 3) rates at 3 months were 76.6% among recanalizers with IV TPA alone and 47.5% among recanalizers after both IV TPA and catheter therapy. Conclusions: When combined IV-endovascular treatment is pursued, recanalization with IV TPA alone occurs in 4 out of 10 patients before catheter therapy is started, is more common with more distal clot location, and is associated with a high rate of excellent clinical outcomes.

Background: Intracerebral hemorrhage (ICH) is associated with early neurological deterioration and death. Prior studies showed that delays in seeking medical attention may occur among minorities. In this study we investigated the factors affecting time from symptom onset to ER arrival (TOA) in a race/ethnic enriched population. Methods: Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) is a prospective study of spontaneous ICH. Baseline characteristics, presenting symptoms, first contact (911 vs. ER vs. primary physician), ICH volume, location and intraventricular extension, insurance status, GCS at presentation, and TOA were collected. Data was analyzed using generalized linear models and Spearman’s rank correlations. TOA was natural log transformed and a multivariate model was developed using backward elimination (P-value=0.05). Results: A total of 1158 subjects were enrolled; 28 were excluded due to lack of TOA. Of the 1,030 included 59% were men with 24% whites, 41% blacks, and 35% Hispanics. Mean age was 61±15 years, mean Glasgow Coma Scale (GCS) at presentation was 12.4±3.7 (median=15), and median TOA was 431 min (interquartile range 106-820). Location of ICH was 56% deep, 28% lobar, 8% cerebellum, and 5% brainstem. Approximately 29% of subjects had no medical insurance, 36% had medicare, 18% medicaid, 36% private insurance, and 1% VA insurance. In univariate analysis women, use of 911, EMS run, different presenting symptoms, lobar and deep location, and low GCS were associated with shorter TOA. In multivariate model only women (p=0.05), GCS (p=0.04), use of 911 (p Conclusion: Ethnicity and insurance status did not affect time to presentation. Women, use of 911, EMS run, weakness and lower GCS were associated with shorter TOA in ICH. Increased education in target populations with higher incidence of ICH such as minorities on stroke signs/symptoms and use of 911 may expedite access to medical care. Further studies are needed to determine the impact of TOA on outcome.

BACKGROUND: Despite its proven efficacy in acute ischemic stroke, thrombolytic treatment rates are exceedingly low. A common barrier is a prerequisite estimation of finite event duration. Whole-brain MR DWI-FLAIR comparative methods of hyperacute-acute ischemic match/mismatch are currently under investigation as a potential surrogate for unknown duration. Profiles that reflect field ischemia but not viability may not detect important voxel-level heterogeneity and, consequently, areas that may potentially benefit from revascularization. Voxel-based MR methods that assess viability (PWI) and ischemia (DWI-FLAIR) may afford a more informative measure to determine and expand treatment eligibility. METHODS: Consecutive, treated M1 ischemic stroke patients with serial MRI were analyzed with voxel-based, volumetric measures of DWI, FLAIR, and PWI for match/mismatch. Co-registration of Day 0 DWI, PWI, and FLAIR with Day 5/discharge FLAIR was then followed by ROI analysis of the affected MCA field. Day 0 DWI, PWI, FLAIR and Day 5/discharge FLAIR voxels were pooled into average populations according to positivity. Serial voxel-populations were then quantified at Day 0 and at Day 5/discharge individually and group-wise. Data processing and analysis were performed with MatLab, 3DSlicer, and Microsoft Excel. RESULTS: 38 treated M1 occlusive patients (mean age 65 years, 25 female) underwent a voxel-based analysis of DWI, PWI, and FLAIR at day 0 and FLAIR at day5/discharge. At baseline, 93% of the affected MCA field was DWI-/PWI+/FLAIR-; 7% was DWI+/PWI+/FLAIR-; and ~3% was FLAIR+. At day 5/discharge, 36% of baseline at-risk field (DWI-/PWI+); >95% of baseline field undergoing ischemia (DWI+/PWI+); and 94% of baseline ischemic tissue (FLAIR+) were FLAIR+. CONCLUSIONS: Voxel-based analyses of DWI, PWI and FLAIR on serial MRI reveal heterogeneity of voxel status at baseline and in tissue fate, and provide a dynamic tissue profile in treated M1 ischemic stroke. Over 1/3 of baseline viable tissue became ischemic at day 5 suggesting nearly 2/3 of the field remained viable. Future evaluations of voxel-based approaches that profile viability and ischemia are warranted to validate this methodology and its potential to expand acute stroke treatment eligibility.

Introduction: Collateral status may predict outcomes after endovascular therapy, yet a reliable noninvasive technique prior to angiography is needed. We developed a novel method for projection of perfusion imaging data and validated it with respect to DSA acquired immediately afterwards. Methods: Consecutive acute ischemic stroke patients with M1 MCA occlusions with perfusion MR imaging prior to endovascular revascularization therapy were included. Collateral status on DSA was graded with the ASITN/SIR scale (0-4). 4-D dynamic susceptibility contrast concentration time images were constructed and projected in 2-D axial and sagittal planes at each time point. Independent review of the resulting MRI-based collateral sequences was conducted to generate a score analogous to the ASITN/SIR scale, followed by correlation studies between the two techniques. Results: 47 patients were included with mean age 68.5 ± 16.3, 76.5% were female, baseline NIHSS was median 14 (range 3-31), and mean time from MRI to groin puncture was 109 min ± 95.5. DSA collateral grade was (0 (n=3); 1 (n=9); 2 (n=12); 3 (n=21); 4 (n=2)) with MRI collateral grade (0 (n=2); 1 (n=11); 2 (n=13); 3 (n=18); 4 (n=2)). MRI and DSA collateral scores were closely correlated, Spearman's rho = 0.91, weighted kappa = 0.82 (P Conclusions: Novel post-processing of noninvasive MRI perfusion data based on routine acquisitions can reliably measure the degree of collaterals on DSA.

Background and Purpose— Epidemiological studies of intracerebral hemorrhage (ICH) have consistently demonstrated variation in incidence, location, age at presentation, and outcomes among non-Hispanic white, black, and Hispanic populations. We report here the design and methods for this large, prospective, multi-center case–control study of ICH. Methods— The Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study is a multi-center, prospective case–control study of ICH. Cases are identified by hot-pursuit and enrolled using standard phenotype and risk factor information and include neuroimaging and blood sample collection. Controls are centrally identified by random digit dialing to match cases by age (±5 years), race, ethnicity, sex, and metropolitan region. Results— As of March 22, 2013, 1655 cases of ICH had been recruited into the study, which is 101.5% of the target for that date, and 851 controls had been recruited, which is 67.2% of the target for that date (1267 controls) for a total of 2506 subjects, which is 86.5% of the target for that date (2897 subjects). Of the 1655 cases enrolled, 1640 cases had the case interview entered into the database, of which 628 (38%) were non-Hispanic black, 458 (28%) were non-Hispanic white, and 554 (34%) were Hispanic. Of the 1197 cases with imaging submitted, 876 (73.2%) had a 24 hour follow-up CT available. In addition to CT imaging, 607 cases have had MRI evaluation. Conclusions— The ERICH study is a large, case–control study of ICH with particular emphasis on recruitment of minority populations for the identification of genetic and epidemiological risk factors for ICH and outcomes after ICH.

Background: Reperfusion is characterized by initial restriction of blood supply followed by subsequent vascular restoration and concomitant reoxygenation of downstream tissue. In spite of mitigating initial tissue hypoxia, exacerbation of tissue injury may occur. Animal models have delineated reperfusion injury on the cellular and molecular levels, yet, no study has quantified voxel-based analyses of tissue fate due to reperfusion injury in human stroke. Methods: Evaluation included 58 stroke patients with an age range of 65±18 years, 65% of whom were woman and 35% men. All patients presented with M1 MCA occlusion and a subset received mechanical thrombectomy (38) while another received intravenous tPA followed by mechanical thrombectomy (20). Serial perfusion MRI images were obtained on presentation as well as 3-6 hours following reperfusion and processed to extract Tmax parameters. These images were co-registered serially at the voxel level with tissue fate outcomes on FLAIR and GRE 4-5 days following presentation. Reperfusion was defined by serial changes observed in Tmax voxels. The volume of reperfusion, injury, as well as tissue fate relative to initial perfusion were calculated. Results: Hemorrhage was noted on GRE in 28.9% of the patients who received thrombectomy alone and in 20% of those who received IV tPA followed by thrombectomy. In pure thrombectomy cases without later hemorrhage, average voxel-based reperfusion was 72.3% with 18% demonstrating reperfusion injury and tissue death as assessed by FLAIR imaging 4-5 days following presentation, averaging 86.2%. In patients who received IV tPA followed by mechanical thrombectomy without any subsequent hemorrhage, average voxel-based reperfusion was 66.0% with 6.2% demonstrating reperfusion injury in reperfused voxels and tissue death as assessed by FLAIR imaging 4-5 following presentation, averaging 90.3%. Conclusions: Non-hemorrhagic forms of reperfusion injury are common in acute stroke patients treated with standard therapies. Despite reperfusion and irrespective of treatment modality, substantial amounts of tissue are destined to infarct. Voxel-based analyses of serial imaging studies may provide a framework to develop therapies for reperfusion injury.

Background: Atrial fibrillation (AF) makes a person five times more likely to experience a stroke. According to the National Stroke Association, atrial fibrillation accounts for about 15 percent of stroke. Many of these patients do not have any previous history of AF, and are diagnosed with this condition post-stroke. We sought to characterize the frequency and features of AF in stroke patients hospitalized after acute presentation, focusing on new diagnoses. Methods: All subjects were enrolled in the Field Administration of Stroke Therapy- Magnesium (FAST-MAG) clinical trial, a phase 3 NIH-funded study of pre-hospital Magnesium Sulfate vs. placebo for patients with symptom onset Results: Of 1478 patients, 69 (4.7%) had no previous history of AF but were diagnosed with AF post-stroke onset. There were 274 cases with AF recorded on the ED ECG (274), only 36 (13.1%) had no documented history of AF. Patients in both groups were of similar age (age 81 vs 79 years) and had similar rates of ICH diagnosis (8.7 vs 7.1%). However, newly diagnosed patients had more severe strokes (median NIHSS 14 vs 10, p=0.008) and a lower burden of cardiac disease by history (coronary artery disease 15.9 vs 31.7%, and myocardial infarction 5.8 vs 15.9%). Female gender women (50.7 vs 48.2%) history of prior stroke (10.1 vs 8.8%), hypertension (89.9 vs 89.5%), and hyperlipidemia (56.5 vs 54.1%) were similar in both groups. Conclusion: Most new diagnoses of AF after stroke were made based on the ED ECG. Strokes in patients who would go on to have new AF diagnoses were more severe than those where AF diagnosis was already established, likely due to less likelihood of anticoagulation.

Background: As “time lost is brain lost” in acute ischemic stroke, earlier start of therapy will maximize access of promising drugs to salvageable brain tissue. We hypothesized that prehospital treatment initiation would accelerate treatment delivery of neuroprotective agent in a prehospital randomized clinical trial. Methods: We analyzed research treatment initiation times in consecutive patients enrolled in the NIH Field Administration of Stroke Therapy – Magnesium (FAST-MAG) Phase 3 clinical trial. In FAST-MAG, patients with suspected acute stroke within 2 hours of onset are randomized to paramedic initiation of magnesium sulfate or placebo in 358 participating ambulances and 59 receiving hospitals. Results: Among 1486 patients, mean age was 69 (SD13.7), 42% were female, median pretreatment Los Angeles Motor Scale score was 4, and final diagnosis was acute cerebral ischemia in 71.9%, intracranial hemorrhage in 24.4%, and stroke mimic in 3.7%. Figure 1 shows the distribution of values for time from onset (last known well) to treatment (OTT). Clustering of experimental treatment start times at the maximum permitted time window, common in in-hospital stroke trials, was not seen in this cohort with prehospital care mandated early transports. Across all patients, the median OTT was 49.0 minutes. 73.5% of patients were treated within the first 60 minutes of onset (the “golden hour”) and 10.8% within the first 30 minutes of onset. Mean time from paramedic arrival on scene to start of treatment was 23.0 (SD 7.6) minutes, and 4.3% of patients were treated within 10 minutes of medic arrival (the “platinum ten minutes”). Conclusions: Prehospital initiation enables start of experimental neuroprotective therapy in times previously not achievable in acute stroke treatment trials. Nearly three-quarters of patients can be treated within the golden hour and more than one in ten within the first 30 minutes of onset.

Background: Availability of 4G cellular network and video cellphone handsets may allow mobile videophone assessment to be employed in prehospital stroke care. The California Brief Stroke Scale (CABSS) is a 4 item scale designed as a mobile videophone test to evaluate a prehospital telemedicine instrument to rate stroke severity. Potential uses include identifying patients who are likely harboring persisting large vessel occlusions and to characterize baseline deficits prior to enrollment in prehospital trials. Methods: One bedside and one remote CABSS score were independently obtained on 15 ischemic stroke patients with persistent neurologic deficits. The bedside examination was performed by a stroke neurologist. The remote examination was performed by a second stroke neurologist through mobile video phone. A CABSS score of 1 or higher (scale 0-7) was an index of global stroke deficit severity. Kappa coefficients were calculated for concordance between bedside and remote scores. Results: The median National Institutes of Health Stroke Scale score was 6 (interquartile range IQR 4-10). On average the CABSS score evaluation took 25 seconds to perform. The median video CABSS was 2, (IQR1-3) and median bedside CABSS was 3, (IQR 1-3). Based on weighted K coefficients, cortical findings (aphasia, gaze deviation/hemineglect) displayed excellent agreement κ=1 (95% CI 1.0) and non-cortical findings (facial droop, arm drift) displayed substantial agreement κ =0.7 (95% CI 0.4-1.0). There was substantial agreement between bedside and remote methods for the total CABSS κ 0.68 (95% CI 0.44-0.92). The CABSS scores obtained by bedside and remote methods were strongly correlated (r= 0.85, P Conclusion: Our prospective study found that mobile videocell phone evaluation using CABSS is a feasible and reliable means of examining hyperacute stroke patients in the field. A physician can rapidly perform an audiovideo examination to increase the accuracy of prehospital identification of patients harboring persisting large vessel occlusions and characterize baseline deficits prior to enrollment in prehospital clinical trials to a clinically important degree.

Introduction: Histopathology has shown that thrombi retrieved acutely from cerebral arteries in acute ischemic stroke patients typically have intermixed fibrin-platelet-dominant and red blood cell (RBC)-dominant regions. Knowledge of the proportions of fibrin-platelet and RBC components in an individual patient could help with pharmacologic and/or device intervention selection. Whether serum markers of inflammation and coagulation status reflect clot composition has not previously been investigated. Methods: We analyzed consecutive patients undergoing mechanical thrombectomy for acute middle cerebral artery ischemic stroke with retrieved thrombi available for histopathologic analysis. Percent of retrieved thrombus that was RBC-dominant, WBC-dominant, and platelet/thrombin-dominant was calculated and compared with routine serum indices of inflammatory and coagulation status obtained on admission. Results: Among the 50 patients meeting entry critera, mean age was 66 (SD 21), 48% were female, and median pretreatment NIHSS was 19 (IQR 15-22). Two serum indices demonstrated correlations with cerebral thrombus histopathology: serum WBC count inversely correlated with thrombus fibrin percentage (R -.317, p=0.024) and partial thromboplastin time positively correlated with thrombus WBC percentage (R 0.336, p=0.032). No relations were found for other serum tests, including hemoglobin, neutrophil count, lymphocyte count, prothrombin time, erythrocyte sedimentation rate, high sensitivity C-reactive protein, homocysteine, fibrinogen, factor VIII, total cholesterol, LDL, and HDL. Conclusions: Serum measures of inflammation and coagulation may provide clues to target thrombus composition in acute ischemic stroke. Systemic inflammation, including during infections, may lead to upregulation of clotting factors and less fibrin-platelet and more RBC and WBC-laden clots.

Background: Arterial spin-labeled (ASL) MRI facilitates repeated noninvasive evaluation of cerebral blood flow without the use of contrast. Hyperperfusion may be readily detected with ASL and serial imaging may therefore chronicle the dynamics of territorial perfusion from acute to chronic phases after stroke. We characterized hyperperfusion on ASL in a prospective series of acute ischemic stroke patients, describing the clinical correlates, time course and association with reperfusion hemorrhage. Methods: A consecutive series of acute ischemic stroke patients admitted during a 1-year period were evaluated with pseudo-continuous ASL with background suppressed 3D GRASE (delay=2s, matrix=64x64; 26 slices, resolution 3.4x3.4x5mm, scan time 4min). Post-processed ASL CBF maps were visually inspected for detection of hyperperfusion. DSA measures of collaterals and reperfusion were scored when available and hemorrhagic transformation (HT) was graded on GRE in all 198 cases. Univariate and multivariate statistical analyses delineated clinical correlates, timing and other imaging features of hyperperfusion. Results: Among 198 patients, mean age was 69.4±15.7 years and 48.5% were women. Among 77 with serial ASL MRI, interval from initial to follow-up MRI was median 25.0 (IQR 10.3-53.9) hours. Hyperperfusion was detected in 15/198 (7.6%) patients at baseline and 30/77 (39.0%) at follow-up. Trajectories included 7/77 (9.1%) with hyperperfusion at both baseline and follow-up and 38/77 (49.4%) showing hyperperfusion at any timepoint during admission. Hyperperfusion correlated with achievement of reperfusion among patients undergoing endovascular therapy (OR 6.5, 95% CI 1.82-23.25, p=0.018) and history of atrial fibrillation (OR 4.4, 95% CI 1.9-10.6, p Conclusions: Hyperperfusion in acute ischemic stroke is frequently demonstrated by ASL MRI, providing novel insight on the dynamics of reperfusion and HT. Hyperperfusion increases the risk of HT 50-fold, likely due to autoregulatory loss. Poor collaterals and sudden reperfusion in vulnerable cases such as those with atrial fibrillation may herald hyperperfusion and HT.

Introduction: Prior studies caution against use of intravenous thrombolysis (IVrtPA) for acute ischemic stroke in patients ≥80 years old, but few have described outcomes in this population treated with intra-arterial therapy (IAT). In this study we describe patterns of treatment with IVrtPA and IAT based on age across a network of academic stroke centers, and in-hospital outcomes in patients ≥80 years treated with IAT. Methods: Stroke centers within the Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) prospectively collected data on all patients treated with IVrtPA or IAT including demographics, pre-treatment National Institutes of Health Stroke Scale (NIHSS), discharge destination, and in-hospital mortality. Symptomatic hemorrhage data was not systematically collected. Pre-stroke modified Rankin scale (mRS) was collected at only 6 sites (n = 2074). Proportions of total treated patients based on two age categories ( Results: Over 6 years a total of 2879 were treated with IVrtPA alone, and 425 with combined IVrtPA and IAT between 1/1/05 and 12/31/10. The proportion of patients ≥80 years treated with IVrtPA varied significantly between the centers (19.4%-50.4, p Conclusions: Older patients are less likely to be treated with IAT, though there is significant variability in patterns of IVrtPA and IAT treatment across a consortium of academic stroke centers. IAT appeared safe in this population.

Background The influence of lesion size and laterality on each component of the National Institutes of Health Stroke Scale has not been delineated. The objective of this study was to use perfusion-weighted imaging to characterize the association of ischaemic volume and laterality on each component item and the total score of the Methods We analysed consecutive right-handed patients with first-ever supratentorial acute ischaemic strokes who underwent acute perfusion-weighted imaging at a single centre. Perfusion deficits were defined as mean transit time > 10 s. Ordinal regression was used to clarify the relationship between ischaemic volume, laterality, and Results Among 111 patients, 58 were left-hemisphere stroke, and 53 right-hemisphere stroke. Median ischaemic volume was 53 ml in left-hand stroke and 65 ml in right-hand stroke and median total National Institutes of Health Stroke Scale was 10 in left-hand stroke and eight in right-hand stroke. For individual National Institutes of Health Stroke Scale items, ischaemic volume correlated most closely with commands and visual field and most weakly with ataxia and neglect. Left-hand stroke predicted higher scores of total National Institutes of Health Stroke Scale and National Institutes of Health Stroke Scale items of questions, commands, right limb weakness, and language. Right-hand stroke predicted higher scores of left limb weakness and extinction. Conclusions Larger perfusion defects contribute to higher scores on the total and most individual items of the National Institutes of Health Stroke Scale. However, lesion laterality contributes substantially to half the item scores, with greater association of left than right-brain side. These findings indicate that imaging-deficit correlations will be improved by designating lesions into an atlas, taking into account side in addition to size.