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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.

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.

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.

© 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: 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.

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: 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: 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.

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.

Background Stenting of symptomatic intracranial atherosclerosis remains under investigation, yet this option to potentially avert subsequent stroke has been offered at select centers under humanitarian device exemption and off-label use for several years. Methods Retrospective case series of consecutive patients undergoing stenting with Wingspan and balloon mounted coronary stents for symptomatic intracranial atherosclerosis at a single institution. Recurrent symptomatic ischemia in the territory of the stented artery was ascertained. Rates of recurrent ischemic stroke were calculated per patient-year of follow-up and were compared with medically treated patients in the Warfarin–Aspirin Symptomatic Intracranial Disease (WASID) trial. Results During the 10 year study period, 41 cases of intracranial stenting were identified. Stenoses were severe (>70%) in 88% of patients. Stenting procedures occurred a median of 14 days from the most recent symptomatic event. 19 Wingspan stents and 22 balloon mounted coronary stents were deployed. Four strokes occurred within 24 h of stenting, seven within 1 month and eight within 3 months. By 3 months after stenting, no further strokes occurred during up to 2 years of follow-up. Patients had 0.194 ischemic strokes per person-year of follow-up, compared with 0.083 ischemic strokes per person-year of follow-up in the aspirin arm of WASID and 0.065 ischemic strokes per person-year of follow-up in the warfarin arm of WASID. Conclusions Stenting of symptomatic intracranial atherosclerosis in a high risk subset of cases with advanced degree of luminal stenosis may be associated with an increased early risk of recurrent ischemic stroke.

Current guidelines do not define the lower severity threshold for thrombolysis. In this study, we describe the variability of treatment of mild stroke patients across a network of academic stroke centers.Stroke centers within the Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) prospectively collect data on patients treated with intravenous recombinant tissue plasminogen activator (IV rt-PA), including demographics, pretreatment National Institutes of Health Stroke Scale (NIHSS) scores, and in-hospital mortality. We examined the variability in proportion of total tissue plasminogen activator-treated patients in the NIHSS categories (0-3, 4-5, or ≥ 6) and associated outcomes.A total of 2514 patients with reported NIHSS scores were treated with IV rt-PA between January 1, 2005 and December 31, 2009. The proportion of patients with mild stroke (NIHSS scores of 0-3) who were treated with IV rt-PA varied substantially across the centers (2.7-18.0%; P.001). There were 5 deaths in the 256 treated with an NIHSS score of 0-3 (2.0%). The proportion of treated patients across the network with an NIHSS score of 0 to 3 increased from 4.8% in 2005 to 10.7% in 2009 (P = .001).There is substantial variability in the proportion of treated patients who have mild stroke across the SPOTRIAS centers, reflecting a paucity of data on how to best treat patients with mild stroke. Randomized trial data for this group of patients are needed to clarify the use of rt-PA in patients with the mildest strokes.

Response: We appreciate the letter of Dr. Di Legge and colleagues presenting comfirmatory findings from an independent dataset. Please let us note that Di Legge and colleagues do not fully accurately characterize our methodology. We used not only lesion size (diameter

Background and Purpose— The purpose of this study was to provide the first correlative study of the hyperdense middle cerebral artery sign (HMCAS) and gradient-echo MRI blooming artifact (BA) with pathology of retrieved thrombi in acute ischemic stroke. Methods— Noncontrast CT and gradient-echo MRI studies before mechanical thrombectomy in 50 consecutive cases of acute middle cerebral artery ischemic stroke were reviewed blinded to clinical and pathology data. Occlusions retrieved by thrombectomy underwent histopathologic analysis, including automated quantitative and qualitative rating of proportion composed of red blood cells (RBCs), white blood cells, and fibrin on microscopy of sectioned thrombi. Results— Among 50 patients, mean age was 66 years and 48% were female. Mean (SD) proportion was 61% (±21) fibrin, 34% (±21) RBCs, and 4% (±2) white blood cells. Of retrieved clots, 22 (44%) were fibrin-dominant, 13 (26%) RBC-dominant, and 15 (30%) mixed. HMCAS was identified in 10 of 20 middle cerebral artery stroke cases with CT with mean Hounsfield Unit density of 61 (±8 SD). BA occurred in 17 of 32 with gradient-echo MRI. HMCAS was more commonly seen with RBC-dominant and mixed than fibrin-dominant clots (100% versus 67% versus 20%, P =0.016). Mean percent RBC composition was higher in clots associated with HMCAS (47% versus 22%, P =0.016). BA was more common in RBC-dominant and mixed clots compared with fibrin-dominant clots (100% versus 63% versus 25%, P =0.002). Mean percent RBC was greater with BA (42% versus 23%, P =0.011). Conclusions— CT HMCAS and gradient-echo MRI BA reflect pathology of occlusive thrombus. RBC content determines appearance of HMCAS and BA, whereas absence of HMCAS or BA may indicate fibrin-predominant occlusive thrombi.

BACKGROUND large, long-term population data indicate an inverse association for adult height with stroke incidence and mortality, whereas the risk of atrial fibrillation appears greater in taller individuals. However, it is unclear whether knowledge of an individual's stature is an important clinical factor to consider when assessing hospitalized patients with ischemic stroke. We determined the relation of body height with clinical characteristics and discharge outcomes among persons with ischemic stroke. METHODS we analyzed prospectively collected data in 881 consecutive patients with ischemic stroke admitted to a university hospital stroke service during a 5-year period starting September 2002. Stroke subtyping was performed per modified Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria. Stroke severity was assessed with the National Institutes of Health Stroke Scale. All patients were assessed at discharge using the modified Rankin scale. Mean adjusted height was compared using linear regression models with height as outcome, and stroke subtype, modified Rankin scale, and potential confounders as covariates. RESULTS mean age was 67.4 years, 48% were women. Mean height was 169 cm (SD ± 11). In multivariable analysis, height decreased per year of age (P=0.003), those with a previous stroke were shorter than those without a previous stroke (P=0.04), and females were shorter than males (P

Background and Purpose— Hemorrhagic transformation (HT) after fibrinolytic therapy may be less common in patients with acute cerebral ischemia confined to single penetrator artery (SPA) territories than in patients with large artery ischemia. Previous investigations of HT diagnosed small vessel ischemia based on lacunar clinical syndromes, an approach known to yield misdiagnosis in one-third to one-half of cases. Methods— Consecutive intravenous tissue plasminogen activator-treated patients in a prospectively maintained hospital registry were analyzed. Patients were classified as having SPA ischemia if they had imaging evidence of: (1) deep location; (2) diameter ≤1.5 cm; and (3) distribution in a single penetrator territory, regardless of presenting clinical syndrome. Lacunar clinical syndrome was defined according to the Oxfordshire Community Stroke Project classification. Results— Among 93 intravenous tissue plasminogen activator-treated patients, mean age was 71.5, 62.4% were female, and median pretreatment National Institutes of Health Stroke Scale score was 14. Single penetrator artery ischemia was imaged in 13 (14.0%) and large artery ischemia was imaged in 75 (80.6%), with no visualized ischemic injury in 5 (5.4%). Lacunar clinical syndromes were present in 23 (24.7%), including 10 with SPA ischemia and 9 with large artery ischemia. No patient with imaging-confirmed SPA infarcts experienced any hemorrhagic transformation, whereas any radiological HT occurred in 29.3% of large artery infarcts ( P =0.03). Symptomatic intracerebral hemorrhage occurred in 0% of SPA infarcts vs 4.0% of large artery infarcts. Conclusion— HT after lytic therapy in imaging-confirmed SPA infarcts is uncommon. Imaging demonstration of ischemia confined to SPA territory better-identifies this population at low risk for hemorrhagic complications than clinical lacunar syndromes.

Background and Purpose— The feasibility of implementing an expert consensus guideline recommending use of a stroke patient’s profile to manage undiagnosed coronary artery disease remains unclear. Methods— Following a guideline-based algorithm, we screened consecutive patients with ischemic stroke and patients with transient ischemic attack for asymptomatic coronary artery disease using the Framingham Heart Study Coronary Risk Score (FCRS) cutoff of high risk (≥20%) for experiencing a hard coronary artery disease event over a 10-year period. Patients with high FCRS received dobutamine stress echocardiogram outpatient screening, additional treatment (β-blocker), or further management (cardiologist referral). Results— From July 2004 to September 2007, among 693 patients, 501 (72%) met study criteria, of which 80 (16%) had FCRS ≥20%. Elevated serum glucose, nonhigh-density lipoprotein, triglycerides, homocysteine, glycosylated hemoglobin as well as large vessel atherosclerotic stroke mechanism were more frequent in high versus low FCRS patients ( P Conclusions— Screening for coronary artery disease risk using FCRS is feasible in hospitalized patients with stroke, but outpatient adherence to stress testing is challenging largely due to patient and primary care physician-related factors.

Background: The utility of clinical measurements of impairments in glomerular barrier or filtration rate among hospitalized stroke patients without known chronic kidney disease (CKD) has not been well studied. We determined whether various indices of CKD would predict discharge outcomes in persons hospitalized with a recent ischemic stroke. Methods: Presence of proteinuria and estimated low glomerular filtration rate (GFR) 2 on admission were assessed in consecutive ischemic stroke and transient ischemic attack patients admitted to a university hospital over 18 months, who had no history of CKD. The primary discharge outcomes assessed (among stroke patients only) were death or disability (modified Rankin Scale score ≥2) and being discharged home directly from hospital. Independent effects of CKD indices on the outcomes were evaluated using multivariable regression modeling. Results: Of 251 patients with recent ischemic cerebrovascular events, 198 ischemic stroke patients (79%), met the study criteria. In crude analyses, persons with proteinuria or low GFR were significantly more likely to die in the hospital (p < 0.05). After adjusting for confounders, proteinuria was independently linked with lower odds of going home directly from the hospital (OR = 0.38, 95% CI = 0.16–0.92) and poorer discharge functional status (OR = 3.19, 95% CI = 1.37–7.46), but low GFR was not independently related to either of these outcomes. Conclusions: Among hospitalized ischemic stroke patients without known CKD, presence of proteinuria on admission is independently associated with poorer discharge functional activity and lower likelihood of being discharged home directly. Low GFR was not related to either outcome in these patients without known CKD.

Background: Cellular phone conversations between on-scene patients or their legally authorized representatives (LARs) and off-scene enrolling physician-investigators require immediate and reliable connection systems to obtain explicit informed research consent in prehospital treatment trials. Methods: The NIH Field Administration of Stroke Therapy – Magnesium (FAST-MAG) Trial implemented a voice-over-internet protocol (VOIP) simultaneous ring system (multiple investigator cell phones called simultaneously and first responder connected to call) to enable physician-investigators to elicit consent immediately from competent patients or LARs encountered by 228 ambulances enrolling patients in a multicenter prehospital stroke trial. For 1 month, the number, origin, duration, and yield of enrolling line calls were monitored prospectively. Results: Six investigators were connected to 106 enrolling line calls, with no identified unanswered calls. Thirty-five percent of new patient calls yielded an enrollment. The most common reasons for non-enrollment were last known well >2 h (n = 7) and uncon sentable patient without LAR available (n = 7). No non-enrollments were directly attributable to the VOIP system. In enrollments, consent was provided by the patient in 67% and a LAR in 33%. The duration of enrollment calls (mean ± SD: 8.4 ± 2.5 min, range 6–14) was longer than non-enrollment calls (5.5 ± 3.5, range 2–13; p < 0.001). The median interval from last known well to study agent start was 46 min, and 70% were enrolled within 60 min of onset. Conclusions: The simultaneous ring system was reliable and effective, permitting enrollment of a substantial number of patients within the first hour after stroke onset. VOIP cellular networks with simultaneous ring are a preferred means of facilitating consent in prehospital treatment trials.

Background and Purpose— The Los Angeles Motor Scale (LAMS) is a brief 3-item stroke severity assessment measure designed for prehospital and Emergency Department use. Methods— The LAMS and NIHSS were scored in under-12-hour acute anterior circulation ischemic stroke patients. Stroke severity ratings were correlated with cervicocerebral vascular occlusion on CTA, MRA, and catheter angiography. Receiver operating curves, c statistics, and likelihood ratios were used to evaluate the predictive value for vascular occlusion of stroke severity ratings. Results— Among 119 patients, mean age was 67 (±18), 45% were male. Time from onset to ED arrival was mean 190 minutes (range 10 to 660). Persisting large vessel occlusions (PLVOs) were present in 62% of patients. LAMS stroke severity scores were higher in patients harboring a vascular occlusion, median 5 (IQR 4 to 5) versus 2 (IQR 1 to 3). Similarly, NIHSS stroke severity scores were higher in PLVO patients, 19 (14 to 24) versus 5 (3 to 7). ROC curves demonstrated that the LAMS was highly effective in identifying patients with PLVOs, c statistic 0.854. At the optimal threshold of 4 or higher, LAMS scores showed sensitivity 0.81, specificity 0.89, and overall accuracy 0.85. LAMS performance was comparable to NIHSS performance (c statistic 0.933). The positive likelihood ratio associated with a LAMS score ≥4 was 7.36 and the negative likelihood ratio 0.21. Conclusions— Stroke severity assessed by the LAMS predicts presence of large artery anterior circulation occlusion with high sensitivity and specificity. The LAMS is a promising instrument for use by prehospital personnel to identify select stroke patients for direct transport to Comprehensive Stroke Centers capable of endovascular interventions.

Background and Purpose— Few data exist on the relationship between differential subpopulations of peripheral leukocytes and early cerebral infarct size in ischemic stroke. Using diffusion-weighted MR imaging (DWI), we assessed the relationship of early total and differential peripheral leukocyte counts and volume of ischemic tissue in acute stroke. Methods— All included patents had laboratory investigations and neuroimaging collected within 24 hours of stroke onset. Total peripheral leukocyte counts and differential counts were analyzed individually and by quartiles. DWI lesions were outlined using a semiautomated threshold technique. The relationship between leukocyte quartiles and DWI infarct volumes was examined using multivariate quartile regression. Results— 173 patients met study inclusion criteria. Median age was 73 years. Total leukocyte counts and DWI volumes showed a strong correlation (Spearman rho=0.371, P P for trend P =0.004). After multivariate analysis, larger DWI volume remained strongly associated with higher total leukocyte and neutrophil counts (both probability values P =0.4971). Compared with the lowest quartiles, DWI volumes were 8.7 mL and 12.9 mL larger in the highest quartiles of leukocyte and neutrophil counts, respectively. Conclusions— Higher peripheral leukocyte and neutrophil counts, but not lymphocyte counts, are associated with larger infarct volumes in acute ischemic stroke. Attenuating neutrophilic response early after ischemic stroke may be a viable therapeutic strategy and warrants further study.

Background Higher levels of serum bilirubin may offer a therapeutic advantage in oxidative stress-mediated diseases, but may also simply reflect intensity of oxidative stress. Little is known about the role of bilirubin in stroke. We assessed the relation of serum bilirubin levels with clinical presentation and outcomes among patients hospitalized with ischemic stroke. Methods Data were collected prospectively during a 5-year period on consecutive ischemic stroke admissions to a university hospital. Serum bilirubin levels, total (Tbil) and direct (Dbil), were measured on admission. Presenting stroke severity was assessed with the National Institutes of Health Stroke Scale (NIHSS). Functional outcome at discharge was assessed using the modified Rankin scale. Results Among 743 patients, mean age was 67.3 years and 47.5% were women. Median presenting NIHSS score was 4, and 24% had a poor (modified Rankin scale 4-6) functional outcome at discharge. Higher Dbil levels were associated with greater stroke severity ( P = .001) and poorer discharge outcome ( P = .034). Multivariable regression analyses showed that those with higher Dbil levels (≥0.4 mg/dL) had significantly greater admission NIHSS scores compared with those with lower levels (≤0.1 mg/dL) (odds ratio 2.79, 95% confidence interval 1.25-6.20, P = .012), but no independent relationship was confirmed between Dbil and discharge outcome. Although higher admission Tbil was associated with greater stroke severity in crude analyses ( P = .003), no independent relationship between Tbil versus stroke severity or outcome was noted after adjusting for confounders. Conclusions Higher Dbil level is associated with greater stroke severity but not outcome among ischemic stroke patients, possibly reflecting the intensity of initial oxidative stress. Further study into the underlying pathophysiology of this relationship is needed.