Mediation of Successful Reperfusion Effect through Infarct Growth and Cerebral Edema: A Pooled, Patient-Level Analysis of EXTEND-IA Trials and SELECT Prospective Cohort.

OBJECTIVE: Reperfusion therapy is highly beneficial for ischemic stroke. Reduction in both infarct growth and edema are plausible mediators of clinical benefit with reperfusion. We aimed to quantify these mediators and their interrelationship. METHODS: In a pooled, patient-level analysis of the EXTEND-IA trials and SELECT study, we used a mediation analysis framework to quantify infarct growth and cerebral edema (midline shift) mediation effect on successful reperfusion (modified Treatment in Cerebral Ischemia ≥ 2b) association with functional outcome (modified Rankin Scale distribution). Furthermore, we evaluated an additional pathway to the original hypothesis, where infarct growth mediated successful reperfusion effect on midline shift. RESULTS: A total 542 of 665 (81.5%) eligible patients achieved successful reperfusion. Baseline clinical and imaging characteristics were largely similar between those achieving successful versus unsuccessful reperfusion. Median infarct growth was 12.3ml (interquartile range [IQR] = 1.8-48.4), and median midline shift was 0mm (IQR = 0-2.2). Of 249 (37%) demonstrating a midline shift of ≥1mm, median shift was 2.75mm (IQR = 1.89-4.21). Successful reperfusion was associated with reductions in both predefined mediators, infarct growth (ß = -1.19, 95% confidence interval [CI] = -1.51 to -0.88, p < 0.001) and midline shift (adjusted odds ratio = 0.36, 95% CI = 0.23-0.57, p < 0.001). Successful reperfusion association with improved functional outcome (adjusted common odds ratio [acOR] = 2.68, 95% CI = 1.86-3.88, p < 0.001) became insignificant (acOR = 1.39, 95% CI = 0.95-2.04, p = 0.094) when infarct growth and midline shift were added to the regression model. Infarct growth and midline shift explained 45% and 34% of successful reperfusion effect, respectively. Analysis considering an alternative hypothesis demonstrated consistent results. INTERPRETATION: In this mediation analysis from a pooled, patient-level cohort, a significant proportion (~80%) of successful reperfusion effect on functional outcome was mediated through reduction in infarct growth and cerebral edema. Further studies are required to confirm our findings, detect additional mediators to explain successful reperfusion residual effect, and identify novel therapeutic targets to further enhance reperfusion benefits. ANN NEUROL 2023;93:793-804.

Thrombectomy versus Medical Management in Mild Strokes due to Large Vessel Occlusion: Exploratory Analysis from the EXTEND-IA Trials and a Pooled International Cohort.

OBJECTIVE: This study was undertaken to evaluate functional and safety outcomes for endovascular thrombectomy (EVT) versus medical management (MM) in patients with large vessel occlusion (LVO) and mild neurological deficits, stratified by perfusion imaging mismatch. METHODS: The pooled cohort consisted of patients with National Institutes of Health Stroke Scale (NIHSS) < 6 and internal carotid artery (ICA), M1, or M2 occlusions from the Extending the Time for Thrombolysis in Emergecy Neurological Deficits - Intra-Arterial (EXTEND-IA) Trial,  Tenecteplase vs Alteplase before Endovascular Thrombectomy in Ischemic Stroke (EXTEND-IA TNK) trials Part I/II and prospective data from 15 EVT centers from October 2010 to April 2020. RAPID software estimated ischemic core and mismatch. Patients receiving primary EVT (EVTpri ) were compared to those who received primary MM (MMpri ), including those who deteriorated and received rescue EVT, in overall and propensity score (PS)-matched cohorts. Patients were stratified by target mismatch (mismatch ratio ≥ 1.8 and mismatch volume ≥ 15ml). Primary outcome was functional independence (90-day modified Rankin Scale = 0-2). Secondary outcomes included safety (symptomatic intracerebral hemorrhage [sICH], neurological worsening, and mortality). RESULTS: Of 540 patients, 286 (53%) received EVTpri and demonstrated larger critically hypoperfused tissue (Tmax > 6 seconds) volumes (median [IQR]: 64 [26-96] ml vs MMpri : 40 [14-76] ml, p < 0.001) and higher presentation NIHSS (median [IQR]: 4 [2-5] vs MMpri : 3 [2-4], p < 0.001). Functional independence was similar (EVTpri : 77.4% vs MMpri : 75.6%, adjusted odds ratio [aOR] = 1.29, 95% confidence interval [CI] = 0.82-2.03, p = 0.27). EVT had worse safety regarding sICH (EVTpri : 16.3% vs MMpri : 1.3%, p < 0.001) and neurological worsening (EVTpri : 19.6% vs MMpri : 6.7%, p < 0.001). In 414 subjects (76.7%) with target mismatch, EVT was associated with improved functional independence (EVTpri : 77.4% vs MMpri : 72.7%, aOR = 1.68, 95% CI = 1.01-2.81, p = 0.048), whereas there was a trend toward less favorable outcomes with primary EVT (EVTpri : 77.4% vs MMpri : 83.3%, aOR = 0.39, 95% CI = 0.12-1.34, p = 0.13) without target mismatch (pinteraction  = 0.06). Similar findings were observed in a propensity score-matched subpopulation. INTERPRETATION: Overall, EVT was not associated with improved clinical outcomes in mild strokes due to LVO, and sICH was increased. However, in patients with target mismatch profile, EVT was associated with increased functional independence. Perfusion imaging may be helpful to select mild stroke patients for EVT. ANN NEUROL 2022;92:364-378.

Early Infarct Growth Rate Correlation With Endovascular Thrombectomy Clinical Outcomes: Analysis From the SELECT Study.

BACKGROUND AND PURPOSE: Time elapsed from last-known well (LKW) and baseline imaging results are influential on endovascular thrombectomy (EVT) outcomes. METHODS: In a prospective multicenter cohort study of imaging selection for endovascular thrombectomy (SELECT [Optimizing Patient's Selection for Endovascular Treatment in Acute Ischemic Stroke], the early infarct growth rate (EIGR) was defined as ischemic core volume on perfusion imaging (relative cerebral blood flow<30%) divided by the time from LKW to imaging. The optimal EIGR cutoff was identified by maximizing the sum of the sensitivity and specificity to correlate best with favorable outcome and to improve its the predictability. Patients were stratified into slow progressors if EIGR2. The primary outcome was 90-day functional independence (modified Rankin Scale score =0-2). RESULTS: Of 445 consented, 361 (285 EVT, 76 medical management only) patients met the study inclusion criteria. The optimal EIGR was <10 mL/h; 200 EVT patients were slow and 85 fast progressors. Fast progressors had a higher median National Institutes of Health Stroke Scale (19 versus 15, P<0.001), shorter time from LKW to groin puncture (180 versus 266 minutes, P<0.001). Slow progressors had better collaterals on computed tomography perfusion: hypoperfusion intensity ratio (adjusted odds ratio [aOR]: 5.11 [2.43-10.76], P<0.001) and computed tomography angiography: collaterals-score (aOR: 4.43 [1.83-10.73], P=0.001). EIGR independently correlated with functional independence after EVT, adjusting for age, National Institutes of Health Stroke Scale, time LKW to groin puncture, reperfusion (modified Thrombolysis in Cerebral Infarction score of ≥2b), IV-tPA (intravenous tissue-type plasminogen activator), and transfer status (aOR: 0.78 [0.65-0.94], P=0.01). Slow progressors had higher functional independence rates (121 [61%] versus 30 [35%], P<0.001) and had 3.5 times the likelihood of achieving modified Rankin Scale score =0-2 with EVT (aOR=2.94 [95% CI, 1.53-5.61], P=0.001) as compared to fast progressors, who had substantially worse clinical outcomes both in early and late time window. The odds of good outcome decreased by 14% for each 5 mL/h increase in EIGR (aOR, 0.87 [0.80-0.94], P<0.001) and declined more rapidly in fast progressors. CONCLUSIONS: The EIGR strongly correlates with both collateral status and clinical outcomes after EVT. Fast progressors demonstrated worse outcomes when receiving EVT beyond 6 hours of stroke onset as compared to those who received EVT within 6 hours. Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT02446587.

Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT): A Prospective, Multicenter Cohort Study of Imaging Selection.

OBJECTIVE: The primary imaging modalities used to select patients for endovascular thrombectomy (EVT) are noncontrast computed tomography (CT) and CT perfusion (CTP). However, their relative utility is uncertain. We prospectively assessed CT and CTP concordance/discordance and correlated the imaging profiles on both with EVT treatment decisions and clinical outcomes. METHODS: A phase 2, multicenter, prospective cohort study of large-vessel occlusions presented up to 24 hours from last known well was conducted. Patients received a unified prespecified imaging evaluation (CT, CT angiography, and CTP with Rapid Processing of Perfusion and Diffusion software mismatch determination). The treatment decision, EVT versus medical management, was nonrandomized and at the treating physicians' discretion. An independent, blinded, neuroimaging core laboratory adjudicated favorable profiles based on predefined criteria (CT:Alberta Stroke Program Early CT Score ≥ 6, CTP:regional cerebral blood flow (<30%) < 70ml with mismatch ratio ≥ 1.2 and mismatch volume ≥ 10ml). RESULTS: Of 4,722 patients screened from January 2016 to February 2018, 361 patients were included. Two hundred eighty-five (79%) received EVT, of whom 87.0% had favorable CTs, 91% favorable CTPs, 81% both favorable profiles, 16% discordant, and 3% both unfavorable. Favorable profiles on the 2 modalities correlated similarly with 90-day functional independence rates (favorable CT = 56% vs favorable CTP = 57%, adjusted odds ratio [aOR] = 1.91, 95% confidence interval [CI] = 0.40-9.01, p = 0.41). Having a favorable profile on both modalities significantly increased the odds of receiving thrombectomy as compared to discordant profiles (aOR = 3.97, 95% CI = 1.97-8.01, p < 0.001). Fifty-eight percent of the patients with favorable profiles on both modalities achieved functional independence as compared to 38% in discordant profiles and 0% when both were unfavorable (p < 0.001 for trend). In favorable CT/unfavorable CTP profiles, EVT was associated with high symptomatic intracranial hemorrhage (sICH) (24%) and mortality (53%) rates. INTERPRETATION: Patients with favorable imaging profiles on both modalities had higher odds of receiving EVT and high functional independence rates. Patients with discordant profiles achieved reasonable functional independence rates, but those with an unfavorable CTP had higher adverse outcomes. Ann Neurol 2020;87:419-433.

Telestroke Across the Continuum of Care: Lessons from the COVID-19 Pandemic.

While use of telemedicine to guide emergent treatment of ischemic stroke is well established, the COVID-19 pandemic motivated the rapid expansion of care via telemedicine to provide consistent care while reducing patient and provider exposure and preserving personal protective equipment. Temporary changes in re-imbursement, inclusion of home office and patient home environments, and increased access to telehealth technologies by patients, health care staff and health care facilities were key to provide an environment for creative and consistent high-quality stroke care. The continuum of care via telestroke has broadened to include prehospital, inter-facility and intra-facility hospital-based services, stroke telerehabilitation, and ambulatory telestroke. However, disparities in technology access remain a challenge. Preservation of reimbursement and the reduction of regulatory burden that was initiated during the public health emergency will be necessary to maintain expanded patient access to the full complement of telestroke services. Here we outline many of these initiatives and discuss potential opportunities for optimal use of technology in stroke care through and beyond the pandemic.

Endovascular Thrombectomy for Acute Ischemic Strokes: Current US Access Paradigms and Optimization Methodology.

Background and Purpose- Timely access to endovascular thrombectomy (EVT) centers is vital for best acute ischemic stroke outcomes. Methods- US stroke-treating centers were mapped utilizing geo-mapping and stratified into non-EVT or EVT if they reported ≥1 acute ischemic stroke thrombectomy code in 2017 to Center for Medicare and Medicaid Services. Direct EVT-access, defined as the population with the closest facility being an EVT-center, was calculated from validated trauma-models adapted for stroke. Current 15- and 30-minute access were described nationwide and at state-level with emphasis on 4 states (TX, NY, CA, IL). Two optimization models were utilized. Model-A used a greedy algorithm to capture the largest population with direct access when flipping 10% and 20% non-EVT to EVT-centers to maximize access. Model-B used bypassing methodology to directly transport patients to the nearest EVT centers if the drive-time difference from the geo-centroid to hospital was within 15 minutes from the geo-centroid to the closest non-EVT center. Results- Of 1941 stroke-centers, 713 (37%) were EVT. Approximately 61 million (19.8%) Americans have direct EVT access within 15 minutes while 95 million (30.9%) within 30 minutes. There were 65 (43%) EVT centers in TX with 22% of the population currently within 15-minute access. Flipping 10% hospitals with top population density improved access to 30.8%, while bypassing resulted in 45.5% having direct access to EVT centers. Similar results were found in NY (current, 20.9%; flipping, 34.7%; bypassing, 50.4%), CA (current, 25.5%; flipping, 37.3%; bypassing, 53.9%), and IL (current, 15.3%; flipping, 21.9%; bypassing, 34.6%). Nationwide, the current direct access within 15 minutes of 19.8% increased by 7.5% by flipping the top 10% non-EVT to EVT-capable in all states. Bypassing non-EVT centers by 15 minutes resulted in a 16.7% gain in coverage. Conclusions- EVT-access within 15 minutes is limited to less than one-fifth of the US population. Optimization methodologies that increase EVT centers or bypass non-EVT to the closest EVT center both showed enhanced access. Results varied by states based on the population size and density. However, bypass showed more potential for maximizing direct EVT-access. National and state efforts should focus on identifying gaps and tailoring solutions to improve EVT-access.

Vision, Aphasia, Neglect Assessment for Large Vessel Occlusion Stroke.

BACKGROUND AND PURPOSE: Vision, Aphasia, Neglect (VAN) is a large vessel occlusion (LVO) screening tool that was initially tested in a small study where emergency department (ED) nurses were trained to perform VAN assessment on stroke code patients. We aimed to validate the VAN assessment in a larger inpatient dataset. METHODS: We utilized a large dataset and used National Institute of Health Stroke Scale (NIHSS) performed by physicians to extrapolate VAN. VAN was compared to NIHSS greater than or equal to 6 and established prehospital LVO screening tools including Rapid Arterial Occlusion Evaluation scale (RACE), Field Assessment Stroke Triage for Emergency Destination (FAST-ED), and Cincinnati Pre-hospital Stroke Scale (CPSS). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under receiver operating characteristics curve was calculated to estimate the predictive value of LVO. RESULTS: VAN was comparable in sensitivity (79% versus 80%) and NPV (88% versus 87%) to NIHSS greater than or equal to 6. It was superior in specificity (69% versus 57%), PPV (53% versus 46%) and accuracy to NIHSS greater than or equal to 6 (72% versus 64%) with significant receiver operating curve (.74 versus .69, P = .02). VAN also had comparable area under the curve when compared to RACE, FAST-ED, and CPSS however slightly lower accuracy (69%-73%) compared to RACE (76%), FAST-ED (77%), and CPSS (75%). VAN had the highest NPV among all screening assessments (88%). CONCLUSIONS: VAN is a simple screening tool that can identify LVOs with adequate accuracy in hospital setting. Future studies need to be conducted in prehospital setting to validate its utility to detect LVOs in the field.

Vision, Aphasia, Neglect Assessment to Predict Neurosurgical Intervention in Patients with Nontraumatic Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: The Vision, Aphasia, and Neglect (VAN) screening tool is a simple bedside test developed to identify patients with large vessel occlusion stroke. In the setting of intracerebral hemorrhage (ICH), there are very few bedside predictors of need for neurosurgical interventions other than age and Glasgow Coma Scale (GCS). We aimed to assess the utility of the VAN screening tool in predicting the need for neurosurgical intervention in patients with ICH. METHODS: We accessed sensitivity, specificity, positive predictive value, negative predictive value (NPV), and area under receiver operating characteristics curve of VAN for identifying ICH patients who require neurosurgical intervention. RESULTS: Among 228 ICH patients, 176 were VAN positive and 52 were VAN negative. On unadjusted analyses, VAN positive patients had a significantly higher ICH volume, GCS score, and National Institutes of Health Stroke Scale score (P < .001 for all). As compared to VAN negative patients, significantly higher proportion of VAN positive ICH patients (15.4% versus 32.4%) underwent a neurosurgical procedure such as external ventricular drain (EVD) and/or hematoma evacuation with craniotomy or craniectomy. The VAN screening tool had high sensitivity and NPV (100%) in predicting the need for craniectomy or hematoma evacuation, but had lower sensitivity (87.7%) for any neurosurgical procedure, as 15.4% of VAN negative patients received EVD. CONCLUSIONS: Our study suggests that VAN screening tool can identify high-risk ICH patients who are more likely to undergo craniotomy or craniectomy but is less sensitive to rule out need for EVD.

Derivation and Validation of the Emergency Medical Stroke Assessment and Comparison of Large Vessel Occlusion Scales.

BACKGROUND: This study aims to develop a simple scale to identify patients with prehospital stroke with large vessel occlusion (LVO), without losing sensitivity for other stroke types. METHODS: The Emergency Medical Stroke Assessment (EMSA) was derived from the National Institutes of Health Stroke Scale (NIHSS) items and validated for prediction of LVO in a separate cohort. We compared the EMSA with the 3-item stroke scale (3I-SS), Cincinnati Prehospital Stroke Severity Scale (C-STAT), Rapid Arterial oCclusion Evaluation (RACE) scale, and Field Assessment Stroke Triage for Emergency Destination (FAST-ED) for prediction of LVO and stroke. We surveyed paramedics to assess ease of use and interpretation of scales. RESULTS: The combination of gaze preference, facial asymmetry, asymmetrical arm and leg drift, and abnormal speech or language yielded the EMSA. An EMSA less than 3, 75% sensitivity, and 50% specificity significantly reduced the likelihood of LVO (LR- = .489, 95% confidence interval .366-0.637) versus 3I-SS less than 4 (.866, .798-0.926). A normal EMSA, 93% sensitivity, and 47% specificity significantly reduced the likelihood of stroke (LR- = .142, .068-0.299) versus 3I-SS (.476, .330-0.688) and C-STAT (.858, .717-1.028). EMSA was rated easy to perform by 72% (13 of 18) of paramedics versus 67% (12 of 18) for FAST-ED and 6% (1 of 18) for RACE (χ2 = 27.25, P < .0001), and easy to interpret by 94% (17 of 18) versus 56% (10 of 18) for FAST-ED and 11% (2 of 18) for RACE (χ2 = 21.13, P < .0001). CONCLUSIONS: The EMSA has superior abilities to identify LVO versus 3I-SS and stroke versus 3I-SS and C-STAT. The EMSA has similar ability to triage patients with stroke compared with the FAST-ED and RACE, but is simpler to perform and interpret.

PR Interval Prolongation and Cryptogenic Stroke: A Multicenter Retrospective Study.

BACKGROUND: Atrial dysfunction or "cardiopathy" has been recently proposed as a mechanism in cryptogenic stroke. A prolonged PR interval may reflect impaired atrial conduction and thus may be a biomarker of atrial cardiopathy. We aim to compare the prevalence of PR interval prolongation in patients with cryptogenic stroke (CS) when compared with known non-cryptogenic non-cardioembolic stroke (NCNCS) subtypes. METHODS: We used prospective ischemic stroke databases of 3 comprehensive stroke centers to identify patients 18 years or older with a discharge diagnosis of ischemic non-cardioembolic stroke between December 1, 2013 and August 31, 2015. The main outcome was ischemic stroke subtype (CS versus NCNCS). We compared PR intervals as a continuous and categorical variable (<200 milliseconds; ≥200 milliseconds) and other clinical and demographic factors between the 2 groups and used multivariate regression analyses to determine the association between PR interval prolongation and CS. RESULTS: We identified 644 patients with ischemic non-cardioembolic stroke (224 CS and 420 NCNCS). Patients with CS were more likely to have a PR of 200 milliseconds or greater when compared with those with NCNCS (23.2% versus 13.8%, P = .009). After adjusting for factors that were significant in univariate analyses, a PR of 200 milliseconds or greater was independently associated with CS (odds ratio [OR] 1.70, 95% CI 1.08-2.70). The association was more pronounced when excluding patients on atrioventricular nodal blocking agents (OR 2.64, 95% CI 1.44-4.83). CONCLUSIONS: A PR of 200 milliseconds or greater is associated with CS and may be a biomarker of atrial cardiopathy in the absence of atrial fibrillation. Prospective studies are needed to confirm this association.

Intravenous Thrombolysis Attenuates Neurologic Deterioration After Ischemic Stroke.

INTRODUCTION: Although intravenous tissue plasminogen activator (IV tPA) is associated with neurologic deterioration (ND) caused by hemorrhage, whether it attenuates deterioration as a result of other etiologies including progressive stroke remains unexplored. The objective of this study was to determine whether IV tPA is associated with a reduced risk of ND caused by progressive stroke. METHODS: A retrospective investigation of consecutively admitted patients with acute ischemic stroke (July 2008-June 2014) within 4.5 hours of symptom onset was conducted at a tertiary care center. Patients treated with IV tPA were compared with those who were not. The primary outcome was ND resulting from progressive infarction (a two-point increase in the National Institutes of Health Stroke Scale score during a 24-hour period). RESULTS: A total of 699 registry patients (median age 65 years, interquartile range 55-76, 48.4% women, 70.4% nonwhite) were included in the study, and 58.1% received IV tPA. In crude regression, IV tPA did not reduce the odds of ND caused by progressive infarction; however, IV tPA-treated patients were at a 55% lower odds of ND from any cause (odds ratio 0.45, 95% confidence interval 0.32-0.61, P < 0.001). After adjusting for covariates, IV tPA use remained strongly associated with a 39% lower odds of ND from any cause (odds ratio 0.61, 95% confidence interval 0.48-0.79, P < 0.001). CONCLUSIONS: Although IV tPA did not correlate with a reduced odds of progressive infarction, it was significantly associated with a lower odds of ND by any mechanism.

A Model for Predicting Persistent Elevation of Factor VIII among Patients with Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Elevated levels of coagulation factor VIII (FVIII) may persist independent of the acute-phase response; however, this relationship has not been investigated relative to acute ischemic stroke (AIS). We examined the frequency and predictors of persistently elevated FVIII in AIS patients. METHODS: AIS patients admitted between July 2008 and May 2014 with elevated baseline FVIII levels and repeat FVIII levels drawn for more than 7 days postdischarge were included. The patients were dichotomized by repeat FVIII level for univariate analysis at 150% and 200% activity thresholds. An adjusted model was developed to predict the likelihood of persistently elevated FVIII levels. RESULTS: Among 1616 AIS cases, 98 patients with elevated baseline FVIII had repeat FVIII levels. Persistent FVIII elevation was found in more than 75% of patients. At the 150% threshold, the prediction score ranged from 0 to 7 and included black race, female sex, prior stroke, hyperlipidemia, smoking, baseline FVIII > 200%, and baseline von Willebrand factor (vWF) level greater than 200%. At the 200% threshold, the prediction score ranged from 0-5 and included female sex, prior stroke, diabetes mellitus, baseline FVIII level greater 200%, and baseline vWF level greater than 200%. For each 1-point increase in score, the odds of persistent FVIII at both the 150% threshold (odds ratio [OR] = 10.4, 95% confidence interval [CI] 1.63-66.9, P = .0134) and 200% threshold (OR = 10.2, 95% CI 1.82-57.5, P = .0083) increased 10 times. CONCLUSION: Because an elevated FVIII level confers increased stroke risk, our model for anticipating a persistently elevated FVIII level may identify patients at high risk for recurrent stroke. FVIII may be a target for secondary stroke prevention.

Intravenous Tissue Plasminogen Activator for Wake-Up Stroke: A Propensity Score-Matched Analysis.

GOAL: To evaluate the safety and efficacy of intravenous (IV) tissue plasminogen activator (tPA) in the treatment of wake-up stroke (WUS) using propensity score (PS) analysis. MATERIALS AND METHODS: Consecutive acute ischemic stroke patients meeting inclusion criteria were retrospectively identified from our stroke registry between July 2008 and May 2014, and classified as stroke onset less than or equal to 4.5 hours treated with tPA (control; n = 369), tPA-treated WUS (n = 46), or nontreated WUS (n = 154). The primary outcome of interest for safety was symptomatic intracerebral hemorrhage (sICH), defined as parenchymal hemorrhage associated with a greater than or equal to 4-point increase in National Institutes of Health Stroke Scale (NIHSS) score. Multivariate logistic regression with adjustment for confounders and PS for receiving IV tPA assessed outcomes, along with PS-matched average treatment effect on the treated (ATT). FINDINGS: No significant difference was found in rates of sICH between tPA-treated WUS, nontreated WUS, and controls (2.2%, .7%, and 3%, respectively), or in the odds of sICH between tPA-treated WUS and controls (OR = .53, 95% CI = .06-4.60, P = .568). Among WUS patients, tPA treatment was significantly associated with higher odds of good functional outcome in fully adjusted analyses (OR = 7.22, 95% CI = 2.28-22.88, P = .001). The ATT of tPA for WUS patients demonstrated a significantly greater decrease in NIHSS score at discharge when compared to nontreated WUS patients (-4.32 versus -.34, P = .032). CONCLUSIONS: Comparable rates of sICH between treated WUS and stroke onset less than or equal to 4.5 hours treated with tPA suggest that tPA may be safely used to treat WUS. Superior outcomes for tPA-treated versus nontreated WUS subjects may suggest clinical efficacy of the treatment.

The impact of absent A1 segment on ischemic stroke characteristics and outcomes.

BACKGROUND: A1 segment is the proximal portion of anterior cerebral artery. Absence of the A1 segment can compromise anterior cerebral collateral blood flow. Few studies have examined the association of an absent A1 segment and ischemic stroke outcome. We sought to determine the association between A1 absence and affected vessel territory, stroke volume, and outcomes among patients with acute ischemic stroke (AIS). METHODS: A retrospective review of prospectively identified patients with AIS from July 2008 to March 2013 was performed. Patients without intracranial vascular imaging were excluded. We compared patients with absent A1 to patients with bilateral A1 segments in terms of demographics, stroke severity (as measured by National Institute of Health Stroke Scale [NIHSS]), vascular distribution, and in-hospital mortality using the chi-square test and logistic regression. RESULTS: Of the 1146 patients with AIS and intracranial vascular imaging, 5.9% patients (n = 68) had absent A1. Compared with other AIS patients, those with absent A1 were older (65 vs. 63 years old, respectively, P = .016). There was no difference between groups in terms of the vascular distribution or the side of the stroke. The median volume of the infracted tissue was similar across the groups even when it was stratified according to the Treatment of Acute Stroke Trial classification. Patients with an absent A1 had twice higher odds of in-hospital mortality (odds ratio, 2.4; 95% confidence interval, 1.1-5.2; P = .028); however, significance was lost after adjusting to age, NIHSS at baseline, and glucose on admission. Other outcome measures were similar across the groups. CONCLUSIONS: In our sample, patients with an absent A1 segment did not have a specific vascular distribution, larger infarct volume, or worse outcomes.

Cryptogenic stroke: clinical consideration of a heterogeneous ischemic subtype.

BACKGROUND: Cryptogenic stroke can be subdivided into 3 distinct categories: stroke of no determined cause (CyNC), stroke due to multiple etiologies (Cy >1), and stroke etiology unclear due to incomplete evaluation. Although these subdivisions may be very different from one another with respect to baseline features and outcomes, they are often reported as a composite group in clinical trials. METHODS: Patients treated at our academic institution between July 2008 and June 2013 for acute ischemic stroke were retrospectively assessed in our prospective registry. CyNC and Cy >1 patients were compared to other Trial of Org 10172 in Acute Stroke Treatment (TOAST) stroke subtypes and to each other using univariate analyses and multivariate logistic regression. The primary outcome of interest was good functional outcome, defined as a discharge modified Rankin Scale score of 0-2. RESULTS: Of the 1311 included patients, 260 (19.8%) experienced a CyNC and 49 (3.7%) experienced a Cy >1. Cy >1 classification was associated with history of atrial fibrillation (odds ratio [OR], 3.17; 95% confidence interval [CI], 1.16-6.12; P = .001). In comparison to other TOAST classifications, CyNC strokes were more likely to have good functional outcome (OR, 1.97; 95% CI, 1.38-2.82; P < .001) after adjusting for baseline National Institutes of Health Stroke Scale, admission glucose, age, and intravenous tissue plasminogen activator (IV tPA). CONCLUSIONS: Even after adjusting for higher IV tPA treatment rates, ischemic stroke patients with no identified cause had better outcomes than other TOAST groups. Conversely, patients coded as cryptogenic with more than 1 likely cause represent a different patient subpopulation. These data argue against the consolidation of cryptogenic stroke subcategories in future investigations.

A simple prediction score for developing a hospital-acquired infection after acute ischemic stroke.

BACKGROUND: Hospital-acquired infections (HAIs) are a major cause of morbidity and mortality in acute ischemic stroke patients. Although prior scoring systems have been developed to predict pneumonia in ischemic stroke patients, these scores were not designed to predict other infections. We sought to develop a simple scoring system for any HAI. METHODS: Patients admitted to our stroke center (July 2008-June 2012) were retrospectively assessed. Patients were excluded if they had an in-hospital stroke, unknown time from symptom onset, or delay from symptom onset to hospital arrival greater than 48 hours. Infections were diagnosed via clinical, laboratory, and imaging modalities using standard definitions. A scoring system was created to predict infections based on baseline patient characteristics. RESULTS: Of 568 patients, 84 (14.8%) developed an infection during their stays. Patients who developed infection were older (73 versus 64, P < .0001), more frequently diabetic (43.9% versus 29.1%, P = .0077), and had more severe strokes on admission (National Institutes of Health Stroke Scale [NIHSS] score 12 versus 5, P < .0001). Ranging from 0 to 7, the overall infection score consists of age 70 years or more (1 point), history of diabetes (1 point), and NIHSS score (0-4 conferred 0 points, 5-15 conferred 3 points, >15 conferred 5 points). Patients with an infection score of 4 or more were at 5 times greater odds of developing an infection (odds ratio, 5.67; 95% confidence interval, 3.28-9.81; P < .0001). CONCLUSION: In our sample, clinical, laboratory, and imaging information available at admission identified patients at risk for infections during their acute hospitalizations. If validated in other populations, this score could assist providers in predicting infections after ischemic stroke.

Von Willebrand factor drives the association between elevated factor VIII and poor outcomes in patients with ischemic stroke.

BACKGROUND AND PURPOSE: Despite clear roles of factor VIII (FVIII) and von Willebrand factor (vWF) in thrombosis, few studies have examined the relationship of these factors with acute ischemic stroke (AIS). We sought to determine whether concurrent elevation in FVIII and vWF was associated with adverse events and outcomes. METHODS: From our prospective stroke registry, patients consecutively admitted with AIS between July 2008 and October 2013 were included if both FVIII and vWF were measured during admission. The primary outcome was the modified Rankin Scale score on discharge. RESULTS: Among 1453 cases in our stroke registry, 148 patients with AIS met inclusion criteria; 62 patients (41.9%) had FVIII-/vWF-, 16 patients (10.8%) had FVIII+/vWF-, and 51 patients (34.5%) had FVIII+/vWF+. In the fully adjusted model, patients with FVIII+/vWF+ had increased odds of inpatient complications (odds ratio, 8.6; 95% confidence interval, 1.58-46.85; P=0.013) and neuroworsening (odds ratio, 3.2; 95% confidence interval, 1.18-8.73; P=0.022) than patients with FVIII-/vWF-. Adjusted for age, baseline stroke severity, and glucose, patients with FVIII+/vWF+ had increased odds of poor functional outcome (modified Rankin Scale>2; odds ratio, 2.87; 95% confidence interval, 1.16-7.06; P=0.021) than patients with FVIII-/vWF-. CONCLUSIONS: Concurrent FVIII/vWF elevation predicts higher odds of inpatient complications, neuroworsening, and worse functional outcomes for patients with AIS compared with patients with normal levels. Our findings suggest that FVIII and vWF levels may serve as clinically useful stroke biomarkers by providing risk profiles for patients with AIS.

Diagnosis and treatment of arterial dissections.

Dissections of the cervical and intracranial vessels represent an important source of stroke in those less than 50 years of age. This can occur spontaneously or following trauma, minor or major. Rapid diagnosis is essential to limit subsequent sequelae and modern computed tomographic angiography represents an appropriately sensitive modality. Treatment must be individualized to the patient and can consist of an antiplatelet regimen, anticoagulation, or endovascular intervention. No evidence demonstrates superiority of either medical modality and even aspirin alone may be efficacious. Consideration should be given to this in the multi-trauma population in which more aggressive anticoagulation is contraindicated. In addition, thrombolytic administration should not be withheld would it otherwise be indicated. Endovascular intervention is reserved for those with hemodynamically significant narrowing, enlarging pseudoaneurysms, fistulas formation, or subarachnoid hemorrhage.

Racial disparities in early mortality in 1,134 young patients with acute stroke.

We sought to investigate potential racial disparities in early outcomes of young individuals with stroke in an international multicenter study. We evaluated consecutive patients with first-ever acute stroke aged 18-45 years from prospective databases involving 12 tertiary-care stroke centers in North America (n = 2), Europe (n = 6), and Asia (n = 4). Demographics, vascular risk factors, stroke subtypes, pre-stroke functional status, stroke severity, blood pressure parameters, and serum glucose at hospital admission were documented. The outcome events of interest were 30-day mortality and 30-day favorable functional outcome (FFO) defined as modified-Rankin Scale score of 0-1. A total of 1,134 young adults (mean age 37.4 ± 7.0 years; 58.8 % men; 48.6 % Whites, 23.9 % Blacks, and 27.5 % Asians; median baseline National Institutes of Health Stroke Scale score 6 points, interquartile range 2-13) were included in the analyses. The 30-day stroke mortality and FFO rates differed (p < 0.001) across races. After adjusting for potential confounders, race was independently associated with 30-day mortality (p = 0.026) and 30-day FFO (p = 0.035). Blacks had a fourfold higher odds of 30-day stroke mortality in comparison to Asians (OR 4.00; 95 % CI 1.38-11.59; p = 0.011). Whites also had an increased likelihood of 30-day stroke mortality in comparison to Asians (OR 3.59; 95 % CI 1.28-10.03; p = 0.015). Blacks had a lower odds of 30-day FFO in comparison to Whites (OR 0.57; 95 % CI 0.35-0.91; p = 0.018). Racial disparities in early outcomes following first-ever stroke in young individuals appear to be independent of other known outcome predictor variables. Whites appear to have higher likelihood of 30-day FFO and Asians have lower odds of 30-day stroke mortality.