Modeling diffusion-weighted imaging lesion expansion between 2 and 24 h after endovascular thrombectomy in acute ischemic stroke.

PURPOSE: Diffusion-weighted imaging (DWI) lesion expansion after endovascular thrombectomy (EVT) is not well characterized. We used serial diffusion-weighted magnetic resonance imaging (MRI) to measure lesion expansion between 2 and 24 h after EVT. METHODS: In this single-center observational analysis of patients with acute ischemic stroke due to large vessel occlusion, DWI was performed post-EVT (< 2 h after closure) and 24-h later. DWI lesion expansion was evaluated using multivariate generalized linear mixed modeling with various clinical moderators. RESULTS: We included 151 patients, of which 133 (88%) had DWI lesion expansion, defined as a positive change in lesion volume between 2 and 24 h. In an unadjusted analysis, median baseline DWI lesion volume immediately post-EVT was 15.0 mL (IQR: 6.6-36.8) and median DWI lesion volume 24 h post-EVT was 20.8 mL (IQR: 9.4-66.6), representing a median change of 6.1 mL (IQR: 1.5-17.7), or a 39% increase. There were no significant associations among univariable models of lesion expansion. Adjusted models of DWI lesion expansion demonstrated that relative lesion expansion (defined as final/initial DWI lesion volume) was consistent across eTICI scores (0-2a, 0.52%; 2b, 0.49%; 2c-3, 0.42%, p = 0.69). For every 1 mL increase in lesion volume, there was 2% odds of an increase in 90-day mRS (OR: 1.021, 95%CI [1.009, 1.034], p < 0.001). CONCLUSION: We observed substantial lesion expansion post-EVT whereby relative lesion expansion was consistent across eTICI categories, and greater absolute lesion expansion was associated with worse clinical outcome. Our findings suggest that alternate endpoints for cerebroprotectant trials may be feasible.

Population analysis of ischemic stroke burden and risk factors in the United States in the pre- and post-mechanical thrombectomy eras.

OBJECTIVES: To provide an updated analysis of the burden of ischemic stroke in the United States. MATERIALS AND METHODS: Using the Global Burden of Disease database, we estimated age-standardized, population-adjusted rates of incidence, prevalence, mortality, and disability-adjusted life years from 2010 to 2019, with regional comparisons. Deaths and disability-adjusted life years were compared in 2010-2014 and 2015-2019 to assess the potential effect of increased mechanical thrombectomy use. The attributable, disability-adjusted life years for twenty risk factors were estimated, ranked, and trended. RESULTS: Incident ischemic strokes decreased by 11.4 % across the study period from 65.7 (55.9-77.3) to 58.2 (49.0-69.5) per 100,000. Prevalence (-8.2 %), mortality (-1.9 %), and disability-adjusted life years (-4.4 %) all declined. All regions showed reductions in all burden measures, with the South consistently having the highest burden yet the largest reduction in incidence (-12.6 %) and prevalence (-10.5 %). Deaths (p < 0.0001) and DALYs (p < 0.0001) significantly differed between the pre- and post-mechanical thrombectomy eras. Total attributable disability-adjusted life years for all risk factors decreased from 304.7 (258.5-353.2) in 2010 to 288.9 (242.2-337.2) in 2019. In 2019, the risk factors with the most disability-adjusted life years were hypertension, hyperglycemia, and obesity with no state-based differences. Across the study period, disability-adjusted life years attributable to leading risk factors decreased among men but decreased less or increased among women. CONCLUSIONS: The burden of ischemic stroke decreased during the study period. Declines in deaths and disability-adjusted life years suggest a mitigating impact of mechanical thrombectomy. While disability-adjusted life years attributable to leading risk factors decreased, sex-based disparities were observed.

Recurrence risk in symptomatic intracranial stenosis treated medically in the real world.

BACKGROUND: The risk of early recurrence in medically treated patients with intracranial atherosclerotic stenosis (ICAS) may differ in clinical trials versus real-world settings. Delayed enrollment may contribute to lower event rates in ICAS trials. We aim to determine the 30-day recurrence risk in a real-world setting of symptomatic ICAS. METHODS: We used a comprehensive stroke center stroke registry to identify hospitalized patients with acute ischemic stroke or TIA due to symptomatic 50-99% ICAS. The outcome was recurrent stroke within 30 days. We used adjusted Cox regression models to identify factors associated with increased recurrence risk. We also performed a comparison of 30-day recurrent stroke rates in real world cohorts and clinical trials. RESULTS: Among 131 hospitalizations with symptomatic 50-99% ICAS over 3 years, 80 hospitalizations of 74 patients (mean age 71.6 years, 55.41% men) met the inclusion criteria. Over 30 days, 20.6 % had recurrent stroke; 61.5% (8/13) occurred within first 7 days. The risk was higher in patients not receiving dual antiplatelet therapy (HR 3.92 95% CI 1.30-11.84, p = 0.015) and hypoperfusion mismatch volume >3.5 mL at a T max>6 s threshold (HR 6.55 95% CI 1.60-26.88, p < 0.001). The recurrence risk was similar to another real world ICAD cohort (20.2%), and higher than that seen in clinical trials (2.2%-5.7%), even in those treated with maximal medical treatment or meeting inclusion criteria for trials. CONCLUSIONS: In patients with symptomatic ICAS, the real-world recurrence of ischemic events is higher than that seen in clinical trials, even in subgroups receiving the same pharmacological treatment strategies.

Recurrent Ischemic Stroke and Bleeding in Patients With Atrial Fibrillation Who Suffered an Acute Stroke While on Treatment With Nonvitamin K Antagonist Oral Anticoagulants: The RENO-EXTEND Study.

BACKGROUND: In patients with atrial fibrillation who suffered an ischemic stroke while on treatment with nonvitamin K antagonist oral anticoagulants, rates and determinants of recurrent ischemic events and major bleedings remain uncertain. METHODS: This prospective multicenter observational study aimed to estimate the rates of ischemic and bleeding events and their determinants in the follow-up of consecutive patients with atrial fibrillation who suffered an acute cerebrovascular ischemic event while on nonvitamin K antagonist oral anticoagulant treatment. Afterwards, we compared the estimated risks of ischemic and bleeding events between the patients in whom anticoagulant therapy was changed to those who continued the original treatment. RESULTS: After a mean follow-up time of 15.0±10.9 months, 192 out of 1240 patients (15.5%) had 207 ischemic or bleeding events corresponding to an annual rate of 13.4%. Among the events, 111 were ischemic strokes, 15 systemic embolisms, 24 intracranial bleedings, and 57 major extracranial bleedings. Predictive factors of recurrent ischemic events (strokes and systemic embolisms) included CHA2DS2-VASc score after the index event (odds ratio [OR], 1.2 [95% CI, 1.0-1.3] for each point increase; P=0.05) and hypertension (OR, 2.3 [95% CI, 1.0-5.1]; P=0.04). Predictive factors of bleeding events (intracranial and major extracranial bleedings) included age (OR, 1.1 [95% CI, 1.0-1.2] for each year increase; P=0.002), history of major bleeding (OR, 6.9 [95% CI, 3.4-14.2]; P=0.0001) and the concomitant administration of an antiplatelet agent (OR, 2.8 [95% CI, 1.4-5.5]; P=0.003). Rates of ischemic and bleeding events were no different in patients who changed or not changed the original nonvitamin K antagonist oral anticoagulants treatment (OR, 1.2 [95% CI, 0.8-1.7]). CONCLUSIONS: Patients suffering a stroke despite being on nonvitamin K antagonist oral anticoagulant therapy are at high risk of recurrent ischemic stroke and bleeding. In these patients, further research is needed to improve secondary prevention by investigating the mechanisms of recurrent ischemic stroke and bleeding.

Penumbra Consumption Rates Based on Time-to-Maximum Delay and Reperfusion Status: A Post Hoc Analysis of the DEFUSE 3 Trial.

BACKGROUND AND PURPOSE: In patients with acute large vessel occlusion, the natural history of penumbral tissue based on perfusion time-to-maximum (Tmax) delay is not well established in relation to late-window endovascular thrombectomy. In this study, we sought to evaluate penumbra consumption rates for Tmax delays in patients with large vessel occlusion evaluated between 6 and 16 hours from last known normal. METHODS: This is a post hoc analysis of the DEFUSE 3 trial (The Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke), which included patients with an acute ischemic stroke due to anterior circulation occlusion within 6 to 16 hours of last known normal. The primary outcome is percentage penumbra consumption, defined as (24-hour magnetic resonance imaging infarct volume-baseline core infarct volume)/(Tmax 6 or 10 s volume-baseline core volume). We stratified the cohort into 4 categories based on treatment modality and Thrombolysis in Cerebral Infarction (TICI score; untreated, TICI 0-2a, TICI 2b, and TICI3) and calculated penumbral consumption rates in each category. RESULTS: We included 141 patients, among whom 68 were untreated. In the untreated versus TICI 3 patients, a median (interquartile range) of 53.7% (21.2%-87.7%) versus 5.3% (1.1%-14.6%) of penumbral tissue was consumed based on Tmax >6 s (P<0.001). In the same comparison for Tmax>10 s, we saw a difference of 165.4% (interquartile range, 56.1%-479.8%) versus 25.7% (interquartile range, 3.2%-72.1%; P<0.001). Significant differences were not demonstrated between untreated and TICI 0-2a patients for penumbral consumption based on Tmax >6 s (P=0.52) or Tmax >10 s (P=0.92). CONCLUSIONS: Among extended window endovascular thrombectomy patients, Tmax >10-s mismatch volume may comprise large volumes of salvageable tissue, whereas nearly half the Tmax >6-s mismatch volume may remain viable in untreated patients at 24 hours.

Radiologic Patterns of Intracranial Hemorrhage and Clinical Outcome after Endovascular Treatment in Acute Ischemic Stroke: Results from the ESCAPE-NA1 Trial.

Background Intracranial hemorrhage is a known complication after endovascular treatment in patients with acute ischemic stroke due to large vessel occlusion, but the association between radiologic hemorrhage severity and outcome is controversial. Purpose To investigate the prevalence and impact on outcome of intracranial hemorrhage and hemorrhage severity after endovascular stroke treatment. Materials and Methods The Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke (ESCAPE-NA1) trial enrolled participants with acute large vessel occlusion stroke who underwent endovascular treatment from March 1, 2017, to August 12, 2019. Evidence of any intracranial hemorrhage, hemorrhage multiplicity, and radiologic severity, according to the Heidelberg classification (hemorrhagic infarction type 1 [HI1], hemorrhagic infarction type 2 [HI2], parenchymal hematoma type 1 [PH1], and parenchymal hematoma type 2 [PH2]) was assessed at CT or MRI 24 hours after endovascular treatment. Good functional outcome, defined as a modified Rankin score of 0-2 at 90 days, was compared between participants with intracranial hemorrhage and those without intracranial hemorrhage at follow-up imaging and between hemorrhage subtypes. Poisson regression was performed to obtain adjusted effect size estimates for the presence of any intracranial hemorrhage and hemorrhage subtypes at good functional outcome. Results Of 1097 evaluated participants (mean age, 69 years ± 14 [standard deviation]; 551 men), any degree of intracranial hemorrhage was observed in 372 (34%). Good outcomes were less often achieved among participants with hemorrhage than among those without hemorrhage at follow-up imaging (164 of 372 participants [44%] vs 500 of 720 [69%], respectively; P < .01). After adjusting for baseline variables and infarct volume, intracranial hemorrhage was not associated with decreased chances of good outcome (adjusted risk ratio [RR] = 0.91 [95% CI: 0.82, 1.02], P = .10), but there was a graded relationship of radiologic hemorrhage severity and outcomes, whereby PH1 (RR = 0.77 [95% CI: 0.61, 0.97], P = .03) and PH2 (RR = 0.41 [95% CI: 0.21, 0.81], P = .01) were associated with decreased chances of good outcome. Conclusion Any degree of intracranial hemorrhage after endovascular treatment was seen in one-third of participants. A graded association existed between radiologic hemorrhage severity and outcome. Hemorrhagic infarction was not associated with outcome, whereas parenchymal hematoma was strongly associated with poor outcome, independent of infarct volume. © RSNA, 2021 Clinical trial registration no. NCT01778335 Online supplemental material is available for this article.

A DELPHI consensus statement on antiplatelet management for intracranial stenting due to underlying atherosclerosis in the setting of mechanical thrombectomy.

PURPOSE: There is little data and lack of consensus regarding antiplatelet management for intracranial stenting due to underlying intracranial atherosclerosis in the setting of endovascular treatment (EVT). In this DELPHI study, we aimed to assess whether consensus on antiplatelet management in this situation among experienced experts can be achieved, and what this consensus would be. METHODS: We used a modified DELPHI approach to address unanswered questions in antiplatelet management for intracranial stenting due to underlying atherosclerosis in the setting of EVT. An expert-panel (19 neurointerventionalists from 8 countries) answered structured, anonymized on-line questionnaires with iterative feedback-loops. Panel-consensus was defined as agreement ≥ 70% for binary closed-ended questions/≥ 50% for closed-ended questions with > 2 response options. RESULTS: Panel members answered a total of 5 survey rounds. They acknowledged that there is insufficient data for evidence-based recommendations in many aspects of antiplatelet management for intracranial stenting due to underlying atherosclerosis in the setting of EVT. They believed that antiplatelet management should follow a standardized regimen, irrespective of imaging findings and reperfusion quality. There was no consensus on the timing of antiplatelet-therapy initiation. Aspirin was the preferred antiplatelet agent for the peri-procedural period, and oral Aspirin in combination with a P2Y12 inhibitor was the favored postprocedural regimen. CONCLUSION: Data on antiplatelet management for intracranial stenting due to underlying atherosclerosis in the setting of EVT are limited. Panel-members in this study achieved consensus on postprocedural antiplatelet management but did not agree upon a preprocedural and intraprocedural antiplatelet regimen. Further prospective studies to optimize antiplatelet regimens are needed.

Effects of multiphase versus single-phase CT angiography for the detection of distal cerebral vessel occlusion.

PURPOSE: The goal of this study was to determine whether the benefits of multiphase CTA (mCTA) over single-phase CTA (sCTA) for the detection of proximal cerebrovascular occlusions similarly extend to the distal cerebral vasculature. METHODS: Four attending radiologists, two neuroradiologists and two emergency radiologists, contributed as readers to this retrospective study. For each reader, two sessions were conducted, one using sCTA and one using mCTA. During each session, the reader interpreted the studies of 104 patients who underwent imaging for suspicion of acute ischemic stroke, resulting in a total of 832 interpretations. Changes in diagnostic accuracy, time to render final decision, and reported levels of reader confidence were quantitatively assessed. Further analysis comparing the effects for neuroradiologists versus emergency radiologists was additionally conducted. RESULTS: Using mCTA resulted in a significant 5.0% absolute increase in sensitivity (91.6% vs. 96.6%, p = .004) and an insignificant increase in specificity (99.5% vs. 99.7%, p = .39). A significant reduction in reading time (66.7 s vs. 59.6 s, p = .001) and an increase in diagnostic confidence (2.26 vs. 2.58, p < .001) were observed. Using sCTA, higher sensitivity was achieved by neuroradiologists than emergency radiologists (96.0% vs. 86.9%, p = .002); using mCTA resulted in an absolute increase in sensitivity of 0.9% (97.4%, p = .44) for neuroradiologists and 9.6% (96.5%, p < .001) for emergency radiologists, eliminating significant differences between the groups (p = 0.57). CONCLUSION: The use of mCTA results in increased sensitivity and negative predictive value, decreased reading time, increased diagnostic confidence, and the elimination of differences in accuracy between neuroradiologists and emergency radiologists.

The Effect of Hyperglycemia on Infarct Growth after Reperfusion: An Analysis of the DEFUSE 3 trial.

BACKGROUND AND PURPOSE: Brain infarct growth, despite successful reperfusion, decreases the likelihood of good functional outcome after ischemic stroke. In patients undergoing reperfusion, admission glucose is associated with poor outcome but the effect of glucose level on infarct growth is not well studied. MATERIALS AND METHODS: This is a secondary analysis of the DEFUSE 3 trial. The primary predictor was baseline glucose level and the primary outcome is the change of the ischemic core volume from the baseline to 24-hour follow-up imaging (∆core), transformed as a cube root to reduce right skew. We included DEFUSE 3 patients who were randomized to endovascular therapy, had perfusion imaging data at baseline, an MRI at 24 hours, and who achieved TICI 2b or 3. Linear regression models, both unadjusted and adjusted, were fit to the primary outcome and all models included the baseline core volume as a covariate to normalize ∆core. RESULTS: We identified 62 patients who met our inclusion criteria. The mean age was 68.1±13.1 (years), 48.4% (30/62) were men, and the median (IQR) cube root of ∆core was 2.8 (2.0-3.8) mL. There was an association between baseline glucose level and normalized ∆core in unadjusted analysis (beta coefficient 0.010, p = 0.01) and after adjusting for potential confounders (beta coefficient 0.008, p = 0.03). CONCLUSION: In acute ischemic stroke patients with large vessel occlusion undergoing successful endovascular reperfusion, baseline hyperglycemia is associated with infarction growth. Further study is needed to establish potential neuroprotective benefits of aggressive glycemic control prior to and after reperfusion.

Mechanical Thrombectomy in Patients With Ischemic Stroke With Prestroke Disability.

Background and Purpose- We aimed to compare functional and procedural outcomes of patients with acute ischemic stroke with none-to-minimal (modified Rankin Scale [mRS] score, 0-1) and moderate (mRS score, 2-3) prestroke disability treated with mechanical thrombectomy. Methods- Consecutive adult patients undergoing mechanical thrombectomy for an anterior circulation stroke were prospectively identified at 2 comprehensive stroke centers from 2012 to 2018. Procedural and 90-day functional outcomes were compared among patients with prestroke mRS scores 0 to 1 and 2 to 3 using χ2, logistic, and linear regression tests. Primary outcome and significant differences in secondary outcomes were adjusted for prespecified covariates. Results- Of 919 patients treated with mechanical thrombectomy, 761 were included and 259 (34%) patients had moderate prestroke disability. Ninety-day mRS score 0 to 1 or no worsening of prestroke mRS was observed in 36.7% and 26.7% of patients with no-to-minimal and moderate prestroke disability, respectively (odds ratio, 0.63 [0.45-0.88], P=0.008; adjusted odds ratio, 0.90 [0.60-1.35], P=0.6). No increase in the disability at 90 days was observed in 22.4% and 26.7%, respectively. Rate of symptomatic intracerebral hemorrhage (7.3% versus 6.2%, P=0.65), successful recanalization (86.7% versus 83.8%, P=0.33), and median length of hospital stay (5 versus 5 days, P=0.06) were not significantly different. Death by 90 days was higher in patients with moderate prestroke disability (14.3% versus 40.3%; odds ratio, 4.06 [2.82-5.86], P<0.001; adjusted odds ratio, 2.83 [1.84, 4.37], P<0.001). Conclusions- One-third of patients undergoing mechanical thrombectomy had a moderate prestroke disability. There was insufficient evidence that functional and procedural outcomes were different between patients with no-to-minimal and moderate prestroke disability. Patients with prestroke disability were more likely to die by 90 days.

Challenging the Ischemic Core Concept in Acute Ischemic Stroke Imaging.

Endovascular treatment is a highly effective therapy for acute ischemic stroke due to large vessel occlusion and has recently revolutionized stroke care. Oftentimes, ischemic core extent on baseline imaging is used to determine endovascular treatment-eligibility. There are, however, 3 fundamental issues with the core concept: First, computed tomography and magnetic resonance imaging, which are mostly used in the acute stroke setting, are not able to precisely determine whether and to what extent brain tissue is infarcted (core) or still viable, due to variability in tissue vulnerability, the phenomenon of selective neuronal loss and lack of a reliable gold standard. Second, treatment decision-making in acute stroke is multifactorial, and as such, the relative importance of single variables, including imaging factors, is reduced. Third, there are often discrepancies between core volume and clinical outcome. This review will address the uncertainty in terminology and proposes a direction towards more clarity. This theoretical exercise needs empirical data that clarify the definitions further and prove its value.

Detecting Large Vessel Occlusion at Multiphase CT Angiography by Using a Deep Convolutional Neural Network.

Background Large vessel occlusion (LVO) stroke is one of the most time-sensitive diagnoses in medicine and requires emergent endovascular therapy to reduce morbidity and mortality. Leveraging recent advances in deep learning may facilitate rapid detection and reduce time to treatment. Purpose To develop a convolutional neural network to detect LVOs at multiphase CT angiography. Materials and Methods This multicenter retrospective study evaluated 540 adults with CT angiography examinations for suspected acute ischemic stroke from February 2017 to June 2018. Examinations positive for LVO (n = 270) were confirmed by catheter angiography and LVO-negative examinations (n = 270) were confirmed through review of clinical and radiology reports. Preprocessing of the CT angiography examinations included vasculature segmentation and the creation of maximum intensity projection images to emphasize the contrast agent-enhanced vasculature. Seven experiments were performed by using combinations of the three phases (arterial, phase 1; peak venous, phase 2; and late venous, phase 3) of the CT angiography. Model performance was evaluated on the held-out test set. Metrics included area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Results The test set included 62 patients (mean age, 69.5 years; 48% women). Single-phase CT angiography achieved an AUC of 0.74 (95% confidence interval [CI]: 0.63, 0.85) with sensitivity of 77% (24 of 31; 95% CI: 59%, 89%) and specificity of 71% (22 of 31; 95% CI: 53%, 84%). Phases 1, 2, and 3 together achieved an AUC of 0.89 (95% CI: 0.81, 0.96), sensitivity of 100% (31 of 31; 95% CI: 99%, 100%), and specificity of 77% (24 of 31; 95% CI: 59%, 89%), a statistically significant improvement relative to single-phase CT angiography (P = .01). Likewise, phases 1 and 3 and phases 2 and 3 also demonstrated improved fit relative to single phase (P = .03). Conclusion This deep learning model was able to detect the presence of large vessel occlusion and its diagnostic performance was enhanced by using delayed phases at multiphase CT angiography examinations. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Ospel and Goyal in this issue.

Detection of emergent large vessel occlusion stroke with CT angiography is high across all levels of radiology training and grayscale viewing methods.

OBJECTIVES: CT angiography (CTA) is essential in acute stroke to detect emergent large vessel occlusions (ELVO) and must be interpreted by radiologists with and without subspecialized training. Additionally, grayscale inversion has been suggested to improve diagnostic accuracy in other radiology applications. This study examines diagnostic performance in ELVO detection between neuroradiologists, non-neuroradiologists, and radiology residents using standard and grayscale inversion viewing methods. METHODS: A random, counterbalanced experimental design was used, where 18 radiologists with varying experiences interpreted the same patient images with and without grayscale inversion. Confirmed positive and negative ELVO cases were randomly ordered using a balanced design. Sensitivity, specificity, positive and negative predictive values as well as confidence, subjective assessment of image quality, time to ELVO detection, and overall interpretation time were examined between grayscale inversion (on/off) by experience level using generalized mixed modeling assuming a binary, negative binomial, and binomial distributions, respectively. RESULTS: All groups of radiologists had high sensitivity and specificity for ELVO detection (all > .94). Neuroradiologists were faster than non-neuroradiologists and residents in interpretation time, with a mean of 47 s to detect ELVO, as compared with 59 and 74 s, respectively. Residents were subjectively less confident than attending physicians. With respect to grayscale inversion, no differences were observed between groups with grayscale inversion vs. standard viewing for diagnostic performance (p = 0.30), detection time (p = .45), overall interpretation time (p = .97), and confidence (p = .20). CONCLUSIONS: Diagnostic performance in ELVO detection with CTA was high across all levels of radiologist training level. Grayscale inversion offered no significant detection advantage. KEY POINTS: • Stroke is an acute vascular syndrome that requires acute vascular imaging. • Proximal large vessel occlusions can be identified quickly and accurately by radiologists across all training levels. • Grayscale inversion demonstrated minimal detectable benefit in the detection of proximal large vessel occlusions.

Increased Left Atrial Appendage Density on Computerized Tomography is Associated with Cardioembolic Stroke.

BACKGROUND AND PURPOSE: While studies have stratified cardioembolic (CE) stroke risk by qualitative left atrial appendage (LAA) morphology and biomarkers of atrial dysfunction, the quantitative properties that underlie these observations are not well established. Accordingly, we hypothesized that LAA volume and contrast density (attenuation) on computerized tomography (CT) may capture the structural and hemodynamic processes that underlie CE stroke risk. METHODS: Data were collected from a single center prospective ischemic stroke database over 18 months and included all patients with ischemic stroke who previously underwent routine, nongated, contrast enhanced thin-slice (≤2.5 mm) chest CT. Stroke subtype was determined based on the inpatient diagnostic evaluation. LAA volume and attenuation were determined from CT studies performed for various clinically appropriate indications. Univariate and multivariable analyses were performed to determine factors associated with ischemic stroke subtype, including known risk factors and biomarkers, as well as LAA density and morphologic measures. RESULTS: We identified 311 patients with a qualifying chest CT (119 CE subtype, 109 Embolic Stroke of Undetermined Source (ESUS), and 83 non-CE). In unadjusted models, there was an association between CE (versus non-CE) stroke subtype and LAA volume (OR per mL increase 1.15, 95% CI 1.07-1.24, P < .001) and LAA density (4th quartile versus 1st quartile; OR 2.95, 95% CI 1.28-6.80, P = .011), but not with ESUS (versus non-CE) subtype. In adjusted models, only the association between LAA density and CE stroke subtype persisted (adjusted OR 3.71, 95% CI 1.37-10.08, P = .010). CONCLUSION: The LAA volume and density values on chest CT are associated with CE stroke subtype but not ESUS subtype. Patients with ESUS and increased LAA volume or attenuation may be a subgroup where the mechanism is CE and anticoagulation can be tested for secondary stroke prevention.

Redefining Early Neurological Improvement After Reperfusion Therapy in Stroke.

BACKGROUND AND PURPOSE: Early neurologic improvement (ENI) in patients treated with alteplase has been shown to correlate with functional outcome. However, the definition of ENI remains controversial and has varied across studies. We hypothesized that ENI defined as a percentage change in the National Institute of Health Stroke Scale (NIHSS) score (percent change NIHSS score) at 24-hours would better correlate with favorable outcomes at 3 months than ENI defined as the change in NIHSS score (delta NIHSS score) at 24 hours. METHODS: Retrospective analysis of prospectively collected single-center quality improvement data was performed of all acute ischemic stroke (AIS) patients treated with alteplase. We examined delta NIHSS score and percent change NIHSS score in unadjusted and adjusted logistic regression models as predictors of a favorable outcome at 3 months (defined as mRS 0-1). RESULTS: Among 586 patients who met the inclusion criteria, 194 (33.1%) had a favorable outcome at 3 months. In fully adjusted models, both delta NIHSS score (OR per point decrease 1.27; 95% confidence interval [CI] 1.19-1.36) and percent change NIHSS score (OR per 10 percent decrease 1.17; 95% CI 1.12-1.22) were associated with favorable functional outcome at 3 months. Receiver operating characteristic (ROC) curve comparison showed that the area under the ROC curve for percent change NIHSS score (.755) was greater than delta NIHSS score (.613) or admission NIHSS (.694). CONCLUSIONS: Percentage change in NIHSS score may be a better surrogate marker of ENI and functional outcome in AIS patients after receiving acute thrombolytic therapy. More studies are needed to confirm our findings.

Mechanical Thrombectomy in Ischemic Stroke Patients with Severe Pre-Stroke Disability.

Frequency and outcomes of mechanical thrombectomy (MT) in clinical practice for patients with severe pre-stroke disability are largely unknown. In this case series, we aim to describe the disability make-up and outcomes of 33 patients with severe pre-stroke disability undergoing MT. Patients with a permanent, severe, pre-stroke disability (modified Rankin Score, mRS, 4-5) were identified from a prospectively-maintained database of consecutive, MT-treated, anterior circulation acute ischemic stroke patients at two comprehensive stroke centers in the United States. We present details on the cause of disability and socio-demographic status as well as procedural and functional outcomes. This study, despite the lack of inferential testing due to limited sample size, provides insight into demographics and outcomes of MT-treated patients with severe pre-stroke disability. Rate of return to functional baseline as well as rates of procedural success and complications were comparable to that reported in the literature for patients without any pre-existing disability.

Indications for the Performance of Intracranial Endovascular Neurointerventional Procedures: A Scientific Statement From the American Heart Association.

Intracranial endovascular interventions provide effective and minimally invasive treatment of a broad spectrum of diseases. This area of expertise has continued to gain both wider application and greater depth as new and better techniques are developed and as landmark clinical studies are performed to guide their use. Some of the greatest advances since the last American Heart Association scientific statement on this topic have been made in the treatment of ischemic stroke from large intracranial vessel occlusion, with more effective devices and large randomized clinical trials showing striking therapeutic benefit. The treatment of cerebral aneurysms has also seen substantial evolution, increasing the number of aneurysms that can be treated successfully with minimally invasive therapy. Endovascular therapies for such other diseases as arteriovenous malformations, dural arteriovenous fistulas, idiopathic intracranial hypertension, venous thrombosis, and neoplasms continue to improve. The purpose of the present document is to review current information on the efficacy and safety of procedures used for intracranial endovascular interventional treatment of cerebrovascular diseases and to summarize key aspects of best practice.

Left Atrial Volume Index Is Associated With Cardioembolic Stroke and Atrial Fibrillation Detection After Embolic Stroke of Undetermined Source.

Background and Purpose- Left atrial enlargement has been shown to be associated with ischemic stroke, but the association with embolic stroke mechanisms remains unknown. We aim to study the associations between left atrial volume index (LAVI) and embolic stroke subtypes and atrial fibrillation (AF) detection on cardiac event monitoring in patients with embolic stroke of unknown source. Methods- Data were collected from a prospective cohort of consecutive patients with ischemic stroke admitted to a comprehensive stroke center over 18 months. Stroke subtype was classified into cardioembolic stroke, noncardioembolic stroke of determined mechanism (NCE), or embolic stroke of undetermined source (ESUS). Univariate and prespecified multivariable analyses were performed to assess associations between LAVI and stroke subtype and AF detection in patients with ESUS. Results- Of 1224 consecutive patients identified during the study period, 1020 (82.6%) underwent transthoracic echocardiography and had LAVI measurements. LAVI was greater in patients with cardioembolic stroke than NCE (41.4 mL/m2±18.0 versus 28.6 mL/m2±12.2; P<0.001) but not in ESUS versus NCE (28.9 mL/m2±12.6 versus 28.6 mL/m2±12.2; P=0.61). In multivariable logistic regression models, LAVI was greater in cardioembolic stroke versus NCE (adjusted odds ratio per mL/m2, 1.07; 95% CI, 1.05-1.09; P<0.001) but not in ESUS versus NCE (adjusted odds ratio per mL/m2, 1.00; 95% CI, 0.99-1.02; P=0.720). Among 99 patients with ESUS who underwent cardiac monitoring, 18.2% had AF detected; LAVI was independently associated with AF detection in ESUS (adjusted odds ratio per mL/m2, 1.09; 95% CI, 1.02-1.15; P=0.007). Conclusions- LAVI is associated with cardioembolic stroke as well as AF detection in patients with ESUS, 2 subsets of ischemic stroke that benefit from anticoagulation therapy. Patients with increased LAVI may be a subgroup where anticoagulation may be tested for stroke prevention.

Blood Pressure after Endovascular Therapy for Ischemic Stroke (BEST): A Multicenter Prospective Cohort Study.

Background and Purpose- To identify the specific post-endovascular stroke therapy (EVT) peak systolic blood pressure (SBP) threshold that best discriminates good from bad functional outcomes (a priori hypothesized to be 160 mm Hg), we conducted a prospective, multicenter, cohort study with a prespecified analysis plan. Methods- Consecutive adult patients treated with EVT for an anterior ischemic stroke were enrolled from November 2017 to July 2018 at 12 comprehensive stroke centers accross the United States. All SBP values within 24 hours post-EVT were recorded. Using Youden index, the threshold of peak SBP that best discriminated primary outcome of dichotomized 90-day modified Rankin Scale score (0-2 versus 3-6) was identified. Association of this SBP threshold with the outcomes was quantified using multiple logistic regression. Results- Among 485 enrolled patients (median age, 69 [interquartile range, 57-79] years; 51% females), a peak SBP of 158 mm Hg was associated with the largest difference in the dichotomous modified Rankin Scale score (absolute risk reduction of 19%). Having a peak SBP >158 mm Hg resulted in an increased likelihood of modified Rankin Scale score 3 to 6 (odds ratio, 2.24 [1.52-3.29], P<0.01; adjusted odds ratio, 1.29 [0.81-2.06], P=0.28, after adjustment for prespecified variables). Conclusions- A peak post-EVT SBP of 158 mm Hg was prospectively identified to best discriminate good from bad functional outcome. Those with a peak SBP >158 had an increased likelihood of having a bad outcome in unadjusted, but not in adjusted analysis. The observed effect size was similar to prior studies. This finding should undergo further testing in a future randomized trial of goal-targeted post-EVT antihypertensive treatment.

Predicting symptomatic intracranial haemorrhage after mechanical thrombectomy: the TAG score.

BACKGROUND: There is limited data on predictors of symptomatic intracranial haemorrhage (sICH) in patients who underwent mechanical thrombectomy. In this study, we aim to determine those predictors with external validation. METHODS: We evaluated mechanical thrombectomy in a derivation cohort of patients at a comprehensive stroke centre over a 30-month period. Clinical and radiographic data on these patients were obtained from the prospective quality improvement database. sICH was defined using the European Cooperative Acute Stroke Study III. We compared clinical and radiographic characteristics between patients with and without sICH using χ2 and t tests to identify independent predictors of sICH with p<0.1. Significant variables were then combined in a multivariate logistic regression model to derive an sICH prediction score. This score was then validated using data from the Blood Pressure After Endovascular Treatment multicentre prospective registry. RESULTS: We identified 578 patients with acute ischaemic stroke who received thrombectomy, 19 had sICH (3.3%). Predictive factors of sICH were: thrombolysis in cerebral ischaemia (TICI) score, Alberta stroke program early CT score (ASPECTS), and glucose level, and from these predictors, we derived the weighted TICI-ASPECTS-glucose (TAG) score, which was associated with sICH in the derivation (OR per unit increase 1.98, 95% CI 1.48 to 2.66, p<0.001, area under curve ((AUC)=0.79) and validation (OR per unit increase 1.48, 95% CI 1.22 to 1.79, p<0.001, AUC=0.69) cohorts. CONCLUSION: High TAG scores are associated with sICH in patients receiving mechanical thrombectomy. Larger studies are needed to validate this scoring system and test strategies to reduce sICH risk and make thrombectomy safer in patients with elevated TAG scores.