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.

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.

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.

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.

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.

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.

Door-in-Door-Out Time at Primary Stroke Centers May Predict Outcome for Emergent Large Vessel Occlusion Patients.

Background and Purpose- Interfacility transfers for thrombectomy in stroke patients with emergent large vessel occlusion (ELVO) are associated with longer treatment times and worse outcomes. In this series, we examined the association between Primary Stroke Center (PSC) door-in to door-out (DIDO) times and outcomes for confirmed ELVO stroke transfers and factors that may modify the interaction. Methods- We retrospectively identified 160 patients transferred to a single Comprehensive Stroke Center (CSC) with anterior circulation ELVO between July 1, 2015 and May 30, 2017. We included patients with acute occlusions of the internal carotid artery or proximal middle cerebral artery (M1 or M2 segments), with a National Institutes of Health Stroke Scale score of ≥6. Workflow metrics included time from onset to recanalization, PSC DIDO, interfacility transfer time, CSC arrival to arterial puncture, and arterial puncture to recanalization. Primary outcome measure was National Institutes of Health Stroke Scale at discharge and modified Rankin Scale (mRS) score at 90 days. Results- The median (Q1-Q3) age and National Institutes of Health Stroke Scale of the 130 ELVO transfers analyzed was 75 (64-84) and 17 (11-22). Intravenous alteplase was administered to 64% of patients. Regarding specific workflow metrics, median (Q1-Q3) times (in minutes) were 241 (199-332) for onset to recanalization, 85 (68-111) for PSC DIDO, 26 (17-32) for interfacility transport, 21 (16-39) for CSC door to arterial puncture, and 24 (15-35) for puncture to recanalization. Median discharge National Institutes of Health Stroke Scale score was 5 (2-16), and 46 (35%) patients had a favorable outcome at 90 days. Complete reperfusion (modified Thrombolysis in Cerebral Ischemia 2c/3) modified the deleterious association of DIDO on outcome. Conclusions- For patients diagnosed with ELVO at a PSC who are being transferred to a CSC for thrombectomy, longer DIDO times may have a deleterious effect on outcomes and may represent the single biggest modifiable factor in onset to recanalization time. PSCs should make efforts to decrease DIDO and routine use of DIDO as a performance measure is encouraged.

Early Elevated Troponin Levels After Ischemic Stroke Suggests a Cardioembolic Source.

BACKGROUND AND PURPOSE: Elevated cardiac troponin is a marker of cardiac disease and has been recently shown to be associated with embolic stroke risk. We hypothesize that early elevated troponin levels in the acute stroke setting are more prevalent in patients with embolic stroke subtypes (cardioembolic and embolic stroke of unknown source) as opposed to noncardioembolic subtypes (large-vessel disease, small-vessel disease, and other). METHODS: We abstracted data from our prospective ischemic stroke database and included all patients with ischemic stroke during an 18-month period. Per our laboratory, we defined positive troponin as ≥0.1 ng/mL and intermediate as ≥0.06 ng/mL and <0.1 ng/mL. Unadjusted and adjusted regression models were built to determine the association between stroke subtype (embolic stroke of unknown source and cardioembolic subtypes) and positive and intermediate troponin levels, adjusting for key confounders, including demographics (age and sex), clinical characteristics (hypertension, hyperlipidemia, diabetes mellitus, renal function, coronary heart disease, congestive heart failure, current smoking, and National Institutes of Health Stroke Scale score), cardiac variables (left atrial diameter, wall-motion abnormalities, ejection fraction, and PR interval on ECG), and insular involvement of infarct. RESULTS: We identified 1234 patients, of whom 1129 had admission troponin levels available; 10.0% (113/1129) of these had a positive troponin. In fully adjusted models, there was an association between troponin positivity and embolic stroke of unknown source subtype (adjusted odds ratio, 4.46; 95% confidence interval, 1.03-7.97; P=0.003) and cardioembolic stroke subtype (odds ratio, 5.00; 95% confidence interval, 1.83-13.63; P=0.002). CONCLUSIONS: We found that early positive troponin after ischemic stroke may be independently associated with a cardiac embolic source. Future studies are needed to confirm our findings using high-sensitivity troponin assays and to test optimal secondary prevention strategies in patients with embolic stroke of unknown source and positive troponin.

Predictors of symptomatic intracranial haemorrhage in patients with an ischaemic stroke with neurological deterioration after intravenous thrombolysis.

OBJECTIVES: Early neurological deterioration prompting urgent brain imaging occurs in nearly 15% of patients with ischaemic stroke receiving intravenous tissue plasminogen activator (tPA). We aim to determine risk factors associated with symptomatic intracranial haemorrhage (sICH) in patients with ischaemic stroke undergoing emergent brain imaging for early neurological deterioration after receiving tPA. METHODS: We abstracted data from our prospective stroke database and included all patients receiving tPA for ischaemic stroke between 1 March 2015 and 1 March 2017. We then identified patients with neurological deterioration who underwent urgent brain imaging prior to their per-protocol surveillance imaging and divided patients into two groups: those with and without sICH. We compared baseline demographics, clinical variables, in-hospital treatments and functional outcomes at 90 days between the two groups. RESULTS: We identified 511 patients who received tPA, of whom 108 (21.1%) had an emergent brain CT. Of these patients, 17.5% (19/108) had sICH; 21.3% (23/108) of emergent scans occurred while tPA was infusing, though only 4.3% of these scans (1/23) revealed sICH. On multivariable analyses, the only predictor of sICH was a change in level of consciousness (OR 6.62, 95% CI 1.64 to 26.70, P=0.008). CONCLUSION: Change in level of consciousness is associated with sICH among patients undergoing emergent brain imaging after receiving tPA. In this group of patients, preparation of tPA reversal agents while awaiting brain imaging may reduce reversal times. Future studies are needed to study the cost-effectiveness of this approach.

Left Atrial Enlargement and Anticoagulation Status in Patients with Acute Ischemic Stroke and Atrial Fibrillation.

BACKGROUND: Despite anticoagulation therapy, ischemic stroke risk in atrial fibrillation (AF) remains substantial. We hypothesize that left atrial enlargement (LAE) is more prevalent in AF patients admitted with ischemic stroke who are therapeutic, as opposed to nontherapeutic, on anticoagulation. METHODS: We included consecutive patients with AF admitted with ischemic stroke between April 1, 2015, and December 31, 2016. Patients were divided into two groups based on whether they were therapeutic (warfarin with an international normalized ratio ≥ 2.0 or non-vitamin K oral anticoagulant with uninterrupted use in the prior 2 weeks) versus nontherapeutic on anticoagulation. Univariable and multivariable models were used to estimate associations between therapeutic anticoagulation and clinical factors, including CHADS2 score and LAE (none/mild versus moderate/severe). RESULTS: We identified 225 patients during the study period; 52 (23.1%) were therapeutic on anticoagulation. Patients therapeutic on anticoagulation were more likely to have a larger left atrial diameter in millimeters (45.6 ± 9.2 versus 42.3 ± 8.6, P = .032) and a higher CHADS2 score (2.9 ± 1.1 versus 2.4 ± 1.1, P = .03). After adjusting for the CHADS2 score, patients who had a stroke despite therapeutic anticoagulation were more likely to have moderate to severe LAE (odds ratio, 2.05; 95% confidence interval, 1.01-4.16). CONCLUSION: LAE is associated with anticoagulation failure in AF patients admitted with an ischemic stroke. This provides indirect evidence that LAE may portend failure of anticoagulation therapy in patients with AF; further studies are needed to delineate the significance of this association and improve stroke prevention strategies.

Rethinking Thrombolysis in Cerebral Infarction 2b: Which Thrombolysis in Cerebral Infarction Scales Best Define Near Complete Recanalization in the Modern Thrombectomy Era?

BACKGROUND AND PURPOSE: Within the thrombolysis in cerebral infarction (TICI) classification, TICI 2b has been historically considered successful recanalization. Recent studies have suggested that TICI 3 and a proposed TICI 2c should be separately reported from TICI 2b, in both the original (>66% reperfusion) and modified (>50% reperfusion) definitions, because of differences in clinical outcomes with greater reperfusion. The purpose of this study was to evaluate differences in early neurological improvement and independence at 90 days using the original TICI, modified TICI, and modified TICI with 2c scales. METHODS: A retrospective review of 129 consecutive patients with middle cerebral artery, M1 segment or intracranial internal carotid artery occlusions. Patient angiograms were graded by 2 experienced readers by percentage recanalization. This was then categorized into original TICI, modified TICI (mTICI), and mTICI with TICI 2c (mTICI 2c) grading scales. Comparison of baseline demographics, early neurological improvement, and independence at 90 days was performed. RESULTS: A significant difference in early neurological improvement was observed between 2b and 3 (P=0.032), as well as between 2b and 2c (P=0.028) under the mTICI 2c grading scale. Similarly, a significant difference in functional independence was observed between 2b and 3 (P=0.037), as well as between 2b and 2c (P=0.047) under the mTICI 2c scale. The difference in early neurological improvement or functional independence between 2b and 3 for the original TICI and mTICI scales was not significant. When combining the 2c and 3 groups under the mTICI 2c scale, there were significant differences between 2b and 2c/3 in regards to both early neurological improvement (P=0.011) and independence (P=0.018). CONCLUSIONS: Using a TICI grading system that includes an additional category beyond TICI 2b allows for refined prediction of early neurological improvement and functional independence.

Unresolved Issues in Thrombectomy.

PURPOSE OF REVIEW: Trials demonstrating marked benefit of mechanical thrombectomy (MT) for acute stroke caused by large vessel occlusion (LVO) in the anterior circulation have been the most significant advance in acute ischemic stroke in the past 20 years. However, despite this marked advance, there are still many hurdles to improving access to thrombectomy worldwide. Additionally, despite these advances, a substantial portion of patients with LVO still are left disabled. RECENT FINDINGS: The major randomized trials focused on patients within 6 h from symptom onset, with occlusion of the ICA or proximal MCA, small amount of permanently damaged brain, and a moderate to large clinical deficit. We will explore the role of thrombectomy outside of these areas, but also explore larger issues as they pertain to re-organization of stroke systems of care to improve access to this remarkable therapy. Now that we have proven, without a shadow of doubt, that rapid revascularization with mechanical thrombectomy improves outcomes in LVO stroke, we must reorganize our systems of care to improve access and assess the role for MT outside of the patients who meet trial criteria.

Alberta stroke program early computed tomographic scoring performance in a series of patients undergoing computed tomography and MRI: reader agreement, modality agreement, and outcome prediction.

BACKGROUND AND PURPOSE: In this study, we compare the performance of pretreatment Alberta Stroke Program Early Computed Tomographic scoring (ASPECTS) using noncontrast CT (NCCT) and MRI in a large endovascular therapy cohort. METHODS: Prospectively enrolled patients underwent baseline NCCT and MRI and started endovascular therapy within 12 hours of stroke onset. Inclusion criteria for this analysis were evaluable pretreatment NCCT, diffusion-weighted MRI (DWI), and 90-day modified Rankin Scale scores. Two expert readers graded ischemic change on NCCT and DWI using the ASPECTS. ASPECTS scores were analyzed with the full scale or were trichotomized (0-4 versus 5-7 versus 8-10) or dichotomized (0-7 versus 8-10). Good functional outcome was defined as a 90-day modified Rankin Scale score of 0 to 2. RESULTS: Seventy-four patients fulfilled our study criteria. The full-scale inter-rater agreement for CT-ASPECTS and DWI-ASPECTS was 0.579 and 0.867, respectively. DWI-ASPECTS correlated with functional outcome (P=0.004), whereas CT-ASPECTS did not (P=0.534). Both DWI-ASPECTS and CT-ASPECTS correlated with DWI volume. The receiver operating characteristic analysis revealed that DWI-ASPECTS outperformed both CT-ASPECTS and the time interval between symptom onset and start of the procedure for predicting good functional outcome (modified Rankin Scale score, ≤2) and DWI volume ≥70 mL. CONCLUSION: Inter-rater agreement for DWI-ASPECTS was superior to that for CT-ASPECTS. DWI-ASPECTS outperformed NCCT ASPECTS for predicting functional outcome at 90 days.

Technique and impact on first pass effect primary results of the ASSIST global registry.

BACKGROUND: Patients treated with mechanical thrombectomy (MT) for acute ischemic strokes from large vessel occlusion (LVO) have better outcomes with effective reperfusion. However, it is unknown which technique leads to better technical and clinical success. We aimed to determine which technique yields the most effective first pass reperfusion during MT. METHODS: In a prospective, multicenter global registry we enrolled patients treated with operator preferred MT technique at 71 hospitals from January 2019 to January 2022. Three techniques were assessed: SR Classic with stent retriever (SR) and balloon guide catheter (BGC); SR Combination which employed SR with contact aspiration with or without BGC; and direct aspiration (DA) with or without BGC. The primary outcome was achieving an expanded Thrombolysis In Cerebral Infarction (eTICI) score of 2c or 3 on the first pass, with the primary technique as adjudicated by core lab. The primary clinical outcome measure was a 90-day modified Rankin Scale (mRS) score of 0-2. RESULTS: A total of 1492 patients were enrolled. Patients treated with SR Classic or SR Combination were more likely to achieve first pass eTICI 2c or 3 reperfusion (P=0.01). There was no significant difference in mRS 0-2 (P=0.46) or safety endpoints. CONCLUSIONS: The use of SR Classic or SR Combination was more likely to achieve first pass eTICI 2c or 3 reperfusion. There were no significant differences in clinical outcomes and safety endpoints.