Trial of Early Minimally Invasive Removal of Intracerebral Hemorrhage.

BACKGROUND: Trials of surgical evacuation of supratentorial intracerebral hemorrhages have generally shown no functional benefit. Whether early minimally invasive surgical removal would result in better outcomes than medical management is not known. METHODS: In this multicenter, randomized trial involving patients with an acute intracerebral hemorrhage, we assessed surgical removal of the hematoma as compared with medical management. Patients who had a lobar or anterior basal ganglia hemorrhage with a hematoma volume of 30 to 80 ml were assigned, in a 1:1 ratio, within 24 hours after the time that they were last known to be well, to minimally invasive surgical removal of the hematoma plus guideline-based medical management (surgery group) or to guideline-based medical management alone (control group). The primary efficacy end point was the mean score on the utility-weighted modified Rankin scale (range, 0 to 1, with higher scores indicating better outcomes, according to patients' assessment) at 180 days, with a prespecified threshold for posterior probability of superiority of 0.975 or higher. The trial included rules for adaptation of enrollment criteria on the basis of hemorrhage location. A primary safety end point was death within 30 days after enrollment. RESULTS: A total of 300 patients were enrolled, of whom 30.7% had anterior basal ganglia hemorrhages and 69.3% had lobar hemorrhages. After 175 patients had been enrolled, an adaptation rule was triggered, and only persons with lobar hemorrhages were enrolled. The mean score on the utility-weighted modified Rankin scale at 180 days was 0.458 in the surgery group and 0.374 in the control group (difference, 0.084; 95% Bayesian credible interval, 0.005 to 0.163; posterior probability of superiority of surgery, 0.981). The mean between-group difference was 0.127 (95% Bayesian credible interval, 0.035 to 0.219) among patients with lobar hemorrhages and -0.013 (95% Bayesian credible interval, -0.147 to 0.116) among those with anterior basal ganglia hemorrhages. The percentage of patients who had died by 30 days was 9.3% in the surgery group and 18.0% in the control group. Five patients (3.3%) in the surgery group had postoperative rebleeding and neurologic deterioration. CONCLUSIONS: Among patients in whom surgery could be performed within 24 hours after an acute intracerebral hemorrhage, minimally invasive hematoma evacuation resulted in better functional outcomes at 180 days than those with guideline-based medical management. The effect of surgery appeared to be attributable to intervention for lobar hemorrhages. (Funded by Nico; ENRICH ClinicalTrials.gov number, NCT02880878.).

Mode of Onset Modifies the Effect of Time to Endovascular Reperfusion on Clinical Outcomes after Acute Ischemic Stroke: An Analysis of the DAWN Trial.

OBJECTIVE: We aimed to assess the impact of time to endovascular thrombectomy (EVT) on clinical outcomes in the DAWN trial, while also exploring the potential effect modification of mode of stroke onset on this relationship. METHODS: The association between every 1-h treatment delay with 90-day functional independence (modified Rankin Scale [mRS] score 0-2), symptomatic intracranial hemorrhage, and 90-day mortality was explored in the overall population and in three modes of onset subgroups (wake-up vs. witnessed vs. unwitnessed). RESULTS: Out of the 205 patients, 98 (47.8%) and 107 (52.2%) presented in the 6 to 12 hours and 12 to 24 hours time window, respectively. Considering all three modes of onset together, there was no statistically significant association between time last seen well to randomization with either functional independence or mortality at 90 days in either the endovascular thrombectomy (mRS 0-2 1-hour delay OR 1.07; 95% CI 0.93-1.24; mRS 6 OR 0.84; 95% CI 0.65-1.03) or medical management (mRS 0-2 1-hour delay OR 0.98; 95% CI 0.80-1.14; mRS 6 1-hour delay OR 0.94; 95% CI 0.79-1.09) groups. Moreover, there was no significant interaction between treatment effect and time (p = 0.439 and p = 0.421 for mRS 0-2 and 6, respectively). However, within the thrombectomy group, the models that tested the association between time last seen well to successful reperfusion (modified Treatment in Cerebral Infarction ≥2b) and 90-day functional independence showed a significant interaction with mode of presentation (p = 0.013). This appeared to be driven by a nominally positive slope for both witnessed and unwitnessed strokes versus a significantly (p = 0.018) negative slope in wake-up patients. There was no association between treatment times and symptomatic intracranial hemorrhage. INTERPRETATION: Mode of onset modifies the effect of time to reperfusion on thrombectomy outcomes, and should be considered when exploring different treatment paradigms in the extended window. ANN NEUROL 2024.

Comparison of CT Perfusion Software Packages for Thrombectomy Eligibility.

INTRODUCTION: Computed tomography perfusion (CTP) has played an important role in patient selection for mechanical thrombectomy (MT) in acute ischemic stroke. We aimed to investigate the agreement between perfusion parametric maps of 3 software packages - RAPID (RapidAI-IschemaView), Viz CTP(Viz.ai), and e-CTP(Brainomix) - in estimating baseline ischemic core volumes of near completely/completely reperfused patients. METHODS: We retrospectively reviewed a prospectively maintained MT database to identify patients with anterior circulation large vessel occlusion strokes (LVOS) involving the internal carotid artery or middle cerebral artery M1-segment and interpretable CTP maps treated during September 2018 to November 2019. A subset of patients with near-complete/complete reperfusion (expanded thrombolysis in cerebral infarction [eTICI] 2c-3) was used to compare the pre-procedural prediction of final infarct volumes. RESULTS: In this analysis of 242 patients with LVOS, RAPID and Viz CTP relative cerebral blood flow (rCBF) < 30% values had substantial agreement (ρ = 0.767 [95% confidence interval [CI] = 0.71-0.81]) as well as for RAPID and e-CTP (ρ = 0.668 [95% CI = 0.61-0.71]). Excellent agreement was seen for time to maximum of the residue function (Tmax ) > 6 seconds between RAPID and Viz CTP (ρ = 0.811 [95% CI = 0.76-0.84]) and substantial for RAPID and e-CTP (ρ = 0.749 [95% CI = 0.69-0.79]). Final infarct volume (FIV) prediction (n = 136) was substantial in all 3 packages (RAPID ρ = 0.744; Viz CTP ρ = 0.711; and e-CTP ρ = 0.600). CONCLUSION: Perfusion parametric maps of the RAPID, Viz CTP, and e-CTP software have substantial agreement in predicting final infarct volume in near-completely/completely reperfused patients. ANN NEUROL 2023;94:848-855.

Higher Procedural Volumes Are Associated with Faster Treatment Times, Better Functional Outcomes, and Lower Mortality in Patients Undergoing Endovascular Treatment for Acute Ischemic Stroke.

OBJECTIVE: We aimed to characterize the association of hospital procedural volumes with outcomes among acute ischemic stroke (AIS) patients undergoing endovascular therapy (EVT). METHODS: This was a retrospective, observational cohort study using data prospectively collected from January 1, 2016 to December 31, 2019 in the Get with the Guidelines-Stroke registry. Participants were derived from a cohort of 60,727 AIS patients treated with EVT within 24 hours at 626 hospitals. The primary cohort excluded patients with pretreatment National Institutes of Health Stroke Scale (NIHSS) < 6, onset-to-treatment time > 6 hours, and interhospital transfers. There were 2 secondary cohorts: (1) the EVT metrics cohort excluded patients with missing data on time from door to arterial puncture and (2) the intravenous thrombolysis (IVT) metrics cohort only included patients receiving IVT ≤4.5 hours after onset. RESULTS: The primary cohort (mean ± standard deviation age = 70.7 ± 14.8 years; 51.2% female; median [interquartile range] baseline NIHSS = 18.0 [13-22]; IVT use, 70.2%) comprised 21,209 patients across 595 hospitals. The EVT metrics cohort and IVT metrics cohort comprised 47,262 and 16,889 patients across 408 and 601 hospitals, respectively. Higher procedural volumes were significantly associated with higher odds (expressed as adjusted odds ratio [95% confidence interval] for every 10-case increase in volume) of discharge to home (1.03 [1.02-1.04]), functional independence at discharge (1.02 [1.01-1.04]), and lower rates of in-hospital mortality (0.96 [0.95-0.98]). All secondary measures were also associated with procedural volumes. INTERPRETATION: Among AIS patients primarily presenting to EVT-capable hospitals (excluding those transferred from one facility to another and those suffering in-hospital strokes), EVT at hospitals with higher procedural volumes was associated with faster treatment times, better discharge outcomes, and lower rates of in-hospital mortality. ANN NEUROL 2023.

Dialect identification, intelligibility ratings, and acceptability ratings of dysarthric speech in two American English dialects.

The current study explored the intelligibility and acceptability ratings of dysarthric speakers with African American English (AAE) and General American English (GAE) dialects by listeners who identify as GAE or AAE speakers, as well as listener ability to identify dialect in dysarthric speech. Eighty-six listeners rated the intelligibility and acceptability of sentences extracted from a passage read by speakers with dysarthria. Samples were used from the Atlanta Motor Speech Disorders Corpus and ratings were collected via self-report. The listeners identified speaker dialect in a forced-choice format. Listeners self-reported their dialect and exposure to AAE. AAE dialect was accurately identified in 63.43% of the the opportunities; GAE dialect was accurately identified in 70.35% of the opportunities. Listeners identifying as AAE speakers rated GAE speech as more acceptable, whereas, listeners identifying as GAE speakers rated AAE speech as more acceptable. Neither group of listeners demonstrated a difference in intelligibility ratings. Exposure to AAE had no effect on intelligibility or acceptability ratings. Listeners can identify dialect (AAE and GAE) with a better than chance degree of accuracy. One's dialect may have an effect on intelligibility and acceptability ratings. Exposure to a dialect did not affect listener ratings of intelligibility or acceptability.

Emergent use of ticagrelor during endovascular reperfusion in large arterial occlusions.

OBJECTIVE: Given many emerging indications for endovascular interventions in ischemic strokes, a safe and effective adjuvant antiplatelet regimen for acute revascularization has become a subject of interest. Ticagrelor is a direct oral P2Y12 inhibitor that may achieve rapid platelet suppression than standard oral therapies. We report our experience of Ticagrelor use in revascularization of acute large arterial steno-occlusive disease, describing procedural post-procedure thrombotic events, major hemorrhages, and other clinical outcomes. METHODS: This was a single-center retrospective case series of large steno-occlusive disease requiring endovascular reperfusion with emergent adjuvant Ticagrelor, defined as 30 min of the procedure from skin puncture to closure of the arteriotomy. Major outcomes investigated were thromboembolism in the target artery, and symptomatic intracranial or extracranial major hemorrhages. Additional analyses were performed with respect to timing of the administration and use of rescue GPIIb/IIIa inhibitors if any. RESULTS: 73 consecutive patients were identified, presenting with severe ischemic stroke (median NIHSS 16) of large artery origin. 67% required stent placement (45% cervical carotid, 22% intracranial artery), 9.5% angioplasty and 23% mechanical thrombectomy only. Two experienced symptomatic in-stent occlusion, and 7 experienced major hemorrhages (9.5%) including 3 fatal symptomatic intracranial hemorrhages (4.1%). Among 19 subjects (26%) who received pretreatment with Ticagrelor, there were fewer GPIIb/IIIa administration, angioplasty and stenting, without yielding benefit in functional outcome or mortality. GPIIb/IIIa was administered as rescue therapy in 45 subjects (62%), which was found associated with increased bleeding compared to patients receiving Ticagrelor only, in whom no bleeding complications were recorded (16% vs. 0%; p = 0.03). CONCLUSION: We report our findings on Ticagrelor as an adjuvant antiplatelet therapy in ischemic stroke of large arterial origin requiring emergent revascularization. Effectiveness, safety, need for additional rescue treatment, and comparison to other commonly used oral antiplatelets should be investigated in future prospective studies.

Carotid Web Phenotype Is Uncommonly Associated With Classic Fibromuscular Dysplasia: A Retrospective Observational Study.

BACKGROUND AND PURPOSE: Carotid web (CaW) is an intimal form of fibromuscular dysplasia (FMD) involving the carotid bulb which has been increasingly recognized as a potential cause of recurrent ischemic strokes. It is overlooked as a separate entity and often dismissed if no coexistent signs of classic FMD changes are observed. We aim to evaluate the frequency of classic FMD in high-yield vascular territories in patients with symptomatic CaW. METHODS: This was a retrospective analysis of a symptomatic CaW database of 2 comprehensive stroke centers (spanning September 2014-October 2020). The diagnosis of a CaW during a stroke workup was defined as the presence of a shelf-like linear filling defect in the posterior aspect of the carotid bulb on computed tomography angiography in patients with acute ischemic stroke or transient ischemic attack of undetermined cause after a thorough evaluation. Neck computed tomography angiography and renal conventional angiography images were independently evaluated by two readers blinded to the laterality and clinical details to inspect the presence of underlying classic FMD. RESULTS: Sixty-six patients with CaW were identified. Median age was 51 years (interquartile range, 42-57), and 74% were women. All patients had neck computed tomography angiography (allowing for bilateral vertebral and carotid evaluation), whereas 47 patients had additional digital subtraction angiography (which evaluated 47 carotids ipsilateral to the stroke and 10 contralateral carotids). Internal carotid artery classic FMD changes were noted in only 6 out of 66 (9%) in the ipsilateral carotids. No contralateral carotid or vertebral artery classic FMD changes were observed. Renal artery catheter-based angiography was obtained in 16 patients/32 arteries and only 1 patient/2 renal arteries demonstrated classic FMD changes. CONCLUSIONS: CaW phenotype is uncommonly associated with classic FMD changes. Coexistent classic FMD does not constitute a useful marker to corroborate or exclude CaW diagnosis.

No Racial Disparity in Outcome Measures After Endovascular Treatment for Stroke in the Elderly.

BACKGROUND AND PURPOSE: Despite the lower rates of good outcomes and higher mortality in elderly patients, age does not modify the treatment effect of mechanical thrombectomy for large vessel occlusion strokes. We aimed to study whether racial background influences the outcome after mechanical thrombectomy in the elderly population. METHODS: We reviewed a prospectively maintained database of patients with acute ischemic stroke treated with mechanical thrombectomy from October 2010 through June 2020 to identify all consecutive patients with age ≥80 years and anterior circulation large vessel occlusion strokes. The patients were categorized according to their race as Black and White. Univariable and multivariable analyses were performed to define the predictors of 90-day modified Rankin Scale and mortality in the overall population and in each race separately. RESULTS: Among 2241 mechanical thrombectomy, a total of 344 patients (median [interquartile range]; age 85 [82-88] years, baseline National Institutes of Health Stroke Scale score of 19 [15-23], Alberta Stroke Program Early CT Score 9 [7-9], 69.5% females) were eligible for the analysis. White patients (n=251; 73%) had significantly lower median body mass index (25.37 versus 26.89, P=0.04) and less frequent hypertension (78.9% versus 90.3%, P=0.01) but more atrial fibrillation (64.5% versus 44.1%, P=0.001) compared with African Americans (n=93; 27%). Other clinical, imaging, and procedural characteristics were comparable between groups. The rates of symptomatic intracerebral hemorrhage, 90-day modified Rankin Scale score of 0 to 2, and mortality were comparable among both groups. On multivariable analysis, race was neither a predictor of 90-day modified Rankin Scale score of 0 to 2 (White race: odds ratio, 0.899 [95% CI, 0.409-1.974], P=0.79) nor 90-day mortality (White race: odds ratio, 1.368; [95% CI, 0.715-2.618], P=0.34). CONCLUSIONS: In elderly patients undergoing mechanical thrombectomy for acute ischemic stroke, there was no racial difference in terms of outcome.

Automated Large Artery Occlusion Detection in Stroke: A Single-Center Validation Study of an Artificial Intelligence Algorithm.

INTRODUCTION: Expediting notification of lesions in acute ischemic stroke (AIS) is critical. Limited availability of experts to assess such lesions and delays in large vessel occlusion (LVO) recognition can negatively affect outcomes. Artificial intelligence (AI) may aid LVO recognition and treatment. This study aims to evaluate the performance of an AI-based algorithm for LVO detection in AIS. METHODS: Retrospective analysis of a database of AIS patients admitted in a single center between 2014 and 2019. Vascular neurologists graded computed tomography angiographies (CTAs) for presence and site of LVO. Studies were analyzed by the Viz-LVO Algorithm® version 1.4 - neural network programmed to detect occlusions from the internal carotid artery terminus (ICA-T) to the Sylvian fissure. Comparisons between human versus AI-based readings were done by test characteristic analysis and Cohen's kappa. Primary analysis included ICA-T and/or middle cerebral artery (MCA)-M1 LVOs versus non-LVOs/more distal occlusions. Secondary analysis included MCA-M2 occlusions. RESULTS: 610 CTAs were analyzed. The AI algorithm rejected 2.5% of the CTAs due to poor quality, which were excluded from the analysis. Viz-LVO identified ICA-T and MCA-M1 LVOs with a sensitivity of 87.6%, specificity of 88.5%, and accuracy of 87.9% (AUC 0.88, 95% CI: 0.85-0.92, p < 0.001). Cohen's kappa was 0.74. In the secondary analysis, the algorithm yielded a sensitivity of 80.3%, specificity of 88.5%, and accuracy of 82.7%. The mean run time of the algorithm was 2.78 ± 0.5 min. CONCLUSION: Automated AI reading allows for fast and accurate identification of LVO strokes with timely notification to emergency teams, enabling quick decision-making for reperfusion therapies or transfer to specialized centers if needed.

Noncontrast Computed Tomography e-Stroke Infarct Volume Is Similar to RAPID Computed Tomography Perfusion in Estimating Postreperfusion Infarct Volumes.

BACKGROUND AND PURPOSE: The e-Stroke Suite software (Brainomix, Oxford, United Kingdom) is a tool designed for the automated quantification of The Alberta Stroke Program Early CT Score and ischemic core volumes on noncontrast computed tomography (NCCT). We sought to compare the prediction of postreperfusion infarct volumes and the clinical outcomes across NCCT e-Stroke software versus RAPID (IschemaView, Menlo Park, CA) computed tomography perfusion measurements. METHODS: All consecutive patients with anterior circulation large vessel occlusion stroke presenting at a tertiary care center between September 2010 and November 2018 who had available baseline infarct volumes on both NCCT e-Stroke Suite software and RAPID CTP as well as final infarct volume (FIV) measurements and achieved complete reperfusion (modified Thrombolysis in Cerebral Infarction scale 2c-3) post-thrombectomy were included. The associations between estimated baseline ischemic core volumes and FIV as well as 90-day functional outcomes were assessed. RESULTS: Four hundred seventy-nine patients met inclusion criteria. Median age was 64 years (55-75), median e-Stroke and computed tomography perfusion ischemic core volumes were 38.4 (21.8-58) and 5 (0-17.7) mL, respectively, whereas median FIV was 22.2 (9.1-56.2) mL. The correlation between e-Stroke and CTP ischemic core volumes was moderate (R=0.44; P<0.001). Similarly, moderate correlations were observed between e-Stroke software ischemic core and FIV (R=0.52; P<0.001) and CTP core and FIV (R=0.43; P<0.001). Subgroup analysis showed that e-Stroke software and CTP performance was similar in the early and late (>6 hours) treatment windows. Multivariate analysis showed that both e-Stroke software NCCT baseline ischemic core volume (adjusted odds ratio, 0.98 [95% CI, 0.97-0.99]) and RAPID CTP ischemic core volume (adjusted odds ratio, 0.98 [95% CI, 0.97-0.99]) were independently and comparably associated with good outcome (modified Rankin Scale score of 0-2) at 90 days. CONCLUSIONS: NCCT e-Stroke Suite software performed similarly to RAPID CTP in assessing postreperfusion FIV and functional outcomes for both early- and late-presenting patients. NCCT e-Stroke volumes seems to represent a viable alternative in centers where access to advanced imaging is limited. Moreover, the future development of fusion maps of NCCT and CTP ischemic core estimates may improve upon the current performance of these tools as applied in isolation.

Lack of Reperfusion Rather Than Number of Passes Defines Futility in Stroke Thrombectomy: A Matched Case-Control Study.

Background and Purpose: There is a robust relationship between the duration of ischemia and functional outcomes after mechanical thrombectomy. Higher number of mechanical thrombectomy passes strongly correlate with lower chances of favorable outcomes. Indeed, previous studies have suggested that after multiple passes the procedure may be futile. However, using uncontrolled thresholds to define thrombectomy futility might be misleading. We aim to compare the outcome of successful reperfusion after 4 to 5 passes and ≥6 passes with those of failed reperfusion. Methods: A prospectively acquired mechanical thrombectomy database from January 2012 to October 2019 was reviewed. Patients were included if they had intracranial internal carotid artery or middle cerebral artery-M1/M2 occlusions and either achieved successful reperfusion after ≥4 passes or failed reperfusion. Reperfused patients (mTICI2b-3) were divided into 2 subgroups; (1) 4 to 5 passes and (2) ≥6 passes. Each subgroup was compared with a matched group of mechanical thrombectomy failure (mTICI0-2a). The primary outcome was the shift in the degree of disability at 90-day as measured by the modified Rankin Scale. Results: A total of 273 patients were included. As compared with matched failed reperfusion patients (n=62), those reperfused after 4 to 5 passes (n=62) had a favorable shift in the overall modified Rankin Scale score distribution (adjusted odds ratio, 3.992 [95% CI, 1.807­8.512], P=0.001] and higher rates of functional independence (31% versus 8.9%, P=0.004, adjusted odds ratio; 9.860 [95% CI, 2.323­41.845], P=0.002) at 90 days. Similarly, when compared with a matched group of failed reperfusion (n=42), patients reperfused after ≥6 passes (n=42) demonstrated a favorable shift in the overall modified Rankin Scale score distribution (adjusted odds ratio, 2.640 [95% CI, 1.073­6.686], P=0.037) and had higher rates of functional independence (36.8% vs 11.1%, P=0.004, adjusted odds ratio, 5.392 [95% CI, 1.185­24.530], P=0.029) at 90 day. Rates of parenchymal hematoma type-2 and 90-day mortality were comparable in the reperfused and nonreperfused groups. Conclusions: Achieving reperfusion despite multiple passes leads to improved outcomes compared with failed procedures. Arbitrary uncontrolled thresholds for a maximum number of passes to predict futile recanalization may lead to inappropriate early termination of procedures.

Reliability of Field Assessment Stroke Triage for Emergency Destination Scale Use by Paramedics: Mobile Stroke Unit First-Year Experience.

Background and Purpose: Field Assessment Stroke Triage for Emergency Destination (FAST-ED) scale is a helpful tool to triage patients with stroke in the field. However, data on its reliability in the prehospital setting are lacking. We aim to test the reliability of FAST-ED scale when used by paramedics in a mobile stroke unit covering a metropolitan area. Methods: As part of standard operating mobile stroke unit procedures, paramedics initially evaluated patients. If the event characterized a stroke alert, the FAST-ED score was determined by the paramedic upon patient contact (in-person) and then independently by a vascular neurologist (VN) immediately after paramedic evaluation (remotely/telemedicine). This allowed testing of the interrater agreement of the FAST-ED scoring performance between on-site prehospital providers and remotely located VN. Results: Of a total of 238 patients transported in the first 15 months of the mobile stroke unit's activity, 173 were included in this study. Median age was 63 (interquartile range, 55.5­75) years and 52.6% were females. A final diagnosis of ischemic stroke was made in 71 (41%), transient ischemic attack in 26 (15%), intracranial hemorrhage in 15 (9%), whereas 61 (35%) patients were stroke mimics. The FAST-ED scores matched perfectly among paramedics and VN in 97 (56%) instances, while there was 0 to 1-point difference in 158 (91.3%), 0 to 2-point difference in 171 (98.8%), and 3 or more point difference in 2 (1.1%) patients. The intraclass correlation between VN and paramedic FAST-ED scores showed excellent reliability, intraclass correlation coefficient 0.94 (95% CI, 0.92­0.96; P<0.001). When VN recorded FAST-ED score ≥3, paramedics also scored FAST-ED≥3 in majority of instances (63/71 patients; 87.5%). A large vessel occlusion was identified in 16 (9.2%) patients; 13 occlusions were identified with a FAST-ED≥3 while 3 were missed. All of the latter patients had National Institutes of Health Stroke Scale score ≤5. Conclusions: We demonstrate excellent reliability of FAST-ED scale performed by paramedics when compared with VN, indicating that it can be accurately performed by paramedics in the prehospital setting.

Stroke Imaging Selection Modality and Endovascular Therapy Outcomes in the Early and Extended Time Windows.

BACKGROUND AND PURPOSE: Advanced imaging has been increasingly used for patient selection in endovascular stroke therapy. The impact of imaging selection modality on endovascular stroke therapy clinical outcomes in extended time window remains to be defined. We aimed to study this relationship and compare it to that noted in early-treated patients. METHODS: Patients from a prospective multicentric registry (n=2008) with occlusions involving the intracranial internal carotid or the M1- or M2-segments of the middle cerebral arteries, premorbid modified Rankin Scale score 0 to 2 and time to treatment 0 to 24 hours were categorized according to treatment times within the early (0-6 hour) or extended (6-24 hour) window as well as imaging modality with noncontrast computed tomography (NCCT)±CT angiography (CTA) or NCCT±CTA and CT perfusion (CTP). The association between imaging modality and 90-day modified Rankin Scale, analyzed in ordinal (modified Rankin Scale shift) and dichotomized (functional independence, modified Rankin Scale score 0-2) manner, was evaluated and compared within and across the extended and early windows. RESULTS: In the early window, 332 patients were selected with NCCT±CTA alone while 373 also underwent CTP. After adjusting for identifiable confounders, there were no significant differences in terms of 90-day functional disability (ordinal shift: adjusted odd ratio [aOR], 0.936 [95% CI, 0.709-1.238], P=0.644) or independence (aOR, 1.178 [95% CI, 0.833-1.666], P=0.355) across the CTP and NCCT±CTA groups. In the extended window, 67 patients were selected with NCCT±CTA alone while 180 also underwent CTP. No significant differences in 90-day functional disability (aOR, 0.983 [95% CI, 0.81-1.662], P=0.949) or independence (aOR, 0.640 [95% CI, 0.318-1.289], P=0.212) were seen across the CTP and NCCT±CTA groups. There was no interaction between the treatment time window (0-6 versus 6-24 hours) and CT selection modality (CTP versus NCCT±CTA) in terms of functional disability at 90 days (P=0.45). CONCLUSIONS: CTP acquisition was not associated with better outcomes in patients treated in the early or extended time windows. While confirmatory data is needed, our data suggests that extended window endovascular stroke therapy may remain beneficial even in the absence of advanced imaging.

Epidemiological Surveillance of the Impact of the COVID-19 Pandemic on Stroke Care Using Artificial Intelligence.

BACKGROUND AND PURPOSE: The degree to which the coronavirus disease 2019 (COVID-19) pandemic has affected systems of care, in particular, those for time-sensitive conditions such as stroke, remains poorly quantified. We sought to evaluate the impact of COVID-19 in the overall screening for acute stroke utilizing a commercial clinical artificial intelligence platform. METHODS: Data were derived from the Viz Platform, an artificial intelligence application designed to optimize the workflow of patients with acute stroke. Neuroimaging data on suspected patients with stroke across 97 hospitals in 20 US states were collected in real time and retrospectively analyzed with the number of patients undergoing imaging screening serving as a surrogate for the amount of stroke care. The main outcome measures were the number of computed tomography (CT) angiography, CT perfusion, large vessel occlusions (defined according to the automated software detection), and severe strokes on CT perfusion (defined as those with hypoperfusion volumes >70 mL) normalized as number of patients per day per hospital. Data from the prepandemic (November 4, 2019 to February 29, 2020) and pandemic (March 1 to May 10, 2020) periods were compared at national and state levels. Correlations were made between the inter-period changes in imaging screening, stroke hospitalizations, and thrombectomy procedures using state-specific sampling. RESULTS: A total of 23 223 patients were included. The incidence of large vessel occlusion on CT angiography and severe strokes on CT perfusion were 11.2% (n=2602) and 14.7% (n=1229/8328), respectively. There were significant declines in the overall number of CT angiographies (-22.8%; 1.39-1.07 patients/day per hospital, P<0.001) and CT perfusion (-26.1%; 0.50-0.37 patients/day per hospital, P<0.001) as well as in the incidence of large vessel occlusion (-17.1%; 0.15-0.13 patients/day per hospital, P<0.001) and severe strokes on CT perfusion (-16.7%; 0.12-0.10 patients/day per hospital, P<0.005). The sampled cohort showed similar declines in the rates of large vessel occlusions versus thrombectomy (18.8% versus 19.5%, P=0.9) and comprehensive stroke center hospitalizations (18.8% versus 11.0%, P=0.4). CONCLUSIONS: A significant decline in stroke imaging screening has occurred during the COVID-19 pandemic. This analysis underscores the broader application of artificial intelligence neuroimaging platforms for the real-time monitoring of stroke systems of care.

Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct.

BACKGROUND: The effect of endovascular thrombectomy that is performed more than 6 hours after the onset of ischemic stroke is uncertain. Patients with a clinical deficit that is disproportionately severe relative to the infarct volume may benefit from late thrombectomy. METHODS: We enrolled patients with occlusion of the intracranial internal carotid artery or proximal middle cerebral artery who had last been known to be well 6 to 24 hours earlier and who had a mismatch between the severity of the clinical deficit and the infarct volume, with mismatch criteria defined according to age (<80 years or ≥80 years). Patients were randomly assigned to thrombectomy plus standard care (the thrombectomy group) or to standard care alone (the control group). The coprimary end points were the mean score for disability on the utility-weighted modified Rankin scale (which ranges from 0 [death] to 10 [no symptoms or disability]) and the rate of functional independence (a score of 0, 1, or 2 on the modified Rankin scale, which ranges from 0 to 6, with higher scores indicating more severe disability) at 90 days. RESULTS: A total of 206 patients were enrolled; 107 were assigned to the thrombectomy group and 99 to the control group. At 31 months, enrollment in the trial was stopped because of the results of a prespecified interim analysis. The mean score on the utility-weighted modified Rankin scale at 90 days was 5.5 in the thrombectomy group as compared with 3.4 in the control group (adjusted difference [Bayesian analysis], 2.0 points; 95% credible interval, 1.1 to 3.0; posterior probability of superiority, >0.999), and the rate of functional independence at 90 days was 49% in the thrombectomy group as compared with 13% in the control group (adjusted difference, 33 percentage points; 95% credible interval, 24 to 44; posterior probability of superiority, >0.999). The rate of symptomatic intracranial hemorrhage did not differ significantly between the two groups (6% in the thrombectomy group and 3% in the control group, P=0.50), nor did 90-day mortality (19% and 18%, respectively; P=1.00). CONCLUSIONS: Among patients with acute stroke who had last been known to be well 6 to 24 hours earlier and who had a mismatch between clinical deficit and infarct, outcomes for disability at 90 days were better with thrombectomy plus standard care than with standard care alone. (Funded by Stryker Neurovascular; DAWN ClinicalTrials.gov number, NCT02142283 .).

Novel selection paradigms for endovascular stroke treatment in the extended time window.

BACKGROUND AND PURPOSE: The optimal selection methodology for stroke thrombectomy beyond 6 hours remains to be established. METHODS: Review of a prospectively collected database of thrombectomy patients with anterior circulation strokes, adequate CT perfusion (CTP) maps, National Institute of Health Stroke Scale (NIHSS)≥10 and presenting beyond 6 hours from January 2014 to October 2018. Patients were categorised according to five selection paradigms: DAWN clinical-core mismatch (DAWN-CCM): between age-adjusted NIHSS and CTP core, DEFUSE 3 perfusion imaging mismatch (DEFUSE-3-PIM): between CTP-derived perfusion defect (Tmax >6 s lesion) and ischaemic core volumes and three non-contrast CT Alberta Stroke Program Early CT Score (ASPECTS)-based criteria: age-adjusted clinical-ASPECTS mismatch (aCAM): between age-adjusted NIHSS and ASPECTS, eloquence-adjusted clinical ASPECTS mismatch (eCAM): ASPECTS 6-10 and non-involvement of the right M6 and left M4 areas and standard clinical ASPECTS mismatch (sCAM): ASPECTS 6-10. RESULTS: 310 patients underwent analysis. DEFUSE-3-PIM had the highest proportion of qualifying patients followed by sCAM, eCAM, aCAM and DAWN-CCM (93.5%, 92.6%, 90.6%, 90% and 84.5%, respectively). Patients meeting aCAM, eCAM, sCAM and DAWN-CCM criteria had higher rates of 90-day good outcome compared with their non-qualifying counterparts(43.2% vs 12%,p=0.002; 42.4% vs 17.4%, p=0.02; 42.4% vs 11.2%, p=0.009; and 43.7% vs 20.5%, p=0.007, respectively). There was no difference between patients meeting DEFUSE-3-PIM criteria versus not(40.8% vs 31.3%,p=0.45). In multivariate analysis, all selection modalities except for DEFUSE-3-PIM were independently associated with 90-day good outcome. CONCLUSIONS: ASPECTS-based selection paradigms for late presenting and wake-up strokes ET have comparable proportions of qualifying patients and similar 90-day functional outcomes as DAWN-CCM and DEFUSE-3-PIM. They also might lead to better outcome discrimination. These could represent a potential alternative for centres where access to advanced imaging is limited.

Stroke Thrombolysis in Patients Taking Ticagrelor -Two Successful Cases and a Review of the Literature.

BACKGROUND: Ticagrelor is a novel antiplatelet agent that is frequently used for secondary prevention in coronary artery disease and has emerging evidence in stroke after the recent results of SOCRATES and THALES trials. The use of intravenous thrombolysis with alteplase in acute ischemic stroke (AIS) patients on ticagrelor is a topic of debate as the safety profile of ticagrelor in this setting is not well established. METHODS: We identified consecutive AIS patients taking ticagrelor who received intravenous alteplase at a comprehensive stroke center from January 2016 to December 2019. We then performed a literature search to capture all known published cases of intravenous thrombolysis in stroke patients on ticagrelor. RESULTS: Of the 3896 patients who were treated for AIS at our local comprehensive stroke center during this time period, two patients received intravenous alteplase while on ticagrelor. Both patients had posterior circulation acute strokes and were successfully treated with intravenous alteplase without a systemic or intracranial bleeding event. Only five other cases of intravenous thrombolysis in AIS patients on ticagrelor have been reported in the literature. Among these cases, four of the five cases had a hemorrhagic complication. CONCLUSION: Despite prior reports of hemorrhagic complications with use of IV alteplase in setting of pre-treatment with ticagrelor, we report the safe use of intravenous thrombolysis in two cases presenting with acute ischemic stroke. Until safety is established in large studies, decision for thrombolysis should be made on case-by-case basis.

Safety of Ticagrelor in Moderate and Severe Acute Ischemic Stroke: A Single-Center Retrospective Review.

OBJECTIVES: Ticagrelor may be superior to aspirin after minor ischemic stroke or TIA, particularly in patients with symptomatic atherosclerotic disease. However, there may be an increased risk of intracerebral hemorrhage in patients with moderate to severe ischemic stroke, and ticagrelor has not been studied in this patient population. Therefore, we sought to evaluate the safety of ticagrelor after moderate or severe ischemic stroke. MATERIALS AND METHODS: Retrospective chart review of all patients admitted with acute ischemic stroke and NIHSS 6 or greater who were discharged on ticagrelor between January 2016 and December 2019. Patients who underwent angioplasty, stenting or carotid revascularization during the hospitalization were excluded. RESULTS: Of 183 patients discharged on ticagrelor, 61 patients were included. Median age was 61 (IQR 52-68); 33 (54%) patients were men. Median NIHSS was 11 (IQR 8-15). Fourteen (23%) patients received IV alteplase and 35 (57%) patients received mechanical thrombectomy. Stroke mechanism was large artery atherosclerosis in 53 (87%) of patients, of which 40 (71%) were deemed intracranial atherosclerosis. Final infarct volume was greater than 10 mL in 32 (52%) patients. Follow-up information was available for 53 (87%) patients; median length of follow-up was 3 (IQR 2-6) months. Six (10%) patients experienced recurrent ischemic stroke. No patients experienced symptomatic intracerebral hemorrhage after initiation of ticagrelor. One (2%) patient experienced major bleeding. CONCLUSIONS: This study provides preliminary evidence supporting the potential safety of ticagrelor following moderate or severe acute ischemic stroke. These findings support the need for future prospective studies.

Baseline Characteristics of Patients with Symptomatic Carotid Webs: A Matched Case Control Study.

BACKGROUND AND PURPOSE: The baseline characteristics of patients with symptomatic carotid web (CaW) are unclear. We investigate demographic and cerebrovascular risk factors in patients with this overlooked stroke etiology. METHODS: We identified consecutive patients diagnosed with symptomatic CaW at a comprehensive stroke center from July 2014-December 2018. These patients were matched at a 1:4 ratio (based on age and NIHSS scores) to create a control group of acute ischemic stroke (AIS) patients with non-CaW etiologies from the local GetWithTheGuidelines stroke database. RESULTS: Thirty patients with symptomatic CaW were compared to 120 AIS patients with non-CaW etiologies. Symptomatic CaW patients were more likely to be female (73.3 vs. 44.2%; p = 0.004) and black (86.7 vs. 64.2%; p = 0.02). Symptomatic CaWs patients had a fewer absolute number of modifiable cerebrovascular risk factors (1.7±1.1 vs. 2.5±1.2; p = 0.002), lower rates of hypertension (43.4 vs. 63.3%; p = 0.04), and a more favorable lipid profile with lower average LDL (89.5±30.3 vs. 111.2±43.7 mg/dL; p = 0.01) and higher average HDL (47.9±11.3 vs. 42.2±13.8 mg/dL; p = 0.01) as compared to strokes with non-CaW etiology. Symptomatic CaW patients were more likely to have a large vessel occlusion (80.0 vs. 51.7%; p = 0.005), despite similar e-ASPECTS between the groups (8.1±2.1 vs. 8.3±2.2; p = 0.30). On multivariable analysis, symptomatic CaW was an independent predictor of independence at discharge (OR 3.72; 95%CI 1.27-10.94). CONCLUSION: A gender and racial predilection of symptomatic CaWs may exist as females and blacks were were found to be more likely affected. Symptomatic CaW patients have a more benign cerebrovascular risk factor profile corroborating the proposed mechanism of local stasis and thromboembolism. Despite presenting more commonly with LVO, symptomatic CaW was associated with good functional outcome, warranting further studies.

Acute Neurological Deterioration in Large Vessel Occlusions and Mild Symptoms Managed Medically.

Background and Purpose- It is unclear which factors predict acute neurological deterioration in patients with large vessel occlusion and mild symptoms. We aim to evaluate the frequency, timing, and potential predictors of acute neurological deterioration ≥4 National Institutes of Health Stroke Scale (NIHSS) points in medically managed patients with large vessel occlusion and mild presentation. Methods- Single-center retrospective study of patients with consecutive minor stroke (defined as NIHSS score of ≤5 on presentation) and large vessel occlusion from January 2014 to December 2017. Primary outcome was acute neurological deterioration ≥4 NIHSS points during the hospitalization. Secondary outcomes included ΔNIHSS (defined as discharge minus admission NIHSS score). Results- Among 1133 patients with acute minor strokes, 122 (10.6%) had visible occlusions on computed tomography angiography/magnetic resonance angiography. Twenty-four (19.7%) patients had ≥4 points deterioration on NIHSS at a median of 3.6 (1-16) hours from arrival. No clinical or radiological predictors of acute neurological deterioration ≥4 NIHSS points were observed on multivariable analysis. Rescue endovascular thrombectomy was performed more often in the ones with acute neurological deterioration ≥4 NIHSS points compared with patients with no deterioration (54% versus 0%; P<0.001). Acute neurological deterioration ≥4 NIHSS points was associated with ΔNIHSS ≥4 points (33% versus 4.9%; P<0.01) and a trend toward lower independence rates at discharge (50% versus 70%; P=0.06) compared with the group with no deterioration. In patients with any degree of neurological worsening, patients who underwent rescue thrombectomy were more likely to be independent at discharge (73% versus 38%; P=0.02) and to have a favorable ΔNIHSS (-2 [-3 to 0] versus 0 [-1 to 6]; P=0.05) compared with the ones not offered rescue thrombectomy. Conclusions- Acute neurological deterioration ≥4 NIHSS points was observed in a fifth of patients with large vessel occlusion and mild symptoms, occurred very early in the hospital course, impacted functional outcomes, and could not be predicted by any of the studied clinical and radiological variables. Rescue thrombectomy was associated with improved clinical outcomes at discharge in patients with neurological deterioration.