Publications by authors named "Andrew M Demchuk"

376 Publications

Automated Prediction of Ischemic Brain Tissue Fate from Multiphase Computed Tomographic Angiography in Patients with Acute Ischemic Stroke Using Machine Learning.

J Stroke 2021 May 31;23(2):234-243. Epub 2021 May 31.

Calgary Stroke Program, Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada.

Background And Purpose: Multiphase computed tomographic angiography (mCTA) provides time variant images of pial vasculature supplying brain in patients with acute ischemic stroke (AIS). To develop a machine learning (ML) technique to predict tissue perfusion and infarction from mCTA source images.

Methods: 284 patients with AIS were included from the Precise and Rapid assessment of collaterals using multi-phase CTA in the triage of patients with acute ischemic stroke for Intra-artery Therapy (Prove-IT) study. All patients had non-contrast computed tomography, mCTA, and computed tomographic perfusion (CTP) at baseline and follow-up magnetic resonance imaging/non-contrast-enhanced computed tomography. Of the 284 patient images, 140 patient images were randomly selected to train and validate three ML models to predict a pre-defined Tmax thresholded perfusion abnormality, core and penumbra on CTP. The remaining 144 patient images were used to test the ML models. The predicted perfusion, core and penumbra lesions from ML models were compared to CTP perfusion lesion and to follow-up infarct using Bland-Altman plots, concordance correlation coefficient (CCC), intra-class correlation coefficient (ICC), and Dice similarity coefficient.

Results: Mean difference between the mCTA predicted perfusion volume and CTP perfusion volume was 4.6 mL (limit of agreement [LoA], -53 to 62.1 mL; P=0.56; CCC 0.63 [95% confidence interval [CI], 0.53 to 0.71; P<0.01], ICC 0.68 [95% CI, 0.58 to 0.78; P<0.001]). Mean difference between the mCTA predicted infarct and follow-up infarct in the 100 patients with acute reperfusion (modified thrombolysis in cerebral infarction [mTICI] 2b/2c/3) was 21.7 mL, while it was 3.4 mL in the 44 patients not achieving reperfusion (mTICI 0/1). Amongst reperfused subjects, CCC was 0.4 (95% CI, 0.15 to 0.55; P<0.01) and ICC was 0.42 (95% CI, 0.18 to 0.50; P<0.01); in non-reperfused subjects CCC was 0.52 (95% CI, 0.20 to 0.60; P<0.001) and ICC was 0.60 (95% CI, 0.37 to 0.76; P<0.001). No difference was observed between the mCTA and CTP predicted infarct volume in the test cohort (P=0.67).

Conclusions: A ML based mCTA model is able to predict brain tissue perfusion abnormality and follow-up infarction, comparable to CTP.
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http://dx.doi.org/10.5853/jos.2020.05064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189856PMC
May 2021

WSO EXPRESS: Thrombolysis outcomes according to arterial characteristics of acute ischemic stroke by alteplase dose and blood pressure target.

Int J Stroke 2021 Jun 7:17474930211025436. Epub 2021 Jun 7.

The George Institute for Global Health, Sydney, Australia.

Background: We explored the influence of low-dose intravenous alteplase and intensive blood pressure (BP) lowering on outcomes of acute ischemic stroke (AIS) according to status/location of vascular obstruction in participants of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED).

Methods: ENCHANTED was a multicenter, quasi-factorial, randomized trial to determine efficacy and safety of low- versus standard-dose intravenous alteplase and intensive- versus guideline-recommended BP lowering in AIS patients. In those who had baseline CT or MRI angiography, the degree of vascular occlusion was grouped according to being no (NVO), medium (MVO), or large (LVO). Logistic regression models were used to determine 90-day outcomes (modified Rankin scale [mRS] shift [primary], other mRS cut-scores, intracranial hemorrhage, early neurologic deterioration [END], and recanalization) by vascular obstruction status/site. Heterogeneity in associations for outcomes across subgroups was estimated by adding an interaction term to the models.

Results: There were 940 participants: 607 in alteplase arm only, 243 in BP arm only, and 90 assigned to both arms. Compared to the NVO group, functional outcome was worse in LVO (mRS shift, adjusted OR [95% CI] 2.13 [1.56-2.90] but comparable in MVO (1.34 [0.96-1.88]) groups. There were no differences in associations of alteplase dose or BP lowering and outcomes across NVO/MVO/LVO groups (mRS shift: low versus standard alteplase dose 0.84 [0.54-1.30]/0.48 [0.25-0.91]/0.99 [0.75-2.09], Pinteraction=0.28; intensive versus standard BP lowering 1.32 [0.74-2.38]/0.78 [0.31-1.94]/1.24 [0.64-2.41], Pinteraction=0.41), except for a borderline significant difference for intensive BP lowering and increased END (0.63 [0.14-2.72]/0.17 [0.02-1.47]/2.69 [0.90-8.04], Pinteraction=0.05).

Conclusions: Functional outcome by dose of alteplase or intensity of BP lowering is not modified by vascular obstruction status/site according to analyzes from ENCHANTED, although these results are compromised by low statistical power.
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http://dx.doi.org/10.1177/17474930211025436DOI Listing
June 2021

Platelets and Clot Stiffness: A Challenge but Also an Opportunity Toward Achieving Consistent Complete Reperfusion.

Stroke 2021 Jun 3:STROKEAHA121035105. Epub 2021 Jun 3.

Acute Stroke Unit, Toulouse University Hospital. (J.-M.O.).

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http://dx.doi.org/10.1161/STROKEAHA.121.035105DOI Listing
June 2021

Effect of Implantable vs Prolonged External Electrocardiographic Monitoring on Atrial Fibrillation Detection in Patients With Ischemic Stroke: The PER DIEM Randomized Clinical Trial.

JAMA 2021 06;325(21):2160-2168

Libin Cardiovascular Institute, University of Calgary, Calgary, Alberta, Canada.

Importance: The relative rates of detection of atrial fibrillation (AF) or atrial flutter from evaluating patients with prolonged electrocardiographic monitoring with an external loop recorder or implantable loop recorder after an ischemic stroke are unknown.

Objective: To determine, in patients with a recent ischemic stroke, whether 12 months of implantable loop recorder monitoring detects more occurrences of AF compared with conventional external loop recorder monitoring for 30 days.

Design, Setting, And Participants: Investigator-initiated, open-label, randomized clinical trial conducted at 2 university hospitals and 1 community hospital in Alberta, Canada, including 300 patients within 6 months of ischemic stroke and without known AF from May 2015 through November 2017; final follow-up was in December 2018.

Interventions: Participants were randomly assigned 1:1 to prolonged electrocardiographic monitoring with either an implantable loop recorder (n = 150) or an external loop recorder (n = 150) with follow-up visits at 30 days, 6 months, and 12 months.

Main Outcomes And Measures: The primary outcome was the development of definite AF or highly probable AF (adjudicated new AF lasting ≥2 minutes within 12 months of randomization). There were 8 prespecified secondary outcomes including time to event analysis of new AF, recurrent ischemic stroke, intracerebral hemorrhage, death, and device-related serious adverse events within 12 months.

Results: Among the 300 patients who were randomized (median age, 64.1 years [interquartile range, 56.1 to 73.7 years]; 121 were women [40.3%]; and 66.3% had a stroke of undetermined etiology with a median CHA2DS2-VASc [congestive heart failure, hypertension, age ≥75 years, diabetes, stroke or transient ischemic attack, vascular disease, age 65 to 74 years, sex category] score of 4 [interquartile range, 3 to 5]), 273 (91.0%) completed cardiac monitoring lasting 24 hours or longer and 259 (86.3%) completed both the assigned monitoring and 12-month follow-up visit. The primary outcome was observed in 15.3% (23/150) of patients in the implantable loop recorder group and 4.7% (7/150) of patients in the external loop recorder group (between-group difference, 10.7% [95% CI, 4.0% to 17.3%]; risk ratio, 3.29 [95% CI, 1.45 to 7.42]; P = .003). Of the 8 specified secondary outcomes, 6 were not significantly different. There were 5 patients (3.3%) in the implantable loop recorder group who had recurrent ischemic stroke vs 8 patients (5.3%) in the external loop recorder group (between-group difference, -2.0% [95% CI, -6.6% to 2.6%]), 1 (0.7%) vs 1 (0.7%), respectively, who had intracerebral hemorrhage (between-group difference, 0% [95% CI, -1.8% to 1.8%]), 3 (2.0%) vs 3 (2.0%) who died (between-group difference, 0% [95% CI, -3.2% to 3.2%]), and 1 (0.7%) vs 0 (0%) who had device-related serious adverse events.

Conclusions And Relevance: Among patients with ischemic stroke and no prior evidence of AF, implantable electrocardiographic monitoring for 12 months, compared with prolonged external monitoring for 30 days, resulted in a significantly greater proportion of patients with AF detected over 12 months. Further research is needed to compare clinical outcomes associated with these monitoring strategies and relative cost-effectiveness.

Trial Registration: ClinicalTrials.gov Identifier: NCT02428140.
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http://dx.doi.org/10.1001/jama.2021.6128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170545PMC
June 2021

International Survey of Mechanical Thrombectomy Stroke Systems of Care During COVID-19 Pandemic.

J Stroke Cerebrovasc Dis 2021 Apr 6;30(8):105806. Epub 2021 Apr 6.

University of Calgary, Calgary, AB, Canada.

Background: The COVID-19 pandemic has strained the healthcare systems across the world but its impact on acute stroke care is just being elucidated. We hypothesized a major global impact of COVID-19 not only on stroke volumes but also on various aspects of thrombectomy systems.

Aims: We conducted a convenience electronic survey with a 21-item questionnaire aimed to identify the changes in stroke admission volumes and thrombectomy treatment practices seen during a specified time period of the COVID-19 pandemic.

Methods: The survey was designed using Qualtrics software and sent to stroke and neuro-interventional physicians around the world who are part of the Global Executive Committee (GEC) of Mission Thrombectomy 2020, a global coalition under the aegis of Society of Vascular and Interventional Neurology, between April 5th and May 15th, 2020.

Results: There were 113 responses to the survey across 25 countries with a response rate of 31% among the GEC members. Globally there was a median 33% decrease in stroke admissions and a 25% decrease in mechanical thrombectomy (MT) procedures during the COVID-19 pandemic period until May 15th, 2020 compared to pre-pandemic months. The intubation policy for MT procedures during the pandemic was highly variable across participating centers: 44% preferred intubating all patients, including 25% of centers that changed their policy to preferred-intubation (PI) from preferred non-intubation (PNI). On the other hand, 56% centers preferred not intubating patients undergoing MT, which included 27% centers that changed their policy from PI to PNI. There was no significant difference in rate of COVID-19 infection between PI versus PNI centers (p=0.60) or if intubation policy was changed in either direction (p=1.00). Low-volume (<10 stroke/month) compared with high-volume stroke centers (>20 strokes/month) were less likely to have neurointerventional suite specific written personal protective equipment protocols (74% vs 88%) and if present, these centers were more likely to report them to be inadequate (58% vs 92%).

Conclusion: Our data provides a comprehensive snapshot of the impact on acute stroke care observed worldwide during the pandemic. Overall, respondents reported decreased stroke admissions as well as decreased cases of MT with no clear preponderance in intubation policy during MT.

Data Access Statement: The corresponding author will consider requests for sharing survey data. The study was exempt from institutional review board approval as it did not involve patient level data.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023209PMC
April 2021

Prediction of Clinical Outcomes in Acute Ischaemic Stroke Patients: A Comparative Study.

Front Neurol 2021 6;12:663899. Epub 2021 May 6.

Depertment of Radiology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

Clinical stroke rehabilitation decision making relies on multi-modal data, including imaging and other clinical assessments. However, most previously described methods for predicting long-term stroke outcomes do not make use of the full multi-modal data available. The aim of this work was to develop and evaluate the benefit of nested regression models that utilise clinical assessments as well as image-based biomarkers to model 30-day NIHSS. 221 subjects were pooled from two prospective trials with follow-up MRI or CT scans, and NIHSS assessed at baseline, as well as 48-hours and 30 days after symptom onset. Three prediction models for 30-day NIHSS were developed using a support vector regression model: one clinical model based on modifiable and non-modifiable risk factors (M) and two nested regression models that aggregate clinical and image-based features that differed with respect to the method used for selection of important brain regions for the modelling task. The first model used the widely accepted RreliefF (M) machine learning method for this purpose, while the second model employed a lesion-symptom mapping technique (M) often used in neuroscience to investigate structure-function relationships and identify eloquent regions in the brain. The two nested models achieved a similar performance while considerably outperforming the clinical model. However, M required fewer brain regions and achieved a lower mean absolute error than M while being less computationally expensive. Aggregating clinical and imaging information leads to considerably better outcome prediction models. While lesion-symptom mapping is a useful tool to investigate structure-function relationships of the brain, it does not lead to better outcome predictions compared to a simple data-driven feature selection approach, which is less computationally expensive and easier to implement.
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http://dx.doi.org/10.3389/fneur.2021.663899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134662PMC
May 2021

Histological evaluation of acute ischemic stroke thrombi may indicate the occurrence of vessel wall injury during mechanical thrombectomy.

J Neurointerv Surg 2021 May 11. Epub 2021 May 11.

Department of Neurology, Grady Memorial Hospital, Atlanta, Georgia, USA.

Background: Several animal studies have demonstrated that mechanical thrombectomy (MT) for acute ischemic stroke (AIS) may cause vessel wall injury (VWI). However, the histological changes in human cerebral arteries following MT are difficult to determine.

Objective: To investigate the occurrence of VWI during MT by histological and immunohistochemical evaluation of AIS clots.

Methods: As part of the multicenter STRIP registry, 277 clots from 237 patients were analyzed using Martius Scarlett Blue stain and immunohistochemistry for CD34 (endothelial cells) and smooth muscle actin (smooth muscle cells).

Results: MT devices used were aspiration catheters (100 cases), stentriever (101 cases), and both (36 cases). VWI was found in 33/277 clots (12%). There was no significant correlation between VWI and MT device. The degree of damage varied from grade I (mild intimal damage, 24 clots), to grade II (relevant intimal and subintimal damage, 3 clots), and III (severe injury, 6 clots). VWI clots contained significantly more erythrocytes (p=0.006*) and less platelets/other (p=0.005*) than non-VWI clots suggesting soft thrombus material.Thrombolysis correlated with a lower rate of VWI (p=0.04*). VWI cases showed a significantly higher number of passes (2 [1-4] vs 1 [1-3], p=0.028*) and poorer recanalization outcome (p=0.01*) than cases without VWI.

Conclusions: Histological markers of VWI were present in 12% of AIS thrombi, suggesting that VWI might be related to MT. VWI was associated with soft thrombus consistency, higher number of passes and poorer revascularization outcome. There was no significant correlation between VWI and MT device.
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http://dx.doi.org/10.1136/neurintsurg-2021-017310DOI Listing
May 2021

A Detailed Analysis of Infarct Patterns and Volumes at 24-hour Noncontrast CT and Diffusion-weighted MRI in Acute Ischemic Stroke Due to Large Vessel Occlusion: Results from the ESCAPE-NA1 Trial.

Radiology 2021 May 11:203964. Epub 2021 May 11.

From the Department of Clinical Neurosciences and Diagnostic Imaging, University of Calgary Cumming School of Medicine, 29th St NW, 1079 A, Calgary, AB, Canada T2N 2T9 (J.M.O., B.K.M., W.Q., N.K., A.M., N.S., P.C., M.M., A.M.D., C.Z., M.J., M.A.A., S.B.C., M.D.H., M.G.); Department of Radiology, University Hospital of Basel, Basel, Switzerland (J.M.O.); Department of Radiology, University of Calgary, Calgary, Alberta, Canada (B.K.M., N.K., A.M.D., C.Z., M.J., M.A.A., S.B.C., M.D.H., M.G.); Department of Medical Imaging, St Anne's University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic (P.C.); International Clinical Research Center, St Anne's University Hospital Brno, Czech Republic (P.C.); Department of Neurology, Emory University School of Medicine, Atlanta, Ga (R.G.N., D.H.); Department of Interventional Radiology, Warren Alpert Medical School of Brown University, Providence, RI (R.A.M.); Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada (A.Y.P., D.R., D.I.); Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI (S.C.); Department of Neuroradiology, Vancouver General Hospital, University of British Columbia, Vancouver, British Columbia, Canada (A.R.); and NoNo, Toronto, Ontario, Canada (M.T.).

Background The effect of infarct pattern on functional outcome in acute ischemic stroke is incompletely understood. Purpose To investigate the association of qualitative and quantitative infarct variables at 24-hour follow-up noncontrast CT and diffusion-weighted MRI with 90-day clinical outcome. Materials and Methods The Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke, or ESCAPE-NA1, randomized controlled trial enrolled patients with large-vessel-occlusion stroke undergoing mechanical thrombectomy from March 1, 2017, to August 12, 2019. In this post hoc analysis of the trial, qualitative infarct variables (predominantly gray [vs gray and white] matter involvement, corticospinal tract involvement, infarct structure [scattered vs territorial]) and total infarct volume were assessed at 24-hour follow-up noncontrast CT or diffusion-weighted MRI. White and gray matter infarct volumes were assessed in patients by using follow-up diffusion-weighted MRI. Infarct variables were compared between patients with and those without good outcome, defined as a modified Rankin Scale score of 0-2 at 90 days. The association of infarct variables with good outcome was determined with use of multivariable logistic regression. Separate regression models were used to report effect size estimates with adjustment for total infarct volume. Results Qualitative infarct variables were assessed in 1026 patients (mean age ± standard deviation, 69 years ± 13; 522 men) and quantitative infarct variables were assessed in a subgroup of 358 of 1026 patients (mean age, 67 years ± 13; 190 women). Patients with gray and white matter involvement (odds ratio [OR] after multivariable adjustment, 0.19; 95% CI: 0.14, 0.25; < .001), corticospinal tract involvement (OR after multivariable adjustment, 0.06; 95% CI: 0.04, 0.10; < .001), and territorial infarcts (OR after multivariable adjustment, 0.22; 95% CI: 0.14, 0.32; < .001) were less likely to achieve good outcome, independent of total infarct volume. Conclusion Infarct confinement to the gray matter, corticospinal tract sparing, and scattered infarct structure at 24-hour noncontrast CT and diffusion-weighted MRI were highly predictive of good 90-day clinical outcome, independent of total infarct volume. Clinical trial registration no. NCT02930018 © RSNA, 2021 See also the editorial by Mossa-Basha in this issue.
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http://dx.doi.org/10.1148/radiol.2021203964DOI Listing
May 2021

Management and outcome of patients with acute ischemic stroke and tandem carotid occlusion in the ESCAPE-NA1 trial.

J Neurointerv Surg 2021 May 4. Epub 2021 May 4.

Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada

Background: The optimal treatment and prognosis for stroke patients with tandem cervical carotid occlusion are unclear. We analyzed outcomes and treatment strategies of tandem occlusion patients in the ESCAPE-NA1 trial.

Methods: ESCAPE-NA1 was a multicenter international randomized trial of nerinetide versus placebo in 1105 patients with acute ischemic stroke who underwent endovascular treatment. We defined tandem occlusions as complete occlusion of the cervical internal carotid artery (ICA) on catheter angiography, in addition to a proximal ipsilateral intracranial large vessel occlusion. Baseline characteristics and outcome parameters were compared between patients with tandem occlusions versus those without, and between patients with tandem occlusion who underwent ICA stenting versus those who did not. The influence of tandem occlusions on functional outcome was analyzed using multivariable regression modeling.

Results: Among 115/1105 patients (10.4%) with tandem occlusions, 62 (53.9%) received stenting for the cervical ICA occlusion. Of these, 46 (74.2%) were stented after and 16 (25.8%) before the intracranial thrombectomy. A modified Rankin Score (mRS) of 0-2 at 90 days was achieved in 82/115 patients (71.3%) with tandem occlusions compared with 579/981 (59.5%) patients without tandem occlusions. Tandem occlusion did not impact functional outcome in the adjusted analysis (OR 1.5, 95% CI 0.95 to 2.4). Among the subgroup of patients with tandem occlusion, cervical carotid stenting was not associated with different outcomes compared with no stenting (mRS 0-2: 75.8% vs 66.0%, adjusted OR 2.0, 95% CI 0.8 to 5.1).

Conclusions: Tandem cervical carotid occlusion in patients with acute large vessel stroke did not lower the odds of good functional outcome in our study. Functional outcomes were similar irrespective of the management of the cervical ICA occlusion (stenting vs not stenting).
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http://dx.doi.org/10.1136/neurintsurg-2021-017474DOI Listing
May 2021

Factors influencing thrombectomy decision making for primary medium vessel occlusion stroke.

J Neurointerv Surg 2021 May 4. Epub 2021 May 4.

Diagnostic Imaging, University of Calgary, Calgary, Alberta, Canada

Background: We aimed to explore the preference of stroke physicians to treat patients with primary medium vessel occlusion (MeVO) stroke with immediate endovascular treatment (EVT) in an international cross-sectional survey, as there is no clear guideline recommendation for EVT in these patients.

Methods: In the survey MeVO-Finding Rationales and Objectifying New Targets for IntervEntional Revascularization in Stroke (MeVO-FRONTIERS), participants were shown four cases of primary MeVOs (six scenarios per case) and asked whether they would treat those patients with EVT. Multivariable logistic regression with clustering by respondent was performed to assess factors influencing the decision to treat. Dominance analysis was performed to assess the influence of factors within the scenarios on decision making.

Results: Overall, 366 participants (56 women; 15%) from 44 countries provided 8784 answers to 24 scenarios. Most physicians (59.2%) would treat patients immediately with EVT. Younger patient age (incidence rate ratio (IRR) 1.24, 99% CI 1.19 to 1.30), higher National Institutes of Health Stroke Scale (NIHSS) score (IRR 1.69, 99% CI 1.57 to 1.82), and small core volume (IRR 1.35, 99% CI 1.24 to 1.46) were positively associated with the decision to treat with EVT. Interventionalists (IRR 1.26, 99% CI 1.01 to 1.56) were more likely to treat patients with MeVO immediately with EVT. In the dominance analysis, factors influencing the decision in favor of EVT were (in order of importance): baseline NIHSS, core volume, alteplase use, patients' age, and occlusion site.

Conclusions: Most physicians in this survey were interventionalists and would treat patients with MeVO stroke immediately with EVT. This finding supports the need for robust clinical evidence.
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http://dx.doi.org/10.1136/neurintsurg-2021-017472DOI Listing
May 2021

Healthy Life-Year Costs of Treatment Speed From Arrival to Endovascular Thrombectomy in Patients With Ischemic Stroke: A Meta-analysis of Individual Patient Data From 7 Randomized Clinical Trials.

JAMA Neurol 2021 Jun;78(6):709-717

Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles.

Importance: The benefits of endovascular thrombectomy (EVT) are time dependent. Prior studies may have underestimated the time-benefit association because time of onset is imprecisely known.

Objective: To assess the lifetime outcomes associated with speed of endovascular thrombectomy in patients with acute ischemic stroke due to large-vessel occlusion (LVO).

Data Sources: PubMed was searched for randomized clinical trials of stent retriever thrombectomy devices vs medical therapy in patients with anterior circulation LVO within 12 hours of last known well time, and for which a peer-reviewed, complete primary results article was published by August 1, 2020.

Study Selection: All randomized clinical trials of stent retriever thrombectomy devices vs medical therapy in patients with anterior circulation LVO within 12 hours of last known well time were included.

Data Extraction/synthesis: Patient-level data regarding presenting clinical and imaging features and functional outcomes were pooled from the 7 retrieved randomized clinical trials of stent retriever thrombectomy devices (entirely or predominantly) vs medical therapy. All 7 identified trials published in a peer-reviewed journal (by August 1, 2020) contributed data. Detailed time metrics were collected including last known well-to-door (LKWTD) time; last known well/onset-to-puncture (LKWTP) time; last known well-to-reperfusion (LKWR) time; door-to-puncture (DTP) time; and door-to-reperfusion (DTR) time.

Main Outcomes And Measures: Change in healthy life-years measured as disability-adjusted life-years (DALYs). DALYs were calculated as the sum of years of life lost (YLL) owing to premature mortality and years of healthy life lost because of disability (YLD). Disability weights were assigned using the utility-weighted modified Rankin Scale. Age-specific life expectancies without stroke were calculated from 2017 US National Vital Statistics.

Results: Among the 781 EVT-treated patients, 406 (52.0%) were early-treated (LKWTP ≤4 hours) and 375 (48.0%) were late-treated (LKWTP >4-12 hours). In early-treated patients, LKWTD was 188 minutes (interquartile range, 151.3-214.8 minutes) and DTP 105 minutes (interquartile range, 76-135 minutes). Among the 298 of 380 (78.4%) patients with substantial reperfusion, median DTR time was 145.0 minutes (interquartile range, 111.5-185.5 minutes). Care process delays were associated with worse clinical outcomes in LKW-to-intervention intervals in early-treated patients and in door-to-intervention intervals in early-treated and late-treated patients, and not associated with LKWTD intervals, eg, in early-treated patients, for each 10-minute delay, healthy life-years lost were DTP 1.8 months vs LKWTD 0.0 months; P < .001. Considering granular time increments, the amount of healthy life-time lost associated with each 1 second of delay was DTP 2.2 hours and DTR 2.4 hours.

Conclusions And Relevance: In this study, care delays were associated with loss of healthy life-years in patients with acute ischemic stroke treated with EVT, particularly in the postarrival time period. The finding that every 1 second of delay was associated with loss of 2.2 hours of healthy life may encourage continuous quality improvement in door-to-treatment times.
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http://dx.doi.org/10.1001/jamaneurol.2021.1055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094030PMC
June 2021

The Story of Intracerebral Hemorrhage: From Recalcitrant to Treatable Disease.

Stroke 2021 May 8;52(5):1905-1914. Epub 2021 Apr 8.

Westchester Medical Center Health Network, Departments of Neurology and Neurosurgery, New York Medical College, Valhalla, NY (S.M.).

This invited special report is based on an award presentation at the World Stroke Organization/European Stroke Organization Conference in November of 2020 outlining progress in the acute management of intracerebral hemorrhage (ICH) over the past 35 years. ICH is the second most common and the deadliest type of stroke for which there is no scientifically proven medical or surgical treatment. Prospective studies from the 1990s onward have demonstrated that most growth of spontaneous ICH occurs within the first 2 to 3 hours and that growth of ICH and resulting volumes of ICH and intraventricular hemorrhage are modifiable factors that can improve outcome. Trials focusing on early treatment of elevated blood pressure have suggested a target systolic blood pressure of 140 mm Hg, but none of the trials were positive by their primary end point. Hemostatic agents to decrease bleeding in spontaneous ICH have included desmopressin, tranexamic acid, and rFVIIa (recombinant factor VIIa) without clear benefit, and platelet infusions which were associated with harm. Hemostatic agents delivered within the first several hours have the greatest impact on growth of ICH and potentially on outcome. No large Phase III surgical ICH trial has been positive by primary end point, but pooled analyses suggest that earlier ICH removal is more likely to be beneficial. Recent trials emphasize maximization of clot removal and minimizing brain injury from the surgical approach. The future of ICH therapy must focus on delivery of medical and surgical therapies as soon as possible if we are to improve outcomes.
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http://dx.doi.org/10.1161/STROKEAHA.121.033484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085038PMC
May 2021

Per pass analysis of thrombus composition retrieved by mechanical thrombectomy.

Interv Neuroradiol 2021 Apr 7:15910199211009119. Epub 2021 Apr 7.

Departments of Radiology and Neurosurgery, Northwestern University, Chicago, IL, USA.

Background And Aim: Mechanical thrombectomy (MT) for large vessel occlusion often requires multiple passes to retrieve the entire thrombus load. In this multi-institutional study we sought to examine the composition of thrombus fragments retrieved with each pass during MT.

Methods: Patients who required multiple passes during thrombectomy were included. Histopathological evaluation of thrombus fragments retrieved from each pass was performed using Martius Scarlet Blue staining and the composition of each thrombus component including RBC, fibrin and platelet was determined using image analysis software.

Results: 154 patients underwent MT and 868 passes was performed which resulted in 263 thrombus fragments retrieval. The analysis of thrombus components per pass showed higher RBC, lower fibrin and platelet composition in the pass 1 and 2 when compared to pass 3 and passes 4 or more combined (P values <0.05). There were no significant differences between thrombus fragments retrieved in pass 1 and pass 2 in terms of RBC, WBC, fibrin, and platelet composition (P values >0.05). Similarly, when each composition of thrombus fragments retrieved in pass 3 and passes 4 or more combined were compared with each other, no significant difference was noted (P values >0.05).

Conclusion: Our findings confirm that thrombus fragments retrieved with each pass differed significantly in histological content. Fragments in the first passes were associated with lower fibrin and platelet composition compared to fragments retrieved in passes three and four or higher. Also, thrombus fragments retrieved after failed pass were associated with higher fibrin and platelet components.
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http://dx.doi.org/10.1177/15910199211009119DOI Listing
April 2021

Which Acute Ischemic Stroke Patients Are Fast Progressors?: Results From the ESCAPE Trial Control Arm.

Stroke 2021 May 5;52(5):1847-1850. Epub 2021 Apr 5.

Clinical Neurosciences (J.M.O., M.D.H., A.M.D., B.K.M., A.M., M.G.), University of Calgary, Canada.

Background And Purpose: Fast infarct progression in acute ischemic stroke has a severe impact on patient prognosis and benefit of endovascular thrombectomy. In this post hoc analysis of the ESCAPE trial (Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke), we identified acute ischemic stroke patients with rapid infarct growth and investigated their baseline clinical and imaging characteristics.

Methods: Control arm patients were included if they had follow-up imaging at 2-8 hours without substantial recanalization, and if their baseline Alberta Stroke Program Early CT Score was ≥9. Fast infarct progression was defined as Alberta Stroke Program Early CT Score decay ≥3 points from baseline to 2- to 8-hour follow-up imaging. Clinical and imaging baseline characteristics were compared between fast progressors and other patients, and occlusion site and collateral flow patterns were assessed in detail.

Results: Fast infarct progression occurred in 15 of 43 included patients (34.9%). Fast progressors had worse collaterals (poor in 3/15 [20%] versus 0/28 patients, =0.021) and more carotid-T or -L occlusions (8/15 [53.4%] versus 3/28[10.7%], =0.021). In 8 out of 15 (53.3%), occlusion site and circle of Willis configuration prevented collateral flow via the anterior or posterior cerebral artery.

Conclusions: Most patients with fast infarct progression had terminal carotid occlusions and impaired collateral flow via the anterior or posterior cerebral artery, indicating that occlusion location and intracranial vascular anatomy are relevant for infarct progression.
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http://dx.doi.org/10.1161/STROKEAHA.120.032950DOI Listing
May 2021

Global Impact of COVID-19 on Stroke Care and IV Thrombolysis.

Neurology 2021 06 25;96(23):e2824-e2838. Epub 2021 Mar 25.

Department of Neurology (R.G.N., M.H.M., M.Frankel, D.C.H.), Marcus Stroke and Neuroscience Center, Grady Memorial Hospital, Emory University School of Medicine, Atlanta; Department of Radiology (M.M.Q., M.A., T.N.N., A.K.) and Radiation Oncology (M.M.Q.), Boston Medical Center, Boston University School of Medicine, Massachusetts; Department of Neurology (S.O.M.), Federal University of Rio Grande do Sul, Porto Alegre; Hospital de Clínicas de Porto Alegre (S.O.M.), Brazil; Department of Stroke Neurology (H. Yamagami), National Hospital Organization, Osaka National Hospital, Japan; Department of Neurology (Z.Q.), Xinqiao Hospital of the Army Medical University, Chongqing, China; Department of Neurology (O.Y.M.), Stroke and Neurointervention Division, Alexandria University Hospital, Alexandria University, Egypt; Boston University School of Medicine (A.S.), Massachusetts; 2nd Department of Neurology (A.C.), Institute of Psychiatry and Neurology, Warsaw, Poland; Department of Neurology (G.T., L.P.), National & Kapodistrian University of Athens, School of Medicine, Attikon University Hospital, Athens, Greece; Faculdade de Medicina (D.A.d.S.), Universidade de Lisboa, Lisbon, Portugal; Department of Neurology (J.D., R.L.), Leuven University Hospital, Belgium; International Clinical Research Center and Department of Neurology (R.M.), St. Anne´s University Hospital in Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic; Department of Neurology (P.V.), Groeninge Hospital, Kortrijk; Department of Neurology (P.V.), University Hospitals Antwerp; Department of Translational Neuroscience (P.V.), University of Antwerp, Belgium; Department of Neurology (J.E.S., T.G.J.), Cooper Neurological Institute, Cooper University Hospital, Camden, New Jersey; Department of Neurology and Neurosurgery (J. Kõrv), University of Tartu, Estonia; Department of Neurology (J.B., R.V.,S.R.), Loyola University Chicago Stritch School of Medicine, Illinois; Department of Neurosurgery (C.W.L.), Kaiser Permanente Fontana Medical Center; Department of Neurology (N.S.S.), Kaiser Permanente Los Angeles Medical Center; Department of Neurology (A.M.Z., S.A.S.), UT Health McGovern Medical School, Houston, Texas; Department of Neurology (A.L.Z.), Medical University of South Carolina, Charleston; Department of Internal Medicine (G.N.), School of Health Sciences, University of Thessaly, Larissa, Greece; Department of Neurology (K.M., A.T.), Allegheny Health Network, Pittsburgh, Pennsylvania; Department of Neurology (A.L.), Ohio Health Riverside Methodist Hospital Columbus; Department of Medicine and Neurology (A.R.), University of Otago and Wellington Hospital, New Zealand; Department of Neurology (E.A.M.), Vanderbilt University Medical Center, Nashville, Tennessee; Department of Neurology (A.W.A., D. Alsbrook), University of Tennessee Health Center, Memphis; Department of Neurology (D.Y.H.), University of North Carolina at Chapel Hill; Departments of Neurology (S.Y.) and Radiology (E.R.), New York University Grossman School of Medicine; Douala Gynaeco-Obstetric and Pediatric Hospital (E.G.B.L.), University of Douala, Faculty of Medicine and Pharmaceutical Science, Cameroon; Ain Shams University Specialized Hospital (H.M.A., H.M.S., A.E., T.R.); Cairo University Affiliated MOH Network (F.H.); Department of Neurology (TM.), Nasser Institute for Research and Treatment, Cairo; Mansoura University Affiliated Private Hospitals Network (W.M.), Egypt; Kwame Nkrumah University of Science and Technology (F.S.S.), Kumasi, Ghana; Stroke Unit (T.O.A., K.W.), University of Ilorin Teaching Hospital; Neurology Unit (B.A.), Department of Medicine, Lagos State University Teaching Hospital; Department of Medicine (E.O.N.), Federal Medical Centre Owerri, Imo State, Nigeria; Neurology Unit (T.A.S.), Department of Medicine, Federal Medical Centre, Owo, Ondo State, Nigeria; University College Hospital (J.Y.), Ibadan, Nigeria; The National Ribat University Affiliated Hospitals (H.H.M.), Khartoum, Sudan; Neurology Section (P.B.A.), Department of Internal Medicine, Aga-Khan University, Medical College East Africa, Dar es Salaam, Tanzania; Tunis El Manar University (A.D.R.), Military Hospital of Tunis; Department of Neurology (S.B.S.), Mongi Ben Hmida National Institute of Neurology, Faculty of Medicine of Tunis, University Tunis El Manar, Tunisia; Department of Physiology (L.G.), Parirenyatwa Hospital, and Departments of Physiology and Medicine (G.W.N.), University of Zimbabwe, Harare; Department of Cerebrovascular/Endovascular Neurosurgery Division (D.S.), Erebouni Medical Center, Yerevan, Armenia; Department of Neurology (A.R.), Sir Salimulah College, Dhaka, Bangladesh; Department of Neurology (Z.A.), Taihe Hospital of Shiyan City, Hubei; Department of Neurology (F.B.), Nanyang Central Hospital, Henan; Department of Neurology (Z.D.), Wuhan No. 1 Hospital, Hubei, China; Department of Neurology (Y. Hao.), Sir Run Run Shaw Hospital, Zhejiang University School of Medicine; Department of Neurology (W.H.), Traditional Chinese Medicine Hospital of Maoming, Guangdong; Department of Neurology (G.Li.), Affiliated Hospital of Qingdao University, Shandong; Department of Neurology (W.L), The First Affiliated Hospital of Hainan Medical College; Department of Neurology (G.Liu.), Wuhan Central Hospital, Hubei; Department of Neurology (J.L.), Mianyang 404th Hospital, Sichuan; Department of Neurology (X.S.), Yijishan Hospital of Wannan Medical College, Anhui; Department of Neurology and Neuroscience (Y.S.), Shenyang Brain Institute, Shenyang First People's Hospital, Shenyang Medical College Affiliated Brain Hospital; Department of Neurology (L.T.), Affiliated Yantai Yuhuangding Hospital of Qingdao University, Shandong; Department of Neurology (H.W.), Xiangyang Central Hospital, Hubei; Department of Neurology (B.W., Y.Yan), West China Hospital, Sichuan University, Chengdu; Department of Neurology (Z.Y.), Affiliated Hospital of Southwest Medical University, Sichuan; Department of Neurology (H.Z.), Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine; Department of Neurology (J.Z.), The First Affiliated Hospital of Shandong First Medical University; Department of Neurology (W.Z.), First Affiliated Hospital of Fujian Medical University, China; Acute Stroke Unit (T.W.L.), The Prince of Wales Hospital, Kwok Tak Seng Centre for Stroke Research and Intervention, The Chinese University of Hong Kong; Interventional Neurology (C.C.), MAX Superspecialty Hospital, Saket, New Delhi; NH Institute of Neurosciences (V.H.), NH Mazumdar Shaw Medical Center, Bangalore; Department of Neurology (B.M.), Apollo Speciality Hospitals Nellore; Department of Neurology (J.D.P.), Christian Medical College, Ludhiana, Punjab; Sree Chitra Tirunal Institute for Medical Sciences and Technology (P.N.S.), Kerala, India; Stroke Unit (F.S.U.), Pelni Hospital, Jakarta, Indonesia; Neurosciences Research Center (M. Farhoudi, E.S.H.), Tabriz University of Medical Sciences, Tabriz, Iran; Beer Sheva Hospital (A.H.); Department of Interventional Neuroradiology, Rambam Healthcare Campus, Haifa, Israel (A.R., R.S.H.); Departments of Neurology (N.O.) and Neurosurgery (N.S.), Kobe City Medical Center General Hospital, Kobe; Department of Stroke and Neurovascular Surgery (D.W.), IMS Tokyo-Katsushika General Hospital; Yokohama Brain and Spine Center (R.Y.); Iwate Prefectural Central (R.D.); Department of Neurology and Stroke Treatment (N.T.), Japanese Red Cross Kyoto Daiichi Hospital; Department of Neurology (T.Y.), Kyoto Second Red Cross Hospital; Department of Neurology (T.T.), Japanese Red Cross Kumamoto Hospital; Department of Stroke Neurology (Y. Yazawa), Kohnan Hospital, Sendai; Department of Cerebrovascular Medicine (T.U.), Saga-Ken Medical Centre; Department of Neurology (T.D.), Saitama Medical Center, Kawagoe; Department of Neurology (H.S.), Nara City Hospital; Department of Neurology (Y.S.), Toyonaka Municipal Hospital, Osaka; Department of Neurology (F. Miyashita), Kagoshima City Hospital; Department of Neurology (H.F.), Japanese Red Cross Matsue Hospital, Shimane; Department of Neurology (K.M.), Shiroyama Hospital, Osaka; Department of Cerebrovascular Medicine (J.E.S.), Niigata City General Hospital; Department of Neurology (Y.S.), Sugimura Hospital, Kumamoto; Stroke Medicine (Y. Yagita), Kawasaki Medical School, Okayama; Department of Neurology (Y.T.), Osaka Red Cross Hospital; Department of Stroke Prevention and Treatment (Y.M.), Department of Neurosurgery, University of Tsukuba, Ibaraki; Department of Neurology (S.Y.), Stroke Center and Neuroendovascular Therapy, Saiseikai Central Hospital, Tokyo; Department of Neurology (R.K.), Kin-ikyo Chuo Hospital, Hokkaido; Department of Cerebrovascular Medicine (T.K.), NTT Medical Center Tokyo; Department of Neurology and Neuroendovascular Treatment (H. Yamazaki), Yokohama Shintoshi Neurosurgical Hospital; Department of Neurology (M.S.), Osaka General Medical Center; Department of Neurology (K.T.), Osaka University Hospital; Department of Advanced Brain Research (N.Y.), Tokushima University Hospital Tokushima; Department of Neurology (K.S.), Saiseikai Fukuoka General Hospital, Fukuoka; Department of Neurology (T.Y.), Tane General Hospital, Osaka; Division of Stroke (H.H.), Department of Internal Medicine, Osaka Rosai Hospital; Department of Comprehensive Stroke (I.N.), Fujita Health University School of Medicine, Toyoake, Japan; Department of Neurology (A.K.), Asfendiyarov Kazakh National Medical University; Republican Center for eHealth (K.F.), Ministry of Health of the Republic of Kazakhstan; Department of Medicine (S.K.), Al-Farabi Kazakh National University; Kazakh-Russian Medical University (M.Z.), Kazakhstan; Department of Neurology (J.-H.B.), Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul; Department of Neurology (Y. Hwang), Kyungpook National University Hospital, School of Medicine, Kyungpook National University; Ajou University Hospital (J.S.L.); Department of Neurology (S.B.L.), Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea; Department of Neurology (J.M.), National Medical Center, Seoul; Department of Neurology (H.P., S.I.S.), Keimyung University School of Medicine, Dongsan Medical Center, Daegu; Department of Neurology (J.H.S.), Busan Paik Hospital, School of Medicine, Inje University, Busan; Department of Neurology (K.-D.S.), National Health Insurance Service Ilsan Hospital, Goyang; Asan Medical Center (C.J.Y.), Seoul, South Korea; Department of Neurology (R.A.), LAU Medical Center-Rizk Hospital, Beirut, Lebanon; Department of Medicine (W.A.W.Z., N.W.Y.), Pusat Perubatan Universiti Kebangsaan Malaysia, Kuala Lumpur; Sultanah Nur Zahirah (Z.A.A., K.A.I.), Kuala Terengganu; University Putra Malaysia (H.b.B.); Sarawak General Hospital, Kuching (L.W.C.); Hospital Sultan Abdul Halim (A.B.I.), Sungai Petani Kedah; Hospital Seberang Jaya (I.L.), Pulau Pinang; Thomson Hospital Kota Damansara (W.Y.T.), Malaysia; "Nicolae Testemitanu" State University of Medicine and Pharmacy (S.G., P.L.), and Department of Neurology, Emergency Medicine Institute, Chisinau, Republic of Moldova; Department of Stroke Unit (A.M.A.H.), Royal Hospital Muscat, Oman; Neuroscience Institute (Y.Z.I., N.A.), Hamad Medical Corporation, Doha, Qatar; St. Luke's Medical Center-Institute of Neurosciences (M.C.P.-F., C.O.C.), Quezon City, Philippines; Endovascular Neurosurgery (D.K.), Saint-Petersburg Dzhanelidze Research Institute of Emergency Medicine, St. Petersburg, Russia; Department of Neurology (A.A.), Stroke Unit, King Saud University, College of Medicine, Riyadh; Department of Neurosurgery (H.A.-J.), Interventional Radiology, and Critical Care Medicine, King Fahad Hospital of the University, Imam Abdulrahman bin Faisal University, Saudi Arabia; Singapore National Neuroscience Institute (C.H.T.); Changi General Hospital (M.J.M.), Singapore; Neuroscience Center, Raffles Hospital (N.V.), Singapore; Department of Neurology (C.-H.C., S.-C.T.), National Taiwan University Hospital; Department of Radiology (A.C.), Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Dicle University Medical School and Hospital (E.A.), Diyarbakir; Stroke and Neurointervention Unit (O.A., A.O.O.), Eskisehir Osmangazi University; Gaziantep University Faculty of Medicine (S.G.), Turkey; Department of Neurology (S.I.H., S.J.), Neurological Institute at Cleveland Clinic Abu Dhabi, United Arab Emirates; Stroke Center (H.L.V., A.D.C.), Hue Central Hospital, Hue, Vietnam; Stroke Department (H.H.N., T.N.P.), Da Nang Hospital, Da Nang City; 115 People's Hospital (T.H.N., T.Q.N.), Ho Chi Minh City, Vietnam; Department of Neurology (T.G., C.E.), Medical University of Graz; Department of Neurology (M. K.-O.), Research Institute of Neurointervention, University Hospital Salzburg/Paracelsus Medical University, Austria; Department of Neurology (F.B., A.D.), Centre Hospitalier Universitaire de Charleroi, Belgium; Department of Neurology (S.D.B., G.V.), Sint Jan Hospital, Bruges; Department of Neurology (S.D.R.), Brussels University Hospital (UZ Brussel); Department of Neurology (N.L.), ULB Erasme Hospitals Brussels; Department of Neurology (M.P.R.), Europe Hospitals Brussels; Department of Neurology (L.Y.), Antwerp University Hospital, Belgium; Neurology Clinic (F.A., T.S.), St. Anna University Hospital, Sofia, Bulgaria; Department of Neurology (M.R.B.), Sestre Milosrdnice University Hospital, Zagreb; Department of Neurology (H.B.), Sveti Duh University Hospital, Zagreb; Department of Neurology (I.C.), General Hospital Virovitica; Department of Neurology (Z.H.), General Hospital Zabok; Department of Radiology (F. Pfeifer), University Hospital Centre Zagreb, Croatia; Regional Hospital Karlovy Vary (I.K.); Masaryk Hospital Usti nad Labem (D.C.); Military University Hospital Praha (M. Sramek); Oblastní Nemocnice Náchod (M. Skoda); Regional Hospital Pribram (H.H.); Municipal Hospital Ostrava (L.K.); Hospital Mlada Boleslav (M. Koutny); Hospital Vitkovice (D.V.); Hospital Jihlava (O.S.); General University Hospital Praha (J.F.); Hospital Litomysl (K.H.); Hospital České Budejovice (M.N.); Hospital Pisek (R.R.); Hospital Uherske Hradiste (P.P.); Hospital Prostejov (G.K.); Regional Hospital Chomutov (J.N.); Hospital Teplice (M.V.); Mining Hospital Karvina (H.B.); Thomayer Hospital Praha (D.H.); Hospital Blansko (D.T.); University Hospital Brno (R.J.); Regional Hospital Liberec (L.J.); Hospital Ceska Lipa (J.N.); Hospital Sokolov (A.N.); Regional Hospital Kolin (Z.T.); Hospital Trutnov (P. Fibrich); Hospital Trinec (H.S.); Department of Neurology (O.V.), University Hospital Ostrava, Faculty of Medicine, Masaryk University, Brno, Czech Republic; Bispebjerg Hospital (H.K.C.), University of Copenhagen; Stroke Center (H.K.I., T.C.T.), Rigshospitalet, University of Copenhagen; Aarhus University Hospital (C.Z.S.), Aarhus; Neurovascular Center, Zealand University Hospital, University of Copenhagen (T.W.), Roskilde, Denmark; Department of Neurology and Neurosurgery (R.V.), University of Tartu, Estonia; Neurology Clinic (K.G.-P.), West Tallinn Central Hospital; Center of Neurology (T.T.), East Tallinn Central Hospital, School of Natural Sciences and Health, Tallinn University; Internal Medicine Clinic (K.A.), Pärnu Hospital, Estonia; Université Lille, Inserm, CHU Lille, Lille Neuroscience & Cognition (C.C., F.C.); Centre Hospitalier d'Arcachon (M.D.), Gujan-Mestras; Centre Hospitalier d'Agen (J.-M.F.); Neurologie Vasculaire (L.M.) and Neuroradiologie (O.E.), Hospices Civils de Lyon, Hôpital Pierre Wertheimer, Bron; Centre Hospitalier et Universitaire de Bordeaux (E.L., F.R.); Centre Hospitalier de Mont de Marsan (B.O.); Neurologie (R.P.), Fondation Ophtalmologique Adolphe de Rothschild; Versailles Saint-Quentin-en-Yvelines University (F. Pico); Neuroradiologie Interventionelle (M.P.), Fondation Ophtalmologique Adolphe de Rothschild; Neuroradiologie Interventionelle (R.P.), Hôpitaux Universitaires de Strasbourg, France; K. Eristavi National Center of Experimental and Clinical Surgery (T.G.), Tbilisi; Department of Neurosurgery (M. Khinikadze), New Vision University Hospital, Tbilisi; Vivamedi Medical Center (M. Khinikadze), Tbilisi; Pineo Medical Ecosystem (N.L.), Tbilisi; Ivane Javakhishvili Tbilisi State University (A.T.), Tbilisi, Georgia; Department of Neurology (S.N., P.A.R.), University Hospital Heidelberg; Department of Neurology (M. Rosenkranz), Albertinen Krankenhaus, Hamburg; Department of Neurology (H.S.), Elbe Klinken Stade, University Medical Center Göttingen; Department of Neurology (T.S.), University Hospital Carl Gustav Carus, Dresden; Kristina Szabo (K.S.), Department of Neurology, Medical Faculty Mannheim, University Heidelberg, Mannheim; Klinik und Poliklinik für Neurologie (G.T.), Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, Germany; Department of Internal Medicine (D.S.), School of Health Sciences, University of Thessaly, Larissa; Second Department of Neurology (O.K.), Stroke Unit, Metropolitan Hospital, Piraeus, Greece; University of Szeged (P.K.), Szeged; University of Pecs (L.S., G.T.), Hungary; Stroke Center (A.A.), IRCCS Istituto di Ricovero e Cura a Carattere Scientifico, Negrar, Verona; Department of Neurology (F.B.), Ospedale San Paolo, Savona,; Institute of Neurology (P.C., G.F.), Fondazione Policlinico Universitario Agostino Gemelli, Rome; Interventional Neurovascular Unit (L.R.), Careggi University Hospital, Florence; Stroke Unit (D.S.), Azienda Socio Sanitaria Territoriale (ASST) di Lecco, Italy; Maastricht University Medical Center; Department of Neurology (M.U.), Radiology, University Medical Center Groningen; Department of Neurology (I.v.d.W.), Haaglanden Medical Center, the Hague, the Netherlands; Department of Neurology (E.S.K.), Akershus University Hospital, Lørenskog, General Practice, HELSAM, University of Oslo, Norway; Neurological Ward with Stroke Unit (W.B.), Specialist Hospital in Konskie, Gimnazjalna, Poland and Collegium Medicum, Jan Kochanowski University, Kielce, Poland; Neurological Ward with Stroke Unit (M.F.), District Hospital in Skarzysko-Kamienna; Department of Neurology (E.H.L.), Szpitala im T. Marciniaka in Wroclaw; 2nd Department of Neurology (M. Karlinski), Institute of Psychiatry and Neurology, Warsaw; Department of Neurology and Cerebrovascular Disorders (R.K., P.K.), Poznan University of Medical Sciences; 107th Military Hospital with Polyclinic (M.R.), Walcz; Department of Neurology (R.K.), St. Queen Jadwiga, Clinical Regional Hospital No. 2, Rzeszow; Department of Neurology (P.L.), Medical University of Lublin; 1st Department of Neurology (H.S.-J.), Institute of Psychiatry and Neurology, Warsaw; Department of Neurology and Stroke Unit (P.S.), Holy Spirit Specialist Hospital in Sandomierz, Collegium Medicum Jan Kochanowski University in Kielce; Copernicus PL (W.F.), Neurology and Stroke Department, Hospital M. Kopernik, Gdansk; Stroke Unit (M.W.), Neurological Department, Stanislaw Staszic University of Applied Sciences, Pila, Poland; Hospital São José (Patricia Ferreira), Centro Hospitalar Universitário de Lisboa Central, Lisbon; Stroke Unit (Paulo Ferreira, V.T.C.), Hospital Pedro Hispano, Matosinhos; Stroke Unit, Internal Medicine Department (L.F.), Neuroradiology Department, Centro Hospitalar Universitário de São João, Porto; Department of Neurology (J.P.M.), Hospital de Egas Moniz, Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal; Department of Neurosciences (T.P.e.M.), Hospital de Santa Maria-CHLN, North Lisbon University Hospital; Hospital São José (A.P.N.), Centro Hospitalar Universitário de Lisboa Central, Lisbon; Department of Neurology (M. Rodrigues), Hospital Garcia de Orta, Portugal; Department of Neurology (C.F.-P.), Transilvania University, Brasov, Romania; Department of Neurology (G.K., M. Mako), Faculty Hospital Trnava, Slovakia; Department of Neurology and Stroke Center (M.A.d.L., E.D.T.), Hospital Universitario La Paz, Madrid; Department of Neurology (J.F.A.), Hospital Clínico Universitario, Universidad de Valladolid; Department of Neurology (O.A.-M.), Complejo Hospitalario Universitario de Albacete; Department of Neurology (A.C.C.), Unidad de Ictus, Hospital Universitario Ramon y Cajal, Madrid; Department of Neurology (S.P.-S), Hospital Universitario Virgen Macarena & Neurovascular Research Laboratory (J.M.), Instituto de Biomedicina de Sevilla-IbiS; Rio Hortega University Hospital (M.A.T.A.), University of Valladolid; Cerebrovascular Diseases (A.R.V.), Hospital Clinic of Barcelona, Spain; Department of Neurology (M. Mazya), Karolinska University Hospital and Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden; Department of Interventional Neuroradiology (G.B.), University Hospitals of Geneva; Department of Interventional and Diagnostic Neuroradiology (A.B., M.-N.P.), Radiology and Nuclear Medicine, University Hospital Basel; Department of Neurology (U.F.), University of Bern; Department of Neuroradiology (J.G.), University of Bern; Department of Neuroscience (P.L.M., D.S.), Lausanne University Hospital, Switzerland; Department of Stroke Medicine (S.B., J. Kwan), Imperial College Healthcare NHS Trust, Charing Cross Hospital, London; Department of Neurology (K.K.), Queen's Medical Centre, Nottingham University Hospitals NHS Trust, United Kingdom; Department of Neurology (A.B., A. Shuaib), University of Alberta, Edmonton; Department of Neurology (L.C., A. Shoamanesh), McMaster University, Hamilton; Department of Clinical Neurosciences and Hotchkiss Brain Institute (A.M.D., M.D.H.), University of Calgary; Department of Neurology (T.F., S.Y.), University of British Columbia, Vancouver; Mackenzie Health (J.H., C.A.S.) Richmond Hill, Ontario; Department of Neurology (H.K.), Sunnybrook Health Sciences Centre, University of Toronto; Department of Neurology (A. Mackey), Hopital Enfant Jesus, Centre Hospitalier de l'Universite Laval, Quebec City; Department of Neurology (A.P.), University of Toronto; Medicine (G.S.), St. Michael's Hospital, University of Toronto, Canada; Department of Neurosciences (M.A.B.), Hospital Dr. Rafael A. Calderon Guardia, CCSS. San Jose, Costa Rica; Neurovascular Service (J.D.B.), Hospital General San Juan de Dios, Guatemala City; Department of Neurología (L.I.P.R.), Hospital General de Enfermedades, Instituto Guatemalteco de Seguridad Social, Guatemala City, Guatemala; Department of Neurology (F.G.-R.), University Hospital Jose Eleuterio Gonzalez, Universidad Autonoma de Nuevo Leon, Mexico; Pacífica Salud-Hospital Punta Pacífica (N.N.-E., A.B., R.K.), Panama; Department of Neurology, Radiology (M.A.), University of Kansas Medical Center; Department of Neurointerventional Neurosurgery (D. Altschul), The Valley Baptist Hospital, Ridgewood, New Jersey; Palmetto General Hospital (A.J.A.-O.), Tenet, Florida; Neurology (I.B., P.K.), University Hospital Newark, New Jersey Medical School, Rutgers, Newark, New Jersey; Community Healthcare System (A.B.), Munster, Indiana; Department of Neurology (N.B., C.B.N.), California Pacific Medical Center, San Francisco; Department of Neurology (C.B.), Mount Sinai South Nassau, New York; University of Toledo (A.C.), Ohio; Department of Neurology (S.C.), University of Maryland School of Medicine, Baltimore, Maryland; Neuroscience (S.A.C.), Inova Fairfax Hospital, Virginia; Department of Neurology (H.C.), Abington Jefferson Hospital, Pennsylvania; Department of Neurology (J.H.C.), Mount Sinai South Nassau, New York; Baptist Health Medical Center (S.D.), Little Rock, Arkansas; Department of Neurology (K.D.), HCA Houston Healthcare Clearlake, Texas; Department of Neurology (T.G.D., R.S.), Erlanger, Tennessee; Wilmington North Carolina (V.T.D.); Department of Vascular and Neurointerventional Services (R.E.), St. Louis University, Missouri; Department of Neurology (M.E.), Massachusetts General Hospital, Boston; Department of Neurology, Neurosurgery, and Radiology (M.F., S.O.-G., N.R.), University of Iowa Hospitals and Clinics, Iowa City; Department of Radiology (D.F.), Swedish Medical Center, Englewood, Colorado; Department of Radiology (D.G.), Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland; Adventist Health Glendale Comprehensive Stroke Center (M.G.), Los Angeles, California; Wellstar Neuroscience Institute (R.G.), Marietta, Georgia; Department of Neurology (A.E.H.), University of Texas Rio Grande Valley-Valley Baptist Medical Center, Texas; Department of Neurology (J.H., B.V.), Lahey Hospital & Medical Center, Beth Israel Lahey Health, Burlington, Massachusetts; Department of Neurology (A.M.K.), Wayne State, Detroit, Michigan; HSHS St. John's Hospital (N.N.K.), Southern Illinois University School of Medicine, Springfield; Virginia Hospital Center (B.S.K.), Arlington; Department of Neurology, University of Michigan, Ann Arbor; Weill-Cornell Medical College (D.O.K.), New York-Presbyterian Queens; Department of Neurology (V.H.L.), Ohio State University, Columbus; Department of Neurology (L.Y.L.), Tufts Medical Center, Boston, Massachusetts; Vascular and Neurointerventional Services (G.L.), St. Louis University, Missouri; Miami Cardiac & Vascular Institute (I.L., A.K.S.), Florida; Department of Neurology (H.L.L.), Oregon Health & Science University, Portland; Department of Emergency Medicine (L.M., M.S.), Steward Holy Family Hospital, Methuen, MA; Vidant Medical Center (S.M.), Greenville, North Carolina; Department of Neurology (A.M.M., D.R.Y.) and Neurosurgery (D.R.Y.), University of Miami Miller School of Medicine, Florida; Department of Neurology (H.M.), SUNY Upstate New York, Syracuse; Memorial Neuroscience Institute (B.P.M.), Pembroke Pines, Florida; Neurosciences (J.M., J.P.T.), Spectrum Health, Michigan State University College of Medicine, Grand Rapids, Michigan; Sutter Health (M.M.), Sacramento, California; Department of Neurology (J.G.M.), Maine Medical Center, Portland; Department of Neurology (S.S.M.), Bayhealth, Dover, Delaware; Department of Neurology and Pediatrics (F.N.), Emory University, Atlanta, Georgia; Department of Neurology (K.N.), University of Arkansas for Medical Sciences, Little Rock; Department of Radiology and Neurology (R.N.-W.), UT Southwestern Medical Center, Dallas, Texas; Ascension St. John Medical Center (R.H.R.), Tulsa, Oklahoma; Riverside Regional Medical Center (P.R.), Newport, Virginia; Department of Neurology (J.R.R., T.N.N.), Boston University School of Medicine, MA; Department of Neurology (A.R.), Hospital of the University of Pennsylvania, Philadelphia; Department of Neurology (M.S.), University of Washington School Medicine, Seattle; Department of Neurology (B.S.), University of Massachusetts Medical Center, Worcester; Department of Neurology (A.S.), CHI-Immanuel Neurological Institute, Creighton University, Omaha, Nebraska; Holy Cross Hospital (S.L.S.), Fort Lauderdale, Florida; Department of Neurology (V.S.), Interventional Neuroradiology, University of California in Los Angeles; Banner Desert Medical Center (M.T.), Mesa, Arizona; Hospital de Agudos Dr. Ignacio Privano (O.B., A.L.), Argentina; Institute for Neurological Research, FLENI (V.A.P.L.), Buenos Aires, Argentina; Hospital das Clinicas/São Paulo University (M.S.A., A.C.); Sumare State Hospital (F.B.C., L.V.), São Paulo; Hospital Vera Cruz (L.D.D.S.), Deus Campinas; Irmanandade Santa Casa de Porto Alegre (L.V.G.); Stroke Unit (F.O.L., F. Mont'alverne), Hospital Geral de Fortaleza; Stroke Unit (A.L.L., P.S.C.M.), Hospital Sao Jose, Joinville, Santa Catarina; Stroke Unit (R.T.M.), Neurology, Nossa Senhora da Conceição Hospital, Porto Alegre; Department of Neurology (D.L.M.C.), Hospital Moinhos de Vento, Porto Alegre; Department of Neurology (L.C.R.), Hospital de Base do Distrito Federal; Hospital Ana (V.F.C.), Hospital Juliane, Federal University of Parana, Curitiba, Brazil; Vascular Neurology Unit (P.M.L., V.V.O.), Neurology Service, Department of Neurology and Psychiatry, Clínica Alemana, Universidad del Desarrollo, Santiago; Hospital Padre Hurtado (V.N., J.M.A.T.) Santiago, Chile; Fundación Valle del Lili (P.F.R.A.), Cali; Stroke Center (H.B.), Fundación Santa Fe de Bogotá; Department of Neurology (A.B.C.-Q.), Hospital Departamental Universitario del Quindio San Juan de Dios, Armenia; Clinica Universitaria Colombia (C.E.R.O.), Bogotá; University Hospital of San Vicente Foundation (D.K.M.B.), Medellin; Barranquilla, Colombia (O.L.); Hospital Infantil Universitario de San Jose (M.R.P.), Bogota; Stroke Unit (L.F.D.-E.), Hospital de Clínicas, Facultad de Ciencias Médicas, Universidad Nacional de Asunción; Neurology Service (D.E.D.M.F., A.C.V.), Hospital Central del Instituto de Prevision Social, Paraguay; Internal Medicine Service (A.J.Z.Z.), Hospital Central de Policia "Rigoberto Caballero", Paraguay; National Institute of Neurological Sciences of Lima Peru (D.M.B.I.); Hospital Edgardo Rebagliati Martins Lima-Peru (L.R.K.); Department of Neurology (B.C.), Royal Melbourne Hospital; Department of Neurology (G.J.H.), Sir Charles Gairdner Hospital and Medical School, Faculty of Health and Medical Sciences, The University of Western Australia, Perth; University of Melbourne (C.H., R.S.), Ballarat Health Service, Australia University of Melbourne; Department of Neurology (T.K.), Royal Adelaide Hospital; Department of Neurosurgery (A. Ma), Royal North Shore Hospital, Sydney; Department of Neurology (R.T.M.), Mater Hospital, Brisbane; Department of Neurology (R.S.), Austin Health, Victoria; Florey Institute of Neuroscience and Mental Health (R.S.), Parkville, Melbourne, Australia; Greymouth Base Hospital (D.S.), New Zealand; Department of Neurology (T.Y.-H.W.), Christchurch Hospital, New Zealand; Department of Neurology (D.L.), University of California in Los Angeles; and Department of Neurology (O.O.Z.), Mercy Health Neurosciences, Toledo, Ohio.

Objective: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods.

Methods: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.

Results: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95% confidence interval [CI] -11.7 to -11.3, < 0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95% CI -13.8 to -12.7, < 0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95% CI -13.7 to -10.3, = 0.001). Recovery of stroke hospitalization volume (9.5%, 95% CI 9.2-9.8, < 0.0001) was noted over the 2 later (May, June) vs the 2 earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was noted in 3.3% (1,722/52,026) of all stroke admissions.

Conclusions: The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months.
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http://dx.doi.org/10.1212/WNL.0000000000011885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205458PMC
June 2021

Association between clot composition and stroke origin in mechanical thrombectomy patients: analysis of the Stroke Thromboembolism Registry of Imaging and Pathology.

J Neurointerv Surg 2021 Jul 15;13(7):594-598. Epub 2021 Mar 15.

Neurosurgery, Baptist Medical Center Jacksonville, Jacksonville, Florida, USA.

Background: We retrospectively evaluated the composition of retrieved clots from ischemic stroke patients to study the association between histological composition and stroke etiology METHODS: Consecutive patients enrolled in the Stroke Thromboembolism Registry of Imaging and Pathology (STRIP) were included in this study. All patients underwent mechanical thrombectomy and retrieved clots were sent to a central core lab for processing. Histological analysis was performed using martius scarlet blue (MSB) staining, and quantification for red blood cells (RBCs), white blood cells (WBCs), fibrin and platelets was performed using Orbit Image Software. A Wilcoxon test was used for continuous variables and χ test for categorical variables.

Results: 1350 patients were included in this study. The overall rate of Thrombolysis In Cerebral Infarction (TICI) 2c/3 was 68%. 501 patients received tissue plasminogen activator (tPA) (37%). 267 patients (20%) had a large artery atherosclerosis (LAA) source, 662 (49%) a cardioembolic (CE) source, 301 (22%) were cryptogenic, and the remainder had other identifiable sources including hypercoagulable state or dissection. LAA thrombi had a higher mean RBC density (46±23% vs 42±22%, p=0.01) and a lower platelet density (24±18% vs 27±18%, p=0.03) than CE thrombi. Clots from dissection patients had the highest mean RBC density (50±24%) while clots from patients with a hypercoagulable state had the lowest mean RBC density (26±21%).

Conclusions: Our study found statistically significant but clinically insignificant differences between clots of CE and LAA etiologies. Future studies should emphasize molecular, proteomic and immunohistochemical characteristics to determine links between clot composition and etiology.
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http://dx.doi.org/10.1136/neurintsurg-2020-017167DOI Listing
July 2021

Health-Related Quality of Life Among Patients With Acute Ischemic Stroke and Large Vessel Occlusion in the ESCAPE Trial.

Stroke 2021 May 11;52(5):1636-1642. Epub 2021 Mar 11.

Department of Clinical Neurosciences, Department of Radiology, Department of Community Health Sciences (B.K.M., M.D.H), Hotchkiss Brain Institute, University of Calgary, Canada.

[Figure: see text].
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http://dx.doi.org/10.1161/STROKEAHA.120.033872DOI Listing
May 2021

Economic Evaluation of Andexanet Versus Prothrombin Complex Concentrate for Reversal of Factor Xa-Associated Intracranial Hemorrhage.

Stroke 2021 Apr 1;52(4):1390-1397. Epub 2021 Mar 1.

Division of Cardiology, Schulich Heart Centre and Department of Medicine, Sunnybrook Health Sciences Centre (H.C.W.), University of Toronto, Ontario, Canada.

[Figure: see text].
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http://dx.doi.org/10.1161/STROKEAHA.120.031108DOI Listing
April 2021

Low-Dose vs Standard-Dose Alteplase in Acute Lacunar Ischemic Stroke: The ENCHANTED Trial.

Neurology 2021 03 3;96(11):e1512-e1526. Epub 2021 Feb 3.

From The George Institute for Global Health, Faculty of Medicine (Z.Z., C.D., C.X., S. Yoshimura, C.C., T.T.-Y., A.M., X.C., M.L.H., M.W., J.C., C.S.A.), and South Western Clinical School (M.W.P.), University of New South Wales Sydney, Australia; Department of Radiology (Z.Z., J.X.), Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, China; Department of Neurology (C.D., C.C., C.S.A.), Royal Prince Alfred Hospital, Sydney Health Partners; Sydney Medical School (C.D., C.C.), University of Sydney, Australia; Department of Neurosurgery (C.X.), West China Hospital, Sichuan University, Chengdu, China; Department of Cerebrovascular Medicine (S. Yoshimura, T.T.-Y.), National Cerebral and Cardiovascular Center, Osaka; Department of Neurology and Neuroscience (T.T.-Y.), Nagoya City University Graduate School of Medical Science, Japan; Department of Neurology (S. You), the Second Affiliated Hospital of Soochow University, Suzhou, China; The George Institute for Global Health, School of Public Health (M.W.), Imperial College, London; Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Center (T.G.R.), University of Leicester, UK; Melbourne Brain Centre, Royal Melbourne Hospital University Department of Medicine (M.W.P.), University of Melbourne, Australia; Departments of Clinical Neurosciences and Radiology, Hotchkiss Brain Institute, Cumming School of Medicine (A.M.D.), University of Calgary, Canada; Westmead Applied Research Centre (R.I.L.), University of Sydney, Australia; Division of Neuroimaging Sciences, Edinburgh Imaging and Centre for Clinical Brain Sciences (G.M., J.M.W.), and UK Dementia Research Institute (J.M.W.), University of Edinburgh; and The George Institute China at Peking University Health Science Center (C.S.A.), Beijing, China.

Objective: To determine any differential efficacy and safety of low- vs standard-dose IV alteplase for lacunar vs nonlacunar acute ischemic stroke (AIS), we performed post hoc analyzes from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) alteplase dose arm.

Methods: In a cohort of 3,297 ENCHANTED participants, we identified those with lacunar or nonlacunar AIS with different levels of confidence (definite/according to prespecified definitions based on clinical and adjudicated imaging findings. Logistic regression models were used to determine associations of lacunar AIS with 90-day outcomes (primary, modified Rankin Scale [mRS] scores 2-6; secondary, other mRS scores, intracerebral hemorrhage [ICH], and early neurologic deterioration or death) and treatment effects of low- vs standard-dose alteplase across lacunar and nonlacunar AIS with adjustment for baseline covariables.

Results: Of 2,588 participants with available imaging and clinical data, we classified cases as definite/probable lacunar (n = 490) or nonlacunar AIS (n = 2,098) for primary analyses. Regardless of alteplase dose received, lacunar AIS participants had favorable functional (mRS 2-6, adjusted odds ratio [95% confidence interval] 0.60 [0.47-0.77]) and other clinical or safety outcomes compared to participants with nonlacunar AIS. Low-dose alteplase (versus standard) had no differential effect on functional outcomes (mRS 2-6, 1.04 [0.87-1.24]) but reduced the risk of symptomatic ICH in all included participants. There were no differential treatment effects of low- vs standard-dose alteplase on all outcomes across lacunar and nonlacunar AIS (all ≥0.07).

Conclusions: We found no evidence from the ENCHANTED trial that low-dose alteplase had any advantages over standard dose for definite/probable lacunar AIS.

Classification Of Evidence: This study provides Class II evidence that for patients with lacunar AIS, low-dose alteplase had no additional benefit or safety over standard-dose alteplase.

Clinical Trial Registration: Clinicaltrials.gov identifier NCT01422616.
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http://dx.doi.org/10.1212/WNL.0000000000011598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032382PMC
March 2021

Global impact of COVID-19 on stroke care.

Int J Stroke 2021 Mar 29:1747493021991652. Epub 2021 Mar 29.

Neurology, Grady Memorial Hospital, Emory University, Atlanta, Georgia, USA.

Background: The COVID-19 pandemic led to profound changes in the organization of health care systems worldwide.

Aims: We sought to measure the global impact of the COVID-19 pandemic on the volumes for mechanical thrombectomy, stroke, and intracranial hemorrhage hospitalizations over a three-month period at the height of the pandemic (1 March-31 May 2020) compared with two control three-month periods (immediately preceding and one year prior).

Methods: Retrospective, observational, international study, across 6 continents, 40 countries, and 187 comprehensive stroke centers. The diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases at participating centers.

Results: The hospitalization volumes for any stroke, intracranial hemorrhage, and mechanical thrombectomy were 26,699, 4002, and 5191 in the three months immediately before versus 21,576, 3540, and 4533 during the first three pandemic months, representing declines of 19.2% (95%CI, -19.7 to -18.7), 11.5% (95%CI, -12.6 to -10.6), and 12.7% (95%CI, -13.6 to -11.8), respectively. The decreases were noted across centers with high, mid, and low COVID-19 hospitalization burden, and also across high, mid, and low volume stroke/mechanical thrombectomy centers. High-volume COVID-19 centers (-20.5%) had greater declines in mechanical thrombectomy volumes than mid- (-10.1%) and low-volume (-8.7%) centers (p < 0.0001). There was a 1.5% stroke rate across 54,366 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.9% (784/20,250) of all stroke admissions.

Conclusion: The COVID-19 pandemic was associated with a global decline in the volume of overall stroke hospitalizations, mechanical thrombectomy procedures, and intracranial hemorrhage admission volumes. Despite geographic variations, these volume reductions were observed regardless of COVID-19 hospitalization burden and pre-pandemic stroke/mechanical thrombectomy volumes.
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http://dx.doi.org/10.1177/1747493021991652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010375PMC
March 2021

A Prospective Economic Evaluation of Rapid Endovascular Therapy for Acute Ischemic Stroke.

Can J Neurol Sci 2021 Jan 12:1-8. Epub 2021 Jan 12.

Department Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

Background: During the Randomized Assessment of Rapid Endovascular Treatment (EVT) of Ischemic Stroke (ESCAPE) trial, patient-level micro-costing data were collected. We report a cost-effectiveness analysis of EVT, using ESCAPE trial data and Markov simulation, from a universal, single-payer system using a societal perspective over a patient's lifetime.

Methods: Primary data collection alongside the ESCAPE trial provided a 3-month trial-specific, non-model, based cost per quality-adjusted life year (QALY). A Markov model utilizing ongoing lifetime costs and life expectancy from the literature was built to simulate the cost per QALY adopting a lifetime horizon. Health states were defined using the modified Rankin Scale (mRS) scores. Uncertainty was explored using scenario analysis and probabilistic sensitivity analysis.

Results: The 3-month trial-based analysis resulted in a cost per QALY of $201,243 of EVT compared to the best standard of care. In the model-based analysis, using a societal perspective and a lifetime horizon, EVT dominated the standard of care; EVT was both more effective and less costly than the standard of care (-$91). When the time horizon was shortened to 1 year, EVT remains cost savings compared to standard of care (∼$15,376 per QALY gained with EVT). However, if the estimate of clinical effectiveness is 4% less than that demonstrated in ESCAPE, EVT is no longer cost savings compared to standard of care.

Conclusions: Results support the adoption of EVT as a treatment option for acute ischemic stroke, as the increase in costs associated with caring for EVT patients was recouped within the first year of stroke, and continued to provide cost savings over a patient's lifetime.Clinical Trial Registration: NCT01778335.
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http://dx.doi.org/10.1017/cjn.2021.4DOI Listing
January 2021

Thrombus Migration and Fragmentation After Intravenous Alteplase Treatment: The INTERRSeCT Study.

Stroke 2021 01 15;52(1):203-212. Epub 2020 Dec 15.

Calgary Stroke Program, Hotchkiss Brain Institute, Departments of Clinical Neurosciences and Radiology, Cumming School of Medicine, University of Calgary, Canada (T.O., B.K.M., M.H., M.N., A.A.-S., M.G., M.D.H., M.A., A.M.D.).

Background And Purpose: There is interest in what happens over time to the thrombus after intravenous alteplase. We study the effect of alteplase on thrombus structure and its impact on clinical outcome in patients with acute stroke.

Methods: Intravenous alteplase treated stroke patients with intracranial internal carotid artery or middle cerebral artery occlusion identified on baseline computed tomography angiography and with follow-up vascular imaging (computed tomography angiography or first run of angiography before endovascular therapy) were enrolled from INTERRSeCT study (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography). Thrombus movement after intravenous alteplase was classified into complete recanalization, thrombus migration, thrombus fragmentation, and no change. Thrombus migration was diagnosed when occlusion site moved distally and graded according to degrees of thrombus movement (grade 0-3). Thrombus fragmentation was diagnosed when a new distal occlusion in addition to the primary occlusion was identified on follow-up imaging. The association between thrombus movement and clinical outcome was also evaluated.

Results: Among 427 patients in this study, thrombus movement was seen in 54% with a median time of 123 minutes from alteplase administration to follow-up imaging, and sub-classified as marked (thrombus migration grade 2-3 + complete recanalization; 27%) and mild to moderate thrombus movement (thrombus fragmentation + thrombus migration grade 0-1; 27%). In patients with proximal M1/internal carotid artery occlusion, marked thrombus movement was associated with a higher rate of good outcome (90-day modified Rankin Scale, 0-2) compared with mild to moderate movement (52% versus 27%; adjusted odds ratio, 5.64 [95% CI, 1.72-20.10]). No difference was seen in outcomes between mild to moderate thrombus movement and no change. In M1 distal/M2 occlusion, marked thrombus movement was associated with improved 90-day good outcome compared with no change (70% versus 56%; adjusted odds ratio, 2.54 [95% CI, 1.21-5.51]).

Conclusions: Early thrombus movement is common after intravenous alteplase. Marked thrombus migration leads to good clinical outcomes. Thrombus dynamics over time should be further evaluated in clinical trials of acute reperfusion therapy.
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http://dx.doi.org/10.1161/STROKEAHA.120.029292DOI Listing
January 2021

Computed Tomography Perfusion-Based Machine Learning Model Better Predicts Follow-Up Infarction in Patients With Acute Ischemic Stroke.

Stroke 2021 01 7;52(1):223-231. Epub 2020 Dec 7.

Department of Clinical Neurosciences (H.K., W.Q., M.D.H., A.M.D., M.G., B.K.M.), University of Calgary.

Background And Purpose: Prediction of infarct extent among patients with acute ischemic stroke using computed tomography perfusion is defined by predefined discrete computed tomography perfusion thresholds. Our objective is to develop a threshold-free computed tomography perfusion-based machine learning (ML) model to predict follow-up infarct in patients with acute ischemic stroke.

Methods: Sixty-eight patients from the PRoveIT study (Measuring Collaterals With Multi-Phase CT Angiography in Patients With Ischemic Stroke) were used to derive a ML model using random forest to predict follow-up infarction voxel by voxel, and 137 patients from the HERMES study (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) were used to test the derived ML model. Average map, T, cerebral blood flow, cerebral blood volume, and time variables including stroke onset-to-imaging and imaging-to-reperfusion time, were used as features to train the ML model. Spatial and volumetric agreement between the ML model predicted follow-up infarct and actual follow-up infarct were assessed. Relative cerebral blood flow <0.3 threshold using RAPID software and time-dependent T thresholds were compared with the ML model.

Results: In the test cohort (137 patients), median follow-up infarct volume predicted by the ML model was 30.9 mL (interquartile range, 16.4-54.3 mL), compared with a median 29.6 mL (interquartile range, 11.1-70.9 mL) of actual follow-up infarct volume. The Pearson correlation coefficient between 2 measurements was 0.80 (95% CI, 0.74-0.86, <0.001) while the volumetric difference was -3.2 mL (interquartile range, -16.7 to 6.1 mL). Volumetric difference with the ML model was smaller versus the relative cerebral blood flow <0.3 threshold and the time-dependent T threshold (<0.001).

Conclusions: A ML using computed tomography perfusion data and time estimates follow-up infarction in patients with acute ischemic stroke better than current methods.
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http://dx.doi.org/10.1161/STROKEAHA.120.030092DOI Listing
January 2021

Imaging criteria across pivotal randomized controlled trials for late window thrombectomy patient selection.

J Neurointerv Surg 2020 Nov 25. Epub 2020 Nov 25.

Calgary Stroke Program, University of Calgary, Calgary, Alberta, Canada

Background: The DAWN and DEFUSE-3 trials showed the benefit of endovascular treatment (EVT) in acute ischemic stroke patients presenting beyond 6 hours from last known well (LKW) and selected by perfusion imaging criteria. The ESCAPE NA1-trial selected patients based on non-contrast CT (NCCT) Alberta Stroke Program Early CT Score (ASPECTS) and multiphase CT angiography (CTA) collateral status. This study compares baseline characteristics, workflow, and outcomes in the EVT arms of DAWN and DEFUSE-3 with late-window patients from the EVT-only arm of ESCAPE-NA1.

Methods: Aggregate data on baseline characteristics, workflow, reperfusion quality, final infarct volume, and clinical outcomes (modified Rankin Score [mRS] at 90 days) in subjects enrolled in the DAWN and DEFUSE-3 EVT arms were compared with similar data from the ESCAPE-NA1 control arm (EVT-only arm) presenting beyond 6 hours from LKW using descriptive statistics.

Results: Baseline characteristics among late-window patients in the ESCAPE NA1 trial were similar to those in the DAWN and DEFUSE-3 EVT arms. Median time from LKW-to-puncture in subjects enrolled in the ESCAPE NA1 trial was 9 hrs (IQR: 7.5-11 hours) when compared with DAWN (n=107; 12.8 hours, IQR: 10.6-16.7 hours) and DEFUSE-3 (n=92; 11.5 hours, IQR: 9.2-12.8 hours). Median post-treatment infarct-volume was largest in the ESCAPE NA1-patients (47 mL [IQR: 19-146] vs median 8 mL [IQR: 0-48] in the DAWN group and 35 mL [IQR: 18-82] in DEFUSE-3), while % mRS 0-2 at 90 days were similar across the three trials (ESCAPE NA1: 50/111 [45%], DAWN: 52/107 [49%], DEFUSE-3: 41/92 [45%]).

Conclusion: Patients enrolled beyond 6 hours from LKW in the ESCAPE-NA1 trial based on NCCT-ASPECTS and mCTA had similar clinical outcomes when compared with patients selected by perfusion imaging in the DAWN and DEFUSE-3 trials.
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http://dx.doi.org/10.1136/neurintsurg-2020-016902DOI Listing
November 2020

Prevalence and the predictive performance of the dynamic CT-angiography spot sign in an observational cohort with intracerebral hemorrhage.

Medicine (Baltimore) 2020 Nov;99(47):e23278

Department of Medical Imaging, University of Ottawa and Ottawa Hospital Research Institute, Ottawa, Canada.

The CT-angiography (CTA) spot sign is a predictor of hematoma expansion (HE). We have previously reported on the use of dynamic CTA (dCTA) to detect spot sign, and to study its formation over the acquisition period. In this study, we report the frequency of dCTA spot sign in acute intracerebral hemorrhage, its sensitivity and specificity to predict HE, and explore the rate of contrast extravasation in relation to hematoma growth.We enrolled consecutive patients presenting with primary intracerebral hemorrhage within 4.5 hours. All patients underwent a dCTA protocol acquired over 60 seconds following contrast injection. We calculated frequency of the dCTA spot sign, predictive performance, and rate of contrast extravasation. We compared extravasation rates to the dichotomous definition of significant HE (defined as 6 mL or 33% growth).In 78 eligible patients, dCTA spot sign frequency was 44.9%. In 61 patients available for expansion analysis, sensitivity and specificity of dCTA spot sign was 65.4% and 62.9%, respectively. Contrast extravasation rate did not significantly predict HE (Odds Ratio 15.6 for each mL/min [95% confidence interval 0.30-820.25], P = .17). Correlation between extravasation rate and HE was low (r = 0.297, P= .11). Patients with significant HE had a higher rate of extravasation as compared to those without (0.12 mL/min vs 0.04 mL/min, P = .03).Dynamic CTA results in a higher frequency of spot sign positivity, but with modest sensitivity and specificity to predict expansion. Extravasation rate is likely related to HE, but a single measurement may be insufficient to predict the magnitude of expansion.
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http://dx.doi.org/10.1097/MD.0000000000023278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676581PMC
November 2020

Early Recanalization With Alteplase in Stroke Because of Large Vessel Occlusion in the ESCAPE Trial.

Stroke 2021 01 20;52(1):304-307. Epub 2020 Nov 20.

Department of Clinical Neurosciences (J.M.O., N.S., M.A.A., B.K.M., A.M.D., M.G., M.D.H.), University of Calgary, Canada.

Background And Purpose: Quantitating the effect of intravenous alteplase on the technical outcome of early recanalization of large vessel occlusions aids understanding. We report the prevalence of early recanalization in patients with stroke because of large vessel occlusion treated with and without intravenous alteplase and endovascular thrombectomy, and its association with clinical outcome.

Methods: Patients with acute ischemic stroke with large vessel occlusion from the ESCAPE trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times Trial) were included in this post hoc analysis. Outcomes of interest were the prevalence of early recanalization (1) and good outcome (2), defined as modified Rankin Scale score of 0 to 2 at 90 days.

Results: Among 147 patients who did not receive endovascular thrombectomy, early recanalization occurred in 4/30 (13.3%) patients without and 48/117 (41.0%) patients with intravenous alteplase (adjusted risk ratios, 3.2 [95% CI, 1.2-8.1]). Good outcome was achieved by 34/116 (29.3%) of patients who received intravenous alteplase versus 10/29 (34.5%) who did not receive alteplase (adjusted risk ratios, 1.0 [95% CI, 0.6-1.5) and by 20/52 (38.5%) patients with versus 24/93 (25.8%) without early recanalization (adjusted risk ratios, 1.9 [95% CI, 1.2-2.9]).

Conclusions: Early recanalization was confirmed as a strong predictor of good outcome in patients who did not undergo endovascular thrombectomy and was improved with intravenous alteplase, yet a majority of patients (59.0%) did not achieve early reperfusion. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01778335.
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http://dx.doi.org/10.1161/STROKEAHA.120.031591DOI Listing
January 2021

Sex Differences in Diagnosis and Diagnostic Revision of Suspected Minor Cerebral Ischemic Events.

Neurology 2021 02 12;96(5):e732-e739. Epub 2020 Nov 12.

From the Department of Medicine (Neurology) (A.Y.X.Y., R.H.S.), University of Toronto, Ontario; Department of Clinical Neurosciences (M.D.H., A.M.D., M.G., B.K.M., S.B.C.), University of Calgary, Alberta, Canada; Department of Neurology (N.A.), University of Miami, FL; Department of Neurology (J.-M.B.), Sherbrooke University, Longueil; Department of Neurosciences (M.-C.C.), Laval University, Québec City, Québec, Canada; Department of Medicine and Neurology (B.C.V.C.), University of Melbourne, Parkville, Australia; Vancouver Stroke Program (T.S.F.), University of British Columbia, Vancouver, Canada; Northern Clinical School (M.K.), University of Sydney, Australia; Department of Clinical Neurosciences (J.M.), Western University, London, Ontario, Canada; Neurological Department (R.M.), St. Anne's University Hospital and Masaryk University, Brno, Czech Republic; Department of Medicine (F.M.), Neurology, Université de Sherbrooke, Québec; and Division of Neurology (A.M.P.), Vancouver Island Health Authority, Victoria, British Columbia, Canada.

Objective: To describe sex differences in the presentation, diagnosis, and revision of diagnosis after early brain MRI in patients who present with acute transient or minor neurologic events.

Methods: We performed a secondary analysis of a prospective multicenter cohort study of patients referred to neurology between 2010 and 2016 with a possible cerebrovascular event and evaluated with brain MRI within 8 days of symptom onset. Investigators documented the characteristics of the event, initial diagnosis, and final diagnosis. We used multivariable logistic regression analyses to evaluate the association between sex and outcomes.

Results: Among 1,028 patients (51% women, median age 63 years), more women than men reported headaches and fewer reported chest pain, but there were no sex differences in other accompanying symptoms. Women were more likely than men to be initially diagnosed with stroke mimic (54% of women vs 42% of men, adjusted odds ratio (OR) 1.60, 95% confidence interval [CI] 1.24-2.07), and women were overall less likely to have ischemia on MRI (10% vs 17%, OR 0.52, 95% CI 0.36-0.76). Among 496 patients initially diagnosed with mimic, women were less likely than men to have their diagnosis revised to minor stroke or TIA (13% vs 20%, OR 0.53, 95% CI 0.32-0.88) but were equally likely to have acute ischemia on MRI (5% vs 8%, OR 0.56, 95% CI 0.26-1.21).

Conclusions: Stroke mimic was more frequently diagnosed in women than men, but diagnostic revisions were common in both. Early brain MRI is a useful addition to clinical evaluation in diagnosing transient or minor neurologic events.
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http://dx.doi.org/10.1212/WNL.0000000000011212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884992PMC
February 2021

Sex Differences in Endovascular Treatment for Stroke: A Population-based Analysis.

Can J Neurol Sci 2020 Oct 21:1-8. Epub 2020 Oct 21.

Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

Background: Acute ischemic stroke may affect women and men differently. We aimed to evaluate sex differences in outcomes of endovascular treatment (EVT) for ischemic stroke due to large vessel occlusion in a population-based study in Alberta, Canada.

Methods And Results: Over a 3-year period (April 2015-March 2018), 576 patients fit the inclusion criteria of our study and constituted the EVT group of our analysis. The medical treatment group of the ESCAPE trial had 150 patients. Thus, our total sample size was 726. We captured outcomes in clinical routine using administrative data and a linked database methodology. The primary outcome of our study was home-time. Home-time refers to the number of days that the patient was back at their premorbid living situation without an increase in the level of care within 90 days of the index stroke event. In adjusted analysis, EVT was associated with an increase of 90-day home-time by an average of 6.08 (95% CI -2.74-14.89, p-value 0.177) days in women compared to an average of 11.20 (95% CI 1.94-20.46, p-value 0.018) days in men. Further analysis revealed that the association between EVT and 90-day home-time in women was confounded by age and onset-to-treatment time.

Conclusions: We found a nonsignificant nominal reduction of 90-day home-time gain for women compared to men in this province-wide population-based study of EVT for large vessel occlusion, which was only partially explained by confounding.
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http://dx.doi.org/10.1017/cjn.2020.237DOI Listing
October 2020

Clinical Course of Acute Ischemic Stroke Due to Medium Vessel Occlusion With and Without Intravenous Alteplase Treatment.

Stroke 2020 11 19;51(11):3232-3240. Epub 2020 Oct 19.

Department of Clinical Neurosciences (J.M.O., B.K.M., A.M.D., M.A.A., N.K., A.M., M.D.H., M.G.), University of Calgary, Canada.

Background And Purpose: Available data on the clinical course of patients with acute ischemic stroke due to medium vessel occlusion (MeVO) are mostly limited to those with M2 segment occlusions. Outcomes are generally better compared with more proximal occlusions, but many patients will still suffer from severe morbidity. We aimed to determine the clinical course of acute ischemic stroke due to MeVO with and without intravenous alteplase treatment.

Methods: Patients with MeVO (M2/M3/A2/A3/P2/P3 occlusion) from the INTERRSeCT (The Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography) and PRoveIT (Precise and Rapid Assessment of Collaterals Using Multi-Phase CTA in the Triage of Patients With Acute Ischemic Stroke for IA Therapy) studies were included. Baseline characteristics and clinical outcomes were summarized using descriptive statistics. The primary outcome was a modified Rankin Scale score of 0 to 1 at 90 days, describing excellent functional outcome. Secondary outcomes were the common odds ratio for a 1-point shift across the modified Rankin Scale and functional independence, defined as modified Rankin Scale score of 0 to 2. We compared outcomes between patients with versus without intravenous alteplase treatment and between patients who did and did not show recanalization on follow-up computed tomography angiography. Logistic regression was used to provide adjusted effect-size estimates.

Results: Among 258 patients with MeVO, the median baseline National Institutes of Health Stroke Scale score was 7 (interquartile range: 5-12). A total of 72.1% (186/258) patients were treated with intravenous alteplase and in 41.8% (84/201), recanalization of the occlusion (revised arterial occlusive lesion score 2b/3) was seen on follow-up computed tomography angiography. Excellent functional outcome was achieved by 50.0% (129/258), and 67.4% (174/258) patients gained functional independence, while 8.9% (23/258) patients died within 90 days. Recanalization was observed in 21.4% (9/42) patients who were not treated with alteplase and 47.2% (75/159) patients treated with alteplase (=0.003). Early recanalization (adjusted odds ratio, 2.29 [95% CI, 1.23-4.28]) was significantly associated with excellent functional outcome, while intravenous alteplase was not (adjusted odds ratio, 1.70 [95% CI, 0.88-3.25]).

Conclusions: One of every 2 patients with MeVO did not achieve excellent clinical outcome at 90 days with best medical management. Early recanalization was strongly associated with excellent outcome but occurred in <50% of patients despite intravenous alteplase treatment.
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November 2020