Publications by authors named "Mohammed A Almekhlafi"

79 Publications

Influence of intravenous alteplase on endovascular treatment decision-making in acute ischemic stroke due to primary medium-vessel occlusion: a case-based survey study.

J Neurointerv Surg 2021 May 25. Epub 2021 May 25.

Diagnostic Imaging, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada.

Background: Intravenous alteplase is currently the only evidence-based treatment for medium-vessel occlusion stroke (MeVO; M2/3, A2/3, and P2/3 vessel segment occlusions), but due to its limited efficacy, endovascular treatment (EVT) is increasingly performed in these patients. In this case-based survey study, we examined the influence of intravenous alteplase treatment on physicians' decision-making for EVT in primary MeVO stroke.

Methods: In an international web-based survey among physicians involved in acute stroke care, participants provided their EVT decision for six quasi-identical fictional MeVO case scenarios (three with and without intravenous alteplase administered). Each scenario showed radiological images and clinical information in the form of a short case vignette. We compared EVT decisions ("immediate EVT", "no EVT", or "wait for alteplase effect" [in case scenarios with alteplase treatment only]) for case scenarios with and without alteplase treatment. Clustered multivariable logistic regression was performed to assess the effect of alteplase on treatment decision.

Results: The survey was completed by 366 physicians from 44 countries, resulting in 2196 responses included in this study. In alteplase-treated cases, 641/1098 (58.4%) responses favored immediate EVT, (279/1098 [25.4%]) favored no EVT and 178/1098 (16.2%) opted to wait for alteplase effect. In non-alteplase-treated case scenarios, 846/1098 (78.7%) were in favor of and 252/1098 (21.3%) against EVT. Intravenous alteplase was associated with a lower chance of a decision in favor of immediate EVT (adjusted OR 0.38 [95%CI 0.31 to 0.46]).

Conclusions: Intravenous alteplase is an important factor in EVT decision-making for MeVO stroke. However, even in alteplase-treated patients, more than half of the physicians decided to proceed with EVT without waiting for alteplase effect.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/neurintsurg-2021-017471DOI Listing
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/neurintsurg-2021-017474DOI 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaneurol.2021.1055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094030PMC
June 2021

Clinical impact of EVT with failed reperfusion in patients with acute ischemic stroke: results from the ESCAPE and ESCAPE-NA1 trials.

Neuroradiology 2021 Apr 29. Epub 2021 Apr 29.

Department of Clinical Neurosciences, University of Calgary, Calgary, Canada.

Background And Purpose: Endovascular treatment (EVT) is a powerful treatment for large vessel occlusion (LVO) stroke if reperfusion can be achieved, while in cases with failed reperfusion, EVT may cause harm, as procedure-related complications may occur. We hypothesized that EVT with failed recanalization does not result in worse outcomes compared to best medical management and compared clinical outcomes of LVO stroke patients who underwent EVT with failed reperfusion to those who were treated with best medical management.

Methods: We included patients with failed reperfusion from the control (EVT-only) arm of the ESCAPE-NA1 trial and the EVT arm of the ESCAPE trial and patients of the ESCAPE control arm who were treated with best medical management. Failed reperfusion following EVT was defined as modified thrombolysis in cerebral infarction score 0-2a. Proportions of good outcome (modified Rankin scale 0-2) were compared between patients who did and did not undergo EVT, and adjusted effect size estimates for EVT on outcomes were obtained.

Results: We included 260 patients (110 failed EVT and 150 non-EVT patients). Proportions of good outcome were 38/110 (34.6%) with failed EVT vs.43/147 (29.3%) without EVT (adjusted odds ratio[aOR]: 1.48 [95%CI: 0.81-2.68]). Mortality and proportions of sICH in the failed EVT group vs. patients treated with best medical management were 26/110 (23.6%) vs. 28/147 (19.1%), aOR: 1.12 (95%CI: 0.56-2.24), and 7/110 (6.4%) vs. 4/150 (2.7%), aOR: 2.34 (95%CI: 0.00-22.97).

Conclusion: Clinical outcomes of EVT patients with failed reperfusion did not differ significantly from patients treated with best medical management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00234-021-02723-wDOI Listing
April 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/15910199211009119DOI Listing
April 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 Mar 15. 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/neurintsurg-2020-017167DOI Listing
March 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/neurintsurg-2020-016902DOI Listing
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.120.031591DOI Listing
January 2021

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.120.030227DOI Listing
November 2020

Utility of Time-Variant Multiphase CTA Color Maps in Outcome Prediction for Acute Ischemic Stroke Due to Anterior Circulation Large Vessel Occlusion.

Clin Neuroradiol 2020 Sep 25. Epub 2020 Sep 25.

Department of Clinical Neurosciences, Foothills Medical Centre, University of Calgary, 1403 29th St. NW, T2N2T9, Calgary, AB, Canada.

Background: Multiphase CTA (mCTA) is an established tool for endovascular treatment decision-making and outcome prediction in acute ischemic stroke, but its interpretation requires some degree of experience. We aimed to determine whether mCTA-based prediction of clinical outcome and final infarct volume can be improved by assessing collateral status on time-variant mCTA color maps rather than using a conventional mCTA display format.

Methods: Patients from the PRove-IT cohort study with anterior circulation large vessel occlusion were included in this study. Collateral status was assessed with a three-point scale using the conventional display format. Collateral extent and filling dynamics were then graded on a three-point scale using time-variant mCTA color-maps (FastStroke, GE Healthcare, Milwaukee, WI, USA). Multivariable logistic regression was performed to determine the association of conventional collateral score, color-coded collateral extent and color-coded collateral filling dynamics with good clinical outcome and final infarct volume (volume below vs. above median infarct volume in the study sample).

Results: A total of 285 patients were included in the analysis and 53% (152/285) of the patients achieved a good outcome. Median infarct volume on follow-up was 12.6 ml. Color-coded collateral extent was significantly associated with good outcome (adjusted odds ratio [OR] 0.53, 95% confidence interval [CI]:0.36-0.77) while color-coded collateral filling dynamics (OR 1.30 [95%CI:0.88-1.95]) and conventional collateral scoring (OR 0.72 [95%C:0.48-1.08]) were not. Both color-coded collateral extent (OR 2.67 [95%CI:1.80-4.00]) and conventional collateral scoring (OR 1.84 [95%CI:1.21-2.79]) were significantly associated with follow-up infarct volume, while color-coded collateral filling dynamics were not (OR 1.21 [95%CI:0.83-1.78]).

Conclusion: In this study, collateral extent assessment on time-variant mCTA maps improved prediction of good outcome and has similar value in predicting follow-up infarct volume compared to conventional mCTA collateral grading.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00062-020-00958-3DOI Listing
September 2020

Public health and cost consequences of time delays to thrombectomy for acute ischemic stroke.

Neurology 2020 11 17;95(18):e2465-e2475. Epub 2020 Sep 17.

From the University of Calgary (W.G.K., M.A.A., B.K.M., A.M.D., M.D.H., M.G.), Alberta, Canada; Department of Radiology (W.G.K.), University Hospital, LMU Munich, Germany; Harvard T.H. Chan School of Public Health (M.G.H.), Boston, MA; Erasmus MC (M.G.H., D.W.J.D.), University Medical Center Rotterdam, the Netherlands; Faculty of Medicine (M.A.A.), King Abdulaziz University, Jeddah, Saudi Arabia; David Geffen School of Medicine (J.L.S.), University of California-Los Angeles; Academic Medical Center (C.B.L.M.M.), Amsterdam, the Netherlands; University of Pittsburgh Medical Center (T.G.J.), PA; Hospital Germans Trias i Pujol (A.D.), Barcelona, Spain; University Hospital of Nancy (S. Bracard, F.G.), France; University of Melbourne (B.C.V.C., P.J.M.), Australia; Newcastle University (P.W.), UK; University of Glasgow (K.W.M.), UK; and Altair Biostatistics (S. Brown), St. Louis Park, MN.

Objective: To determine public health and cost consequences of time delays to endovascular thrombectomy (EVT) for patients, health care systems, and society, we estimated quality-adjusted life-years (QALYs) of EVT-treated patients and associated costs based on times to treatment.

Methods: The Markov model analysis was performed from US health care and societal perspectives over a lifetime horizon. Contemporary data from 7 trials within the Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials (HERMES) collaboration served as data source. Aside from cumulative lifetime costs, we calculated the net monetary benefit (NMB) to determine the economic value of care. We used a contemporary willingness-to-pay threshold of $100,000 per QALY for NMB calculations.

Results: Every 10 minutes of earlier treatment resulted in an average gain of 39 days (95% prediction interval 23-53 days) of disability-free life. Overall, the cumulative lifetime costs for patients with earlier or later treatment were similar. Patients with later treatment had higher morbidity-related costs but over a shorter time span due to their shorter life expectancy, resulting in similar lifetime costs as in patients with early treatment. Regarding the economic value of care, every 10 minutes of earlier treatment increased the NMB by $10,593 (95% prediction interval $5,549-$14,847) and by $10,915 (95% prediction interval $5,928-$15,356) taking health care and societal perspectives, respectively.

Conclusions: Any time delay to EVT reduces QALYs and decreases the economic value of care provided by this intervention. Health care policies to implement efficient prehospital triage and to accelerate in-hospital workflow are urgently needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000010867DOI Listing
November 2020

Prevalence of Non-Stenotic (<50%) Carotid Plaques in Acute Ischemic Stroke and Transient Ischemic Attack: A Systematic Review and Meta-Analysis.

J Stroke Cerebrovasc Dis 2020 Oct 12;29(10):105117. Epub 2020 Jul 12.

Department of Radiology, University of Calgary, Calgary, Canada. Electronic address:

Introduction: Non-stenotic (<50%) carotid plaques have recently been recognized as a potential source of stroke. This meta-analysis aims to summarize the prevalence of non-stenotic carotid plaques in stroke patients in general and in patients with embolic stroke of undetermined source in particular.

Methods: We performed a comprehensive systematic review of the literature and meta-analysis on acute ischemic stroke patients in whom carotid imaging was performed using the MEDLINE, Embase and Cochrane database, including studies published up to December 2019. Keywords were "stroke", "transient ischemic attack", "carotid", "plaque", "atherosclerosis" and "disease". Included studies had ≥10 patients with acute ischemic stroke and reported the prevalence of non-stenotic (<50%%stenosis) carotid plaques detected on any imaging modality.

Results: We included forty-five studies (n = 18304 patients, 48.4% males, mean age 63.6 years) in our meta-analysis. Imaging modalities used were ultrasound (n = 26 studies), CT-angiography (n = 7), magnetic resonance-imaging (n = 8) and catheter angiography (n = 4). The overall prevalence of non-stenotic carotid plaques was 51% (95% CI: 43 - 59). 10 studies included mainly patients with embolic stroke of undetermined source (>50% of all patients). The pooled prevalence of non-stenotic carotid plaques in these studies was 55% (95% CI: 42 - 68). 23 studies explicitly reported ipsilateral non-stenotic carotid plaques, the pooled prevalence of which was 51% (95% CI: 45 - 59).

Conclusions: In this meta-analysis, non-stenotic carotid plaques were present in more than 50% of all acute ischemic stroke patients, with a slightly higher prevalence in ESUS patients. Given the potential role of non-stenotic carotid plaques in stroke etiology, particularly in ESUS, further research should aim to identify criteria that predict the stroke risk associated with non-stenotic carotid plaques.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105117DOI Listing
October 2020

A System for Continuous Pre- to Post-reperfusion Intra-carotid Cold Infusion for Selective Brain Hypothermia in Rodent StrokeModels.

Transl Stroke Res 2020 Sep 10. Epub 2020 Sep 10.

Department of Neurology & Stroke, Eberhard-Karls University of Tübingen, Tübingen, Germany.

Intra-carotid cold infusion (ICCI) appears as a promising method for hypothermia-mediated brain protection from ischemic stroke. Recent clinical pilot studies indicate easy implementation of ICCI into endovascular acute ischemic stroke treatment. Current rodent ICCI-in-stroke models limit ICCI to the post-reperfusion phase. To establish a method for continuous ICCI over the duration of intra-ischemia to post-reperfusion in rodent stroke models, a novel system was developed. Eighteen male Sprague-Dawley rats were included. Intraluminal filament method was used for transient middle cerebral artery occlusion (MCAO). Normal saline (~ 0 °C) was delivered (≤ 2.0 mL/min) into the internal carotid artery via a customized infusion system without interruption during MCAO (intra-ischemia) to after filament withdrawal (post-reperfusion). Bilateral cortical and striatal temperatures were monitored. Hypothermia goals were a temperature reduction in the ischemic hemisphere by 2 °C prior to reperfusion and thereafter maintenance of regional brain hypothermia at ~ 32 °C limiting the administered ICCI volume to ½ of each rat's total blood volume. During ischemia, maximum brain cooling rate was achieved with ICCI at 0.5 mL/min. It took 2 min to reduce ischemic striatal temperature by 2.3 ± 0.3 °C. After reperfusion, brain cooling was continued at 2 mL/min ICCI first (over 42 s) and maintained at 32.1 ± 0.3 °C at 0.7 mL/min ICCI over a duration of 15 ± 0.8 min. ICCI (total 12.6 ± 0.6 mL) was uninterrupted over the duration of the studied phases. First system that allows continuous ICCI during the phases of intra-ischemia to post-reperfusion in small animals for selective brain cooling and for investigations of other neuroprotective infusions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12975-020-00848-3DOI Listing
September 2020

Prevalence and Outcomes of Medium Vessel Occlusions With Discrepant Infarct Patterns.

Stroke 2020 09 6;51(9):2817-2824. Epub 2020 Aug 6.

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

Background And Purpose: The prognosis of medium vessel occlusions (MeVOs), that is, M2/3 middle cerebral artery, A2/3 anterior cerebral artery, and P2/3 posterior cerebral artery occlusions, is generally better compared with large vessel occlusions, since brain ischemia is less extensive. However, in some MeVO patients, infarcts are seen outside the territory of the occluded vessel (MeVO with discrepant infarcts). This study aims to determine the prevalence and clinical impact of discrepant infarct patterns in acute ischemic stroke due to MeVO.

Methods: We pooled data of MeVO patients from INTERRSeCT (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography) and PRove-IT (Precise and Rapid Assessment of Collaterals Using Multi-Phase CTA in the Triage of Patients With Acute Ischemic Stroke for IA Therapy)-2 prospective cohort studies of patients with acute ischemic stroke. The combination of occlusion location on baseline computed tomography angiography and infarct location on follow-up computed tomography/magnetic resonance imaging was used to identify MeVOs with discrepant infarct patterns. Two definitions for discrepant infarcts were applied; one was more restrictive and purely based on infarct patterns of the basal ganglia, whereas the second one took cortical infarct patterns into account. Clinical outcomes of patients with versus without discrepant infarcts were summarized using descriptive statistics. Logistic regression was performed to obtain adjusted effect size estimates for the association of discrepant infarcts and good outcome, defined as a modified Rankin Scale score of 0 to 2, and excellent outcome (modified Rankin Scale score 0-1).

Results: Two hundred sixty-two patients with MeVO were included in the analysis. The prevalence of discrepant infarcts was 39.7% (definition 1) and 21.0% (definition 2). Patients with discrepant infarcts were less likely to achieve good outcome (definition 1: adjusted odds ratio, 0.48 [95% CI, 0.25-0.91]; definition 2: adjusted odds ratio, 0.47 [95% CI, 0.22-0.99]). When definition 1 was applied, patients with discrepant infarcts were also less likely to achieve excellent outcome (definition 1: adjusted odds ratio, 0.55 [95% CI, 0.31-0.99]; definition 2: adjusted odds ratio, 0.62 [95% CI, 0.31-1.25]).

Conclusions: MeVO patients with discrepant infarcts are common, and they are associated with more severe deficits and poor outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.120.030041DOI Listing
September 2020

Current and future usefulness and potential of virtual simulation in improving outcomes and reducing complications in endovascular treatment of unruptured intracranial aneurysms.

J Neurointerv Surg 2021 Mar 15;13(3):251-254. Epub 2020 Jul 15.

Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada

Background: Simulation training has been used in the aviation industry and surgical specialties for many years, but integration into neurointerventional practice is lagging behind.

Objective: To investigate how neurointerventionalists perceive the usefulness and limitations of simulation tools for the treatment of unruptured intracranial aneurysms (UIAs), and to identify simulation applications that were perceived to be most valuable for endovascular UIA treatment.

Methods: A web-based international multidisciplinary survey was conducted among neurointerventionalists. Participants were asked for their perceptions on the usefulness of current simulation tools and the potential impact of future simulation tools in endovascular UIA treatment. They identified simulation applications that could add most value to endovascular UIA treatment and help to specifically reduce endovascular UIA treatment complications.

Results: 233 neurointerventionalists from 38 countries completed the survey, most of whom (157/233 (67.4%)) had access to a simulator as a trainee, but only 15.3% used it frequently. Most participants (117/233 (50.2%)) considered currently available simulation tools relatively useful for endovascular UIA treatment, with greater value for trainees than for staff. Simulation of new devices (147/233 (63.1%)) and virtual practice runs in individual patient anatomy (119/233 (51.1%)) were considered most valuable for reducing endovascular UIA treatment complications.

Conclusion: Although neurointerventionalists perceived currently available simulation tools relatively useful, they did not use them regularly during their training. A priori testing of new devices and practice runs in individual patient anatomy in a virtual environment were thought to have the greatest potential for reducing endovascular UIA treatment complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/neurintsurg-2020-016343DOI Listing
March 2021

Therapeutic Hypothermia in Patients with Malignant Ischemic Stroke and Hemicraniectomy-A Systematic Review and Meta-analysis.

World Neurosurg 2020 09 19;141:e677-e685. Epub 2020 Jun 19.

Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Radiology Department, Hotchkiss Brain Institute, Calgary, Alberta, Canada; Department of Clinical Neurosciences, Calgary, Alberta, Canada. Electronic address:

Background: Therapeutic hypothermia (TH) offers cerebral protection following ischemic stroke and may improve outcomes in conjunction with decompressive hemicraniectomy (DHC). We aimed to assess the effectiveness of TH in patients with malignant ischemic stroke and DHC.

Methods: We performed a meta-analysis in patients with malignant ischemic stroke undergoing DHC comparing TH versus normothermia in studies published up to August 2019. Included studies had ≥10 adults with acute ischemic stroke. Primary outcome was functional independence, and secondary outcomes included complications. Effect size was pooled and described by relative risk (RR) ratios and 95% confidence intervals (CIs).

Results: Five studies (n = 269 patients; n = 130 TH, n = 139 controls) were included, 4 of which were prospective (n = 2 randomized controlled trials). Median achieved body temperature of TH was 33.6°C (range 33°C-35°C). Median modified Rankin Scale at the study completion was similar between TH and controls (RR 1.08, 95% CI 0.56-2.07, P = 0.8). Three studies reported individual patient modified Rankin Scale outcomes demonstrated a shift toward worse outcomes with TH (unadjusted common odds ratio 1.74; 95% CI 1.05-2.88, P = 0.01). Overall complications were similar between groups (RR 1.20, 95% CI 0.70-2.05, random effects P = 0.5). A suggestion of higher mortality was seen in TH (RR 1.50, 95% CI 0.97-2.32, P = 0.07).

Conclusions: Clinical and functional outcomes were not overall different between patients undergoing systemic TH and controls following DHC despite the shift toward worse outcomes with TH observed in some studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wneu.2020.05.277DOI Listing
September 2020

Therapeutic Hypothermia in Acute Ischemic Stroke-a Systematic Review and Meta-Analysis.

Curr Neurol Neurosci Rep 2020 05 5;20(5):13. Epub 2020 May 5.

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

Purpose Of Review: Therapeutic hypothermia (TH) in stroke demonstrates robust neuroprotection in animals but clinical applications remain controversial. We assessed current literature on the efficacy of TH in ischemic stroke.

Recent Findings: We conducted a meta-analysis comparing TH versus controls in studies published until June 2019. Controlled studies reporting on ≥ 10 adults with acute ischemic stroke were included. Primary outcome was functional independence (modified Rankin Scale [mRS] ≤ 2). Twelve studies (n = 351 TH, n = 427 controls) were included. Functional independence did not differ between groups (RR 1.17, 95% CI 0.93-1.46, random-effects p = 0.2). Five studies reported individual mRS outcomes and demonstrated a shift toward better outcome with TH (unadjusted cOR 1.57, 95% CI 1.01-2.44, p = 0.05). Overall complications were higher with TH (RR 1.18, 95% CI 1.06-1.32, p < 0.01). We did not observe an overall beneficial effect of TH in this analysis although some studies showed a shift toward better outcome. TH was associated with increased complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11910-020-01029-3DOI Listing
May 2020

Workflow patterns and potential for optimization in endovascular stroke treatment across the world: results from a multinational survey.

J Neurointerv Surg 2020 Dec 6;12(12):1194-1198. Epub 2020 Apr 6.

Diagnostic Imaging, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada

Background: The benefit of endovascular treatment (EVT) is highly time-dependent, and treatment delays reduce patients' chances to achieve a good outcome. In this survey-based study, we aimed to evaluate current in-hospital EVT workflow characteristics across different countries and hospital settings, and to quantify the time-savings that could be achieved by optimizing particular workflow steps.

Methods: In a multinational survey, neurointerventionalists were asked to provide specific information about EVT workflows in their current working environment. Workflow characteristics were summarized using descriptive statistics and stratified by country and physician characteristics, such as age, career stage, personal and institutional caseload.

Results: Among 248 respondents from 48 countries, pre-notification of the neurointerventional team was used in 70% of cases. The emergency department (ED) and CT scanner, and the CT scanner and neuroangiography suite, were on different floors in 23% and 38%, respectively. Redundant procedures in the ED were often routinely performed, such as chest x-rays (in 6%). General anesthesia was the most frequently used anesthesia protocol for EVT (42%), and an anesthesiologist was available in 82% for this purpose. 52% of the participants used a pre-prepared EVT kit.

Conclusion: The current structure of EVT workflows offers possibilities for improvement. While some bottlenecks, such as the spatial department set-up, cannot easily be resolved, pre-notification tools and pre-prepared EVT kits are more straightforward to implement and could help to reduce treatment delays, and thereby improve patient outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/neurintsurg-2020-015902DOI Listing
December 2020

Embolic Stroke of Undetermined Source and Symptomatic Nonstenotic Carotid Disease.

Stroke 2020 04 6;51(4):1321-1325. Epub 2020 Mar 6.

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

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.119.028853DOI Listing
April 2020

Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke (ESCAPE-NA1): a multicentre, double-blind, randomised controlled trial.

Lancet 2020 03 20;395(10227):878-887. Epub 2020 Feb 20.

McMaster University, Hamilton, ON, Canada.

Background: Nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, is a neuroprotectant that is effective in preclinical stroke models of ischaemia-reperfusion. In this trial, we assessed the efficacy and safety of nerinetide in human ischaemia-reperfusion that occurs with rapid endovascular thrombectomy in patients who had an acute ischaemic stroke.

Methods: For this multicentre, double-blind, randomised, placebo-controlled study done in 48 acute care hospitals in eight countries, we enrolled patients with acute ischaemic stroke due to large vessel occlusion within a 12 h treatment window. Eligible patients were aged 18 years or older with a disabling ischaemic stroke at the time of randomisation, had been functioning independently in the community before the stroke, had an Alberta Stroke Program Early CT Score (ASPECTS) greater than 4, and vascular imaging showing moderate-to-good collateral filling, as determined by multiphase CT angiography. Patients were randomly assigned (1:1) to receive intravenous nerinetide in a single dose of 2·6 mg/kg, up to a maximum dose of 270 mg, on the basis of estimated or actual weight (if known) or saline placebo by use of a real-time, dynamic, internet-based, stratified randomised minimisation procedure. Patients were stratified by intravenous alteplase treatment and declared endovascular device choice. All trial personnel and patients were masked to sequence and treatment allocation. All patients underwent endovascular thrombectomy and received alteplase in usual care when indicated. The primary outcome was a favourable functional outcome 90 days after randomisation, defined as a modified Rankin Scale (mRS) score of 0-2. Secondary outcomes were measures of neurological disability, functional independence in activities of daily living, excellent functional outcome (mRS 0-1), and mortality. The analysis was done in the intention-to-treat population and adjusted for age, sex, baseline National Institutes of Health Stroke Scale score, ASPECTS, occlusion location, site, alteplase use, and declared first device. The safety population included all patients who received any amount of study drug. This trial is registered with ClinicalTrials.gov, NCT02930018.

Findings: Between March 1, 2017, and Aug 12, 2019, 1105 patients were randomly assigned to receive nerinetide (n=549) or placebo (n=556). 337 (61·4%) of 549 patients with nerinetide and 329 (59·2%) of 556 with placebo achieved an mRS score of 0-2 at 90 days (adjusted risk ratio 1·04, 95% CI 0·96-1·14; p=0·35). Secondary outcomes were similar between groups. We observed evidence of treatment effect modification resulting in inhibition of treatment effect in patients receiving alteplase. Serious adverse events occurred equally between groups.

Interpretation: Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo.

Funding: Canadian Institutes for Health Research, Alberta Innovates, and NoNO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(20)30258-0DOI Listing
March 2020

Public Health and Cost Benefits of Successful Reperfusion After Thrombectomy for Stroke.

Stroke 2020 03 22;51(3):899-907. Epub 2020 Jan 22.

From the University of Calgary, Alberta, Canada (W.G.K., M.A.A., B.K.M., A.M.D., M.D.H., M.G.).

Background and Purpose- The benefit that endovascular thrombectomy offers to patients with stroke with large vessel occlusions depends strongly on reperfusion grade as defined by the expanded Thrombolysis in Cerebral Infarction (eTICI) scale. Our aim was to determine the lifetime health and cost consequences of the quality of reperfusion for patients, healthcare systems, and society. Methods- A Markov model estimated lifetime quality-adjusted life years (QALY) and lifetime costs of endovascular thrombectomy-treated patients with stroke based on eTICI grades. The analysis was performed over a lifetime horizon in a United States setting, adopting healthcare and societal perspectives. The reference case analysis was conducted for stroke at 65 years of age. National health and cost consequences of improved eTICI 2c/3 reperfusion rates were estimated. Input parameters were based on best available evidence. Results- Lifetime QALYs increased for every grade of improved reperfusion (median QALYs for eTICI 0/1: 2.62; eTICI 2a: 3.46; eTICI 2b: 5.42; eTICI 2c: 5.99; eTICI 3: 6.73). Achieving eTICI 3 over eTICI 2b reperfusion resulted on average in 1.31 incremental QALYs as well as healthcare and societal cost savings of $10 327 and $20 224 per patient. A 10% increase in the eTICI 2c/3 reperfusion rate of all annually endovascular thrombectomy-treated patients with stroke in the United States is estimated to yield additional 3656 QALYs and save $21.0 million and $36.8 million for the healthcare system and society, respectively. Conclusions- Improved reperfusion grants patients with stroke additional QALYs and leads to long-term cost savings. Procedural strategies to achieve complete reperfusion should be assessed for safety and feasibility, even when initial reperfusion seems to be adequate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.119.027874DOI Listing
March 2020

Therapeutic hypothermia in stroke: Quo Vadis?

Brain Circ 2019 Oct-Dec;5(4):157-159. Epub 2019 Dec 27.

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

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/bc.bc_62_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950514PMC
December 2019

Antiplatelet therapy for prevention of thromboembolic complications in coiling-only procedures for unruptured brain aneurysms.

J Neurointerv Surg 2020 Mar 20;12(3):298-302. Epub 2019 Sep 20.

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

Background And Purpose: Thromboembolic events are recognized complications of aneurysm coiling.

Objective: To identify any protective effects of antiplatelet therapy use before coiling of unruptured aneurysms.

Methods: We conducted a meta-analysis of clinical studies published up to February 2019. We included studies reporting symptomatic thromboembolic events (defined as clinical stroke or transient ischemic attacks) in patients who received antiplatelet therapy before coiling of unruptured aneurysms using unassisted coiling, balloon assistance, or multiple microcatheters. We excluded ruptured aneurysms and those treated with stent coiling or flow diverters.

Results: We identified 14 studies (2486 patients). All were single-center studies and four were prospective. In three studies with a control (no treatment) arm, the pooled risk ratio for symptomatic thromboembolic events with versus without antiplatelet therapy was 0.33 (95% CI 0.17 to 0.92, p= 0.035). The cumulative risk of symptomatic thromboembolic events with single antiplatelet agents was 5.0% '56/1122' (95% CI 1.6% to 8.4%, I83.63%), and with dual or multiple agents 2.7% '33/1237' (95% CI 1.0% to 3.0%, I39.9%). The incidence of diffusion lesions was reported in seven studies. It was 50.5% '96/190' (95% CI 7.3% to 93.9%, I94.4%) with single agents compared with 43.9% '196/446' (95% CI 25.9% to 61.9%, I73.4%) with dual or multiple agents.

Conclusion: Periprocedural antiplatelet therapy was associated with a low symptomatic thromboembolic event after coiling-only for unruptured aneurysms. However, available evidence is of limited quality with significant heterogeneity, requiring evidence from randomized controlled trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/neurintsurg-2019-015173DOI Listing
March 2020

Endovascular treatment decision in acute stroke: does physician gender matter? Insights from UNMASK EVT, an international, multidisciplinary survey.

J Neurointerv Surg 2020 Mar 30;12(3):256-259. Epub 2019 Jul 30.

Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.

Background And Purpose: Differences in the treatment practice of female and male physicians have been shown in several medical subspecialties. It is currently not known whether this also applies to endovascular stroke treatment. The purpose of this study was to explore whether there are differences in endovascular treatment decisions made by female and male stroke physicians and neurointerventionalists.

Methods: In an international survey, stroke physicians and neurointerventionalists were randomly assigned 10 case scenarios and asked how they would treat the patient: (A) assuming there were no external constraints and (B) given their local working conditions. Descriptive statistics were used to describe baseline demographics, and the adjusted OR for physician gender as a predictor of endovascular treatment decision was calculated using logistic regression.

Results: 607 physicians (97 women, 508 men, 2 who did not wish to declare) participated in this survey. Physician gender was neither a significant predictor for endovascular treatment decision under assumed ideal conditions (endovascular therapy was favored by 77.0% of female and 79.3% of male physicians, adjusted OR 1.03, P=0.806) nor under current local resources (endovascular therapy was favored by 69.1% of female and 76.9% of male physicians, adjusted OR 1.03, P=0.814).

Conclusion: Endovascular therapy decision making between male and female physicians did not differ under assumed ideal conditions or under current local resources.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/neurintsurg-2019-015003DOI Listing
March 2020

Therapeutic hypothermia: Applications in adults with acute ischemic stroke.

Brain Circ 2019 Apr-Jun;5(2):43-54. Epub 2019 Jun 27.

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

The advent of mechanical thrombectomy and increasing alteplase use have transformed the care of patients with acute ischemic stroke. Patients with major arterial occlusions with poor outcomes now have a chance of returning to independent living in more than half of the cases. However, many patients with these severe strokes suffer major disability despite these therapies. The search is ongoing for agents that can be combined with thrombectomy to achieve better recovery through halting infarct growth and mitigating injury after ischemic stroke. Several studies in animals and humans have demonstrated that therapeutic hypothermia (TH) offers potential to interrupt the ischemic cascade, reduce infarct volume, and improve functional independence. We performed a literature search to look up recent advances in the use of TH surrounding the science, efficacy, and feasibility of inducing TH in modern stroke treatments. While protocols remain controversial, there is a real opportunity to combine TH with the existing therapies to improve outcome in adults with acute ischemic stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/bc.bc_5_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6611191PMC
June 2019

Time of day and endovascular treatment decision in acute stroke with relative endovascular treatment indication: insights from UNMASK EVT international survey.

J Neurointerv Surg 2020 Feb 8;12(2):122-126. Epub 2019 Jul 8.

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

Background And Purpose: The decision to proceed with endovascular thrombectomy should ideally be made independent of inconvenience factors, such as daytime. We assessed the influence of patient presentation time on endovascular therapy decision making under current local resources and assumed ideal conditions in acute ischemic stroke with level 2B evidence for endovascular treatment.

Methods And Materials: In an international cross sectional survey, 607 stroke physicians from 38 countries were asked to give their treatment decisions to 10 out of 22 randomly assigned case scenarios. Eleven scenarios had level 2B evidence for endovascular treatment: 7 daytime scenarios (7:00 am-5:00 pm) and four night time cases (5:01 pm- 6:59 am). Participants provided their treatment approach assuming (A) there were no practice constraints and (B) under their current local resources. Endovascular treatment decisions in the 11 scenarios were analyzed according to presentation time with adjustment for patient and physician characteristics.

Results: Participants selected endovascular therapy in 74.2% under assumed ideal conditions, and 70.7% under their current local resources of night time scenarios, and in 67.2% and 63.8% of daytime scenarios. Night time presentation did not increase the probability of a treatment decision against endovascular therapy under current local resources or assumed ideal conditions.

Conclusion: Presentation time did not influence endovascular treatment decision making in stroke patients in this international survey.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/neurintsurg-2019-014976DOI Listing
February 2020

Outcome of intracranial flow diversion according to the antiplatelet regimen used: a systematic review and meta-analysis.

J Neurointerv Surg 2020 Feb 4;12(2):148-155. Epub 2019 Jul 4.

Clinical Neuroscience, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada.

Background: Thromboembolic complications are not uncommon in patients undergoing neurointerventional procedures. The use of flow diverting stents is associated with higher risks of these complications despite current dual antiplatelet regimens.

Objective: To explore contemporary evidence on the safety of emerging dual antiplatelet regimens in flow diverting stenting procedures.

Methods: We performed a systematic review and meta-analysis to identify relevant articles in electronic databases, and relevant references. Studies reporting the complications and mortality of flow diverting stenting procedures using acetyl salicylic acid (ASA) + ticagrelor or ASA + prasugrel compared with ASA + clopidogrel were included.

Results: Of 452 potentially relevant studies, we identified 49 studies (2526 patients) which reported the safety of ticagrelor or prasugrel for pooled analysis, and five studies (1005 patients) for meta-analysis. The pooled overall mortality in all studies was 2.14%, ischemic complications 6.89%, and hemorrhagic complications 3.68%. The use of ticagrelor or prasugrel was associated with a lower risk of mortality compared with clopidogrel (RR=4.57, 95% CI 1.23 to 16.99; p=0.02). Considering ischemic events, ASA + clopidogrel was as safe as ASA + prasugrel (RR=0.55, 95% CI 0.11 to 2.74; p=0.47) and ASA + ticagrelor (RR=0.74, 95% CI 0.32 to 1.74; p=0.49). ASA +ticagrelor was not associated with a higher risk of hemorrhagic complications (RR=0.92, 95% CI 0.27 to 3.16; p=0.89).

Conclusions: Evidence suggests that dual antiplatelet regimens including ticagrelor or prasugrel are safe for patients undergoing flow diversion procedures. Regimens using ticagrelor were associated with better survival than those using clopidogrel in the included studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/neurintsurg-2019-014996DOI Listing
February 2020

Stroke Laterality Did Not Modify Outcomes in the HERMES Meta-Analysis of Individual Patient Data of 7 Trials.

Stroke 2019 08 5;50(8):2118-2124. Epub 2019 Jul 5.

Departments of Clinical Neurosciences and Radiology (M. Goyal), Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Canada.

Background and Purpose- There is contradictory evidence on the impact of the stroke side (hemisphere) on outcomes. We investigated any effect modification by laterality on stroke patients' outcomes in recent endovascular trials. Methods- Individual patient-level data were combined in this meta-analysis of all patients included in randomized trials comparing endovascular thrombectomy predominantly done with stent retrievers with standard care in anterior circulation ischemic patients with stroke (HERMES [Highly Effective Reperfusion Using Multiple Endovascular Devices] Collaboration). We stratified the 90-day functional outcome assessed by ordinal analysis of the modified Rankin Scale according to the stroke side of patients treated with endovascular therapy versus standard care, adjusted for important prognostic variables. Results- The meta-analysis included 1737 patients (871 right hemispheric strokes and 866 left hemispheric) from 7 trials. Baseline median National Institutes of Health Stroke Scale scores were significantly higher in left (20) versus right (16) hemispheric strokes (P<0.001). Other clinical and radiological baseline characteristics were similar. The beneficial response to endovascular therapy assessed by 90-day modified Rankin Scale shift was not modified by the side of the stroke. There were no significant differences between right and left hemispheric stroke in the 90-day functional outcome (modified Rankin Scale score ≤2; 40.7% [95% CI, 37.4%-44.1%] versus 37.6% [95% CI, 37.4%-44.1%]; P=0.19), median final infarct volumes (45 versus 39.5 mL, P=0.51), nor 90-day mortality (15.1% vs 16.8%, P=0.31). Conclusions- Stroke side was not a prognostic factor and did not modify the treatment effect among patients treated in the endovascular or control groups in recent endovascular thrombectomy trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.118.023102DOI Listing
August 2019