Trial of Endovascular Therapy for Acute Ischemic Stroke with Large Infarct.

BACKGROUND: The role of endovascular therapy for acute stroke with a large infarction has not been extensively studied in differing populations. METHODS: We conducted a multicenter, prospective, open-label, randomized trial in China involving patients with acute large-vessel occlusion in the anterior circulation and an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower values indicating larger infarction) or an infarct-core volume of 70 to 100 ml. Patients were randomly assigned in a 1:1 ratio within 24 hours from the time they were last known to be well to undergo endovascular therapy and receive medical management or to receive medical management alone. The primary outcome was the score on the modified Rankin scale at 90 days (scores range from 0 to 6, with higher scores indicating greater disability), and the primary objective was to determine whether a shift in the distribution of the scores on the modified Rankin scale at 90 days had occurred between the two groups. Secondary outcomes included scores of 0 to 2 and 0 to 3 on the modified Rankin scale. The primary safety outcome was symptomatic intracranial hemorrhage within 48 hours after randomization. RESULTS: A total of 456 patients were enrolled; 231 were assigned to the endovascular-therapy group and 225 to the medical-management group. Approximately 28% of the patients in both groups received intravenous thrombolysis. The trial was stopped early owing to the efficacy of endovascular therapy after the second interim analysis. At 90 days, a shift in the distribution of scores on the modified Rankin scale toward better outcomes was observed in favor of endovascular therapy over medical management alone (generalized odds ratio, 1.37; 95% confidence interval, 1.11 to 1.69; P = 0.004). Symptomatic intracranial hemorrhage occurred in 14 of 230 patients (6.1%) in the endovascular-therapy group and in 6 of 225 patients (2.7%) in the medical-management group; any intracranial hemorrhage occurred in 113 (49.1%) and 39 (17.3%), respectively. Results for the secondary outcomes generally supported those of the primary analysis. CONCLUSIONS: In a trial conducted in China, patients with large cerebral infarctions had better outcomes with endovascular therapy administered within 24 hours than with medical management alone but had more intracranial hemorrhages. (Funded by Covidien Healthcare International Trading [Shanghai] and others; ANGEL-ASPECT ClinicalTrials.gov number, NCT04551664.).

Does ASTRAL score at hospital admission predict symptomatic haemorrhagic transformation in acute ischaemic stroke after revascularisation? A pilot single-centre study.

INTRODUCTION: Accurately predicting outcomes after acute ischaemic stroke (AIS) is a major clinical goal. The aim of this pilot study was to evaluate the prognostic validity and accuracy of the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) score in predicting symptomatic haemorrhagic transformation (sHT) in patients with AIS who have undergone revascularisation. MATERIAL AND METHODS: Consecutive patients hospitalised for AIS who underwent treatment with intravenous thrombolysis (IVT) and/or mechanical thrombectomy (MT) were identified, and their ASTRAL scores at hospital admission were estimated. The study endpoint was sHT within 24 hours of stroke onset. The predictive performance of the ASTRAL score was investigated through logistic regression analysis and discrimination and calibration tests. RESULTS: Sixty-eight AIS patients, with a median age of 69 (58-79) years, were included. sHT occurred in 20 (29.4%) of the 68 patients. The ASTRAL score was significantly higher in patients who developed sHT compared to non-sHT patients [36 (34-38) versus 24 (17-32); p<0.001]. The ASTRAL score was an independent predictor of sHT, and showed good discriminative power (area under the curve 0.88; 95% confidence interval, 0.789-0.965). CONCLUSIONS AND CLINICAL IMPLICATIONS: ASTRAL score is an independent predictor of sHT and shows high predictive accuracy in patients with AIS. Future studies are warranted to confirm these results.

Shortening door-to-puncture time and improving patient outcome with workflow optimization in patients with acute ischemic stroke associated with large vessel occlusion.

OBJECTIVE: We aimed to evaluate door-to-puncture time (DPT) and door-to-recanalization time (DRT) without directing healthcare by neuro-interventionalist support in the emergency department (ED) by workflow optimization and improving patients' outcomes. METHODS: Records of 98 consecutive ischemic stroke patients who had undergone endovascular therapy (EVT) between 2018 to 2021 were retrospectively reviewed in a single-center study. Patients were divided into three groups: pre-intervention (2018-2019), interim-intervention (2020), and post-intervention (January 1st 2021 to August 16th, 2021). We compared door-to-puncture time, door-to-recanalization time (DRT), puncture-to-recanalization time (PRT), last known normal time to-puncture time (LKNPT), and patient outcomes (measured by 3 months modified Rankin Scale) between three groups using descriptive statistics. RESULTS: Our findings indicate that process optimization measures could shorten DPT, DRT, PRT, and LKNPT. Median LKNPT was shortened by 70 min from 325 to 255 min(P < 0.05), and DPT was shortened by 119 min from 237 to 118 min. DRT shortened by 132 min from 338 to 206 min, and PRT shortened by 33 min from 92 to 59 min from the pre-intervention to post-intervention groups (all P < 0.05). Only 21.4% of patients had a favorable outcome in the pre-intervention group as compared to 55.6% in the interventional group (P= 0.026). CONCLUSION: This study demonstrated that multidisciplinary cooperation was associated with shortened DPT, DRT, PRT, and LKNPT despite challenges posed to the healthcare system such as the COVID-19 pandemic. These practice paradigms may be transported to other stroke centers and healthcare providers to improve endovascular time metrics and patient outcomes.

Comparison of COVID-19 patients who underwent thrombectomy with those in the pre-pandemic period in terms of etiology and prognosis.

OBJECTIVE: We aimed at determining the effectiveness of mechanical thrombectomy (MT) in patients with major vessel occlusion and infected with COVID-19, evaluating its clinical outcome and comparing it with non-COVID patients. PATIENTS AND METHODS: During the pandemic, 729 patients who underwent MT in stroke centers due to Acute Ischemic Stroke (AIS) with large vessel occlusion were evaluated. This study included 40 patients with a confirmed COVID-19 diagnosis by a positive PCR test between March 11, 2020, and December 31, 2020. These patients were compared to 409 patients who underwent MT due to major vessel occlusion between March 11, 2019, and December 31, 2019. RESULTS: Of the patients with AIS who are infected with COVID-19, 62.5% were males, and all patients have a median age of 63.5 ± 14.4 years. The median NIHSS score of the COVID-19 group was significantly higher than that of the non-COVID-19 groups. Dissection was significantly more in the COVID-19 group. The mortality rates at 3 months were higher in the COVID-19 groups compared to non-COVID-19 groups. CONCLUSIONS: This study revealed an increased frequency of dissection in patients with COVID-19. COVID-19-related ischemic strokes are associated with worse functional outcomes and higher mortality rates than non-COVID-19 ischemic strokes.

Mechanical thrombectomy in COVID-19-associated ischaemic stroke: patient characteristics and outcomes in a single-centre study.

INTRODUCTION: The aim of this study was to assess the clinical profiles and outcomes of patients with confirmed COVID-19 infection and acute ischaemic stroke (AIS) treated with mechanical thrombectomy (MT) at the Comprehensive Stroke Centre (CSC) of the University Hospital in Krakow. CLINICAL RATIONALE FOR THE STUDY: COVID-19 is a risk factor for AIS and worsens prognosis in patients with large artery occlusions. During the pandemic, the global number of MT has dropped. At the same time, studies assessing outcomes of this treatment in COVID-19-associated AIS have produced divergent results. MATERIAL AND METHODS: In this single-centre study, we retrospectively analysed and compared the clinical profiles (age, sex, presence of cardiovascular risk factors, neurological deficit at admission), stroke size (measured using postprocessing analysis of perfusion CT with RAPID software), time from stroke onset to arrival at the CSC, time from arrival at the CSC to groin puncture, treatment with intravenous thrombolysis, length of hospitalisation, laboratory test results, and short-term outcomes (measured with Thrombolysis in Cerebral Infarction scale, modified Rankin Scale and National Health Institute Stroke Scale) in patients with AIS treated with MT during the pandemic. A comparison between patients with and without concomitant SARS-CoV2 infection was then performed. RESULTS: There were no statistically significant differences between 15 COVID (+) and 167 COVID (-) AIS patients treated with AIS with respect to clinical profiles (p > 0.05), stroke size (p > 0.05) or outcomes (NIHSS at discharge, 8.1 (SD = 7.1) vs. 8.8 (SD = 9.6), p = 0.778, mRS at discharge 2.9 (SD = 2) vs. 3.1 (SD = 2.1), p = 0.817, death rate 6.7% vs. 12.6%, p = 0.699). There was a significant difference between patients with and without COVID-19 concerning time from arrival at the CSC to groin puncture [104.27 (SD = 51.47) vs. 97.63 (SD = 156.94) min., p = 0.044] and the length of hospitalisation [23.7 (SD = 11.9) vs. 10.5 (SD = 6.9) days, p < 0.001]. CONCLUSION: In AIS patients treated with MT, concomitant SARS-CoV2 infection did not affect the outcome. Our observations need to be confirmed in larger, and preferably multicentre, studies.

Effect of Intra-arterial Alteplase vs Placebo Following Successful Thrombectomy on Functional Outcomes in Patients With Large Vessel Occlusion Acute Ischemic Stroke: The CHOICE Randomized Clinical Trial.

Importance: It is estimated that only 27% of patients with acute ischemic stroke and large vessel occlusion who undergo successful reperfusion after mechanical thrombectomy are disability free at 90 days. An incomplete microcirculatory reperfusion might contribute to these suboptimal clinical benefits. Objective: To investigate whether treatment with adjunct intra-arterial alteplase after thrombectomy improves outcomes following reperfusion. Design, Setting, and Participants: Phase 2b randomized, double-blind, placebo-controlled trial performed from December 2018 through May 2021 in 7 stroke centers in Catalonia, Spain. The study included 121 patients with large vessel occlusion acute ischemic stroke treated with thrombectomy within 24 hours after stroke onset and with an expanded Treatment in Cerebral Ischemia angiographic score of 2b50 to 3. Interventions: Participants were randomized to receive intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) infused over 15 to 30 minutes (n = 61) or placebo (n = 52). Main Outcomes and Measures: The primary outcome was the difference in proportion of patients achieving a score of 0 or 1 on the 90-day modified Rankin Scale (range, 0 [no symptoms] to 6 [death]) in all patients treated as randomized. Safety outcomes included rate of symptomatic intracranial hemorrhage and death. Results: The study was terminated early for inability to maintain placebo availability and enrollment rate because of the COVID-19 pandemic. Of 1825 patients with acute ischemic stroke treated with thrombectomy at the 7 study sites, 748 (41%) patients fulfilled the angiographic criteria, 121 (7%) patients were randomized (mean age, 70.6 [SD, 13.7] years; 57 women [47%]), and 113 (6%) were treated as randomized. The proportion of participants with a modified Rankin Scale score of 0 or 1 at 90 days was 59.0% (36/61) with alteplase and 40.4% (21/52) with placebo (adjusted risk difference, 18.4%; 95% CI, 0.3%-36.4%; P = .047). The proportion of patients with symptomatic intracranial hemorrhage within 24 hours was 0% with alteplase and 3.8% with placebo (risk difference, -3.8%; 95% CI, -13.2% to 2.5%). Ninety-day mortality was 8% with alteplase and 15% with placebo (risk difference, -7.2%; 95% CI, -19.2% to 4.8%). Conclusions and Relevance: Among patients with large vessel occlusion acute ischemic stroke and successful reperfusion following thrombectomy, the use of adjunct intra-arterial alteplase compared with placebo resulted in a greater likelihood of excellent neurological outcome at 90 days. However, because of study limitations, these findings should be interpreted as preliminary and require replication. Trial Registration: ClinicalTrials.gov Identifier: NCT03876119; EudraCT Number: 2018-002195-40.

Mechanical thrombectomy for acute ischemic stroke in COVID-19 patients: multicenter experience in 111 cases.

BACKGROUND: Data on the frequency and outcome of mechanical thrombectomy (MT) for large vessel occlusion (LVO) in patients with COVID-19 is limited. Addressing this subject, we report our multicenter experience. METHODS: A retrospective cohort study was performed of consecutive acute stroke patients with COVID-19 infection treated with MT at 26 tertiary care centers between January 2020 and November 2021. Baseline demographics, angiographic outcome and clinical outcome evaluated by the modified Rankin Scale (mRS) at discharge and 90 days were noted. RESULTS: We identified 111 out of 11 365 (1%) patients with acute or subsided COVID-19 infection who underwent MT due to LVO. Cardioembolic events were the most common etiology for LVO (38.7%). Median baseline National Institutes of Health Stroke Scale score and Alberta Stroke Program Early CT Score were 16 (IQR 11.5-20) and 9 (IQR 7-10), respectively. Successful reperfusion (mTICI ≥2b) was achieved in 97/111 (87.4%) patients and 46/111 (41.4%) patients were reperfused completely. The procedure-related complication rate was 12.6% (14/111). Functional independence was achieved in 20/108 (18.5%) patients at discharge and 14/66 (21.2%) at 90 days follow-up. The in-hospital mortality rate was 30.6% (33/108). In the subgroup analysis, patients with severe acute COVID-19 infection requiring intubation had a mortality rate twice as high as patients with mild or moderate acute COVID-19 infection. Acute respiratory failure requiring ventilation and time interval from symptom onset to groin puncture were independent predictors for an unfavorable outcome in a logistic regression analysis. CONCLUSION: Our study showed a poor clinical outcome and high mortality, especially in patients with severe acute COVID-19 infection undergoing MT due to LVO.

COVID-19 and supra-aortic trunks disease: review of literature about critical phase and sequelae.

The acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 disease, a global pandemic. A strong association has been documented between COVID-19 and cardiovascular events, although the exact pathophysiological mechanism is still unclear. Carotid atherothrombosis and ischemic stroke represents one of the possible severe manifestations of COVID-19, as a leading cause of long-term disability and death. Different complex intertwined mechanisms seem to underlie the endothelitis which is the cause of multiple cardiovascular manifestations. To date, few case series describing COVID-19 and acute ischemic stroke caused by cervical carotid thrombosis have been published. All the patients shared common similar radiographic features, comorbidities, and biomarker profiles. The aim of this brief review was to analyze the impact of COVID-19 pandemic in the management of a Vascular Surgery Department, changing the daily vascular practice, as well as to provide practical suggestions for symptomatic carotid stenosis, while reviewing published literature.

Management of endovascular therapy for acute ischemic stroke amid the COVID-2019 pandemic: a multicenter survey in China.

Objectives: The impact of COVID-19 pandemic on endovascular therapy (EVT) for acute ischemic stroke in China is unknown. This study was aimed to verify the volume change of EVT for acute ischemic stroke affected by COVID-19 and its potential factors.Methods: This cross-sectional study was conducted via an online questionnaire survey in China. The questionnaire was mainly composed of descriptive information, volume change of EVT for acute ischemic stroke, and the protection status of medical staff.Results: A total of 103 stroke physicians in 28 provinces across China completed the survey questionnaire. A volume decline in EVT for acute stroke occurred in 93 (90.3%) hospitals after lockdown (23 January 2020). Nearly half of the hospitals (51/103, 49.5%) experienced a volume decline of EVT case more than 50% and 14 (13.6%) hospitals completely ceased offering EVT. Hospitals with decline >50% of EVT case had higher proportion of hospitals with a designated area for COVID-19 screening in the emergency room (44/51, 86.3% vs 34/52, 65.4%, p= 0.01) and medical staff in quarantine (19/51, 37.3% vs 7/52, 13.5%, p< 0.01), with lower proportion of hospitals with personal protective equipment protocol (41/51, 80.4% vs 49/52, 94.2%, p= 0.03) than hospitals with decline ≤50%.Conclusions: The volume of EVT for acute ischemic stroke severely declined after lockdown in China. Designating a specific area for COVID-19 screening, insufficient personal protection and understaffing may exacerbate the volume decline of EVT.

COVID-19 and Changes in Neurosurgical Workload in the United Kingdom.

BACKGROUND: Cessation of elective procedures and lower bed capacity during the COVID-19 pandemic have led to a rise in the waiting lists for surgery, but it is unclear if workload has recovered sufficiently to account for this backlog. We describe the change in neurosurgical workload at a tertiary neurosciences center in the United Kingdom after the first pandemic wave in comparison with the months before and during the first wave. METHODS: A retrospective review of theatre records and electronic referrals-between December 1, 2019, and August 31, 2020-was performed. The months of December 2019-February 2020 were designated as pre-COVID months and March-May 2020 were designated as COVID months. The time period from June to August 2020 was designated as post-wave months. Statistical analyses were performed on SPSS v22 (IBM). RESULTS: Referrals declined from 572 in January to a nadir of 352 in April before a steady rise to August. Referral volumes for degenerative spinal disease and traumatic brain injuries showed a statistically significant change during the year. On average, 212 procedures per month were performed in the pre-COVID months, 167 procedures per month during COVID months, and 232 procedures per month in the post-wave months. The number of patients on the waiting list for scheduled operations rose from March (785 patients) onward to a peak of 997 patients in July. CONCLUSIONS: In the aftermath of COVID-19, higher referral volumes and operative procedures were apparent in the post-wave months as services returned to normal. With the expectation of a second wave of infections, it is unclear whether this will be sustainable.

European Multicenter Study of ET-COVID-19.

BACKGROUND AND PURPOSE: Acute ischemic stroke and large vessel occlusion can be concurrent with the coronavirus disease 2019 (COVID-19) infection. Outcomes after mechanical thrombectomy (MT) for large vessel occlusion in patients with COVID-19 are substantially unknown. Our aim was to study early outcomes after MT in patients with COVID-19. METHODS: Multicenter, European, cohort study involving 34 stroke centers in France, Italy, Spain, and Belgium. Data were collected between March 1, 2020 and May 5, 2020. Consecutive laboratory-confirmed COVID-19 cases with large vessel occlusion, who were treated with MT, were included. Primary investigated outcome: 30-day mortality. SECONDARY OUTCOMES: early neurological improvement (National Institutes of Health Stroke Scale improvement ≥8 points or 24 hours National Institutes of Health Stroke Scale 0-1), successful reperfusion (modified Thrombolysis in Cerebral Infarction grade ≥2b), and symptomatic intracranial hemorrhage. RESULTS: We evaluated 93 patients with COVID-19 with large vessel occlusion who underwent MT (median age, 71 years [interquartile range, 59-79]; 63 men [67.7%]). Median pretreatment National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT Score were 17 (interquartile range, 11-21) and 8 (interquartile range, 7-9), respectively. Anterior circulation acute ischemic stroke represented 93.5% of cases. The rate modified Thrombolysis in Cerebral Infarction 2b to 3 was 79.6% (74 patients [95% CI, 71.3-87.8]). Thirty-day mortality was 29% (27 patients [95% CI, 20-39.4]). Early neurological improvement was 19.5% (17 patients [95% CI, 11.8-29.5]), and symptomatic intracranial hemorrhage was 5.4% (5 patients [95% CI, 1.7-12.1]). Patients who died at 30 days exhibited significantly lower lymphocyte count, higher levels of aspartate, and LDH (lactate dehydrogenase). After adjustment for age, initial National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, and successful reperfusion, these biological markers remained associated with increased odds of 30-day mortality (adjusted odds ratio of 2.70 [95% CI, 1.21-5.98] per SD-log decrease in lymphocyte count, 2.66 [95% CI, 1.22-5.77] per SD-log increase in aspartate, and 4.30 [95% CI, 1.43-12.91] per SD-log increase in LDH). CONCLUSIONS: The 29% rate of 30-day mortality after MT among patients with COVID-19 is not negligible. Abnormalities of lymphocyte count, LDH and aspartate may depict a patient's profiles with poorer outcomes after MT. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT04406090.

Emergent Carotid Artery Stenting Following Intravenous Alteplase Infusion After Rapid Negative Diagnosis for COVID-19 by Loop-Mediated Isothermal Amplification Assay.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, a rapid screening method for COVID-19 detection is needed to decide the appropriate strategy to treat stroke patients. In acute ischemic stroke treatment, the efficacy and safety of emergent carotid artery stenting (eCAS) for hyperacute ischemic stroke (hAIS) due to internal carotid artery stenosis (ICS) have not been sufficiently established. CASE DESCRIPTION: A 71-year-old man with hAIS caused by severe ICS was treated via intravenous alteplase infusion. The patient underwent screening for COVID-19 by the loop-mediated isothermal amplification (LAMP) assay shortly after arrival at our institution. The LAMP result was obtained within 90 minutes, during intravenous alteplase infusion, and turned out to be negative. The symptom of hemiplegia worsened during alteplase infusion, and he, therefore, underwent eCAS after administration of aspirin (200 mg). Recanalization was achieved successfully by eCAS, and dual antiplatelet therapy and argatroban were administrated following eCAS. Hemorrhagic complications or restenosis/occlusion of the carotid artery were not observed. He was discharged without neurologic deficits 15 days following eCAS. Because of the rapid negative diagnosis for COVID-19 using the LAMP method, eCAS could be performed following standard procedures, along with infectious defense, without delay. CONCLUSIONS: This case report suggests that eCAS for hAIS due to ICS following intravenous alteplase can be an effective treatment, along with appropriate antiplatelet medication and management in select patients. During the COVID-19 pandemic, the LAMP assay for COVID-19 detection might be a suitable diagnostic strategy preceding stroke treatment because of the rapid turnaround time.