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Background and ObjectivesCOVID-19–related inflammation, endothelial dysfunction, and coagulopathy may increase the bleeding risk and lower the efficacy of revascularization treatments in patients with acute ischemic stroke (AIS). We aimed to evaluate the safety and outcomes of revascularization treatments in patients with AIS and COVID-19.MethodsThis was a retrospective multicenter cohort study of consecutive patients with AIS receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021 tested for severe acute respiratory syndrome coronavirus 2 infection. With a doubly robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes. Subgroup analyses were performed according to treatment groups (IVT-only and EVT).ResultsOf a total of 15,128 included patients from 105 centers, 853 (5.6%) were diagnosed with COVID-19; of those, 5,848 (38.7%) patients received IVT-only and 9,280 (61.3%) EVT (with or without IVT). Patients with COVID-19 had a higher rate of symptomatic intracerebral hemorrhage (SICH) (adjusted OR 1.53; 95% CI 1.16–2.01), symptomatic subarachnoid hemorrhage (SSAH) (OR 1.80; 95% CI 1.20–2.69), SICH and/or SSAH combined (OR 1.56; 95% CI 1.23–1.99), 24-hour mortality (OR 2.47; 95% CI 1.58–3.86), and 3-month mortality (OR 1.88; 95% CI 1.52–2.33). Patients with COVID-19 also had an unfavorable shift in the distribution of the modified Rankin score at 3 months (OR 1.42; 95% CI 1.26–1.60).DiscussionPatients with AIS and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non–COVID-19 patients receiving treatment. Current available data do not allow direct conclusions to be drawn on the effectiveness of revascularization treatments in patients with COVID-19 or to establish different treatment recommendations in this subgroup of patients with ischemic stroke. Our findings can be taken into consideration for treatment decisions, patient monitoring, and establishing prognosis.Trial Registration InformationThe study was registered under ClinicalTrials.gov identifierNCT04895462.

OBJECTIVES: Standard medical management of spontaneous intracerebral haemorrhage (ICH) and surgical hematoma evacuation starkly differ, and whilst landmark randomised control trials report no clinical benefit of early surgical evacuation compared with medical treatment in supratentorial ICH, minimally invasive surgery (MIS) with thrombolysis has been neglected within these studies. However, recent technological advancements in MIS have renewed interest in the surgical treatment of ICH. Several economic evaluations have focused on the benefits of MIS in ischaemic stroke management, but no economic evaluations have yet been performed comparing MIS to standard medical treatment for ICH.MATERIALS AND METHOD: All costs were sourced from the UK in GBP. Where possible, the 2019/2020 NHS reference costs were used. The MISTIE III study was used to analyse the outcomes of patients undergoing either MIS or standard medical treatment in this economic evaluation.RESULTS: The incremental cost-effectiveness ratio (ICER) for MIS was £485,240.26 for every quality-adjusted life year (QALY) gained. Although MIS resulted in a higher QALY compared to medical treatment, the gain was insignificant at 0.011 QALY. Four sensitivity analyses based on combinations of alternative EQ-5D values and categorisation of MIS outcomes, alongside alterations to the cost of significant adverse events, were performed to check the robustness of the ICER calculation. The most realistic sensitivity analysis showed a potential increase in cost effectiveness when clot size is reduced to DISCUSSION: From the perspective of the NHS, MIS with thrombolysis is not cost-effective compared to optimal medical treatment. ICER shows that intention-to-treat MIS would require a cost of £485,240.26 to gain one extra QALY, which is significantly above the NHS threshold of £30,000. Further UK studies with ICH survivor utilities, more replicable surgical technique, and the reporting of clot size reduction are indicated as the present sensitivity analysis suggests that MIS is promising. Greater detail about outcomes and complications would ensure improved cost-benefit analyses and support valid and efficient allocation of resources by the NHS.

Objectives: There is a paucity of data on the risk of nursing home admission or domiciliary care initiation according to time to intravenous thrombolysis for ischemic stroke. We investigated the association between time to intravenous thrombolysis and the composite of nursing home admission or domiciliary care initiation in patients with acute ischemic stroke. Materials and Methods: In this nationwide cohort study, all stroke patients treated with intravenous thrombolysis (2011–2015) and alive at discharge were identified from the Danish Stroke Registry and other nationwide registries. The composite of nursing home admission or domiciliary care initiation one year post-discharge according to time to thrombolysis was examined with multivariable Cox regression. Results: The study population comprised 4,349 patients (median age 67 years [25th-75th percentile 57–75], 65.2% men). The median National Institutes of Health Stroke Scale score at presentation was 5, and the median time from symptom-onset to initiation of thrombolysis was 143 min. The absolute 1-year risk of the composite endpoint was 14.0% (95%CI, 11.5–16.8%) in the ≤90 min group, 16.6% (15.1–18.1%) in the 91–180min group, and 16.0% (14.0–18.2%) in the 181–270 min group. Compared with thrombolysis ≤90 min, time to thrombolysis between 91–180 min and 181–270 min was associated with a significantly higher risk of the composite endpoint (hazard ratio 1.31 [1.04–1.65] and 1.47 [1.14–1.91], respectively). Conclusions: In patients admitted with ischemic stroke, increasing time to thrombolysis was associated with a greater risk of the composite of nursing home admission or domiciliary care initiation. Continued efforts to shorten the time delay from symptom-onset to initiation of thrombolysis are warranted.

Intravenous thrombolysis and endovascular therapy (IVT/EVT) are evidence-based treatments for adults with arterial ischemic stroke (AIS). However, randomized controlled trials in pediatric patients are lacking. This study aimed to describe feasibility, safety, and outcome of IVT/EVT in children with AIS.This retrospective study (01/2000-12/2015) included a multicenter, population-based consecutive cohort of patients aged 1 month to 16 years, diagnosed with AIS and presenting with pediatric National Institutes of Health Stroke Scale (pedNIHSS) ≥ 4. Clinical and radiological data of patients receiving IVT/EVT were compared to those receiving standard care (SC) using linear regression to adjust for potential confounders. EVT included intra-arterial thrombolysis and/or mechanical thrombectomy. Outcome was assessed 6 months after stroke using the pediatric stroke outcome measure (PSOM).Overall, 150 patients (age 7.1 ± 4.9 years, 55 [37%] females) presented with pedNIHSS ≥ 4. Recanalization treatment was performed in 16 (11%), of whom 5 (3%) were treated with IVT and 11 (7%) with EVT. Patients receiving recanalization treatment were older (mean age = 11.0 vs 6.9 years, p = 0.01) and more severely affected (median pedNIHSS = 13.5 vs 8.0, p 0.001). Death and bleeding complications did not differ between the 2 groups. Median (interquartile range) PSOM 6 months after AIS was 2.5 (1-4.3) and 1 (0-2) in the IVT/EVT and SC groups, respectively (p = 0.014). However, after multiple linear regression analysis, only higher baseline pedNIHSS remained associated with an unfavorable outcome (p 0.001).Recanalization treatment is feasible and seems to be safe in severely affected pediatric AIS patients. The assessment of efficacy of IVT/EVT in pediatric stroke patients requires larger studies. Ann Neurol 2018;83:1125-1132.

Thrombolytic therapy involves thrombolytic agents administered to patients suffering from venous or arterial thrombosis. The therapy induces systemic effects interrelated with the thrombolytic agent used. Bleeding is a prominent complication of thrombolytic therapy. Exhaustion of coagulation factors, generation of excessive amounts of fibrin degradation products (FDPs), therapy-induced activation of coagulation, therapy-induced anticoagulation, and formation of new fibrin all illustrate the complexity of effects of the treatment and challenges the hemostatic balance in the patients. The therapy-induced effects can be modulated by parallel administration of anticoagulants. Risk assessment is mandatory prior to thrombolytic therapy. Anticoagulated and unconscious patients represent particular safety concerns, and should be fully evaluated. Several guidelines describe the choice of tests and their safety limits in relation to pretreatment evaluation of anticoagulated patients. Fibrinogen depletion and FDPs during treatment may be promising markers for the evaluation of bleeding risk posttreatment. Future risk assessment measures should focus on the dynamics of the hemostatic balance. Here, thromboelastography may be considered a tool addressing clot formation, fibrin structure, and fibrinolytic resistance in parallel. Suitable laboratory analysis performed shortly after treatment may help to recognize severe treatment-induced systemic effects that can be counteracted by rational treatment, thereby reducing bleeding risk.

Intramural dissecting hematoma is an unusual esophageal condition with a threatening presentation but excellent prognosis when managed conservatively.We report the case of an 88-year-old woman who developed an intramural hematoma of the esophagus after intravenous thrombolysis for an acute ischemic stroke. Before thrombolysis, nasogastric intubation was attempted unsuccessfully. She was kept on nil by mouth, intravenous hydration, proton pump inhibitor, antiemetics,and an antibiotic initiated 2 days before for periodontal disease. The esophageal hematoma regressed, and she resumed oral diet asymptomatically.To our knowledge, this is the first report of this type of lesion after thrombolysis for an ischemic stroke. A brief discussion and literature review are presented.

Seizures appear at stroke presentation, during the acute phase or as a late complication of stroke. Thrombolysis has not been investigated as a risk factor despite its potential neurotoxic effect. We try to identify risk factors for seizures during the acute phase of ischemic stroke in a cohort including thrombolysed patients. We undertook a case-control study at a single stroke center using data from Acute Stroke Registry and Analyse of Lausanne (ASTRAL). Patients with seizure occurring during the first 7 days following stroke were retrospectively identified. Bi-variable and multivariable statistical analyses were applied to compare cases and randomly selected controls. We identified 28 patients experiencing from seizures in 2,327 acute ischemic strokes (1.2 %). All seizures occurred during the first 72 h. Cortical involvement, thrombolysis with rt-PA, arterial recanalization, and higher initial NIHSS were statistically associated with seizures in univariated analysis. Backward linear regression identified cortical involvement (OR 7.53, 95 % CI 1.6-35.2, p < 0.01) and thrombolysis (OR 4.6, 95 % CI 1.6-13.4, p = 0.01) as being independently associated with seizure occurrence. Overall, 3-month outcome measured by the modified Rankin scale (mRS) was comparable in both groups. In the subgroup of thrombolysed patients, outcome was significantly worse at 3 months in the seizure group with 9/12 (75 %) patients with mRS ≥ 3, compared to 6/18 (33.3 %) in the seizure-free group (p = 0.03). Acute seizures in acute ischemic stroke were relatively infrequent. Cortical involvement and thrombolysis with rt-PA are the principal risk factors. Seizures have a potential negative influence on clinical outcome in thrombolysed patients.

BACKGROUND AND PURPOSE: There has been speculation that the risk of secondary symptomatic intracranial hemorrhage (SICH) may be increased after thrombolytic therapy in ischemic stroke patients who have cerebral microbleeds (CMBs) on T2*-weighted magnetic resonance imaging. Because of this concern, some centers withhold potentially beneficial thrombolytic therapy from these patients.METHODS: We analyzed magnetic resonance imaging data acquired within 6 hours after symptom onset from 570 ischemic stroke patients treated with intravenous tissue plasminogen activator in 13 centers in Europe, North America, and Asia. Baseline T2*-weighted magnetic resonance images were evaluated for the presence of CMBs. The primary end point was SICH, defined as clinical deterioration with an increase in the National Institutes of Health Stroke Scale score by >or=4 points, temporally related to a parenchymal hematoma on follow-up-imaging.RESULTS: A total of 242 CMBs were detected in 86 of 570 patients (15.1%). The number of CMBs ranged from 1 to 77 in the individual patient, with >or=5 CMBs in 6 of 570 patients (1.1%). Proportions of patients with SICH were 5.8% (95% CI, 1.9 to 13.0) in the presence of CMBs and 2.7% (95% CI, 1.4 to 4.5) in patients without CMBs (P=0.170, Fisher's exact test), resulting in no significant absolute increase in the risk of SICH of 3.1% (95% CI, -2.0 to 8.3).CONCLUSIONS: The data suggest that if there is any increased risk of SICH attributable to CMBs, it is likely to be small and unlikely to exceed the benefits of thrombolytic therapy. No reliable conclusion regarding risk in the rare patient with multiple CMBs can be reached.