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and the Cerebral Venous Sinus Thrombosis With Thrombocytopenia Syndrome Study Group IMPORTANCE Thrombosis with thrombocytopenia syndrome (TTS) has been reported after vaccination with the SARS-CoV-2 vaccines ChAdOx1 nCov-19 (Oxford-AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson).OBJECTIVE To describe the clinical characteristics and outcome of patients with cerebral venous sinus thrombosis (CVST) after SARS-CoV-2 vaccination with and without TTS. DESIGN, SETTING, AND PARTICIPANTSThis cohort study used data from an international registry of consecutive patients with CVST within 28 days of SARS-CoV-2 vaccination included between March 29 and June 18, 2021, from 81 hospitals in 19 countries. For reference, data from patients with CVST between 2015 and 2018 were derived from an existing international registry. Clinical characteristics and mortality rate were described for adults with (1) CVST in the setting of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia, (2) CVST after SARS-CoV-2 vaccination not fulling criteria for TTS, and(3) CVST unrelated to SARS-CoV-2 vaccination.EXPOSURES Patients were classified as having TTS if they had new-onset thrombocytopenia without recent exposure to heparin, in accordance with the Brighton Collaboration interim criteria. MAIN OUTCOMES AND MEASURES Clinical characteristics and mortality rate.RESULTS Of 116 patients with postvaccination CVST, 78 (67.2%) had TTS, of whom 76 had been vaccinated with ChAdOx1 nCov-19; 38 (32.8%) had no indication of TTS. The control group included 207 patients with CVST before the COVID-19 pandemic. A total of 63 of 78 (81%), 30 of 38 (79%), and 145 of 207 (70.0%) patients, respectively, were female, and the mean (SD) age was 45 ( 14), 55 (20), and 42 (16) years, respectively. Concomitant thromboembolism occurred in 25 of 70 patients (36%) in the TTS group, 2 of 35 (6%) in the no TTS group, and 10 of 206 (4.9%) in the control group, and in-hospital mortality rates were 47% (36 of 76; 95% CI, 37-58), 5% (2 of 37; 95% CI, 1-18), and 3.9% (8 of 207; 95% CI, 2.0-7.4), respectively. The mortality rate was 61% (14 of 23) among patients in the TTS group diagnosed before the condition garnered attention in the scientific community and 42% (22 of 53) among patients diagnosed later. CONCLUSIONS AND RELEVANCEIn this cohort study of patients with CVST, a distinct clinical profile and high mortality rate was observed in patients meeting criteria for TTS after SARS-CoV-2 vaccination.

Question: Is early neurological deterioration of ischemic origin (END i ) predictable in minor strokes with large vessel occlusion (LVO) treated with intravenous thrombolysis (IVT)?Findings: In a multicentric retrospective cohort of minor stroke patients (NIHSS≤5) with LVO intended for IVT alone (n=729), an easily applicable score based on occlusion site and thrombus length -two independent predictors of END i -showed good discriminative power for END i risk prediction, and was successfully validated in an independent cohort (n=347).Meaning: END i can be reliably predicted in IVT-treated minor strokes with LVO, which may help to select the best candidates for direct transfer for additional thrombectomy.

IMPORTANCE Achieving complete reperfusion is a key determinant of good outcome in patients treated with mechanical thrombectomy (MT). However, data on treatments geared toward improving reperfusion after incomplete MT are sparse.OBJECTIVE To determine whether administration of intra-arterial urokinase is safe and improves reperfusion after failed or incomplete MT. DESIGN, SETTING, AND PARTICIPANTSThis observational cohort study included a consecutive sample of patients treated with second-generation MT from January 1, 2010, through August 4, 2017. Data were collected from the prospective registry of a tertiary care stroke center. Of 1274 patients screened, 69 refused to participate, and 993 met the observational studies inclusion criteria of a large vessel occlusion in the anterior circulation. Data were analyzed from September 1, 2017, through September 20, 2019.INTERVENTION One hundred patients received intra-arterial urokinase after failed or incomplete MT using manual microcatheter injections. MAIN OUTCOMES AND MEASURESPrimary safety outcome was the occurrence of symptomatic intracranial hemorrhage (sICH) according to the Prolyse in Acute Cerebral Thromboembolism II criteria. Secondary end points included 90-day mortality and 90-day functional independence (defined as modified Rankin Scale score of Յ2). Efficacy was evaluated angiographically, applying the Thrombolysis in Cerebral Infarction (TICI) scale. RESULTSAfter exclusion of patients with posterior circulation strokes and those treated with intra-arterial thrombolytics only, 993 patients were included in the final analyses (median age, 74.6 [interquartile range, 62.6-82.2] years; 505 [50.9%] women). Additional intra-arterial urokinase was administered in 100 patients (10.1%). The most common reason for administering intra-arterial urokinase was incomplete reperfusion (TICI<3) after MT (53 [53.0%]). After adjusting for baseline characteristics underlying case selection, intra-arterial urokinase was not associated with an increased risk of sICH (adjusted odds ratio [aOR], 0.81; 95% CI, 0.31-2.13) or 90-day mortality (aOR, 0.78; 95% CI, 0.43-1.40). Among 53 cases of partial or near-complete reperfusion and treated with intra-arterial urokinase, 32 (60.4%) had early reperfusion improvement, and 18 of 53 (34.0%) had an improvement in TICI grade. Correspondingly, patients treated with intra-arterial urokinase had higher rates of functional independence after adjusting for the selection bias favoring a priori poor TICI grades in the intra-arterial urokinase group (aOR, 1.93; 95% CI, 1.11-3.37). CONCLUSIONS AND RELEVANCEIn selected patients, adjunctive treatment with intra-arterial urokinase during or after MT was safe and improved angiographic reperfusion. Systemic evaluation of this approach in a multicenter prospective registry or a randomized clinical trial seems warranted.

Recurrent stroke affects 9-15% of people after 1 year. This European Stroke Organisation (ESO) guideline provides evidence-based recommendations on pharmacological management of blood pressure (BP), diabetes mellitus, lipid levels and antiplatelet therapy for the prevention of recurrent stroke and other important outcomes in people with ischaemic stroke or transient ischaemic attack (TIA). It does not cover interventions for specific causes of stroke, including treatment of cardioembolic stroke, which are addressed in other guidelines. This guideline was developed through ESO standard operating procedures and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. The working group identified clinical questions, selected outcomes, performed systematic reviews, with meta-analyses where appropriate, and made evidence-based recommendations, with expert consensus statements where evidence was insufficient to support a recommendation. To reduce the long-term risk of recurrent stroke or other important outcomes after ischaemic stroke or TIA, we recommend: BP lowering treatment to a target of <130/80 mmHg, except in subgroups at increased risk of harm; HMGCoA-reductase inhibitors (statins) and targeting a low density lipoprotein level of <1.8 mmol/l (70 mg/dl); avoidance of dual antiplatelet therapy with aspirin and clopidogrel after the first 90 days; to not give direct oral anticoagulant drugs (DOACs) for embolic stroke of undetermined source and to consider pioglitazone in people with diabetes or insulin resistance, after careful consideration of potential risks. In addition to the evidence-based recommendations, the majority of working group members supported: out-of-office BP monitoring; use of combination treatment for BP control; consideration of ezetimibe or PCSK9 inhibitors when lipid targets are not achieved; consideration of use of low-dose DOACs in addition to an antiplatelet in selected groups of people with coronary or peripheral artery disease; and aiming for an HbA1c level of <53 mmol/mol (7%) in people with diabetes mellitus. These guidelines aim to standardise long-term pharmacological treatment to reduce the burden of recurrent stroke in Europe.

Background and Purpose: Endovascular treatment of tandem occlusions is an emerging option. We describe our multicenter experience with endovascular management of atherosclerotic tandem occlusions in the anterior circulation, particularly the technical aspects and complications in comparison to isolated intracranial occlusions.Materials and Methods: Consecutive patients with tandem occlusions due to atherosclerotic causes who underwent mechanical thrombectomy at two major stroke centers between January 2010 and September 2015 were reviewed. Clinical data, procedural aspects, recanalization rates, complication rates, and clinical outcome were analyzed and compared to findings in patients with isolated intracranial occlusions.Results: One hundred and twenty-one patients with tandem occlusions and 456 patients with isolated intracranial occlusions (carotid-T/M1) were included. Mean intervention time was faster (33 min vs. 57 min, p < 0.001) and recanalization success was higher (TICI 2b/3 83.6 vs. 70.2%, p = 0.002) in patients with isolated occlusions. No difference was seen in clinical outcome and complications, except for a higher rate of asymptomatic hemorrhage in the tandem group (29.8 vs. 17.1%, p = 0.003). Choice of recanalization approach (antegrade vs. retrograde) in the tandem group made no difference, except for a trend toward less distal emboli using the retrograde approach (4.0 vs. 13.0%, p = 0.082). Stenting of the extracranial internal carotid artery (ICA) was performed in 81%, PTA alone in 7.4%, and deferred stenting in 11.6%. Rate of stent/ICA occlusion within 7 days was 10.3% after stenting and 33.3% after PTA (p = 0.127). In the tandem group, age (p = 0.034), National Institutes of Health Stroke Scale score (NIHSS) at admission (p = 0.002), recanalization rate (p < 0.001), complications (p = 0.016), and symptomatic intracranial hemorrhage (sICH) (p = 0.001) were associated with poor outcome, whereas extracranial treatment modality and stent/ICA occlusion within 7 days did not affect outcome.Conclusion: Endovascular treatment of tandem occlusions is technically feasible, achieves recanalization rates and rates of good clinical outcome comparable to those in patients with isolated intracranial occlusions. Following acute ICA stenting, the risk of stent occlusion and sICH appeared to be low, but was associated with an increased rate of asymptomatic ICH.

Background and Purpose: Timely reperfusion is an important goal in treatment of eligible patients with acute ischemic stroke. However, during the coronavirus disease 2019 (COVID-19) pandemic, prehospital and in-hospital emergency procedures faced unprecedented challenges, which might have caused a decline in the number of acute reperfusion therapy applied and led to a worsening of key quality measures for this treatment during lockdown. Methods: This prospective multicenter cohort study used data from the TRISP (Thrombolysis in Ischemic Stroke Patients) registry of patients with acute ischemic stroke treated with reperfusion therapies, that is, intravenous thrombolysis or endovascular therapy. We compared prehospital and in-hospital time-based performance measures (stroke-onset-to-admission, admission-to-treatment, admission-to-image, and image-to-treatment time) during the first 6 weeks after announcement of lockdown (lockdown period) with the same period in 2019 (reference period). Secondary outcomes included stroke severity (National Institutes of Health Stroke Scale) after 24 hours and occurrence of symptomatic intracranial hemorrhage (following the ECASS [European-Australasian Acute Stroke Study]-II criteria). Results: Across 20 stroke centers, 540 patients were treated with intravenous thrombolysis/endovascular therapy during lockdown period compared with 578 patients during reference period (−7% [95% CI, 5%–9%]). Performance measures did not change significantly during the lockdown period (2020/2019 minutes median: onset-to-admission 133/145; admission-to-treatment 51/48). Same was true for admission-to-image (20/19) and image-to-treatment (31/30) time in patients with available time of first image (n=871, 77.9%). Median National Institutes of Health Stroke Scale on admission (2020/2019: 11/11) and after 24 hours (2020/2019: 6/5) and percentage of symptomatic intracranial hemorrhage (2020/2019: 6.2/5.7) did not differ significantly between both periods. Conclusions: The COVID-19 pandemic lockdown resulted in a mild decline in the number of patients with stroke treated with acute reperfusion therapies. More importantly, the solid stability of key quality performance measures between the 2020 and 2019 period may indicate resilience of acute stroke care service during the lockdown, at least in well-established European stroke centers.

Background and Purpose— We aimed to determine the safety and mortality after mechanical thrombectomy in patients taking vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs). Methods— In a multicenter observational cohort study, we used multiple logistic regression analysis to evaluate associations of symptomatic intracranial hemorrhage (sICH) with VKA or DOAC prescription before thrombectomy as compared with no anticoagulation. The primary outcomes were the rate of sICH and all-cause mortality at 90 days, incorporating sensitivity analysis regarding confirmed therapeutic anticoagulation. Additionally, we performed a systematic review and meta-analysis of literature on this topic. Results— Altogether, 1932 patients were included (VKA, n=222; DOAC, n=98; no anticoagulation, n=1612); median age, 74 years (interquartile range, 62–82); 49.6% women. VKA prescription was associated with increased odds for sICH and mortality (adjusted odds ratio [aOR], 2.55 [95% CI, 1.35–4.84] and 1.64 [95% CI, 1.09–2.47]) as compared with the control group, whereas no association with DOAC intake was observed (aOR, 0.98 [95% CI, 0.29–3.35] and 1.35 [95% CI, 0.72–2.53]). Sensitivity analyses considering only patients within the confirmed therapeutic anticoagulation range did not alter the findings. A study-level meta-analysis incorporating data from 7462 patients (855 VKAs, 318 DOACs, and 6289 controls) from 15 observational cohorts corroborated these observations, yielding an increased rate of sICH in VKA patients (aOR, 1.62 [95% CI, 1.22–2.17]) but not in DOAC patients (aOR, 1.03 [95% CI, 0.60–1.80]). Conclusions— Patients taking VKA have an increased risk of sICH and mortality after mechanical thrombectomy. The lower risk of sICH associated with DOAC may also be noticeable in the acute setting. Improved selection might be advisable in VKA-treated patients. Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT03496064. Systematic Review and Meta-Analysis: CRD42019127464.