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Background: Tenecteplase has potential benefits over alteplase, the standard agent for intravenous thrombolysis in acute ischaemic stroke, because it is administered as a single bolus and might have superior efficacy. The ATTEST-2 trial investigated whether tenecteplase was non-inferior or superior to alteplase within 4·5 h of onset., Methods: We undertook a prospective, randomised, parallel-group, open-label trial with masked endpoint evaluation in 39 UK stroke centres. Previously independent adults with acute ischaemic stroke, eligible for intravenous thrombolysis less than 4·5 h from last known well, were randomly assigned 1:1 to receive intravenous alteplase 0·9 mg/kg or tenecteplase 0·25 mg/kg, by use of a telephone-based interactive voice response system. The primary endpoint was the distribution of the day 90 modified Rankin Scale (mRS) score and was analysed using ordinal logistic regression in the modified intention-to-treat population. We tested the primary outcome for non-inferiority (odds ratio for tenecteplase vs alteplase non-inferiority limit of 0·75), and for superiority if non-inferiority was confirmed. Safety outcomes were mortality, symptomatic intracranial haemorrhage, radiological intracranial haemorrhage, and major extracranial bleeding. The trial was prospectively registered on ClinicalTrials.gov (NCT02814409)., Findings: Between Jan 25, 2017, and May 30, 2023, 1858 patients were randomly assigned to a treatment group, of whom 1777 received thrombolytic treatment and were included in the modified intention-to-treat population (n=885 allocated tenecteplase and n=892 allocated alteplase). The mean age of participants was 70·4 (SD 12·9) years and median National Institutes of Health Stroke Scale was 7 (IQR 5-13) at baseline. Tenecteplase was non-inferior to alteplase for mRS score distribution at 90 days, but was not superior (odds ratio 1·07; 95% CI 0·90-1·27; p value for non-inferiority<0·0001; p=0·43 for superiority). 68 (8%) patients in the tenecteplase group compared with 75 (8%) patients in the alteplase group died, symptomatic intracerebral haemorrhage (defined by SITS-MOST criteria) occurred in 20 (2%) versus 15 (2%) patients, parenchymal haematoma type 2 occurred in 37 (4%) versus 26 (3%) patients, post-treatment intracranial bleed occurred in 94 (11%) versus 78 (9%) patients, significant extracranial haemorrhage occurred in 13 (1%) versus six (1%) patients, respectively, and angioedema occurred in six (1%) participants in both groups., Interpretation: Tenecteplase 0·25 mg/kg was non-inferior to 0·9 mg/kg alteplase within 4·5 h of symptom onset in acute ischaemic stroke. Easier administration of tenecteplase, especially in the context of interhospital transfers, indicates that tenecteplase should be preferred to alteplase for thrombolysis in acute ischaemic stroke. The ATTEST-2 population was large and representative of thrombolysis-eligible patients in the UK and, together with findings from other trials, provides robust evidence supporting the introduction of tenecteplase in preference to alteplase., Funding: The Stroke Association and British Heart Foundation., Competing Interests: Declaration of interests KWM reports lecture and advisory board fees from Boehringer Ingelheim; lecture fees from Brainomix and IschemaView; and consultancy fees from Abbvie, Biogen, Hyperfine, Lumosa, and Woolsey. GAF reports personal remuneration for advisory board or steering committee activity from CSL Behring; educational activities from Bayer; and his employer (University of Oxford and Oxford University Hospitals NHS Foundation Trust) has received remuneration for consultancy with AstraZeneca. IF reports research grants to the University of Glasgow from The Stroke Association and the British Heart Foundation. JMW reports academic research grants but no industry, advisory or speaker fees or stock interests. AM reports research grants to the University of Glasgow from The Stroke Association and the British Heart Foundation. NG reports research grants to the University of Glasgow from The Stroke Association and the British Heart Foundation. GM reports personal remuneration for consultancy with Canon Medical Research Europe. MJM reports advisory board and educational meeting remuneration from Astra Zeneca. WNW reports drafting the European Stroke Organisation guideline for thrombolysis; and Data Monitoring Committee for TEMPO-2. AH reports being a clinical advisor to the Peninsula Technology Assessment Group, University of Exeter Medical School (External Advisory Group National Institute for Health & Care Excellence Technology Appraisal of Tenecteplase for treating acute ischaemic stroke, NICE reference number ID6306), all unpaid. MB reports research meeting remuneration for the LIBREXIA trial from Janssen and Bristol Myers Squibb. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: A new syndrome of vaccine-induced immune thrombotic thrombocytopenia (VITT) has emerged as a rare side-effect of vaccination against COVID-19. Cerebral venous thrombosis is the most common manifestation of this syndrome but, to our knowledge, has not previously been described in detail. We aimed to document the features of post-vaccination cerebral venous thrombosis with and without VITT and to assess whether VITT is associated with poorer outcomes., Methods: For this multicentre cohort study, clinicians were asked to submit all cases in which COVID-19 vaccination preceded the onset of cerebral venous thrombosis, regardless of the type of vaccine, interval between vaccine and onset of cerebral venous thrombosis symptoms, or blood test results. We collected clinical characteristics, laboratory results (including the results of tests for anti-platelet factor 4 antibodies where available), and radiological features at hospital admission of patients with cerebral venous thrombosis after vaccination against COVID-19, with no exclusion criteria. We defined cerebral venous thrombosis cases as VITT-associated if the lowest platelet count recorded during admission was below 150 × 10 9 per L and, if the D-dimer was measured, the highest value recorded was greater than 2000 μg/L. We compared the VITT and non-VITT groups for the proportion of patients who had died or were dependent on others to help them with their activities of daily living (modified Rankin score 3-6) at the end of hospital admission (the primary outcome of the study). The VITT group were also compared with a large cohort of patients with cerebral venous thrombosis described in the International Study on Cerebral Vein and Dural Sinus Thrombosis., Findings: Between April 1 and May 20, 2021, we received data on 99 patients from collaborators in 43 hospitals across the UK. Four patients were excluded because they did not have definitive evidence of cerebral venous thrombosis on imaging. Of the remaining 95 patients, 70 had VITT and 25 did not. The median age of the VITT group (47 years, IQR 32-55) was lower than in the non-VITT group (57 years; 41-62; p=0·0045). Patients with VITT-associated cerebral venous thrombosis had more intracranial veins thrombosed (median three, IQR 2-4) than non-VITT patients (two, 2-3; p=0·041) and more frequently had extracranial thrombosis (31 [44%] of 70 patients) compared with non-VITT patients (one [4%] of 25 patients; p=0·0003). The primary outcome of death or dependency occurred more frequently in patients with VITT-associated cerebral venous thrombosis (33 [47%] of 70 patients) compared with the non-VITT control group (four [16%] of 25 patients; p=0·0061). This adverse outcome was less frequent in patients with VITT who received non-heparin anticoagulants (18 [36%] of 50 patients) compared with those who did not (15 [75%] of 20 patients; p=0·0031), and in those who received intravenous immunoglobulin (22 [40%] of 55 patients) compared with those who did not (11 [73%] of 15 patients; p=0·022)., Interpretation: Cerebral venous thrombosis is more severe in the context of VITT. Non-heparin anticoagulants and immunoglobulin treatment might improve outcomes of VITT-associated cerebral venous thrombosis. Since existing criteria excluded some patients with otherwise typical VITT-associated cerebral venous thrombosis, we propose new diagnostic criteria that are more appropriate., Funding: None., Competing Interests: Declaration of interests RJP receives grants from Randox Laboratories on an unrelated subject and from The Stroke Association for work on COVID-19 and stroke, not related to vaccination. PA-F receives grants from the Wellcome Trust for work on an unrelated subject. EH receives grants from MND Scotland and the National Institute for Health Research (NIHR) for work on an unrelated subject. TS sits on the Medicines and Healthcare products Regulatory Agency Vaccine Benefit Versus Risk Expert Working Group and was on the Data Safety Monitoring Committee of the GSK study to evaluate the safety and immunogenicity of a candidate Ebola vaccine in children GSK3390107A (ChAd3 EBO-Z) vaccine. MS receives grants from Shire and Novartis, and has received personal fees from Takeda, Novartis, Octapharma, and Sanofi for work on unrelated subjects. BS received a grant from the Medical Research Council, via the UK Research Institutes/NIHR Global Effort on COVID-19 Research to study neurological disease in relation to COVID-19, and has been a case management consultant to WHO-South-East Asia via the Global Outbreak Alert and Response Network since April, 2020, but vaccination against the infection is not the focus in either case. CR receives grants from the NIHR for work on an unrelated subject and is also collaborating with FirstKind Medical on a grant on an unrelated subject. CR is chair of the NIHR Hyperacute Stroke Research Oversight Group and is a member of the European Stroke Organization board of directors. DJW has received personal fees from Bayer, Alnylam, and Portola, unrelated to the work presented here. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: We set out to determine which characteristics and outcomes of stroke are associated with COVID-19., Methods: This case-control study included patients admitted with stroke to 13 hospitals in England and Scotland between 9 March and 5 July 2020. We collected data on 86 strokes (81 ischaemic strokes and 5 intracerebral haemorrhages) in patients with evidence of COVID-19 at the time of stroke onset (cases). They were compared with 1384 strokes (1193 ischaemic strokes and 191 intracerebral haemorrhages) in patients admitted during the same time period who never had evidence of COVID-19 (controls). In addition, the whole group of stroke admissions, including another 37 patients who appeared to have developed COVID-19 after their stroke, were included in two logistic regression analyses examining which features were independently associated with COVID-19 status and with inpatient mortality., Results: Cases with ischaemic stroke were more likely than ischaemic controls to occur in Asians (18.8% vs 6.7%, p<0.0002), were more likely to involve multiple large vessel occlusions (17.9% vs 8.1%, p<0.03), were more severe (median National Institutes of Health Stroke Scale score 8 vs 5, p<0.002), were associated with higher D-dimer levels (p<0.01) and were associated with more severe disability on discharge (median modified Rankin Scale score 4 vs 3, p<0.0001) and inpatient death (19.8% vs 6.9%, p<0.0001). Recurrence of stroke during the patient's admission was rare in cases and controls (2.3% vs 1.0%, NS)., Conclusions: Our data suggest that COVID-19 may be an important modifier of the onset, characteristics and outcome of acute ischaemic stroke., Competing Interests: Competing interests: CJS has received honoraria from Bayer, Sanofi and Pfizer, not related to the work presented here. DJW has received personal fees from Bayer, Alnylam and Portola, not related to the work presented here., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Subarachnoid haemorrhage may result in seizures both acutely and in the longer term. The use of antiepileptic drugs (AEDs) in the primary and secondary prevention of seizures after subarachnoid haemorrhage is uncertain, and there is currently no consensus on treatment., Objectives: To assess the effects of AEDs for the primary and secondary prevention of seizures after subarachnoid haemorrhage., Search Methods: We searched the Cochrane Epilepsy Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 1) in The Cochrane Library, and MEDLINE (1946 to 12th March 2013). We checked the reference lists of articles retrieved from these searches., Selection Criteria: We considered all randomised and quasi-randomised controlled trials in which patients were assigned to a treatment (one or more AEDs) or placebo., Data Collection and Analysis: Two review authors (RM and JK) independently screened and assessed the methodological quality of the studies. If studies were included, one author extracted the data and the other checked it., Main Results: No relevant studies were found., Authors' Conclusions: There was no evidence to support or refute the use of antiepileptic drugs for the primary or secondary prevention of seizures related to subarachnoid haemorrhage. Well-designed randomised controlled trials are urgently needed to guide clinical practice.