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.

Background: Emerging data suggest that direct oral anticoagulants may be a suitable choice for anticoagulation for cerebral venous thrombosis (CVT). However, conducting high-quality trials in CVT is challenging as it is a rare disease with low rates of adverse outcomes such as major bleeding and functional dependence. To facilitate the design of future CVT trials, SECRET (Study of Rivaroxaban for Cerebral Venous Thrombosis) assessed (1) the feasibility of recruitment, (2) the safety of rivaroxaban compared with standard-of-care anticoagulation, and (3) patient-centered functional outcomes. Methods: This was a phase II, prospective, open-label blinded-end point 1:1 randomized trial conducted at 12 Canadian centers. Participants were aged ≥18 years, within 14 days of a new diagnosis of symptomatic CVT, and suitable for oral anticoagulation; they were randomized to receive rivaroxaban 20 mg daily, or standard-of-care anticoagulation (warfarin, target international normalized ratio, 2.0–3.0, or low-molecular-weight heparin) for 180 days, with optional extension up to 365 days. Primary outcomes were annual rate of recruitment (feasibility); and a composite of symptomatic intracranial hemorrhage, major extracranial hemorrhage, or mortality at 180 days (safety). Secondary outcomes included recurrent venous thromboembolism, recanalization, clinically relevant nonmajor bleeding, and functional and patient-reported outcomes (modified Rankin Scale, quality of life, headache, mood, fatigue, and cognition) at days 180 and 365. Results: Fifty-five participants were randomized. The rate of recruitment was 21.3 participants/year; 57% of eligible candidates consented. Median age was 48.0 years (interquartile range, 38.5–73.2); 66% were female. There was 1 primary event (symptomatic intracranial hemorrhage), 2 clinically relevant nonmajor bleeding events, and 1 recurrent CVT by day 180, all in the rivaroxaban group. All participants in both arms had at least partial recanalization by day 180. At enrollment, both groups on average reported reduced quality of life, low mood, fatigue, and headache with impaired cognitive performance. All metrics improved markedly by day 180. Conclusions: Recruitment targets were reached, but many eligible participants declined randomization. There were numerically more bleeding events in patients taking rivaroxaban compared with control, but rates of bleeding and recurrent venous thromboembolism were low overall and in keeping with previous studies. Participants had symptoms affecting their well-being at enrollment but improved over time. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03178864.

Background: Recent advances in the treatment of ischemic stroke have focused on revascularization and led to better clinical and functional outcomes. A systematic review and pooled analyses of 6 recent multicentered prospective randomized controlled trials (MPRCT) were performed to compare intravenous tissue plasminogen activator (IV tPA) and endovascular therapy (intervention) with IV tPA alone (control) for anterior circulation ischemic stroke (AIS) secondary to large vessel occlusion (LVO). Objectives: Six MPRCTs (MR CLEAN, ESCAPE, EXTEND IA, SWIFT PRIME, REVASCAT and THERAPY) incorporating image-based LVO AIS were selected for assessing the following: (1) prespecified primary clinical outcomes of AIS patients in intervention and control arms: good outcomes were defined by a modified Rankin Scale score of 0-2 at 90 days; (2) secondary clinical outcomes were: (a) revascularization rates [favorable outcomes defined as modified Thrombolysis in Cerebral Infarction scale (mTICI) score of 2b/3]; (b) symptomatic intracranial hemorrhage (sICH) rates and mortality; (c) derivation of number needed to harm (NNH), number needed to treat (NNT), and relative percent difference (RPD) between intervention and control groups, and (d) random effects model to determine overall significance (forest and funnel plots). Results: A total of 1,386 patients were included. Good outcomes at 90 days were seen in 46% of patients in the intervention (p < 0.00001) and in 27% of patients in the control groups (p < 0.00002). An mTICI score of 2b/3 was achieved in 70.2% of patients in the intervention arm. The sICH and mortality in the intervention arm compared with the control arm were 4.7 and 14.3% versus 7.9 and 17.8%, respectively. The NNT and NNH in the intervention and control groups were 5.3 and 9.1, respectively. Patients in the intervention arm had a 50.1% (RPD) better chance of achieving a good 90-day outcome as compared to controls. Conclusions: Endovascular therapy combined with IV tPA (in appropriately selected patients) for LVO-related AIS is superior to IV tPA alone. These results support establishing an endovascular therapy in addition to IV tPA as the standard of care for AIS secondary to LVO.

Background and Objective: The safety of eptifibatide in combination with IV tPA for ischemic stroke has recently been demonstrated in the CLEAR-ER trial which used .6 mg/kg IV tPA plus eptifibatide (135 mcg/kg bolus and .75mcg/kg/min two-hour infusion) versus standard tPA (.9 mg/kg). Prior studies have also looked into the combination of intra-arterial (IA) tPA and eptifibatide at dosing and duration similar to cardiology literature. Our aim was to compare the safety and efficacy of eptifibatide after full dose IV tPA and endovascular treatment versus full dose IV tPA and endovascular treatment alone. Materials and Methods: We reviewed the records and procedure reports of patients who underwent endovascular treatment for ischemic stroke from 2010-2013 at a university affiliated comprehensive stroke center. Patients who received full dose IV tPA (.9 mg/kg) followed by endovascular treatment were compared with those who had the same treatment, but also received a bolus of 135 mcg/kg of eptifibatide followed by a .5 mcg/kg/min for 20 hours (based on IMPACT-II trial protocol). The initial and discharge NIH Stroke Scale as well as the discharge mRS (DCmRS) were evaluated. A DCmRS of 0 or 1 was considered a favorable outcome, and 2 or more was considered as a unfavorable. Initial stroke severity (NIHSS) was analyzed with logistic regression for baseline comparison and Fisher’s exact test were used for categorical data analysis. Results: We evaluated 2,016 patients with ischemic stroke, of which 230 received IV tPA and 91 (55% female) underwent endovascular treatment, 44 of them also received eptifibatide. Of the 44 patients who received eptifibatide (bolus and 20 hour infusion), 18% (n=8) had a favorable outcome, and in the group that did not receive eptifibatide , 9% (n=4) had a favorable outcome (OR=2.389, 95% CI 0.6645 to 8.589, p= 0.2217). Conclusion: Eptifibatide in combination with full dose IV tPA and endovascular treatment did not increase morbidity in our patient population, and may have improved outcome. Further, larger trials need to be conducted for more definitive results.

Background and Objective: Patients with ischemic or hemorrhagic stroke require strict BP control to prevent hemorrhagic transformation or hematoma expansion. Acute elevations in BP are often treated with IV labetalol. Dedicated stroke units often have automated bedside monitoring of vital signs. Standard automated BP monitoring alerts practitioners to trends that lead to more steady control of BP rather than frequent acute interventions. We evaluated patients who were treated in a stroke unit after the institution of automated bedside monitoring. Comparison was made to the number of times the patients were dosed acutely using labetalol with a control group of patients who were not receiving automated bedside monitoring. The objective was to determine if there was a significant difference in care. Methods: Patients were evaluated over a 12-month period (2014) after the incorporation of bedside automated BP monitoring in a dedicated stroke unit at a university affiliated, comprehensive stroke center. The number of times each patient during this time frame received IV labetalol for acute elevations in BP was compared with a time period spanning 12-months prior (2013); there was no automated BP monitoring performed. The average interventions were compared with a t-test by using SPSS V22. Comparisons of patient population and type of pathology were matched appropriately. Results: Of the 1,326 patients who presented for ischemic or hemorrhagic strokes during the 24-month period evaluated, 25 required multiple injections of IV labetalol for acute BP control. Of these, 12 patients were on automated vital signs and BP monitoring, and 13 were not. The mean number of IV labetalol interventions implemented in the group being monitored was 2.8, while the mean number of treatments given to patients not being monitored was 5.9 (p=.016). Conclusion: In our study there is a trend towards better blood pressure control with adequate adjustment of oral medications for monitored patients in our dedicated stroke unit. Prevention of sudden elevations in BP may translate into lower rates of hemorrhagic transformation or hematoma expansion and confer better outcomes in stroke patients. Larger prospective studies are required to corroborate our findings.