The effectiveness of endovascular therapy in patients with stroke caused by basilar-artery occlusion has not been well studied. We randomly assigned patients within 6 hours after the estimated time of onset of a stroke due to basilar-artery occlusion, in a 1:1 ratio, to receive endovascular therapy or standard medical care. The primary outcome was a favorable functional outcome, defined as a score of 0 to 3 on the modified Rankin scale (range, 0 to 6, with 0 indicating no disability, 3 indicating moderate disability, and 6 indicating death) at 90 days. The primary safety outcomes were symptomatic intracranial hemorrhage within 3 days after the initiation of treatment and mortality at 90 days. A total of 300 patients were enrolled (154 in the endovascular therapy group and 146 in the medical care group). Intravenous thrombolysis was used in 78.6% of the patients in the endovascular group and in 79.5% of those in the medical group. Endovascular treatment was initiated at a median of 4.4 hours after stroke onset. A favorable functional outcome occurred in 68 of 154 patients (44.2%) in the endovascular group and 55 of 146 patients (37.7%) in the medical care group (risk ratio, 1.18; 95% confidence interval [CI], 0.92 to 1.50). Symptomatic intracranial hemorrhage occurred in 4.5% of the patients after endovascular therapy and in 0.7% of those after medical therapy (risk ratio, 6.9; 95% CI, 0.9 to 53.0); mortality at 90 days was 38.3% and 43.2%, respectively (risk ratio, 0.87; 95% CI, 0.68 to 1.12). Among patients with stroke from basilar-artery occlusion, endovascular therapy and medical therapy did not differ significantly with respect to a favorable functional outcome, but, as reflected by the wide confidence interval for the primary outcome, the results of this trial may not exclude a substantial benefit of endovascular therapy. Larger trials are needed to determine the efficacy and safety of endovascular therapy for basilar-artery occlusion. (Funded by the Dutch Heart Foundation and others; BASICS ClinicalTrials.gov number, NCT01717755; Netherlands Trial Register number, NL2500.)

Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. UK Medical Research Council and Health Technology Assessment Programme.

Background and Purpose—: Intravenous thrombolysis for acute ischemic stroke is beneficial within 4.5 hours of symptom onset, but the effect rapidly decreases over time, necessitating quick diagnostic in-hospital work-up. Initial time strain occasionally results in treatment of patients with an alternate diagnosis (stroke mimics). We investigated whether intravenous thrombolysis is safe in these patients. Methods—: In this multicenter observational cohort study containing 5581 consecutive patients treated with intravenous thrombolysis, we determined the frequency and the clinical characteristics of stroke mimics. For safety, we compared the symptomatic intracranial hemorrhage (European Cooperative Acute Stroke Study II [ECASS-II] definition) rate of stroke mimics with ischemic strokes. Results—: One hundred stroke mimics were identified, resulting in a frequency of 1.8% (95% confidence interval, 1.5–2.2). Patients with a stroke mimic were younger, more often female, and had fewer risk factors except smoking and previous stroke or transient ischemic attack. The symptomatic intracranial hemorrhage rate in stroke mimics was 1.0% (95% confidence interval, 0.0–5.0) compared with 7.9% (95% confidence interval, 7.2–8.7) in ischemic strokes. Conclusions—: In experienced stroke centers, among patients treated with intravenous thrombolysis, only a few had a final diagnosis other than stroke. The complication rate in these stroke mimics was low.

Trimethylamine-N-oxide (TMAO) is a small organic molecule, derived from the intestinal and hepatic metabolism of dietary choline and carnitine. Although the involvement of TMAO in the framework of many chronic diseases has been recently described, no evidence on its putative role in the central nervous system has been provided. The aim of this study was to evaluate whether TMAO is present at detectable levels in human cerebrospinal fluid (CSF). CSF was collected for diagnostic purposes from 58 subjects by lumbar puncture and TMAO was quantified by using liquid chromatography coupled with multiple-reaction monitoring mass spectrometry. The molecule was detected in all samples, at concentrations ranging between 0.11 and 6.43 µmol/L. Further analysis on CSF revealed that a total of 22 subjects were affected by Alzheimer’s disease (AD), 16 were affected by non-AD related dementia, and 20 were affected by other neurological disorders. However, the stratification of TMAO levels according to the neurological diagnoses revealed no differences among the three groups. In conclusion, we provide the first evidence that TMAO can be assessed in human CSF, but the actual impact of this dietary metabolite in the patho-physiolgy of the central nervous system requires further study.

Background and Purpose—: Among patients with acute ischemic stroke, we determine computed tomographic perfusion (CTP) thresholds associated with follow-up infarction at different stroke onset-to-CTP and CTP-to-reperfusion times. Methods—: Acute ischemic stroke patients with occlusion on computed tomographic angiography were acutely imaged with CTP. Noncontrast computed tomography and magnectic resonance diffusion–weighted imaging between 24 and 48 hours were used to delineate follow-up infarction. Reperfusion was assessed on conventional angiogram or 4-hour repeat computed tomographic angiography. T _max , cerebral blood flow, and cerebral blood volume derived from delay-insensitive CTP postprocessing were analyzed using receiver–operator characteristic curves to derive optimal thresholds for combined patient data (pooled analysis) and individual patients (patient-level analysis) based on time from stroke onset-to-CTP and CTP-to-reperfusion. One-way ANOVA and locally weighted scatterplot smoothing regression was used to test whether the derived optimal CTP thresholds were different by time. Results—: One hundred and thirty-two patients were included. T _max thresholds of >16.2 and >15.8 s and absolute cerebral blood flow thresholds of <8.9 and <7.4 mL·min ⁻¹ ·100 g ⁻¹ were associated with infarct if reperfused <90 min from CTP with onset 0.05). A statistically significant relationship existed between CTP-to-reperfusion time and the optimal thresholds for cerebral blood flow ( P <0.001; r=0.59 and 0.77 for gray and white matter, respectively) and T _max ( P <0.001; r=−0.68 and −0.60 for gray and white matter, respectively) parameters. Conclusions—: Optimal CTP thresholds associated with follow-up infarction depend on time from imaging to reperfusion.

Background Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection predisposes patients to arterial and venous thrombosis. This study aimed to systematically review the available evidence in the literature for cerebral venous thrombosis (CVT) in association with coronavirus disease‐2019 (COVID‐19). Methods We searched MEDLINE, EMBASE and Cochrane CENTRAL databases to identify cases of COVID‐19‐associated CVT. The search period spanned January 1^st to December 1^st 2020 and the review protocol (PROSPERO‐CRD42020214327) followed PRISMA guidelines. Identified studies were evaluated for bias using the Newcastle‐Ottawa scale (NOS). Proportion meta‐analysis was performed to estimate the frequency of CVT among hospitalized COVID‐19 patients. Results We identified 57 cases from 28 reports. Study quality was mostly classified as low. CVT symptoms developed after respiratory disease in 90%, the mean interval was 13 days. CVT involved multiple sites in 67% of individuals, the deep venous system was affected in 37% and parenchymal hemorrhage was found in 42%. Predisposing factors for CVT beyond SARS‐CoV‐2 infection were present in 31%. In‐hospital mortality was 40%. Using data from 34331 patients, the estimated frequency of CVT among hospitalized for SARS‐CoV‐2 infection was 0.08% (95%CI=0.01‐0.5). In an in‐patient setting, CVT accounted for 4.2% of cerebrovascular disorders in individuals with COVID‐19 (cohort of 406 patients, 95%CI=1.47‐11.39). Conclusion CVT in the context of SARS‐CoV‐2 infection is a rare, although there seems to be an increased relative risk. High suspicion is necessary, since the diagnosis of this potentially life‐threatening condition in COVID‐19 patients can be challenging. Evidence is still scarce on the pathophysiology and potential prevention of COVID‐19 associated CVT.