Among patients who had had a recent cryptogenic stroke attributed to PFO with an associated atrial septal aneurysm or large interatrial shunt, the rate of stroke recurrence was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone. PFO closure was associated with an increased risk of atrial fibrillation. (Funded by the French Ministry of Health; CLOSE ClinicalTrials.gov number, NCT00562289 .).

Objective: We aimed to create an index to stratify cryptogenic stroke (CS) patients with patent foramen ovale (PFO) by their likelihood that the stroke was related to their PFO.Methods: Using data from 12 component studies, we used generalized linear mixed models to predict the presence of PFO among patients with CS, and derive a simple index to stratify patients with CS. We estimated the stratum-specific PFO-attributable fraction and stratum-specific stroke/TIA recurrence rates.Results: Variables associated with a PFO in CS patients included younger age, the presence of a cortical stroke on neuroimaging, and the absence of these factors: diabetes, hypertension, smoking, and prior stroke or TIA. The 10-point Risk of Paradoxical Embolism score is calculated from these variables so that the youngest patients with superficial strokes and without vascular risk factors have the highest score. PFO prevalence increased from 23% (95% confidence interval [CI]: 19%-26%) in those with 0 to 3 points to 73% (95% CI: 66%-79%) in those with 9 or 10 points, corresponding to attributable fraction estimates of approximately 0% to 90%. Kaplan-Meier estimated stroke/TIA 2-year recurrence rates decreased from 20% (95% CI: 12%-28%) in the lowest Risk of Paradoxical Embolism score stratum to 2% (95% CI: 0%-4%) in the highest. Conclusion:Clinical characteristics identify CS patients who vary markedly in PFO prevalence, reflecting clinically important variation in the probability that a discovered PFO is likely to be stroke-related vs incidental. Patients in strata more likely to have stroke-related PFOs have lower recurrence risk. Case-control studies suggest that patent foramen ovale (PFO) is a common cause of cryptogenic stroke (CS), likely through a paradoxical (venous-to-arterial) embolism.1,2 However, CS has many potential causes, and PFO is a common anatomical variant found in approximately 25% of the general population.3 Thus, a PFO discovered in the setting of a CS may be incidental or stroke-related.Percutaneous mechanical closure of a PFO is frequently considered in patients with CS and PFO. The recently reported CLOSURE trial, however, found no benefit for this approach over medical therapy. 4 Nonetheless, stroke recurrence rates were low overall (limiting statistical power) and most stroke recurrence in both treatment groups was due to stroke of known mechanism, suggesting that many patients with incidental PFOs may have been enrolled.The premise of the Risk of Paradoxical Embolism (RoPE) Study 3 is that only patients with a high attributable recurrence risk have the opportunity to benefit from PFO closure for secondary

Recent case-series of small size implied a pathophysiological association between coronavirus disease 2019 (COVID-19) and severe large-vessel acute ischemic stroke. Given that severe strokes are typically associated with poor prognosis and can be very efficiently treated with recanalization techniques, confirmation of this putative association is urgently warranted in a large representative patient cohort to alert stroke clinicians, and inform pre- and in-hospital acute stroke patient pathways. We pooled all consecutive patients hospitalized with laboratory-confirmed COVID-19 and acute ischemic stroke in 28 sites from 16 countries. To assess whether stroke severity and outcomes (assessed at discharge or at the latest assessment for those patients still hospitalized) in patients with acute ischemic stroke are different between patients with COVID-19 and non-COVID-19, we performed 1:1 propensity score matching analyses of our COVID-19 patients with non-COVID-19 patients registered in the Acute Stroke Registry and Analysis of Lausanne Registry between 2003 and 2019. Between January 27, 2020, and May 19, 2020, 174 patients (median age 71.2 years; 37.9% females) with COVID-19 and acute ischemic stroke were hospitalized (median of 12 patients per site). The median National Institutes of Health Stroke Scale was 10 (interquartile range [IQR], 4–18). In the 1:1 matched sample of 336 patients with COVID-19 and non-COVID-19, the median National Institutes of Health Stroke Scale was higher in patients with COVID-19 (10 [IQR, 4–18] versus 6 [IQR, 3–14]), P =0.03; (odds ratio, 1.69 [95% CI, 1.08–2.65] for higher National Institutes of Health Stroke Scale score). There were 48 (27.6%) deaths, of which 22 were attributed to COVID-19 and 26 to stroke. Among 96 survivors with available information about disability status, 49 (51%) had severe disability at discharge. In the propensity score-matched population (n=330), patients with COVID-19 had higher risk for severe disability (median mRS 4 [IQR, 2–6] versus 2 [IQR, 1–4], P <0.001) and death (odds ratio, 4.3 [95% CI, 2.22–8.30]) compared with patients without COVID-19. Our findings suggest that COVID-19 associated ischemic strokes are more severe with worse functional outcome and higher mortality than non-COVID-19 ischemic strokes.

SummaryBackgroundStents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy.MethodsThe International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470.FindingsThe trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4·0%) events of disabling stroke or death in the stenting group compared with 27 (3·2%) events in the endarterectomy group (hazard ratio [HR] 1·28, 95% CI 0·77–2·11). The incidence of stroke, death, or procedural myocardial infarction was 8·5% in the stenting group compared with 5·2% in the endarterectomy group (72 vs 44 events; HR 1·69, 1·16–2·45, p=0·006). Risks of any stroke (65 vs 35 events; HR 1·92, 1·27–2·89) and all-cause death (19 vs seven events; HR 2·76, 1·16–6·56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0·0197).InterpretationCompletion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.FundingMedical Research Council, the Stroke Association, Sanofi-Synthélabo, European Union.

OBJECTIVETo compare the clinical outcomes of patients selected for mechanical thrombectomy by noncontrast computed tomography (CT) vs those selected by computed tomography perfusion (CTP) or magnetic resonance imaging (MRI) in the extended time window. DESIGN, SETTING, AND PARTICIPANTSThis multinational cohort study included consecutive patients with proximal anterior circulation occlusion stroke presenting within 6 to 24 hours of time last seen well from January 2014 to December 2020. This study was conducted at 15 sites across 5 countries in Europe and North America. The duration of follow-up was 90 days from stroke onset.EXPOSURES Computed tomography with Alberta Stroke Program Early CT Score, CTP, or MRI. MAIN OUTCOMES AND MEASURESThe primary end point was the distribution of modified Rankin Scale (mRS) scores at 90 days (ordinal shift). Secondary outcomes included the rates of 90-day functional independence (mRS scores of 0-2), symptomatic intracranial hemorrhage, and 90-day mortality. RESULTSOf 2304 patients screened for eligibility, 1604 patients were included, with a median (IQR) age of 70 (59-80) years; 848 (52.9%) were women. A total of 534 patients were selected to undergo mechanical thrombectomy by CT, 752 by CTP, and 318 by MRI. After adjustment of confounders, there was no difference in 90-day ordinal mRS shift between patients selected by CT vs CTP (adjusted odds ratio [aOR], 0.95 [95% CI, 0.77-1.17]; P = .64) or CT vs MRI (aOR, 0.95 [95% CI, 0.8-1.13]; P = .55). The rates of 90-day functional independence (mRS scores 0-2 vs 3-6) were similar between patients selected by CT vs CTP (aOR, 0.90 [95% CI, 0.7-1.16]; P = .42) but lower in patients selected by MRI than CT (aOR, 0.79 [95% CI, 0.64-0.98]; P = .03). Successful reperfusion was more common in the CT and CTP groups compared with the MRI group (474 [88.9%] and 670 [89.5%] vs 250 [78.9%]; P < .001). No significant differences in symptomatic intracranial hemorrhage (CT, 42 [8.1%]; CTP, 43 [5.8%]; MRI, 15 [4.7%]; P = .11) or 90-day mortality (CT, 125 [23.4%]; CTP, 159 [21.1%]; MRI, 62 [19.5%]; P = .38) were observed. CONCLUSIONS AND RELEVANCEIn patients undergoing proximal anterior circulation mechanical thrombectomy in the extended time window, there were no significant differences in the clinical outcomes of patients selected with noncontrast CT compared with those selected with CTP or MRI. These findings have the potential to widen the indication for treating patients in the extended window using a simpler and more widespread noncontrast CT-only paradigm.

Background and Purpose-We compared among young patients with ischemic stroke the distribution of vascular risk factors among sex, age groups, and 3 distinct geographic regions in Europe. Methods-We included patients with first-ever ischemic stroke aged 15 to 49 years from existing hospital-or population-based prospective or consecutive young stroke registries involving 15 cities in 12 countries. Geographic regions were defined as northern (Finland, Norway), central (Austria, Belgium, France, Germany, Hungary, The Netherlands, Switzerland), and southern (Greece, Italy, Turkey) Europe. Hierarchical regression models were used for comparisons. Results-In the study cohort (nϭ3944), the 3 most frequent risk factors were current smoking (48.7%), dyslipidemia (45.8%), and hypertension (35.9%). Compared with central (nϭ1868; median age, 43 years) and northern (nϭ1330; median age, 44 years) European patients, southern Europeans (nϭ746; median age, 41 years) were younger. No sex difference emerged between the regions, male:female ratio being 0.7 in those aged Ͻ34 years and reaching 1.7 in those aged 45 to 49 years. After accounting for confounders, no risk-factor differences emerged at the region level. Compared with females, males were older and they more frequently had dyslipidemia or coronary heart disease, or were smokers, irrespective of region. In both sexes, prevalence of family history of stroke, dyslipidemia, smoking, hypertension, diabetes mellitus, coronary heart disease, peripheral arterial disease, and atrial fibrillation positively correlated with age across all regions. Conclusions-Primary preventive strategies for ischemic stroke in young adults-having high rate of modifiable risk factors-should be targeted according to sex and age at continental level. (Stroke. 2012;43:2624-2630.)

Paquid is an epidemiological study designed to gather and follow-up a cohort of 3,777 elderly subjects (65 years and older) living at home. In order to study normal and pathological brain ageing, these subjects were randomly chosen in the general population of 75 communities of Gironde and Dordogne, two administrative areas of South-Western France. The subjects were interviewed at home by trained psychologists and followed-up with the same procedure at 1,3 and 5 years after the initial data collection. The identification of the demented cases is made with a two-stage design: the first stage is a systematic screening by the psychologists with application of the DSM-IIIR criteria and the second stage consists in a confirmation of the diagnosis by a neurologist according to the NINCDS-ADRDA criteria. Paquid is complemented by the study of a random sample of 357 subjects riving in institutions in Gironde.

Background and Purpose— If anterior circulation large vessel occlusion acute ischemic stroke patients presenting with ASPECTS 0–5 (Alberta Stroke Program Early CT Score) should be treated with mechanical thrombectomy remains unclear. Purpose of this study was to report on the outcome of patients with ASPECTS 0–5 treated with mechanical thrombectomy and to provide data regarding the effect of successful reperfusion on clinical outcomes and safety measures in these patients. Methods— Multicenter, pooled analysis of 7 institutional prospective registries: Bernese-European Registry for Ischemic Stroke Patients Treated Outside Current Guidelines With Neurothrombectomy Devices Using the SOLITAIRE FR With the Intention for Thrombectomy (Clinical Trial Registration—URL: https://www.clinicaltrials.gov . Unique identifier: NCT03496064). Primary outcome was defined as modified Rankin Scale 0–3 at day 90 (favorable outcome). Secondary outcomes included rates of day 90 modified Rankin Scale 0–2 (functional independence), day 90 mortality and occurrence of symptomatic intracerebral hemorrhage. Multivariable logistic regression analyses were performed to assess the association of successful reperfusion with clinical outcomes. Outputs are displayed as adjusted Odds Ratios (aOR) and 95% CI. Results— Two hundred thirty-seven of 2046 patients included in this registry presented with anterior circulation large vessel occlusion and ASPECTS 0–5. In this subgroup, the overall rates of favorable outcome and mortality at day 90 were 40.1% and 40.9%. Achieving successful reperfusion was independently associated with favorable outcome (aOR, 5.534; 95% CI, 2.363–12.961), functional independence (aOR, 5.583; 95% CI, 1.964–15.873), reduced mortality (aOR, 0.180; 95% CI, 0.083–0.390), and lower rates of symptomatic intracerebral hemorrhage (aOR, 0.235; 95% CI, 0.062–0.887). The mortality-reducing effect remained in patients with ASPECTS 0–4 (aOR, 0.167; 95% CI, 0.056–0.499). Sensitivity analyses did not change the primary results. Conclusions— In patients presenting with ASPECTS 0–5, who were treated with mechanical thrombectomy, successful reperfusion was beneficial without increasing the risk of symptomatic intracerebral hemorrhage. Although the results do not allow for general treatment recommendations, formal testing of mechanical thrombectomy versus best medical treatment in these patients in a randomized controlled trial is warranted.