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Objective To evaluate the relationship between infarct pattern, inferred stroke mechanism and risk of recurrence in patients with ischaemic stroke. The question is clinically relevant to optimise secondary stroke prevention investigations and treatment.Design We conducted a retrospective analysis of the dabigatran treatment of acute stroke II (DATAS II) trial (ClinicalTrials.gove NCT NCT02295826), in which patients underwent diffusion-weighted imaging (DWI) at baseline and 30 days after randomisation to one of two antithrombotic therapies. Patients were classified as embolic, isolated small subcortical infarcts or transient ischaemic attack TIA (no infarct) at baseline and day 30. Stroke mechanism was determined by traditional and modified (based on DWI lesion findings) Trial of Org 10 172 in Acute Stroke Treatment (TOAST) criteria (DWI-TOAST).Setting Multicentre (6) tertiary acute stroke treatment hospitals.Participants 305 adults with minor ischaemic stroke (National Institutes of Health Stroke Scale (NIHSS) score≤9).Results Of 305 patients, 148 had embolic pattern infarcts, 93 were isolated small subcortical infarcts and 64 had no infarct on baseline MRI (TIA). In the absence of DWI, TOAST classification indicated the mechanism was cryptogenic in 147 patients (48.2%), and small-vessel occlusion in 127 (41.6%). Using, DWI-TOAST, the number of cryptogenic strokes decreased to 123 (40.3%), and the number of small-vessel occlusion strokes increased to 151 (49.5%). Recurrent infarcts were seen in 13% of patients with an MRI-defined embolic infarct pattern and cryptogenic mechanism on DWI-TOAST. The relative risk of recurrent infarction in patients with undetermined aetiology was increased compared with other categories (standardised coefficient=1.0 (0.1, 1.9), p=0.029). The topography of recurrent infarcts was most often embolic (60.9%), but in 39.1% an isolated small subcortical infarct was seen.Conclusions Definitive identification of infarct topography with DWI has a significant impact on infarct mechanism classification. The variable relationship between baseline infarct patterns, clinical presentation and recurrent infarct distribution is a challenge to both the lacunar and embolic stroke of uncertain source (ESUS) concepts. Irrespective of aetiological classification, patients with MRI-defined cryptogenic embolic pattern infarcts are at high risk for recurrent events.Trial registration number Linked to the DATAS II trial. ClinicalTrials.gov ID NCT02295826.

IntroductionLong-term cardiac monitoring studies have unveiled low-burden, occult atrial fibrillation (AF) in some patients with otherwise cryptogenic stroke (CS), but occult AF is also found in some individuals without a stroke history and in patients with stroke of a known cause (KS). Clinical management would be aided by estimates of how often occult AF in a patient with CS is causal vs. incidental.MethodsThrough a systematic search, we identified all case–control and cohort studies applying identical long-term monitoring techniques to both patients with CS and KS. We performed a random-effects meta-analysis across these studies to determine the best estimate of the differential frequency of occult AF in CS and KS among all patients and across age subgroups. We then applied Bayes' theorem to determine the probability that occult AF is causal or incidental.ResultsThe systematic search identified three case–control and cohort studies enrolling 560 patients (315 CS, 245 KS). Methods of long-term monitoring were implantable loop recorder in 31.0%, extended external monitoring in 67.9%, and both in 1.2%. Crude cumulative rates of AF detection were CS 47/315 (14.9%) vs. KS 23/246 (9.3%). In the formal meta-analysis, the summary odds ratio for occult AF in CS vs. KS in all patients was 1.80 (95% CI, 1.05–3.07), p = 0.03. With the application of Bayes' theorem, the corresponding probabilities indicated that, when present, occult AF in patients with CS is causal in 41.2% (95% CI, 15.5–77.7%) of patients. Analyses stratified by age suggested that detected occult AF in patients with CS was causal in 62.3% (95 CI, 0–87.1%) of patients under the age of 65 years and 28.5% (95 CI, 0–63.7%) of patients aged 65 years and older but estimates had limited precision.ConclusionCurrent evidence is preliminary, but it indicates that in cryptogenic stroke when occult AF is found, it is causal in about 41.2% of patients. These findings suggest that anticoagulation therapy may be beneficial to prevent recurrent stroke in a substantial proportion of patients with CS found to have occult AF.

Background Although the association between cortical venous opacification (VO) and clinical outcomes has been shown in previous studies, little is known about the relationship between parenchymal hemorrhage (PH) and VO in patients with acute stroke. We aimed to determine whether cortical VO assessed on computed tomography angiography correlates with the risk of PH following endovascular treatment. Methods This is a post hoc analysis of the ESCAPE NA‐1 (Efficacy and Safety of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke) trial. Control‐arm patients with adequate venous assessment on computed tomography angiography were included. Any PH and symptomatic intracranial hemorrhage were compared between patients with poor VO (cortical vein opacification score

Abstract Mobile Stroke Unit (MSU) expedites the delivery of intravenous thrombolysis in acute stroke patients. We further evaluated the functional outcome of patients shipped to a tertiary care centre or repatriated to local hospitals after triage by MSU in acute stroke syndrome in rural northern Alberta. Consecutive patients with suspected acute stroke syndrome were included. On the basis of neurology consultation and, Computed Tomography findings, patients, who were thrombolysed or needed advanced care were transported to the Comprehensive stroke center (CSC) (Triage to CSC group). Other patients were repatriated to local hospital care (Triage to LHC group). A total of 156 patients were assessed in MSU, 73 (46.8%) were female and the mean age was 66.6 ± 15 years. One hundred and eight (69.2%) patients, including 41 (26.3%) treated with thrombolysis were transported to the CSC (Triage to CSC group) and 48 (30.8%) were repatriated to local hospital care. The diagnosis made in MSU and final diagnosis were matching in 88% (95) and 91.7% (44, p = 0.39) in Triage to CSC and Triage to LHC groups respectively. Prehospital triage by MSU of acute stroke syndrome can reliably repatriate patients to the home hospital. The proposed model has the potential to triage patients according to their medical needs by enabling treatment in home hospitals whenever reasonable.

Background In ischaemic stroke, minor deficits (National Institutes of Health Stroke Scale (NIHSS) ≤5) at presentation are common but often progress, leaving patients with significant disability. We compared the efficacy and safety of intravenous thrombolysis with tenecteplase versus alteplase in patients who had a minor stroke enrolled in the Alteplase Compared to Tenecteplase in Patients With Acute Ischemic Stroke (AcT) trial.Methods The AcT trial included individuals with ischaemic stroke, aged >18 years, who were eligible for standard-of-care intravenous thrombolysis. Participants were randomly assigned 1:1 to intravenous tenecteplase (0.25 mg/kg) or alteplase (0.9 mg/kg). Patients with minor deficits pre-thrombolysis were included in this post-hoc exploratory analysis. The primary efficacy outcome was the proportion of patients with a modified Rankin Score (mRS) of 0–1 at 90–120 days. Safety outcomes included mortality and symptomatic intracranial haemorrhage (sICH).Results Of the 378 patients enrolled in AcT with an NIHSS of ≤5, the median age was 71 years, 39.7% were women; 194 (51.3%) received tenecteplase and 184 (48.7%) alteplase. The primary outcome (mRS score 0–1) occurred in 100 participants (51.8%) in the tenecteplase group and 86 (47.5 %) in the alteplase group (adjusted risk ratio (RR) 1.14 (95% CI 0.92 to 1.40)). There were no significant differences in the rates of sICH (2.9% in tenecteplase vs 3.3% in alteplase group, unadjusted RR 0.79 (0.24 to 2.54)) and death within 90 days (5.5% in tenecteplase vs 11% in alteplase group, adjusted HR 0.99 (95% CI 0.96 to 1.02)).Conclusion In this post-hoc analysis of patients with minor stroke enrolled in the AcT trial, safety and efficacy outcomes with tenecteplase 0.25 mg/kg were not different from alteplase 0.9 mg/kg.

Abstract Background Early diagnosis of large vessel occlusion (LVO) in acute stroke often requires CT angiography (CTA). Automated CT perfusion (CTP) software, which identifies blood flow abnormalities, enhances LVO diagnosis and patient selection for endovascular thrombectomy (EVT). This study evaluates the sensitivity of automated CTP images in detecting perfusion abnormalities in patients with acute ischemic stroke (AIS) and LVO or medium vessel occlusion (MeVO), compared to CTA. Methods We screened acute ischemic stroke patients presenting within 24 h who underwent CT, CTA, and CTP as per institutional protocol. RAPID AI software processed CTP images, while neuroradiologists reviewed CTA for intracranial arterial occlusions. Sensitivity, specificity, and accuracy of automated CTP maps in detecting occlusions were assessed. Results Of 790 screened patients, 31 were excluded due to lack of RAPID CTP data or poor‐quality scans, leaving 759 for analysis. The median age was 71 years (IQR: 61–81), with 47% female. Among them, 678 had AIS, and 81 had AIS ruled out. CTA identified arterial occlusion in 562 patients (74%), with corresponding CTP abnormalities in 537 patients (Tmax > 6 sec). In the 197 without occlusion, CTP was negative in 161. Automated CTP maps had a sensitivity of 95.55% (CI 95: 93.50–97.10%), specificity of 81.73% (CI 95: 75.61–86.86%), negative predictive value of 98.22% (CI 95: 97.39–98.79%), positive predictive value of 63.54% (CI 95: 56.46–70.09%), and overall accuracy of 85.18% (CI 95: 82.45–87.64%). Conclusions Automated CTP maps demonstrated high sensitivity and negative predictive value for LVOs and MeVOs, suggesting their usefulness as a rapid diagnostic tool, especially in settings without expert neuroradiologists.

Background About 25% of patients with acute ischemic stroke have lacunar infarct on follow‐up imaging. In this secondary analysis from the AcT (Alteplase Compared With Tenecteplase) trial, we assessed if there is variation in safety or efficacy of intravenous thrombolysis by infarct type in patients with no visible occlusion. We also determined if this effect differed between tenecteplase and alteplase. Methods and Results This is a secondary analysis from the AcT trial. Lacunar infarct was defined as single, ≤15 mm, and in regions supplied by perforating arterioles on 24‐hour imaging. Outcomes included symptomatic intracerebral hemorrhage at 24 hours, any hemorrhage on imaging, and 90‐day modified Rankin Scale score. Mixed‐effects regression models adjusted for age, sex, stroke severity, thrombolytic type, and onset‐to‐needle time were used. Of 1577 patients, 456/29.9% had no visible occlusion and interpretable follow‐up imaging (magnetic resonance imaging: 41.2%). Of these 93 (20.4%) (magnetic resonance imaging: 62.3%) had lacunar infarct, 171 (37.5%) (magnetic resonance imaging: 67.4%) had nonlacunar infarct, and 192 (42.1%) (magnetic resonance imaging: 7.3%) had no visible infarct. Four patients (2.3%) in the group with nonlacunar infarct and none in the groups with lacunar infarct and no visible infarct developed symptomatic intracerebral hemorrhage. Any intracranial hemorrhage was highest (21; 12.4%) in the group with nonlacunar infarct. There was no significant interaction between thrombolytic type and treatment outcomes. Conclusions In the AcT trial, safety of intravenous thrombolysis was similar across all infarct types in patients with no visible occlusion but functional outcomes were worst in patients with nonlacunar infarct. Safety and functional outcomes after intravenous thrombolysis were better in the groups with lacunar infarct and no visible infarct as compared with the overall trial population.

Background Nerinetide treatment was associated with better clinical outcomes among patients with stroke undergoing endovascular treatment who were not treated with concurrent alteplase in the randomized ESCAPE‐NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke) trial. In patients receiving alteplase, no such effect was seen due to an inactivation of nerinetide by plasmin – the product of tissue plasminogen activation. We hypothesized that improved outcomes in the no‐alteplase patients were associated with reduced infarct growth, a radiological correlate of improved stroke outcomes. Methods Data are from the no‐alteplase stratum of the ESCAPE‐NA1 trial. Patients who underwent computer tomography perfusion (CTP) as part of routine clinical care were included. Admission CTP source data were processed using RAPID software. Infarct core at baseline was defined as areas of relative cerebral blood flow

AbstractMimics account for almost half of hospital admissions for suspected stroke. Stroke mimics may present as a functional (conversion) disorder or may be part of the symptomatology of a neurological or medical disorder. While many underlying conditions can be recognized rapidly by careful assessment, a significant proportion of patients unfortunately still receive thrombolysis and admission to a high-intensity stroke unit with inherent risks and unnecessary costs. Accurate diagnosis is important as recurrent presentations may be common in many disorders. A non-contrast CT is not sufficient to make a diagnosis of acute stroke as the test may be normal very early following an acute stroke. Multi-modal CT or magnetic resonance imaging (MRI) may be helpful to confirm an acute ischaemic stroke and are necessary if stroke mimics are suspected. Treatment in neurological and medical mimics results in prompt resolution of the symptoms. Treatment of functional disorders can be challenging and is often incomplete and requires early psychiatric intervention.

Background Subacute ischemic lesions in intracerebral hemorrhage (ICH) have been hypothesized to result from hypoperfusion. Although studies of cerebral blood flow (CBF) indicate modest hypoperfusion in ICH, these investigations have been limited to early time points. Arterial spin labeling (ASL), a magnetic resonance imaging technique, can be used to measure CBF without a contrast agent. We assessed CBF in patients with ICH using ASL and tested the hypothesis that CBF is related to systolic blood pressure (SBP). Methods and Results In this cross‐sectional study, patients with ICH were assessed with ASL at 48 hours, 7 days, and/or 30 days after onset. Relative CBF (rCBF; ratio of ipsilateral/contralateral perfusion) was measured in the perihematomal regions, hemispheres, border zones, and the perilesional area in patients with diffusion‐weighted imaging hyperintensities. Twenty‐patients (65% men; mean±SD age, 68.5±12.7 years) underwent imaging with ASL at 48 hours (N=12), day 7 (N=6), and day 30 (N=11). Median (interquartile range) hematoma volume was 13.1 (6.3–19.3) mL. Mean±SD baseline SBP was 185.4±25.5 mm Hg. Mean perihematomal rCBF was 0.9±0.2 at 48 hours at all time points. Baseline SBP and other SBP measurements were not associated with a decrease in rCBF in any of the regions of interest (P≥0.111). rCBF did not differ among time points in any of the regions of interest (P≥0.097). Mean perilesional rCBF was 1.04±0.65 and was unrelated to baseline SBP (P=0.105). Conclusions ASL can be used to measure rCBF in patients with acute and subacute ICH. Perihematomal CBF was not associated with SBP changes at any time point. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00963976.