In this randomized trial involving patients with acute ischemic stroke with proximal anterior circulation occlusion, endovascular treatment with a Solitaire stent retriever was more effective than ...medical therapy alone in improving functional outcomes at 90 days.
Recently completed prospective, randomized trials involving patients with acute stroke have consistently shown a clinical benefit for mechanical thrombectomy.
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Our study, called the Randomized Trial of Revascularization with Solitaire FR Device versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting within Eight Hours of Symptom Onset (REVASCAT), shares the following four features with the previously cited trials: enrollment limited to patients with imaging-based evidence of proximal occlusion of the M1 segment (main trunk) of the middle cerebral artery with or without concomitant occlusion of the internal carotid artery, imaging-based exclusion . . .
Objective
The purpose of this study was to test e‐ASPECTS software in patients with stroke. Marketed as a decision‐support tool, e‐ASPECTS may detect features of ischemia or hemorrhage on computed ...tomography (CT) imaging and quantify ischemic extent using Alberta Stroke Program Early CT Score (ASPECTS).
Methods
Using CT from 9 stroke studies, we compared software with masked experts. As per indications for software use, we assessed e‐ASPECTS results for patients with/without middle cerebral artery (MCA) ischemia but no other cause of stroke. In an analysis outside the intended use of the software, we enriched our dataset with non‐MCA ischemia, hemorrhage, and mimics to simulate a representative “front door” hospital population. With final diagnosis as the reference standard, we tested the diagnostic accuracy of e‐ASPECTS for identifying stroke features (ischemia, hyperattenuated arteries, and hemorrhage) in the representative population.
Results
We included 4,100 patients (51% women, median age = 78 years, National Institutes of Health Stroke Scale NIHSS = 10, onset to scan = 2.5 hours). Final diagnosis was ischemia (78%), hemorrhage (14%), or mimic (8%). From 3,035 CTs with expert‐rated ASPECTS, most (2084/3035, 69%) e‐ASPECTS results were within one point of experts. In the representative population, the diagnostic accuracy of e‐ASPECTS was 71% (95% confidence interval CI = 70–72%) for detecting ischemic features, 85% (83–86%) for hemorrhage. Software identified more false positive ischemia (12% vs 2%) and hemorrhage (14% vs <1%) than experts.
Interpretation
On independent testing, e‐ASPECTS provided moderate agreement with experts and overcalled stroke features. Therefore, future prospective trials testing impacts of artificial intelligence (AI) software on patient care and outcome are required before widespread implementation of stroke decision‐support software. ANN NEUROL 2022;92:943–957
In this randomized trial involving patients with acute ischemic stroke, endovascular therapy after the administration of intravenous tissue plasminogen activator (t-PA) was compared with t-PA alone. ...Endovascular therapy did not achieve superior clinical outcomes.
Intravenous tissue plasminogen activator (t-PA; alteplase Activase, Genentech, or Actilyse, Boehringer Ingelheim) is the only proven reperfusion therapy for acute ischemic stroke, and its clinical effectiveness is critically time-dependent.
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A key advantage of intravenous t-PA is that it can be started rapidly after clinical assessment and computed tomography (CT) of the brain without the use of contrast material. However, few patients with ischemic stroke (<10%) meet current eligibility criteria for the use of intravenous t-PA, including arrival within a relatively short therapeutic time window (<4.5 hours) after symptom onset.
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Limitations of intravenous t-PA include dependence on available serum . . .
Intravenous thrombolysis with alteplase improves the outcomes after acute stroke when alteplase is given within 3 hours after the onset of symptoms. In this randomized trial involving patients who ...presented between 3 and 4.5 hours after the onset of stroke, clinical outcomes were modestly better in patients treated with alteplase than in patients given placebo (favorable outcome in 52% vs. 45% of patients).
In this trial involving patients who presented between 3 and 4.5 hours after the onset of stroke, clinical outcomes were modestly better in patients treated with alteplase than in patients given placebo.
Intravenous thrombolytic treatment with alteplase, initiated within 3 hours after the onset of symptoms, is the only medical therapy currently available for acute ischemic stroke. In 1995, the National Institute of Neurological Disorders and Stroke (NINDS) study group reported that patients with acute ischemic stroke who received alteplase (0.9 mg per kilogram of body weight) within 3 hours after the onset of symptoms were at least 30% more likely to have minimal or no disability at 3 months than those who received placebo.
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Two European trials, the European Cooperative Acute Stroke Study (ECASS) and ECASS II, investigated a time window . . .
OBJECTIVEIn this secondary analysis of the Glyburide Advantage in Malignant Edema and Stroke (GAMES-RP) Trial, we report the effect of IV glyburide on adjudicated, edema-related endpoints.
...METHODSBlinded adjudicators assigned designations for hemorrhagic transformation, neurologic deterioration, malignant edema, and edema-related death to patients from the GAMES-RP phase II randomized controlled trial of IV glyburide for large hemispheric infarct. Rates of these endpoints were compared between treatment arms in the per-protocol sample. In those participants with malignant edema, the effects of treatment on additional markers of edema and clinical deterioration were examined.
RESULTSIn the per-protocol sample, 41 patients received glyburide and 36 received placebo. There was no difference in the frequency of hemorrhagic transformation (n = 24 58.5% in IV glyburide vs n = 23 63.9% in placebo, p = 0.91) or the incidence of malignant edema (n = 19 46% in IV glyburide vs n = 17 47% in placebo, p = 0.94). However, treatment with IV glyburide was associated with a reduced proportion of deaths attributed to cerebral edema (n = 1 2.4% with IV glyburide vs n = 8 22.2% with placebo, p = 0.01). In the subset of patients with malignant edema, those treated with IV glyburide had less midline shift (p < 0.01) and reduced MMP-9 (matrix metalloproteinase 9) levels (p < 0.01). The glyburide treatment group had lower rate of NIH Stroke Scale (NIHSS) increase of ≥4 during the infusion period (n = 7 37% in IV glyburide vs n = 12 71% in placebo, p = 0.043), and of change in level of alertness (NIHSS subscore 1a; n = 11 58% vs n = 15 94%, p = 0.016).
CONCLUSIONIV glyburide was associated with improvements in midline shift, level of alertness, and NIHSS, and there were fewer deaths attributed to edema. Additional studies of IV glyburide in large hemispheric infarction are warranted to corroborate these findings.
CLINICALTRIALS.GOV IDENTIFIERNCT01794182.
LEVEL OF EVIDENCEThis study provides Class II evidence that for patients with large hemispheric infarction, IV glyburide improves some edema-related endpoints.
BACKGROUND AND PURPOSE—In acute ischemic stroke, the hyperdense artery sign (HAS) on noncontrast computed tomography (CT) is thought to represent intraluminal thrombus and, therefore, is a surrogate ...of arterial obstruction. We sought to assess the accuracy of HAS as a marker of arterial obstruction by thrombus.
METHODS—The Third International Stroke Trial (IST-3) was a randomized controlled trial testing the use of intravenous thrombolysis for acute ischemic stroke in patients who did not clearly meet the prevailing license criteria. Some participating IST-3 centers routinely performed CT or MR angiography at baseline. One reader assessed all relevant scans independently, blinded to all other data; we checked observer reliability. We combined IST-3 data with a systematic review and meta-analysis of all studies that assessed the accuracy of HAS using angiography (any modality).
RESULTS—IST-3 had 273 patients with baseline CT or MR angiography and was the largest study of HAS accuracy. The meta-analysis (n=902+273=1175, including IST-3) found sensitivity and specificity of HAS for arterial obstruction on angiography to be 52% and 95%, respectively. HAS was more commonly identified in proximal than distal arteries (47% versus 37%; P=0.015), and its sensitivity increased with thinner CT slices (r=−0.73; P=0.001). Neither extent of obstruction nor time after stroke influenced HAS accuracy.
CONCLUSIONS—When present in acute ischemic stroke, HAS indicates a high likelihood of arterial obstruction, but its absence indicates only a 50/50 chance of normal arterial patency. Thin-slice CT improves sensitivity of HAS detection.
CLINICAL TRIAL REGISTRATION—URLhttp://www.controlled-trials.com/ISRCTN25765518. Unique identifierISRCTN25765518.
Summary Background Early administration of intravenous recombinant tissue plasminogen activator (rt-PA) after ischaemic stroke improves outcome. Previous analysis of combined data from individual ...patients suggested potential benefit beyond 3 h from stroke onset. We re-examined the effect of time to treatment with intravenous rt-PA (alteplase) on therapeutic benefit and clinical risk by adding recent trial data to the analysis. Methods We added data from ECASS III (821 patients) and EPITHET (100 patients) to a pool of common data elements from six other trials of alteplase for acute stroke (2775 patients). We used multivariate logistic regression to assess the relation of stroke onset to start of treatment (OTT) with treatment on favourable 3-month outcome (defined as modified Rankin score 0–1), mortality, and occurrence and outcome of clinically relevant parenchymal haemorrhage. The presence of an arterial occlusion was inferred from the patient's symptoms and absence of haemorrhage or other causes of ischaemic stroke. Vascular imaging was not a requirement in the trials. All patients with confirmed OTT within 360 min were included in the analysis. Findings Treatment was started within 360 min of stroke onset in 3670 patients randomly allocated to alteplase (n=1850) or to placebo (n=1820). Odds of a favourable 3-month outcome increased as OTT decreased (p=0·0269) and no benefit of alteplase treatment was seen after around 270 min. Adjusted odds of a favourable 3-month outcome were 2·55 (95% CI 1·44–4·52) for 0–90 min, 1·64 (1·12–2·40) for 91–180 min, 1·34 (1·06–1·68) for 181–270 min, and 1·22 (0·92–1·61) for 271–360 min in favour of the alteplase group. Large parenchymal haemorrhage was seen in 96 (5·2%) of 1850 patients assigned to alteplase and 18 (1·0%) of 1820 controls, with no clear relation to OTT (p=0·4140). Adjusted odds of mortality increased with OTT (p=0·0444) and were 0·78 (0·41–1·48) for 0–90 min, 1·13 (0·70–1·82) for 91–180 min, 1·22 (0·87–1·71) for 181–270 min, and 1·49 (1·00–2·21) for 271–360 min. Interpretation Patients with ischaemic stroke selected by clinical symptoms and CT benefit from intravenous alteplase when treated up to 4·5 h. To increase benefit to a maximum, every effort should be taken to shorten delay in initiation of treatment. Beyond 4·5 h, risk might outweigh benefit. Funding None.
Purpose
In acute cerebral ischemia, the assessment of irreversible injury is crucial for treatment decisions and the patient’s prognosis. There is still uncertainty how imaging can safely ...differentiate reversible from irreversible ischemic brain tissue in the acute phase of stroke.
Methods
We have searched PubMed and Google Scholar for experimental and clinical papers describing the pathology and pathophysiology of cerebral ischemia under controlled conditions.
Results
Within the first 6 h of stroke onset, ischemic cell injury is subtle and hard to recognize under the microscope. Functional impairment is obvious, but can be induced by ischemic blood flow allowing recovery with flow restoration. The critical cerebral blood flow (CBF) threshold for irreversible injury is ~15 ml/100 g × min. Below this threshold, ischemic brain tissue takes up water in case of any residual capillary flow (ionic edema). Because tissue water content is linearly related to X-ray attenuation, computed tomography (CT) can detect and measure ionic edema and, thus, determine ischemic brain infarction. In contrast, diffusion-weighted magnetic resonance imaging (DWI) detects cytotoxic edema that develops at higher thresholds of ischemic CBF and is thus highly sensitive for milder levels of brain ischemia, but not specific for irreversible brain tissue injury.
Conclusion
CT and MRI are complimentary in the detection of ischemic stroke pathology and are valuable for treatment decisions.
Summary Background The clinical benefit of preventive eradication of unruptured brain arteriovenous malformations remains uncertain. A Randomised trial of Unruptured Brain Arteriovenous malformations ...(ARUBA) aims to compare the risk of death and symptomatic stroke in patients with an unruptured brain arteriovenous malformation who are allocated to either medical management alone or medical management with interventional therapy. Methods Adult patients (≥18 years) with an unruptured brain arteriovenous malformation were enrolled into this trial at 39 clinical sites in nine countries. Patients were randomised (by web-based system, in a 1:1 ratio, with random permuted block design block size 2, 4, or 6, stratified by clinical site) to medical management with interventional therapy (ie, neurosurgery, embolisation, or stereotactic radiotherapy, alone or in combination) or medical management alone (ie, pharmacological therapy for neurological symptoms as needed). Patients, clinicians, and investigators are aware of treatment assignment. The primary outcome is time to the composite endpoint of death or symptomatic stroke; the primary analysis is by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00389181. Findings Randomisation was started on April 4, 2007, and was stopped on April 15, 2013, when a data and safety monitoring board appointed by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health recommended halting randomisation because of superiority of the medical management group (log-rank Z statistic of 4·10, exceeding the prespecified stopping boundary value of 2·87). At this point, outcome data were available for 223 patients (mean follow-up 33·3 months SD 19·7), 114 assigned to interventional therapy and 109 to medical management. The primary endpoint had been reached by 11 (10·1%) patients in the medical management group compared with 35 (30·7%) in the interventional therapy group. The risk of death or stroke was significantly lower in the medical management group than in the interventional therapy group (hazard ratio 0·27, 95% CI 0·14–0·54). No harms were identified, other than a higher number of strokes (45 vs 12, p<0·0001) and neurological deficits unrelated to stroke (14 vs 1, p=0·0008) in patients allocated to interventional therapy compared with medical management. Interpretation The ARUBA trial showed that medical management alone is superior to medical management with interventional therapy for the prevention of death or stroke in patients with unruptured brain arteriovenous malformations followed up for 33 months. The trial is continuing its observational phase to establish whether the disparities will persist over an additional 5 years of follow-up. Funding National Institutes of Health, National Institute of Neurological Disorders and Stroke.
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