Among patients with acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation, less than 40% regain functional independence when treated with intravenous tissue plasminogen activator (t-PA) alone. Thrombectomy with the use of a stent retriever, in addition to intravenous t-PA, increases reperfusion rates and may improve long-term functional outcome. We randomly assigned eligible patients with stroke who were receiving or had received intravenous t-PA to continue with t-PA alone (control group) or to undergo endovascular thrombectomy with the use of a stent retriever within 6 hours after symptom onset (intervention group). Patients had confirmed occlusions in the proximal anterior intracranial circulation and an absence of large ischemic-core lesions. The primary outcome was the severity of global disability at 90 days, as assessed by means of the modified Rankin scale (with scores ranging from 0 [no symptoms] to 6 [death]). The study was stopped early because of efficacy. At 39 centers, 196 patients underwent randomization (98 patients in each group). In the intervention group, the median time from qualifying imaging to groin puncture was 57 minutes, and the rate of substantial reperfusion at the end of the procedure was 88%. Thrombectomy with the stent retriever plus intravenous t-PA reduced disability at 90 days over the entire range of scores on the modified Rankin scale (P<0.001). The rate of functional independence (modified Rankin scale score, 0 to 2) was higher in the intervention group than in the control group (60% vs. 35%, P<0.001). There were no significant between-group differences in 90-day mortality (9% vs. 12%, P=0.50) or symptomatic intracranial hemorrhage (0% vs. 3%, P=0.12). In patients receiving intravenous t-PA for acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation, thrombectomy with a stent retriever within 6 hours after onset improved functional outcomes at 90 days. (Funded by Covidien; SWIFT PRIME ClinicalTrials.gov number, NCT01657461.)

Background and Purpose—: The authors present an overview of the current evidence and management recommendations for evaluation and treatment of adults with acute ischemic stroke. The intended audiences are prehospital care providers, physicians, allied health professionals, and hospital administrators responsible for the care of acute ischemic stroke patients within the first 48 hours from stroke onset. These guidelines supersede the prior 2007 guidelines and 2009 updates. Methods—: Members of the writing committee were appointed by the American Stroke Association Stroke Council’s Scientific Statement Oversight Committee, representing various areas of medical expertise. Strict adherence to the American Heart Association conflict of interest policy was maintained throughout the consensus process. Panel members were assigned topics relevant to their areas of expertise, reviewed the stroke literature with emphasis on publications since the prior guidelines, and drafted recommendations in accordance with the American Heart Association Stroke Council’s Level of Evidence grading algorithm. Results—: The goal of these guidelines is to limit the morbidity and mortality associated with stroke. The guidelines support the overarching concept of stroke systems of care and detail aspects of stroke care from patient recognition; emergency medical services activation, transport, and triage; through the initial hours in the emergency department and stroke unit. The guideline discusses early stroke evaluation and general medical care, as well as ischemic stroke, specific interventions such as reperfusion strategies, and general physiological optimization for cerebral resuscitation. Conclusions—: Because many of the recommendations are based on limited data, additional research on treatment of acute ischemic stroke remains urgently needed.

Background and Purpose— The phrase “time is brain” emphasizes that human nervous tissue is rapidly lost as stroke progresses and emergent evaluation and therapy are required. Recent advances in quantitative neurostereology and stroke neuroimaging permit calculation of just how much brain is lost per unit time in acute ischemic stroke. Methods— Systematic literature-review identified consensus estimates of number of neurons, synapses, and myelinated fibers in the human forebrain; volume of large vessel, supratentorial ischemic stroke; and interval from onset to completion of large vessel, supratentorial ischemic stroke. Results— The typical final volume of large vessel, supratentorial ischemic stroke is 54 mL (varied in sensitivity analysis from 19 to 100 mL). The average duration of nonlacunar stroke evolution is 10 hours (range 6 to 18 hours), and the average number of neurons in the human forebrain is 22 billion. In patients experiencing a typical large vessel acute ischemic stroke, 120 million neurons, 830 billion synapses, and 714 km (447 miles) of myelinated fibers are lost each hour. In each minute, 1.9 million neurons, 14 billion synapses, and 12 km (7.5 miles) of myelinated fibers are destroyed. Compared with the normal rate of neuron loss in brain aging, the ischemic brain ages 3.6 years each hour without treatment. Altering single input variables in sensitivity analyses modestly affected the estimated point values but not order of magnitude. Conclusions— Quantitative estimates of the pace of neural circuitry loss in human ischemic stroke emphasize the time urgency of stroke care. The typical patient loses 1.9 million neurons each minute in which stroke is untreated.

This scientific statement is intended for use by physicians and allied health personnel caring for patients with transient ischemic attacks. Formal evidence review included a structured literature search of Medline from 1990 to June 2007 and data synthesis employing evidence tables, meta-analyses, and pooled analysis of individual patient-level data. The review supported endorsement of the following, tissue-based definition of transient ischemic attack (TIA): a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction. Patients with TIAs are at high risk of early stroke, and their risk may be stratified by clinical scale, vessel imaging, and diffusion magnetic resonance imaging. Diagnostic recommendations include: TIA patients should undergo neuroimaging evaluation within 24 hours of symptom onset, preferably with magnetic resonance imaging, including diffusion sequences; noninvasive imaging of the cervical vessels should be performed and noninvasive imaging of intracranial vessels is reasonable; electrocardiography should occur as soon as possible after TIA and prolonged cardiac monitoring and echocardiography are reasonable in patients in whom the vascular etiology is not yet identified; routine blood tests are reasonable; and it is reasonable to hospitalize patients with TIA if they present within 72 hours and have an ABCD ² score ≥3, indicating high risk of early recurrence, or the evaluation cannot be rapidly completed on an outpatient basis.

Background and Purpose— For a biomarker to serve as an auxiliary or surrogate outcome measure, it must be tightly correlated with and causally related to functional clinical outcome. Vessel recanalization is a potential surrogate outcome marker for functional outcome in trials of thrombolytic and mechanical recanalization therapies in acute stroke, but the correlation of recanalization and clinical outcome has not been previously systematically reviewed. Methods— Through Medline search, we identified and abstracted recanalization and outcome data from all articles published between 1985 and 2002 that assessed vessel recanalization, either spontaneous or therapeutically induced, in acute ischemic stroke. Results— Fifty-three studies encompassing 2066 patients reported recanalization rates. Recanalization rates categorized according to intervention were: spontaneous (24.1%), intravenous fibrinolytic (46.2%), intra-arterial fibrinolytic (63.2%), combined intravenous–intra-arterial (67.5%), and mechanical (83.6%). Clinical outcome data categorized by success or failure in achieving recanalization was available from 33 articles encompassing 998 patients. Good functional outcomes at 3 months were more frequent in recanalized versus nonrecanalized patients with odds ratio of 4.43 (95% CI, 3.32 to 5.91). Three-month mortality was reduced in recanalized patients (odds ratio, 0.24; 95% CI, 0.16 to 0.35). Rates of symptomatic hemorrhagic transformation did not differ between the 2 groups (odds ratio, 1.11; 95% CI, 0.71 to 1.74). Conclusions— Formal meta-analysis confirms a strong correlation between recanalization and outcome in acute ischemic stroke. Recanalization is strongly associated with improved functional outcomes and reduced mortality. These findings suggest that recanalization is an appropriate biomarker of therapeutic activity in early phase trials of thrombolytic treatment in acute ischemic stroke.