Chelsea S. Kidwell

Guidelines for the Early Management of Patients With Ischemic Stroke: A Scientific Statement From the Stroke Council of the American Stroke Association

In 1994, a panel appointed by the Stroke Council of the American Heart Association authored guidelines for the management of patients with acute ischemic stroke.1 After the approval of the use of intravenous recombinant tissue plasminogen activator (rtPA) for treatment of acute ischemic stroke by the Food and Drug Administration, the guidelines were supplemented by a series of recommendations 2 years later.2 Several promising interventions for the treatment of acute ischemic stroke have subsequently been tested in clinical trials, and other components of acute management have been evaluated since the previous guidelines were published. These new data have prompted the present revision of the prior guideline statement. The goal of these guidelines is to provide updated recommendations that can be used by primary care physicians, emergency medicine physicians, neurologists, and other physicians who provide acute stroke care from admission to an emergency department through the first 24 to 48 hours of hospitalization by addressing the diagnosis and emergent treatment of the acute ischemic stroke in addition to the management of its acute and subacute neurological and medical complications. Several groups have now written statements about management of stroke.3–7 These statements also include recommendations about public educational programs, the organization of stroke resources, and other aspects of patient management. For example, the Brain Attack Coalition published recommendations for organizing stroke services in a community, and the recommendations of the American Heart Association Emergency Cardiovascular Care Committee provide an outline for emergency medical services.6 The current panel elected not to duplicate these recent efforts. Therapies to prevent recurrent stroke, also a component of acute management, are similar to prophylactic medical or surgical therapies used for patients with transient ischemic attacks and other high-risk patients. The reader is referred to relevant recent statements for additional information.8,9 In developing …

Safety and Efficacy of Mechanical Embolectomy in Acute Ischemic Stroke Results of the MERCI Trial

Background and Purpose— The only Food and Drug Administration (FDA)-approved treatment for acute ischemic stroke is tissue plasminogen activator (tPA) given intravenously within 3 hours of symptom onset. An alternative strategy for opening intracranial vessels during stroke is mechanical embolectomy, especially for patients ineligible for intravenous tPA. Methods— We investigated the safety and efficacy of a novel embolectomy device (Merci Retriever) to open occluded intracranial large vessels within 8 hours of the onset of stroke symptoms in a prospective, nonrandomized, multicenter trial. All patients were ineligible for intravenous tPA. Primary outcomes were recanalization and safety, and secondary outcomes were neurological outcome at 90 days in recanalized versus nonrecanalized patients. Results— Recanalization was achieved in 46% (69/151) of patients on intention to treat analysis, and in 48% (68/141) of patients in whom the device was deployed. This rate is significantly higher than that expected using an historical control of 18% (P<0.0001). Clinically significant procedural complications occurred in 10 of 141 (7.1%) patients. Symptomatic intracranial hemorrhages was observed in 11 of 141 (7.8%) patients. Good neurological outcomes (modified Rankin score ≤2) were more frequent at 90 days in patients with successful recanalization compared with patients with unsuccessful recanalization (46% versus 10%; relative risk [RR], 4.4; 95% CI, 2.1 to 9.3; P<0.0001), and mortality was less (32% versus 54%; RR, 0.59; 95% CI, 0.39 to 0.89; P=0.01). Conclusions— A novel endovascular embolectomy device can significantly restore vascular patency during acute ischemic stroke within 8 hours of stroke symptom onset and provides an alternative intervention for patients who are otherwise ineligible for thrombolytics.

A Trial of Imaging Selection and Endovascular Treatment for Ischemic Stroke

BACKGROUND Whether brain imaging can identify patients who are most likely to benefit from therapies for acute ischemic stroke and whether endovascular thrombectomy improves clinical outcomes in such patients remains unclear. METHODS In this study, we randomly assigned patients within 8 hours after the onset of large-vessel, anterior-circulation strokes to undergo mechanical embolectomy (Merci Retriever or Penumbra System) or receive standard care. All patients underwent pretreatment computed tomography or magnetic resonance imaging of the brain. Randomization was stratified according to whether the patient had a favorable penumbral pattern (substantial salvageable tissue and small infarct core) or a nonpenumbral pattern (large core or small or absent penumbra). We assessed outcomes using the 90-day modified Rankin scale, ranging from 0 (no symptoms) to 6 (dead). RESULTS Among 118 eligible patients, the mean age was 65.5 years, the mean time to enrollment was 5.5 hours, and 58% had a favorable penumbral pattern. Revascularization in the embolectomy group was achieved in 67% of the patients. Ninety-day mortality was 21%, and the rate of symptomatic intracranial hemorrhage was 4%; neither rate differed across groups. Among all patients, mean scores on the modified Rankin scale did not differ between embolectomy and standard care (3.9 vs. 3.9, P=0.99). Embolectomy was not superior to standard care in patients with either a favorable penumbral pattern (mean score, 3.9 vs. 3.4; P=0.23) or a nonpenumbral pattern (mean score, 4.0 vs. 4.4; P=0.32). In the primary analysis of scores on the 90-day modified Rankin scale, there was no interaction between the pretreatment imaging pattern and treatment assignment (P=0.14). CONCLUSIONS A favorable penumbral pattern on neuroimaging did not identify patients who would differentially benefit from endovascular therapy for acute ischemic stroke, nor was embolectomy shown to be superior to standard care. (Funded by the National Institute of Neurological Disorders and Stroke; MR RESCUE ClinicalTrials.gov number, NCT00389467.).

2015 American Heart Association/American Stroke Association Focused Update of the 2013 Guidelines for the Early Management of Patients With Acute Ischemic Stroke Regarding Endovascular Treatment: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association

Purpose— The aim of this guideline is to provide a focused update of the current recommendations for the endovascular treatment of acute ischemic stroke. When there is overlap, the recommendations made here supersede those of previous guidelines. Methods— This focused update analyzes results from 8 randomized, clinical trials of endovascular treatment and other relevant data published since 2013. It is not intended to be a complete literature review from the date of the previous guideline publication but rather to include pivotal new evidence that justifies changes in current recommendations. Members of the writing committee were appointed by the American Heart Association/American Stroke Association Stroke Council’s Scientific Statement Oversight Committee and the American Heart Association/American Stroke Association Manuscript Oversight Committee. Strict adherence to the American Heart Association conflict of interest policy was maintained throughout the consensus process. Recommendations follow the American Heart Association/American Stroke Association methods of classifying the level of certainty of the treatment effect and the class of evidence. Prerelease review of the draft guideline was performed by 6 expert peer reviewers and by the members of the Stroke Council Scientific Statement Oversight Committee and Stroke Council Leadership Committee. Results— Evidence-based guidelines are presented for the selection of patients with acute ischemic stroke for endovascular treatment, for the endovascular procedure, and for systems of care to facilitate endovascular treatment. Conclusions— Certain endovascular procedures have been demonstrated to provide clinical benefit in selected patients with acute ischemic stroke. Systems of care should be organized to facilitate the delivery of this care.Purpose— The aim of this guideline is to provide a focused update of the current recommendations for the endovascular treatment of acute ischemic stroke. Where there is overlap, the recommendations made here supersede those of previous guidelines. Methods— This focused update analyzes results from 8 randomized clinical trials of endovascular treatment and other relevant data published since 2013. It is not intended to be a complete literature review from the date of the previous guideline publication but rather to include pivotal new evidence that justifies changes in current recommendations. Members of the writing committee were appointed by the American Heart Association/American Stroke Association Stroke Council’s Scientific Statement Oversight Committee and the American Heart Association/American Stroke Association Manuscript Oversight Committee (MOC). Strict adherence to the American Heart Association conflict of interest policy was maintained throughout the consensus process. Recommendations follow the American Heart Association/American Stroke Association methods of classifying the level of certainty of the treatment effect and the class of evidence. Prerelease review of the draft guideline was performed by 6 expert peer reviewers and by the members of the Stroke Council Scientific Statement Oversight Committee and Stroke Council Leadership Committee. Results— Evidence-based guidelines are presented for the selection of patients with acute ischemic stroke for endovascular treatment, the endovascular procedure and for systems of care to facilitate endovascular treatment. Conclusions— Certain endovascular procedures have been demonstrated to provide clinical benefit in selected patients with acute ischemic stroke. Systems of care should be organized to facilitate the delivery of this care.

Acute seizures after intracerebral hemorrhage A factor in progressive midline shift and outcome

Objective: To determine whether early seizures that occur frequently after intracerebral hemorrhage (ICH) lead to increased brain edema as manifested by increased midline shift. Methods: A total of 109 patients with ischemic stroke (n = 46) and intraparenchymal hemorrhage (n = 63) prospectively underwent continuous EEG monitoring after admission. The incidence, timing, and factors associated with seizures were defined. Serial CT brain imaging was conducted at admission, 24 hours, and 48 to 72 hours after hemorrhage and assessed for hemorrhage volume and midline shift. Outcome at time of discharge was assessed using the Glasgow Outcome Scale score. Results: Electrographic seizures occurred in 18 of 63 (28%) patients with ICH, compared with 3 of 46 (6%) patients with ischemic stroke (OR = 5.7, 95% CI 1.4 to 26.5, p < 0.004) during the initial 72 hours after admission. Seizures were most often focal with secondary generalization. Seizures were more common in lobar hemorrhages but occurred in 21% of subcortical hemorrhages. Posthemorrhagic seizures were associated with neurologic worsening on the NIH Stroke Scale (14.8 vs 18.6, p < 0.05) and with an increase in midline shift (+ 2.7 mm vs −2.4 mm, p < 0.03). There was a trend toward increased poor outcome (p < 0.06) in patients with posthemorrhagic seizures. On multivariate analysis, age and initial NIH Stroke Scale score were independent predictors of outcome. Conclusion: Seizures occur commonly after ICH and may be nonconvulsive. Seizures are independently associated with increased midline shift after intraparenchymal hemorrhage.

Recommendations for Imaging of Acute Ischemic Stroke A Scientific Statement From the American Heart Association

Stroke is a common and serious disorder, with an incidence of ≈795 000 each year in the United States alone. Worldwide, stroke is a leading cause of death and disability. Recombinant tissue plasminogen activator (rtPA) was approved a decade ago for the treatment of acute ischemic stroke. The guidelines for its use include stroke onset within 3 hours of intravenous drug administration, preceded by a computed tomographic (CT) scan to exclude the presence of hemorrhage, which is a contraindication to the use of the drug. Although randomized, controlled studies in Europe and North America demonstrated the efficacy of this treatment, it also was associated with an incidence of intracranial hemorrhage of 6.4%,1,2⇓ which was shown on subsequent studies to be even greater if there was not strict adherence to the administration protocol.3 The goal of these controlled studies was to evaluate patient outcome. There was no attempt to determine the site, or even the actual presence, of a vascular occlusion, the degree of tissue injury, or the amount of tissue at risk for further injury that might be salvageable. More than a decade later, progress for treating acute ischemic stroke has been slow,4,5⇓ yet the goals for treating this common disease have expanded. First, there is the need to extend the therapeutic window from 3 to ≥6 hours. Even with the rapid communication and transportation in our societies today, very few patients present for treatment within 3 hours.6 Second, there is the desire to improve the efficacy of treatment. It had been shown even before the randomized, controlled studies that intravenous rtPA works better in small peripheral vessels than in the large vessels at the skull base.7 Third, there is a need to decrease the complication rate, especially if patients are to be …

Prehospital Neuroprotective Therapy for Acute Stroke Results of the Field Administration of Stroke Therapy–Magnesium (FAST–MAG) Pilot Trial

Background and Purpose— To demonstrate that paramedic initiation of intravenous magnesium sulfate (Mg) in the field in focal stroke patients is feasible, safe, and yields significant time-savings compared with in-hospital initiation of neuroprotective therapy. Methods— We performed an open-label clinical trial. Inclusion criteria were: (1) likely stroke as identified by the Los Angeles Prehospital Stroke Screen; (2) age 45 to 95; and (3) treatment initiation within 12 hours of symptom onset. Paramedics initiated 4 g Mg loading dose in the field, followed by 16 g over 24 hours in hospital. Results— Twenty patients were enrolled, with mean age 74 (range 44 to 92), and 50% were male. Final diagnosis was acute cerebrovascular disease in all (ischemic 80%, hemorrhagic 20%). Study agent infusion began a median of 100 minutes after symptom onset (range 24 to 703), and 70% received study agent within 2 hours of onset. The interval from paramedic arrival on scene to study agent start was: field-initiated, 26 minutes (range 15 to 64) versus in-hospital initiated (historic controls), 139 minutes (range 66 to 300; P <0.0001). Paramedics rated patient status on hospital arrival as improved 20%, worsened 5%, and unchanged 75%. Median NIHSS on hospital arrival was 11 in all patients and 16 in patients unchanged since field treatment start. Good functional outcome at 3 months (Rankin ≤ 2) occurred in 60%. No serious adverse events were associated with field therapy initiation. Conclusions— Field initiation of Mg sulfate in acute stroke patients is feasible and safe. Prehospital trial conduct substantially reduces on-scene to needle time and permits hyperacute delivery of neuroprotective therapy.

Evidence-based guideline: The role of diffusion and perfusion MRI for the diagnosis of acute ischemic stroke Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology

Objective: To assess the evidence for the use of diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) in the diagnosis of patients with acute ischemic stroke. Methods: We systematically analyzed the literature from 1966 to January 2008 to address the diagnostic and prognostic value of DWI and PWI. Results and Recommendations: DWI is established as useful and should be considered more useful than noncontrast CT for the diagnosis of acute ischemic stroke within 12 hours of symptom onset. DWI should be performed for the most accurate diagnosis of acute ischemic stroke (Level A); however, the sensitivity of DWI for the diagnosis of ischemic stroke in a general sample of patients with possible acute stroke is not perfect. The diagnostic accuracy of DWI in evaluating cerebral hemorrhage is outside the scope of this guideline. On the basis of Class II and III evidence, baseline DWI volumes probably predict baseline stroke severity in anterior territory stroke (Level B) but possibly do not in vertebrobasilar artery territory stroke (Level C). Baseline DWI lesion volumes probably predict (final) infarct volumes (Level B) and possibly predict early and late clinical outcome measures (Level C). Baseline PWI volumes predict to a lesser degree the baseline stroke severity compared with DWI (Level C). There is insufficient evidence to support or refute the value of PWI in diagnosing acute ischemic stroke (Level U).

Secondary preventive medication persistence and adherence 1 year after stroke

Objective: Data on long-term use of secondary prevention medications following stroke are limited. The Adherence eValuation After Ischemic stroke–Longitudinal (AVAIL) Registry assessed patient, provider, and system-level factors influencing continuation of prevention medications for 1 year following stroke hospitalization discharge. Methods: Patients with ischemic stroke or TIA discharged from 106 hospitals participating in the American Heart Association Get With The Guidelines–Stroke program were surveyed to determine their use of warfarin, antiplatelet, antihypertensive, lipid-lowering, and diabetes medications from discharge to 12 months. Reasons for stopping medications were ascertained. Persistence was defined as continuation of all secondary preventive medications prescribed at hospital discharge, and adherence as continuation of prescribed medications except those stopped according to health care provider instructions. Results: Of the 2,880 patients enrolled in AVAIL, 88.4% (2,457 patients) completed 1-year interviews. Of these, 65.9% were regimen persistent and 86.6% were regimen adherent. Independent predictors of 1-year medication persistence included fewer medications prescribed at discharge, having an adequate income, having an appointment with a primary care provider, and greater understanding of why medications were prescribed and their side effects. Independent predictors of adherence were similar to those for persistence. Conclusions: Although up to one-third of stroke patients discontinued one or more secondary prevention medications within 1 year of hospital discharge, self-discontinuation of these medications is uncommon. Several potentially modifiable patient, provider, and system-level factors associated with persistence and adherence may be targets for future interventions.

Blood–Brain Barrier Disruption in Humans Is Independently Associated With Increased Matrix Metalloproteinase-9

Background and Purpose— Matrix metalloproteinases (MMP) may play a role in blood–brain barrier (BBB) disruption after ischemic stroke. We hypothesized that plasma concentrations of MMP-9 are associated with a marker of BBB disruption in patients evaluated for acute stroke. Methods— Patients underwent MRI on presentation and ≈24 hours later. The MRI marker, termed hyperintense acute reperfusion injury marker (HARM), is gadolinium enhancement of cerebrospinal fluid on fluid-attenuated inversion recovery MRI. Plasma MMP-9 and tissue inhibitor of matrix metalloproteinase-1 were measured by enzyme-linked immunosorbent assay. Logistic regression models tested for predictors of HARM on 24-hour follow-up scans separately for MMP-9 and the ratio of MMP-9 to TIMP-1. Results— For the 41 patients enrolled, diagnoses were: acute ischemic cerebrovascular syndrome, 33 (80.6%); intracerebral hemorrhage, 6 (14.6%); stroke mimic, 1 (2.4%); and no stroke, 1 (2.4%). HARM was present in 17 (41.5%) patients. In model 1, HARM was associated with baseline plasma MMP-9 concentration (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.001–1.019; P=0.033). In model 2, HARM was associated with the ratio of MMP-9 to tissue inhibitor of matrix metalloproteinase-1 (OR, 4.94; 95% CI, 1.27–19.14; P=0.021). Conclusions— Baseline MMP-9 was a significant predictor of HARM at 24-hour follow-up, supporting the hypothesis that MMP-9 is associated with BBB disruption. If the association between MMP-9 and BBB disruption is confirmed in future studies, HARM may be a useful imaging marker to evaluate MMP-9 inhibition in ischemic stroke and other populations with BBB disruption.