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 audienc...

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Guidelines for the Early Management of Patients With Acute Ischemic Stroke A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association

Background and Purpose- The purpose of these guidelines is to provide an up-to-date comprehensive set of recommendations in a single document for clinicians caring for adult patients with acute arterial ischemic stroke. The intended audiences are prehospital care providers, physicians, allied health professionals, and hospital administrators. These guidelines supersede the 2013 Acute Ischemic Stroke (AIS) Guidelines and are an update of the 2018 AIS Guidelines. Methods- Members of the writing group were appointed by the American Heart Association (AHA) Stroke Council's Scientific Statements Oversight Committee, representing various areas of medical expertise. Members were not allowed to participate in discussions or to vote on topics relevant to their relations with industry. An update of the 2013 AIS Guidelines was originally published in January 2018. This guideline was approved by the AHA Science Advisory and Coordinating Committee and the AHA Executive Committee. In April 2018, a revision to these guidelines, deleting some recommendations, was published online by the AHA. The writing group was asked review the original document and revise if appropriate. In June 2018, the writing group submitted a document with minor changes and with inclusion of important newly published randomized controlled trials with >100 participants and clinical outcomes at least 90 days after AIS. The document was sent to 14 peer reviewers. The writing group evaluated the peer reviewers' comments and revised when appropriate. The current final document was approved by all members of the writing group except when relationships with industry precluded members from voting and by the governing bodies of the AHA. These guidelines use the American College of Cardiology/AHA 2015 Class of Recommendations and Level of Evidence and the new AHA guidelines format. Results- These guidelines detail prehospital care, urgent and emergency evaluation and treatment with intravenous and intra-arterial therapies, and in-hospital management, including secondary prevention measures that are appropriately instituted within the first 2 weeks. The guidelines support the overarching concept of stroke systems of care in both the prehospital and hospital settings. Conclusions- These guidelines provide general recommendations based on the currently available evidence to guide clinicians caring for adult patients with acute arterial ischemic stroke. In many instances, however, only limited data exist demonstrating the urgent need for continued research on treatment of acute ischemic stroke.

Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association.

Despite the global impact and advances in understanding the pathophysiology of cerebrovascular diseases, the term "stroke" is not consistently defined in clinical practice, in clinical research, or in assessments of the public health. The classic definition is mainly clinical and does not account for advances in science and technology. The Stroke Council of the American Heart Association/American Stroke Association convened a writing group to develop an expert consensus document for an updated definition of stroke for the 21st century. Central nervous system infarction is defined as brain, spinal cord, or retinal cell death attributable to ischemia, based on neuropathological, neuroimaging, and/or clinical evidence of permanent injury. Central nervous system infarction occurs over a clinical spectrum: Ischemic stroke specifically refers to central nervous system infarction accompanied by overt symptoms, while silent infarction by definition causes no known symptoms. Stroke also broadly includes intracerebral hemorrhage and subarachnoid hemorrhage. The updated definition of stroke incorporates clinical and tissue criteria and can be incorporated into practice, research, and assessments of the public health.

An Updated Definition of Stroke for the 21st Century A Statement for Healthcare Professionals From the American Heart Association/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 …

https://www.pennstatehershey.org/c/document_library/get_file?folderId=115233&name=DLFE-2413.pdf

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

Background and Purpose— The National Institutes of Health (NIH) estimates that stroke costs now exceed $45 billion per year. Stroke is the third leading cause of death and one of the leading causes of adult disability in North America, Europe, and Asia. A number of well-designed randomized stroke trials and case series have now been reported in the literature to evaluate the safety and efficacy of thrombolytic therapy for the treatment of acute ischemic stroke. These stroke trials have included intravenous studies, intra-arterial studies, and combinations of both, as well as use of mechanical devices for removal of thromboemboli and of neuroprotectant drugs, alone or in combination with thrombolytic therapy. At this time, the only therapy demonstrated to improve outcomes from an acute stroke is thrombolysis of the clot responsible for the ischemic event. There is room for improvement in stroke lysis studies. Divergent criteria, with disparate reporting standards and definitions, have made direct compariso...

Trial Design and Reporting Standards for Intra-Arterial Cerebral Thrombolysis for Acute Ischemic Stroke

Diffusion magnetic resonance imaging provides an early marker of acute cerebral ischemic injury. Thrombolytic reversal of diffusion abnormalities has not previously been demonstrated in humans. Serial diffusion and perfusion imaging studies were acquired in patients experiencing acute hemispheric cerebral ischemia treated with intra-arterial thrombolytic therapy within 6 hours of symptom onset. Seven patients met inclusion criteria of prethrombolysis and postthrombolysis magnetic resonance studies, presence of large artery anterior circulation occlusion at angiography, and achievement of vessel recanalization. Mean diffusion-weighted imaging lesion volume at baseline was 23 cm3 (95% confidence interval [95% CI], 8-38 cm3) and decreased to 10 cm3 (95% CI, 3-17 cm3) 2.5 to 9.5 hours after thrombolysis. Mean apparent diffusion coefficient lesion volume decreased from 9 cm3 (95% CI, 2-16 cm3) at baseline to 1 cm3 (95% CI, 0.4-2 cm3) early after thrombolysis. A secondary increase in diffusion volumes was seen in 3 of 6 patients at day 7. In all 4 patients in whom perfusion imaging was obtained before and after treatment, complete resolution of the perfusion deficit was shown. Diffusion magnetic resonance signatures of early tissue ischemic injury can be reversed in humans by prompt thrombolytic vessel recanalization. The ischemic penumbra includes not only the region of diffusion/perfusion mismatch, but also portions of the region of initial diffusion abnormality.

Thrombolytic reversal of acute human cerebral ischemic injury shown by diffusion/perfusion magnetic resonance imaging

Although brain ischemia has been extensively studied using diffusion-weighted magnetic resonance imaging, most studies performed so far have not had adequate time resolution to follow the temporal changes in the water apparent diffusion coefficient (ADC) in hyperacute ischemia. Using diffusion echo planar imaging, we obtained ADC maps (calculated from measurements made with 8 b-values) with a time resolution of 43 s in a feline model of global brain ischemia and reperfusion. Different protocols were performed: 10-min hypoperfusion, 10- and 22-min ischemia followed by reperfusion, and cardiac arrest. ADC values were obtained from white matter of the internal capsule and from the thalamus. Cortical gray matter measurements were not deemed reliable due to the close proximity of CSF in the cortical sulci. Following occlusion, the ADC declined in the thalamus to < 2 SD of its normal baseline value within 1.5-2.5 min. This decay was exponential with a time constant (tau +/- SD) of 6.0 +/- 2.6 min; no further decrease in the ADC was observed 10 min following ischemia. Following reperfusion, in animals that showed ADC recovery, the ADC began increasing immediately, returning to its preischemic value in approximately 15 min. No significant ADC changes were observed during hypoperfusion. Following cardiac arrest, the decay of ADC was more rapid in the thalamus (tau = 2.6 +/- 0.6 min) than in white matter (tau = 6.6 +/- 1.8 min). We observed that the ADC at 40 min after cardiac arrest was similar to the ADC at 10 min after ischemia. Given that all animals subjected to 10-min ischemic episodes showed ADC recovery with reperfusion, doubt is cast on whether it is possible to define a threshold value of the ADC below which brain tissue is irreversibly damaged. Finally, despite variability in the time constants of the ADC decay induced by ischemia, the ADC values at 10 min were very similar in all the animals. This suggests that when blood flow is diminished sufficiently to induce an ADC reduction, differences in perfusion affect the rapidity of the decrease but not the final asymptotic value reached.

https://journals.sagepub.com/doi/pdf/10.1097/00004647-199609000-00013

High Temporal Resolution Diffusion MRI of Global Cerebral Ischemia and Reperfusion

8 Background: Late secondary injury following vessel recanalization, recently observed in animal stroke models, may limit the benefit of reperfusion therapy. The frequency and clinical correlates of secondary injury in humans have not been previously characterized. Methods: Diffusion-perfusion MRIs were performed prior to treatment, early after recanalization (median 4 hrs), and at day 7 in patients undergoing vessel recanalization with intra-arterial (IA) thrombolytics. Post-treatment MRIs were co-registered to the pretreatment scan to allow a voxel-by-voxel analysis of tissue fate over time. Results: Eighteen patients (13 females, 5 males) were studied. Mean age was 71 and median entry NIHSS score 13. Early after recanalization, partial or complete normalization of DWI abnormalities occurred in 8/18 (44%) patients, and of apparent diffusion coefficient (ADC) abnormalities in 13/18 (72%). Among the 8 patients with early DWI reversal, late secondary injury on day 7 (on DWI or T2W sequences) occurred in 5 (63%), and sustained normalization of all reversed tissue in 3 (38%). Across all patients, of tissues showing pretreatment DWI abnormality, 41% of voxels showed no early reversal, 33% early reversal with sustained normalization at day 7, and 18% early reversal but late secondary injury. Pretreatment ADC values were lowest in regions experiencing no reversal (mean ADC 624 um2/sec), intermediate in regions with reversal and secondary decline (641), and highest in regions with sustained reversal (677). Evolution of neurologic deficit (NIHSS) did not differ in patients with secondary injury vs. those with sustained reversal, nor did age, time to recanalization, degree of recanalization, or presence of post-ischemic hyperperfusion. Conclusions: Following vessel recanalization with IA thrombolysis, partial or complete reversal of initial DWI abnormality occurs in ∼40% of patients. A late, secondary signature of injury compromising some or all of the initially normalized tissue occurs in over 50% of these patients, but is not associated with clinical worsening.

Late Secondary Injury in Patients Undergoing Vessel Recanalization with Intra-arterial Thrombolysis: Visualization with MRI, Frequency, and Clinical Correlates

James Mattiello

Papers

Thrombolytic reversal of acute human cerebral ischemic injury shown by diffusion/perfusion magnetic resonance imaging

High Temporal Resolution Diffusion MRI of Global Cerebral Ischemia and Reperfusion

Late Secondary Injury in Patients Undergoing Vessel Recanalization with Intra-arterial Thrombolysis: Visualization with MRI, Frequency, and Clinical Correlates