(Stroke. 2007;38:1655.)
© 2007 American Heart Association, Inc.
AHA/ASA Guideline |

Purpose— Our goal is to provide an overview of the current evidence about components of the evaluation and treatment of adults with acute ischemic stroke. The intended audience is physicians and other emergency healthcare providers who treat patients within the first 48 hours after stroke. In addition, information for healthcare policy makers is included.
Methods— Members of the panel were appointed by the American Heart Association Stroke Councils Scientific Statement Oversight Committee and represented different areas of expertise. The panel reviewed the relevant literature with an emphasis on reports published since 2003 and used the American Heart Association Stroke Councils Levels of Evidence grading algorithm to rate the evidence and to make recommendations. After approval of the statement by the panel, it underwent peer review and approval by the American Heart Association Science Advisory and Coordinating Committee. It is intended that this guideline be fully updated in 3 years.
Results— Management of patients with acute ischemic stroke remains multifaceted and includes several aspects of care that have not been tested in clinical trials. This statement includes recommendations for management from the first contact by emergency medical services personnel through initial admission to the hospital. Intravenous administration of recombinant tissue plasminogen activator remains the most beneficial proven intervention for emergency treatment of stroke. Several interventions, including intra-arterial administration of thrombolytic agents and mechanical interventions, show promise. Because many of the recommendations are based on limited data, additional research on treatment of acute ischemic stroke is needed.
Key Words: AHA Scientific Statements emergency medical services stroke acute cerebral infarction tissue plasminogen activator
The present document is a comprehensive guideline statement on the management of patients with acute ischemic stroke that supercedes the prior statement and interim updates.1–3 These guidelines have been developed by a panel of physicians with a broad range of expertise, including vascular neurology, neurocritical care, emergency medicine, neurosurgery, and interventional neuroradiology/endovascular neurosurgery. The intended audience for these guidelines includes physicians, emergency medical services (EMS) personnel, and other medical personnel who deal with the emergency diagnosis and treatment of patients with suspected ischemic stroke. In addition, components of these guidelines are very relevant to health policy decision makers and administrators. The goal of these guidelines is to provide updated recommendations that may be used by physicians who provide acute stroke care within the first hours to time of initial diagnosis, treatment, and initial hospitalization. In addition, the guideline also includes information that should be useful for nonphysician EMS personnel and for hospitals. The emphasis of these guidelines is the diagnosis and emergency treatment of patients with acute ischemic stroke. Information about the management of acute and subacute neurological and medical complications is also included. The panel recognizes that measures to prevent early recurrent stroke are also a component of acute management. In general, the medical or surgical interventions administered to prevent recurrent stroke are similar to those prescribed to patients with recent transient ischemic attacks or to other high-risk persons. The reader is referred to another recent statement that addresses the management of risk factors, the prescription of antithrombotic medications, and the use of surgical or endovascular interventions to prevent recurrent stroke.4
In writing these guidelines, the panel applied the rules of evidence and the formulation of strength of recommendations used by other panels of the American Heart Association (AHA)4 (see the Figure and Table 1). The data were collected through a systematic review of the literature. Because of the wide scope of the guidelines, the members of the panel were assigned primary reviews for individual sections. Then the panel assessed the complete guidelines. If the panel concluded that data supported or did not support the use of a specific intervention, appropriate recommendations were made. In some cases in which definitive data were not available, no specific recommendation was made. Italics indicate recommendations that have been changed or added since the publication of the previous guideline. In other instances, supporting evidence based on clinical trial research was not available for a specific intervention, but the panel has made a specific recommendation on the basis of pathophysiological reasoning and expert practice experience. For many of these interventions, it is unlikely that randomized trials will ever be performed. An example is the recommendation to perform endotracheal intubation to protect the airway in a comatose patient.
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I. Prehospital Management and Field Treatment
Recent data indicate that 29% to 65% of patients with signs or symptoms of acute stroke access their initial medical care via local EMS (Table 2), which confirms the role of EMS in the chain of survival.5–13 Notably, an estimated 19% to 60% of stroke patients present within 3 hours of stroke and 14% to 32% of those arrive within 2 hours of symptom onset. Although just over half of all stroke patients use EMS access to health care, those who do utilize EMS comprise the majority of patients presenting within the 3-hour window.13–16
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EMS activation appears to be a function primarily of individuals other than the patient, with one report indicating that a family member, paid caregiver, coworker, or other bystander accounted for 62% to 95% of 9-1-1 activation calls.6,9 In addition to bystander recognition of a problem, other reported predictors of EMS use by stroke patients include stroke severity,17 presence of intracranial hemorrhage,9,18 age,9,18 sense of urgency,9 unemployment,6 and race (black).18
The benefits of EMS activation by patients with stroke symptoms appear to occur in both the prehospital and in-hospital settings. Hospital arrival is faster for patients who use EMS/9-1-1 as their initial medical contact than for those who contact their primary physician or hospital directly18 or a primary care site.19 Not surprisingly, EMS use is strongly associated with shorter time periods from symptom onset to hospital arrival, although this may reflect a greater sense of urgency on the patients or bystanders part rather than reduced transport time.8,9,12 Similarly, EMS use is strongly associated with decreased time to initial physician examination,9,10,13,20 initial computed tomography (CT) imaging,9,10,12 and neurological evaluation.9
On the basis of the aforementioned information, communities should encourage 9-1-1 activation and use for patients with symptoms of acute stroke.
Data from the TLL Temple Foundation Stroke Project controlled trial indicate that educational interventions on stroke identification and management targeting patients, EMS, hospitals, and community physicians increased thrombolytic use in patients with ischemic stroke from 2.21% to 8.65% as compared with communities that did not have such programs, which saw only a 0.06% increase. For patients with ischemic stroke who were eligible for thrombolytic therapy, rates of tissue-type plasminogen activator (tPA) use increased from 14% to 52% in intervention communities. The benefit from this aggressive intervention program was sustained at 6 months after intervention.21,22
A. EMS Assessment
EMS assessment begins with the initial 9-1-1 contact (Table 2). The role of the dispatch system is to ensure immediate triage and dispatch of appropriate EMS providers when acute stroke is suspected by either the caller or the dispatcher.23 Data from 2 systems indicate that dispatchers correctly suspected or identified 52% of patients ultimately proven to have had a stroke on initial telephone evaluation.7,24 These data imply that educational programs should be aimed at dispatchers to increase their awareness of stroke symptoms. Stroke should be given a priority dispatch similar to that for acute myocardial infarction or trauma.25
After ambulance arrival on the scene, EMS providers should obtain a focused history and patient assessment, provide necessary stabilization and treatment, and transport immediately to the closest, most appropriate facility (Table 3). The word appropriate is key because it means that an ambulance may bypass a hospital that does not have the resources or institutional commitment to treat patients with stroke if a more appropriate hospital is available within a reasonable transport interval. Advance notice to the receiving emergency department (ED) of the impending arrival of a potential stroke patient, along with information on comorbid conditions and estimated time of symptom onset, will speed the subsequent ED assessment.
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Critical elements of the patients history must include information on time of symptom onset (Table 4). This may require obtaining information from bystanders or, preferably, transporting witnesses with the patient. Similarly, next of kin, if available, may be needed for information or consent and should travel to the receiving hospital concurrently. Telephone numbers, including cellular telephone numbers, of witnesses or relatives may help the ED to clarify the history or seek consent for treatment. A list of the patients medications, or the medication containers themselves, should be sought, with particular attention paid to identifying anticoagulant (both oral and injectable), antiplatelet, and antihypertensive drug use.
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After the patients airway, breathing, and circulation (ABCs) are assessed and stabilized, common presenting signs of stroke should be sought and a focused examination completed. Prehospital stroke assessment tools have proved effective in identifying stroke patients in the field. The Los Angeles Prehospital Stroke Screen uses patient history, physical findings, and finger stick glucose determination to identify stroke patients.26 The Cincinnati Prehospital Stroke Scale is an alternative instrument with fewer data elements (Table 5), requiring only 30 to 60 seconds to complete.27 Other prehospital stroke evaluation tools exist, although data on their validity are limited.
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B. EMS Management
Guidelines for EMS management are presented in Table 3.25,28 After initial stabilization, it is recommended that patient transport commence as soon as possible, with cardiac monitoring and intravenous access established during transport, if possible. Isotonic crystalloids (most commonly normal saline solution) are recommended for resuscitation, if needed. Dextrose-containing fluids should be avoided unless hypoglycemia is present or strongly suspected because excessive glucose may be injurious to stroke patients. No recommendations can be offered on the prehospital management of hypertension in patients with suspected stroke, and intervention is best accomplished after hospital arrival.
It is well recognized that hypoglycemic patients may have symptoms that mimic an acute stroke, manifesting focal symptoms, altered speech, and/or cognitive changes, and therefore EMS assessment of blood glucose has been a routine practice for many years. A single report suggests that a more selective approach may be possible, with blood glucose measurement advocated only in the presence of a history suspicious for hypoglycemia or inability to obtain adequate patient information.29 That study is limited, however, by its retrospective methodology and an upper confidence interval of 2.4% for the likelihood of failing to identify a hypoglycemic patient. At present, checking blood glucose concentrations in most patients with stroke is a prudent step, even among patients without a history of diabetes mellitus or use of insulin.
The availability of resources to care for patients with acute stroke varies widely both among and within communities. The National Institutes of Health (NIH) Task Force report, "Improving the Chain of Recovery for Acute Stroke in Your Community," recommends identifying hospitals capable of providing acute stroke care and creating a transport system to these centers based on patient location. Such systems require advanced planning and frequent updating and should incorporate EMS representatives, community leaders, hospitals, and physicians to ensure clear guidance for EMS providers with regard to patient destination.
Identification of an effective neuroprotective therapy may further expand the role of EMS in the treatment of acute stroke. The feasibility of initiation of hypothermia has also been demonstrated in the prehospital setting.30 Of importance for future research is the fact that it appears possible to incorporate EMS into the research process, with EMS personnel having demonstrated success in facilitating physician cell phone elicitation of consent from patients and in delivering experimental stroke therapy.31,32
C. Air Medical Transport
Air medical (helicopter) transport for patients with acute stroke appears beneficial, although the data are limited. Helicopters may extend the range of thrombolytic therapy to rural areas.33 They could deliver teams to administer tPA and subsequently transfer treated patients,34 expand enrollment for acute stroke studies,35 and facilitate early definitive diagnosis and operative intervention in nontraumatic intracranial hemorrhage.36 It is important to note that helicopter transfer of stroke patients for potential thrombolysis is cost-effective for a wide range of system variables.37
Protocols for the use of air medical transfer from facilities unable to provide acute stroke care should be developed in advance. Air medical transfer should be considered for patients who cannot receive treatment locally and who could reach a treating facility within the available time window.33,38
In addition, telemedicine may be used as a way to bring stroke expertise to patients in rural or small hospitals. Preliminary data suggest that such electronic methods may be increasingly useful.39–43
D. Conclusions and Recommendations
Public educational programs likely will increase the proportion of patients with stroke who will utilize EMS as their first contact with the healthcare system. This trend should be encouraged. In response, EMS should have protocols in place to rapidly assess, treat, and transport patients. The objectives of the EMS phase of stroke care are as follows: (1) rapid identification of stroke as the cause of the patients findings, (2) elimination of comorbid conditions that could mimic stroke, (3) stabilization, (4) rapid transportation of the patient to the closest appropriate ED, and (5) notification of the receiving institution about impending arrival of a patient with suspected stroke. Such steps are especially critical for the use of time-dependent therapies. Community and physician educational programs on acute stroke treatment appear to enhance the use of recombinant tPA (rtPA), and these programs should be encouraged. Strategies such as telemedicine or air medical transport (helicopter) may provide access to specialized stroke care when it is not available locally. Such approaches may increase the number of patients who can be treated, especially in rural or otherwise underserved areas. To maximize therapeutic options, treatment guidelines and transfer protocols should be established in advance to ensure orderly patient transition from a prehospital to a hospital environment.
The recommendations that follow were not included in the previous guidelines.
Class I Recommendations
Class II Recommendation
II. Designation of Stroke Centers
In an attempt to improve the organization and delivery of care to stroke patients, the Brain Attack Coalition published 2 sets of recommendations, one for primary stroke centers (PSCs) and, more recently, one for comprehensive stroke centers (CSCs).44,45 A PSC has the personnel, programs, expertise, and infrastructure to care for many patients with uncomplicated strokes, uses many acute therapies (such as intravenous rtPA), and admits such patients into a stroke unit. The CSC is designed to care for patients with complicated types of strokes, patients with intracerebral hemorrhage or subarachnoid hemorrhage, and those requiring specific interventions (eg, surgery or endovascular procedures) or an intensive care unit type of setting.
The specific elements of a PSC and a CSC will not be reviewed in the present document because they are well covered in the articles cited above. Many of the elements in a PSC or a CSC, including stroke units, written care protocols, availability of physicians with neurological expertise, and neurosurgical volumes, are associated with improved outcomes among patients treated for stroke.44,45 Since the publication of the PSC article in 2000,44 numerous published studies have demonstrated the utility and effectiveness of such centers.22,46–51 One study found that a PSC increased the use of intravenous rtPA from 1.5% to 10.2% in 2 years.46 Another study found that 7 of the 11 elements of a PSC were associated with increased use of intravenous tPA.47 Additional areas of disease performance that may be added include performance of a lipid profile, dysphagia screening, and the presence of a rehabilitation plan.
The utility of a CSC is beginning to emerge. Studies show that a CSC increases the use of lytic agents and that a CSC may improve overall care and outcomes.52,53 In-hospital death rates were reduced by almost 50% in hospitals with a vascular neurologist and were reduced by 24% in those with a stroke team.54 Such centers have acted as a regional resource for stroke care with good results and will be pivotal for further advancements in acute stroke care, stroke prevention, and rehabilitation.38,55,56
A. Stroke Center Certification
The certification or designation of some hospitals as PSCs or CSCs is progressing rapidly. The American Stroke Association convened an expert panel to study this issue for PSCs, with the conclusion that a variety of certification processes might be developed and lead to improved care and outcomes.57 Another panel is currently meeting to evaluate various options for CSC certification. One study showed that self-certification was likely to lead to a significant overestimation of a hospitals compliance with published recommendations for a PSC.58 Thus, these data and anecdotal experience suggest that outside independent evaluations of hospitals as stroke centers should lead to more accurate assessment of a facilitys true capabilities.
The Joint Commission on the Accreditation of Healthcare Organizations (JCAHO) began a formal process for the certification of PSCs in February 2004 (Table 6). As of February 2006,
200 hospitals in the United States had been certified as PSCs by the JCAHO. The JCAHO certification process includes a detailed evaluation of a hospitals staffing, education, disease management programs, outcomes, and infrastructure (see www.JCAHO.org for details). Several states have developed or are exploring a state-based certification process for PSCs, primarily using the state health department or a related government agency as the certifier. At this time the American Stroke Association and JCAHO have taken preliminary steps that may lead to a formal certification process for CSCs.
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The preferential routing of acute stroke patients to a PSC has been demonstrated to increase the proportion of patients cared for at stroke-capable centers and to increase the proportion of patients treated with thrombolytic therapy to >10%.48 Direct routing of stroke patients whose symptoms started <3 hours ago to a PSC or a CSC has been implemented or is in the process of implementation in 7 states, covering >25% of the US population. The states of Florida, New Jersey, Maryland, Massachusetts, New Mexico, New York, and Texas have laws or policies mandating that acute stroke patients be taken to the nearest stroke center. In other states, the limited number of such centers makes preferential routing logistically infeasible. Stroke centers in rural areas often use helicopter transportation or telemedicine technologies to provide rapid transportation and expertise to expedite treatment at outlying hospitals.33,53 However, this is clearly an area that will evolve as the number of stroke centers increases, their geographic distribution expands, and the concept is embraced by the medical community.
Stroke centers should not be viewed in isolation. Rather, they should be part of a larger support network sometimes referred to as a stroke system of care. Such a system would encompass issues such as prevention, education, acute care, rehabilitation, and quality improvement.59 In addition, as the number of stroke centers increases, such facilities may form a network of hospitals that would be useful for testing new therapies for acute stroke.
B. Conclusions and Recommendations
Robust data demonstrate the efficacy of specialized stroke services in improving outcomes of patients with stroke. Thus, there is a strong impetus to develop such specialized stroke services across the United States. Both primary (PSC) and comprehensive (CSC) centers are needed. At present, the process of identification of PSCs is ahead of that used to develop CSCs. The details of the organization of such services may vary among institutions or in different parts of the country to reflect demographic or geographic variables. Statewide or regional programs are being developed. A method to designate stroke centers, such as the JCAHO program, is being used to ensure that centers have the expertise and resources to provide modern stroke care. Plans for EMS to bypass institutions that do not have the capability to provide modern stroke care need to be developed.
The following recommendations were not included in the prior stroke guidelines.
Class I Recommendations
III. Emergency Evaluation and Diagnosis of Acute Ischemic Stroke
Given the narrow therapeutic windows for treatment of acute ischemic stroke, timely evaluation and diagnosis of ischemic stroke are paramount.60 Hospitals that maintain an ED must create efficient pathways and processes to rapidly identify and evaluate potential stroke patients. The physicians evaluation, diagnostic testing, including neuroimaging, and contact with a physician with stroke expertise should be performed concurrently. A consensus panel convened by the National Institute of Neurological Disorders and Stroke (NINDS) established goals for time frames in these steps in the evaluation of stroke patients in the ED.25,61 At this same symposium, the "Stroke Chain of Survival" was promoted as a template for identifying critical events in the ED identification, evaluation, and treatment of stroke patients (Table 2).61 By using this template and the time goals, hospitals and EDs can create effective systems for optimizing stroke patient care.62
All patients with suspected acute stroke should be triaged with the same priority as patients with acute myocardial infarction or serious trauma, regardless of the severity of the deficits. Roughly half of all acute stroke patients access the ED through 9-1-1 and EMS. Prehospital notification of the arrival of a patient with a potential stroke expedites evaluation and diagnosis, and therefore hospitals should request notification from local EMS providers.63,64 For the remaining 50% of stroke patients, the ED staff should maintain a high level of suspicion for stroke in patients presenting through the ED lobby to minimize delays in triage. Early implementation of stroke pathways and stroke team notification should occur in parallel with the ED evaluation and management.
A. Immediate Evaluation
The initial evaluation of a potential stroke patient is similar to that of other critically ill patients: stabilization of the ABCs. This is quickly followed by a secondary assessment of neurological deficits and possible comorbidities. The overall goal is not only to identify patients with possible stroke but also to exclude stroke mimics (conditions with stroke-like symptoms), identify other conditions requiring immediate intervention, and determine potential causes of the stroke for early secondary prevention (Table 7).
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1. History
The single most important piece of historical information is the time of symptom onset. The current definition of the time of stroke onset is when patients were at their previous baseline or symptom-free state. For patients unable to provide this information or who awaken with stroke symptoms, the time of onset is defined as when the patient was last awake and symptom free or known to be "normal." Often a patients current symptoms were preceded by similar symptoms that subsequently resolved. Currently, for patients who had neurological symptoms that completely resolved, the therapeutic clock is reset, and the time of symptom onset begins anew. It is important to note, however, that the longer the transient neurological deficits last, the greater is the chance of detecting neuroanatomically relevant focal abnormalities on diffusion-weighted and apparent diffusion coefficient imaging.65 Whether this represents an increased risk of hemorrhage with thrombolysis remains to be determined.
Additional historical items include circumstances around the development of the neurological symptoms and features that may point to other potential causes of the symptoms. Although not absolutely accurate, some early historical data and clinical findings may direct the physician toward a diagnosis of another cause for the patients symptoms (Table 7). It is important to ask about risk factors for arteriosclerosis and cardiac disease in all patients, as well as any history of drug abuse, migraine, seizure, infection, trauma, or pregnancy. Historical data related to eligibility for therapeutic interventions in acute ischemic stroke are equally important.66 Bystanders or family witnesses should be asked for information about onset time and historical issues, and therefore EMS personnel should be encouraged to identify witnesses and bring them in the ambulance when patients are unable to speak or provide history. Validated tools for identification of stroke patients within an ED are available.67
2. Physical Examination
The general physical examination continues from the original assessment of the ABCs and should include pulse oximetry and body temperature. Examination of the head and neck may reveal signs of trauma or seizure activity (eg, contusions, tongue lacerations), carotid disease (bruits), or congestive heart failure (jugular venous distention). The cardiac examination focuses on identifying concurrent myocardial ischemia, valvular conditions, irregular rhythm, and, in rare cases, aortic dissection, which could precipitate a cardioembolic event. Similarly, the respiratory and abdominal examinations seek to identify other comorbidities. Examination of the skin and extremities may also provide insight into important systemic conditions such as hepatic dysfunction, coagulopathies, or platelet disorders (eg, jaundice, purpura, petechia).
3. Neurological Examination and Stroke Scale Scores
The emergency physicians neurological examination should be brief but thorough. It is enhanced by use of a formal stroke score or scale, such as the NIH Stroke Scale (NIHSS). The scale may be used by a broad spectrum of non-neurological healthcare providers (Table 8).24,68,69 Use of a standardized examination helps to ensure that the major components of a neurological examination are performed in a timely fashion. These scores not only help to quantify the degree of neurological deficit but also facilitate communication between healthcare professionals, identify the possible location of vessel occlusion, provide early prognosis, and help to identify patient eligibility for various interventions and the potential for complications.42,70–72 Several studies have demonstrated that emergency physicians committed to stroke care may correctly identify and safely treat stroke patients, especially with the use of such standardized scales.73,74 All hospital systems should ensure access to neurological expertise when required.75
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4. Diagnostic Tests
Several tests should be performed routinely in patients with suspected ischemic stroke to identify systemic conditions that may mimic or cause stroke or that may influence therapeutic options (Table 9). These tests include blood glucose, electrolytes, complete blood count with platelet count, prothrombin time, activated partial thromboplastin time, international normalized ratio, and renal function studies. Hypoglycemia may cause focal symptoms and signs that mimic stroke, and hyperglycemia is associated with unfavorable outcomes. Determination of the platelet count and, in patients taking warfarin or with liver dysfunction, the prothrombin time/international normalized ratio is important. Because time is critical, thrombolytic therapy should not be delayed while waiting for the results of the prothrombin time, activated partial thromboplastin time, or platelet count unless a bleeding abnormality or thrombocytopenia is suspected, the patient has been taking warfarin and heparin, or anticoagulation use is uncertain.
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5. Cardiac Tests
A clinical cardiovascular examination, cardiac enzyme tests, and a 12-lead ECG should be performed in all stroke patients (Table 9).76 Cardiac abnormalities are prevalent among patients with stroke, and the patient can have an acute cardiac condition that mandates urgent treatment. For example, acute myocardial infarction can lead to stroke, and acute stroke can lead to myocardial ischemia.77–79 In addition, cardiac arrhythmias can occur among patients with acute ischemic stroke.77,78,80,81 Atrial fibrillation, an important potential cause of stroke, can be detected in the acute setting.82 Cardiac monitoring should be conducted routinely after an acute cerebrovascular event to screen for serious cardiac arrhythmias.83
Chest radiography was previously recommended for the evaluation of all patients with acute ischemic stroke.1 A subsequent study found that clinical management was altered in only 3.8% of patients who had routine chest radiographs at the time of admission for stroke, which suggests that the test is of modest, but not nil, value.83
Examination of the cerebrospinal fluid is indicated if the patient has symptoms suggestive of subarachnoid hemorrhage and a CT scan does not demonstrate blood. Fortunately, the clinical features of subarachnoid hemorrhage differ considerably from those of ischemic stroke. Electroencephalography may be helpful for evaluating patients in whom seizures are suspected as the cause of the neurological deficits or in whom seizures could have been a complication of the stroke.84 Seizure in the absence of imaging confirmation of acute ischemia is a relative contraindication for the use of rtPA in acute ischemic stroke.
Additional tests may be performed as indicated by the patients history, symptoms, physical findings, or comorbidities (Table 9). A toxicology screen, blood alcohol level, arterial blood gas, and pregnancy test should be obtained if the physician is uncertain about the patients history or as suggested by findings on examination.
B. Conclusions and Recommendations
The evaluation and initial treatment of patients with stroke should be performed as a priority in the hospital ED. The development of an organized protocol and stroke team should speed the clinical assessment, the performance of diagnostic studies, and decisions for early management. The clinical assessment (history, general examination, and neurological examination) remains the cornerstone of the evaluation. This evaluation should be performed by the physicians in the ED. The goals are to determine whether the patient has had a stroke and to establish potential contraindications for emergency treatment with agents such as rtPA. A stroke rating scale, such as the NIHSS, provides important information about the severity of stroke. It provides prognostic information, and the score may influence decisions about acute treatment. Some of the recommendations included in the present statement are influenced by the NIHSS. This scale can be performed with a reasonable degree of accuracy by practitioners in a broad range of specialties. Education in the nuances of NIHSS can improve the accuracy of this scale.
Because time is critical, a limited number of diagnostic tests are recommended. These tests should be available on a 24-hours-per-day, 7-days-per-week basis. These tests are used to screen for ischemic stroke, to exclude important alternative diagnoses (especially intracerebral hemorrhage), to assess for serious comorbid diseases, and to search for acute medical or neurological complications of the stroke (Table 9). Examination of the cerebrospinal fluid has a limited role in the evaluation of patients with suspected stroke. Additional diagnostic studies, including cardiac and vascular imaging, often are time consuming and may delay emergency treatment. Thus, most of these tests are not done until after the acute treatment or after the patient is admitted to the hospital.
The recommendations that follow are similar to those included in previous statements except recommendation 1 under Class III.
Class I Recommendations
Class III Recommendations
IV. Early Diagnosis: Brain and Vascular Imaging
A. Brain Imaging
As therapeutic options evolve, brain imaging strategies are playing an increasingly important role in the initial evaluation of patients with acute stroke (Table 9). Brain imaging findings, including the size, location, and vascular distribution of the infarction, as well as the presence of bleeding, affect both short-term and long-term treatment decisions. In addition, information about the possible degree of reversibility of ischemic injury, intracranial vessel status, and cerebral hemodynamic status may be obtained by modern imaging studies.85 Neuroimaging tests might improve selection of patients who could be treated with reperfusion therapies by identifying those with regions of salvageable brain tissue, a low risk for hemorrhagic transformation, or occlusions of large arteries that might or might not be amenable to therapy. CT and magnetic resonance imaging (MRI) are being used as initial imaging options. The most commonly obtained brain imaging test is noncontrast CT, but individual centers able to obtain MRI with efficiency equal to that of CT are using an MRI strategy in patients without MR contraindications.86–90 Additional research is required.91,92 As a result, it is generally agreed that the performance of these tests should not delay treatment with intravenous rtPA.86,91–93
1. Non–Contrast-Enhanced CT Scan of the Brain
It is agreed that emergency, non–contrast-enhanced CT scanning of the brain accurately identifies most cases of intracranial hemorrhage and helps discriminate nonvascular causes of neurological symptoms (eg, brain tumor). The prior guidelines recommended that CT be the primary diagnostic brain imaging study for evaluation of patients with suspected stroke.94 Although CT is the "criterion standard" with which other brain imaging studies are compared, it is relatively insensitive in detecting acute and small cortical or subcortical infarctions, especially in the posterior fossa.95 In most cases, the use of a contrast infusion does not provide additional information and is not necessary unless it is required for CT angiography (and, more recently, CT perfusion) or concern exists about a brain tumor or infectious process.
With the advent of rtPA treatment, interest has grown in using CT to identify subtle, early signs of ischemic brain injury (early infarct signs) or arterial occlusion (hyperdense vessel sign) that might affect decisions about treatment. In addition, the loss of the gray-white differentiation in the cortical ribbon (particularly at the lateral margins of the insula) or the lentiform nucleus and sulcal effacement can often be detected within 6 hours in up to 82% of patients with large-vessel anterior circulation occlusions.96,97 These signs are associated with poorer outcomes.98,99
In addition, widespread signs of early infarction are correlated with a higher risk of hemorrhagic transformation after treatment with thrombolytic agents. In combined data from 2 trials of intravenous rtPA administered within 3 hours of symptom onset, CT evidence of early edema or mass effect was accompanied by an 8-fold increase in the risk of symptomatic hemorrhage.66 In a second analysis, early infarct signs involving more than one third of the territory of the middle cerebral artery (MCA) were not independently associated with increased risk of adverse outcome after rtPA treatment, and as a group these patients still benefited from therapy.100 In a European trial in which thrombolytic therapy was administered within 6 hours of symptom onset, patients estimated to have involvement of more than one third of the territory of the MCA had an increased risk of intracerebral hemorrhage, whereas those with less involvement benefited the most from thrombolytic treatment.99,101 However, physicians ability to reliably and reproducibly recognize the early CT changes is variable.102–106 Use of scoring systems for early CT changes may improve identification of cerebral ischemia and may provide valuable prognostic information but is not validated for outcome or patient selection for acute treatments.107,108 Further studies are needed to determine the significance of early infarct signs and their role in treatment decision making.109
For patients who are candidates for treatment with rtPA, the goal is to complete the CT examination within 25 minutes of arrival at the ED, with the study interpreted within an additional 20 minutes (door-to-interpretation time of 45 minutes).61 A subsequent CT scan often is obtained if the patient worsens neurologically and may be especially helpful in identifying hemorrhagic transformation after administration of rtPA.66
2. Multimodal CT
Recent technological advances have led to increased interest in more sophisticated multimodal approaches to acute stroke imaging. The multimodal CT approach may include noncontrast CT, perfusion CT, and CT angiography studies. Two types of perfusion techniques are currently available. Whole-brain perfusion CT provides a map of cerebral blood volume, and it is postulated that regions of hypoattenuation on these cerebral blood volume maps represent the ischemic core.110 Although this technique has the advantage of providing whole-brain coverage, it is limited by its inability to provide measures of cerebral blood flow or mean transit time. Alternatively, the second technique, dynamic perfusion CT, has the potential to provide absolute measures of cerebral blood flow, mean transit time, and cerebral blood volume. Dynamic perfusion CT is currently limited to 2 to 4 brain slices and provides incomplete visualization of all pertinent vascular territories.
Recent reports demonstrate a high degree of sensitivity and specificity for detecting cerebral ischemia with both of these perfusion CT techniques.111–113 In addition, several studies have suggested that perfusion CT may be able to differentiate thresholds of reversible and irreversible ischemia and thus identify the ischemic penumbra.114,115
Helical CT angiography provides a means to rapidly and noninvasively evaluate the vasculature, both intracranially and extracranially, in acute, subacute, and chronic stroke settings and thus to provide potentially important information about the presence of vessel occlusions or stenoses.116,117 The feasibility of this technique has been demonstrated in the acute stroke setting, with preliminary data suggesting high diagnostic accuracy for evaluation of large-vessel intracranial occlusions as compared with ultrasound and digital subtraction angiography.118–120
These techniques have the advantage of relatively rapid data acquisition and can be performed with conventional CT equipment. Disadvantages include iodine contrast and additional radiation exposure. The role of perfusion CT and CT angiography in making acute treatment decisions has not yet been established.
3. Multimodal MRI
The multimodal MRI approach for acute stroke evaluation includes diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), MR angiography, gradient echo, and often fluid-attenuated inversion recovery or T2-weighted sequences. Standard MRI sequences (T1 weighted, T2 weighted, and proton density) are relatively insensitive to the changes of acute ischemia.121 DWI allows visualization of ischemic regions within minutes of symptom onset122–131 and early identification of the lesion size, site, and age. It can detect relatively small cortical or subcortical lesions, including those in the brain stem or cerebellum, areas often poorly visualized with standard CT scan techniques. DWI also provides information about the involved vascular territory and has a high sensitivity (88% to 100%) and specificity (95% to 100%) for detecting ischemic lesions, even at very early time points.
PWI, usually performed with the rapid administration of an intravenous paramagnetic contrast agent, provides relative measures of cerebral hemodynamic status. Investigations of the best PWI analytical method focus on identifying the highest correlation of ischemic volume with acute clinical deficits (symptomatic hypoperfusion) or with volume of chronic infarct (tissue at risk).
Studies have demonstrated that the initial volumes of the lesions seen on DWI and PWI correlate well with the final size of the stroke found on follow-up brain imaging.129,132,133 In addition, these lesion volumes correlate well with severity of stroke as rated by both clinical scales and outcomes. These findings suggest that DWI might provide helpful early prognostic information.125,132
The ischemic penumbra is roughly approximated on MRI as regions of perfusion change without a corresponding diffusion abnormality (diffusion–perfusion mismatch). However, several studies indicate that, at least in some circumstances, the initial diffusion abnormality is reversible and the visually thresholded perfusion volumes overestimate the penumbra.134,135 Sequential MRI studies performed in patients being treated with thrombolytic therapy have shown that the technique may visualize salvage of mismatch-defined penumbral tissue with smaller volumes of infarction among patients who have successful recanalization.134,136
Efforts are under way to develop multiparametric MRI criteria that could identify regions of irreversible infarction from potentially reversible ischemia or portend a high risk of hemorrhagic complications after thrombolytic therapy.137–139 A recent phase II trial of intravenous administration of the thrombolytic agent desmoteplase showed a signal of potential therapeutic benefit when MRI was used to select patients with diffusion–perfusion mismatch for treatment 3 to 9 hours from onset.140 However, insufficient evidence currently exists to recommend this approach for selecting patients for acute therapies in routine practice.
Two prospective studies recently demonstrated that MRI is as accurate as CT in detecting hyperacute intraparenchymal hemorrhage in patients presenting with stroke symptoms within 6 hours of onset when gradient echo MRI sequences were used.88,141 These findings suggest that MRI may be used as the sole imaging modality to evaluate acute stroke patients, including candidates for thrombolytic treatment. However, in patients presenting with symptoms suggestive of subarachnoid hemorrhage, a CT scan should be performed.
Gradient echo sequences also have the ability to detect clinically silent prior microbleeds not visualized on CT. Some data suggest that microbleeds represent markers of bleeding-prone angiopathy and increased risk of hemorrhagic transformation after antithrombotic and thrombolytic therapy.142–144 However, other studies have not found an increased risk in patients with small numbers of microbleeds.145 The importance of the presence of large numbers of microbleeds on MRI in thrombolytic decision making remains uncertain.
MR angiography is increasingly used for noninvasive screening of the extracranial and intracranial circulation. When compared with digital subtraction angiography for detection of cervical and intracranial stenoses, sensitivity and specificity have ranged from 70% to 100%.146,147 In the intracranial vasculature, MR angiography is useful in identifying acute proximal large-vessel occlusions but cannot reliably identify distal or branch occlusions.
A potential diagnostic advantage of MRI over CT in non-tPA situations in suspected stroke has been demonstrated. MRI is better at distinguishing acute, small cortical, small deep, and posterior fossa infarcts; at distinguishing acute from chronic ischemia; and at identifying subclinical satellite ischemic lesions that provide information on stroke mechanism.95,124,129,148–167 Limitations of MRI in the acute setting include cost, relatively limited availability of the test, and patient contraindications such as claustrophobia, cardiac pacemakers, or metal implants. Advantages include the avoidance of exposure to ionizing radiation and iodinated contrast and greater spatial resolution.
4. Other Brain Imaging Techniques
Oxygen-15 positron-emission tomography may quantify regional brain perfusion and oxygen consumption.168–172 However, logistical and pragmatic considerations limit the application of positron-emission tomography in the setting of acute stroke. Xenon-enhanced CT provides a quantitative measurement of cerebral blood flow by using inhaled xenon but is not currently widely available.173 Single-photon emission CT, which is minimally invasive and measures relative cerebral blood flow, might be able to identify thresholds for reversible ischemia and could be helpful in predicting outcomes or monitoring responses to treatment.174–176 Limitations include lack of availability, expense, and difficulty associated with tracer preparation.
B. Other Vascular Imaging
In addition to the aforementioned CT and MR angiography, transcranial Doppler ultrasonography, carotid duplex sonography, and catheter angiography have been used to detect intracranial or extracranial vessel abnormalities. Transcranial Doppler ultrasonography and angiography have been used to monitor the effects of thrombolytic therapy over time and can help to determine prognosis.177–179
In patients whose symptoms started <8 hours ago, these tests may be helpful in selecting candidates for intervention. A variety of ancillary tests are available to help clinicians reach accurate pathophysiological and etiologic stroke diagnoses and provide information that can be critical for effective prevention of recurrent stroke.180,181 Vascular imaging is a key component of the evaluation. The selection of tests needs to be tailored to the individual patient and clinical setting.
C. Conclusions and Recommendations
Brain imaging remains a required component of the emergency assessment of patients with suspected stroke. Both CT and MRI are options for imaging the brain, but for most cases and at most institutions, CT remains the most practical initial brain imaging test. A physician skilled in assessing CT or MRI studies should be available to examine the initial scan. In particular, the scan should be evaluated for evidence of early signs of infarction. Baseline CT findings, including the presence of ischemic changes involving more than one third of a hemisphere, have not been predictors of responses to treatment with rtPA when the agent is administered within the 3-hour treatment window. Information about multimodal CT and MRI of the brain suggests that these diagnostic studies may help in the diagnosis and treatment of patients with acute stroke. Imaging of the intracranial or extracranial vasculature in the emergency assessment of patients with suspected stroke is useful at institutions providing endovascular recanalization therapies. The usefulness of vascular imaging for predicting responses to treatment before intravenous administration of thrombolytic agents has not been demonstrated.
Class I Recommendations