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AHA/ASA Scientific Statement
Guidelines for the Early Management of Patients With
2005 Guidelines Update
A Scientific Statement From the Stroke Council of the American Heart
Harold Adams, MD, FAHA; Robert Adams, MS, MD, FAHA; Gregory Del Zoppo, MD, MS, FAHA; Larry B. Goldstein, MD, FAHA This article serves as an update of "Guidelines for the demonstrated relevant abnormalities in 21% of cases.3 Early Management of Patients With Ischemic Stroke," Changes in ⬇44% of cases are detected by T2-weighted or published in Stroke in 2003 ( fluid attenuation inversion recovery MRI studies.
content/full/34/4/1056). This update is intended to reflect A scientific statement authored by a panel of the American advances in the field since the publication of the full Heart Association focused on perfusion imaging in the setting guidelines. See Tables 1 and 2, reprinted in this article from of acute ischemic stroke was published simultaneously with the 2003 document, for explanations of grade (strength of the original 2003 ischemic stroke guidelines.4 Information about the advantages and disadvantages of each imagingtechnique is included in the statement. The panel concluded that more comparison testing of the different techniques is CT remains the most widely used neuroimaging technique for needed to determine their relative abilities to differentiate the evaluation of patients with suspected acute ischemic tissues having normal perfusion and reversible or irreversible stroke. Quantitative CT-based scoring systems (eg, the Al- ischemic injury. Clinical trials must determine whether per- berta Stroke Program Early CT Score [ASPECTS]) are useful fusion data help forecast outcomes after stroke and the ability for identifying patients who are unlikely to recover fully to triage patients to specific interventions.
despite thrombolytic therapy.1 Substantial agreement between The 2003 ischemic stroke guidelines indicated that addi- the ASPECTS rating performed in real time and the score tional research was needed to determine the utility of MRI as obtained later by an expert can be achieved when used by an a substitute for CT among patients with suspected acute experienced reader, but correlations are not perfect (weighted stroke because detection of acute intracerebral hemorrhage ␬ 0.69, 95% CI 0.59 to 0.79).2 This scoring system has not via MRI had not been fully validated. A study addressing this been assessed in general clinical practice and is limited to use need has been reported. In comparison with CT, MRI in patients with infarctions suspected to be in the distribution detected intracranial bleeding with 100% sensitivity and of the middle cerebral artery. In addition, advances in CT 100% accuracy, as identified by 3 experienced readers. Three technology, including the development of CT angiography medical students also interpreted the studies with a sensitivity and perfusion studies, may affect future recommendations of 95%. Additional studies have produced similar results.5,6 about the use of CT in the evaluation of patients with These results suggest that MRI may replace CT in the initial suspected stroke.
screening for hemorrhage among patients with suspected MRI techniques also are used widely in the assessment of stroke. Additional experience for detection in the acute patients with suspected stroke or transient ischemic attack setting in real time and outside specialized academic centers (TIA). For example, a retrospective analysis of patients in the United States is needed. Besides its utility in the having diffusion-weighted MRI studies within 3 days of TIA diagnosis of acute brain ischemia, MRI also may help in The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are requiredto complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.
This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on January 19, 2005. A single reprint is available by calling 800-242-8721 (US only) or writing the American Heart Association, Public Information, 7272 Greenville Ave, Dallas, TX75231-4596. Ask for reprint No. 71-0317. To purchase additional reprints: up to 999 copies, call 800-611-6083 (US only) or fax 413-665-2671; 1000or more copies, call 410-528-4121, fax 410-528-4264, or e-mail [email protected]. To make photocopies for personal or educational use, call theCopyright Clearance Center, 978-750-8400.
Expert peer review of AHA Scientific Statements is conducted at the AHA National Center. For more on AHA statements and guidelines development, (Stroke. 2005;36:916-921.)
2005 American Heart Association, Inc.
Stroke is available at
Adams et al
Guidelines for the Early Management of Patients With Ischemic Stroke
Levels of Evidence
that MRI is superior to CT for selecting patients who could betreated with intravenous recombinant tissue plasminogen activa- Level of evidence tor (rtPA). The use of MRI outside the setting of clinical research Data from randomized trials with low studies should not delay treatment of a patient who is otherwise false-positive and low false-negative errors eligible for treatment with intravenous rtPA (grade B, no change Data from randomized trials with high false-positive or high false-negative errors Data from nonrandomized concurrent Treatment of Arterial Hypertension
The treatment of arterial hypertension immediately after Data from nonrandomized cohort studies stroke is problematic, as stated in the 2003 guidelines. Since using historical controls then, a placebo-controlled phase II safety trial tested the Data from anecdotal case series utility of candesartan administered from day 1 to hyperten- Strength of recommendation sive patients with acute ischemic stroke.10 At 12 months, Supported by level I evidence patients treated with candesartan had improved survival and Supported by level II evidence few subsequent vascular events. No differences in blood Supported by level III, IV, or V evidence pressure values were noted, however, and the effects on theoutcome of the stroke are not described. This preliminary identifying patients with previous microhemorrhages that observation must be confirmed by a larger clinical trial.
could be associated with an increased risk of bleedingsecondary to thrombolysis.7,8 Pharmacological (Intravenous or
MRI with susceptibility-weighted imaging may be useful in detecting areas of hemorrhage after intraarterial Symptomatic hemorrhagic transformation of the infarction thrombolysis in situations in which CT findings could be remains the primary concern with the administration of equivocal because of residual contrast staining.9 The impor- intravenous rtPA in the treatment of acute ischemic stroke.11 tance of this finding needs clarification. Prospective studies A recent pooled analysis of several trials of rtPA confirms are needed to determine whether the findings of that symptomatic hemorrhagic transformation is the primary susceptibility-weighted MRI affect either prognosis or complication of acute treatment with rtPA.12 A meta-analysis of the postmarketing open-label studies demonstrates that the Brain imaging is required to guide the selection of acute risk of hemorrhage is ⬇5.2%.13 A subsequent report by the interventions to treat patients with stroke (grade A, no change same group demonstrated a marked decline in major bleeding from 2003). For most cases and at most institutions, CT remains complications when the guidelines were followed.14 Schmull- the most important brain imaging test; however, new studies ing et al15 found that previous use of aspirin does not increase suggest that MRI also may be used to detect acute intracerebral the risk of symptomatic intracranial bleeding after the admin- hemorrhage and that it could be an alternative to CT. Additional istration of rtPA. The studies show that rtPA can be given studies are under way. There is general agreement that perfusion with an acceptable margin of safety in a community setting and diffusion-weighted MRI may be helpful in diagnosing and when the guidelines for selection and treatment of patients are treating patients with acute stroke under some circumstances, but logistical issues, including the availability of the equipment and Hill et al16 reported orolingual angioedema in 9 of 176 the presence of physicians with expertise in interpreting the tests, patients treated with intravenous rtPA. In most cases, the limit the use of MRI. At present, no data are available to show findings were mild, transient, and contralateral to the in- Quality of Evidence Ratings for Radiological Diagnostic Tests
Level of evidence Evidence provided by a prospective study in a broad spectrum of persons with the suspected condition, using a "gold standard" for casedefinition, where test is applied in a blinded evaluation, and enabling the assessment of the appropriate tests of diagnostic accuracy.
Evidence provided by a prospective study of a narrow spectrum of persons with a suspected condition, or a well-designed retrospectivestudy of a broad spectrum of persons with an established condition (by the "gold standard") is compared to a broad spectrum of controls,where test is applied evaluation and enabling the assessment of appropriate tests of diagnostic accuracy.
Evidence supplied by a retrospective study where either persons with an established condition or controls are of a narrow spectrum, andwhere test is applied in a blinded evaluation.
Any design where test is not applied in blinded evaluation OR evidence provided by expert opinion alone or in descriptive case series(without controls).
Strength of recommendation Established as useful/predictive or not useful/predictive for the given condition in the specified population.
Probably useful/predictive or not useful/predictive for the given condition in the specified population.
Possibly useful/predictive or not useful/predictive for the given condition in the specified population.
Data are inadequate or conflicting. Given current knowledge, the test/predictor is unproven.
April 2005
volved cerebral hemisphere. They noted that the likelihood tional data are needed to support a recommendation for was increased among patients who were taking angiotensin- converting enzyme inhibitors and among those who had Using transcranial Doppler ultrasonography, Alexandrov evidence of ischemia in the frontal cortex and insula on CT.
and Grotta32 found that approximately one third of patients Other cases of more severe edema of the throat and mouth develop reocclusion of the artery after intravenous also have been described.17–19 Although the previous use of thrombolysis. Patients with partial recanalization were the angiotensin-converting enzyme inhibitors is not a contraindi- most likely to experience reocclusion and poorer neurological cation for the administration of rtPA, physicians should be outcomes. These results are stimulating research on adjunctive aware of this potential complication. Presumably, medica- antithrombotic therapies that help maintain arterial patency.
tions used to treat angioedema would be indicated to treat a Among the interventions are anticoagulants and rapidly acting severely affected patient.
parenterally administered antiplatelet agents.15,33–36 Although A recent report offered a pooled analysis of data from preliminary results are promising, experience is limited. Addi- several clinical trials of rtPA.12 The data from each of these tional data are needed before changing the current recommen- trials have been reported independently. Although the trials dations to withhold adjunctive antithrombotic therapy for the used different definitions of outcomes, the combined analysis first 24 hours after administration of rtPA.
applied definitions used in the National Institute of Neuro- Because of the current time requirements for the adminis- logical Disorders and Stroke trials (eg, no or minimal disabil- tration of rtPA, all aspects of the healthcare system must ity at 3 months as measured by modified Rankin Scale, the respond with a sense of urgency. Community-wide stroke Barthel Index, and the National Institutes of Health [NIH] programs are increasing the number of patients that can be Stroke Scale) plus a global statistical test. The lower 95% treated.37–39 Delays within the hospital emergency department confidence limit for the adjusted odds ratio for a favorable also need to be addressed.39 Telemedicine and emergency air outcome crossed unity at 4.5 hours from symptom onset. This transportation are among the ways to speed the treatment of finding suggests that some patients may benefit from treat- patients with acute stroke.40,41 ment beyond the current 3-hour window; however, additional Novel thrombolytic agents such as desmotoplase, rete- information is necessary to move the maximal time window plase, and tenecteplase are being evaluated, but prospective to 4.5 hours in the guidelines. Ongoing studies are evaluating data comparing these drugs with intravenous rtPA are few.
the potential utility of rtPA given ⬎3 hours after the onset of Although experience is limited, thrombolytic agents have been given successfully to children with acute ischemic Hsia et al20 found that the subtypes of ischemic stroke do not influence responses to treatment with rtPA. This findingimplies that the determination of the subtype of stroke (eg, cardioembolism, large artery atherosclerosis, or small artery The recommendation for the intravenous administration of occlusion) is not a prerequisite for the administration of rtPA.
rtPA within 3 hours of onset of stroke in carefully selected Intraarterial administration of thrombolytic agents has patients should not be changed (grade A, no change from considerable appeal.21 A review of the available data shows 2003). The evidence is strong that all delays in treating that intraarterial thrombolysis is associated with a reduction patients should be avoided (grade A, new recommendation).
in mortality and an improvement in favorable outcomes after Although intraarterial thrombolysis alone or in combination a stroke, but it is also associated with an increased risk of with intravenous thrombolysis holds great promise, the use of hemorrhagic complications.22 Additional studies have been these approaches is preferable in the setting of randomized published since the development of the 2003 guidelines. In clinical trials. A correction is needed in Table 7 of the 2003 general, the results are similar to those published previous- Guidelines. Patients with an INR level of 1.7 or below can be ly.23–26 Studies testing the utility of intraarterial thrombolysis treated with rtPA.
are ongoing. Recommendations for the design and organiza-tion of such trials were published recently.27 At present, no evidence is available to show that intraarterial thrombolysis is Current data do not provide evidence in support of the superior to intravenous treatment. Therapy should not be efficacy of early anticoagulation in improving outcomes after withheld from patients who are eligible for treatment with acute ischemic stroke.43 The recommendations of the 2003 intravenous thrombolysis so that medications can be admin- guidelines are in agreement with other statements indicating istered intraarterially, except in the setting of a comparative that most stroke patients do not need emergency administra- research clinical trial.
tion of anticoagulants.44–46 Despite the lack of supporting The combination of administering intravenous therapy and data, anticoagulants are still given frequently.47 then intraarterial therapy is being tested. This strategy could A preliminary clinical study of argatroban has been com- allow for early treatment of stroke with intravenous medica- pleted and the agent was deemed to be safe.48 Burak et al49 tion while the resources to deliver intraarterial therapy are administered enoxaparin to 8 children with stroke and con- organized.21,28,29 Additional reports that have become avail- cluded that the low-molecular-weight heparin was a safe and able since the 2003 guidelines reflect mixed results.30,31 effective alternative to heparin for children. Anticoagulants Clinical trials testing the utility of the combination of intra- also are being explored as an adjunct to thrombolytic thera- venous and intraarterial therapy are in progress, and addi- py.15 Although the preponderance of past acute anticoagula- Adams et al
Guidelines for the Early Management of Patients With Ischemic Stroke
Characteristics of Patients With Ischemic Stroke
form and are apparently promising but have not been Who Could Be Treated With rtPA
Diagnosis of ischemic stroke causing measurable neurological deficit The neurological signs should not be clearing spontaneously Recommendations
Although the new data do not change the recommendation
The neurological signs should not be minor and isolated that most patients should receive aspirin within 48 hours of Caution should be exercised in treating a patient with major deficits stroke, the data also support the conclusion that the effects of The symptoms of stroke should not be suggestive of subarachnoid aspirin are modest (grade A, no change from 2003). Aspirin should not be considered as an alternative to intravenous Onset of symptoms ⬍3 hours before beginning treatment thrombolysis or acute therapies aimed at improving outcomes No head trauma or prior stroke in previous 3 months after stroke. Additional research on abciximab or other No myocardial infarction in the previous 3 months rapidly acting antiplatelet agents is needed before any rec- No gastrointestinal or urinary tract hemorrhage in previous 21 days ommendation about their use can be made.
No major surgery in the previous 14 days No arterial puncture at a noncompressible site in the previous 7 days Volume Expansion and
No history of previous intracranial hemorrhage Blood pressure not elevated (systolic ⬍185 mm Hg and diastolic Medical measures to improve cerebral blood flow are being evaluated. In addition to its ability to improve flow to the No evidence of active bleeding or acute trauma (fracture) on examination ischemic region, albumin may have neuroprotective effects Not taking an oral anticoagulant or if anticoagulant being taken, INR ⱕ1.7 and is being tested. In a pilot study, Hillis et al52 found that If receiving heparin in previous 48 hours, aPTT must be in normal range drug-induced hypertension can improve blood flow and Platelet count ⱖ100 000 mm3 lessen the neurological consequences of stroke. This regimenhas been used to treat patients with vasospasm after subarach- Blood glucose concentration ⱖ50 mg/dL (2.7 mmol/L) noid hemorrhage. Although drug-induced hypertension holds No seizure with postictal residual neurological impairments promise, this therapy may be associated with an increased CT does not show a multilobar infarction (hypodensity ⬎1⁄3 cerebral risk of brain edema, hypertensive encephalopathy, or hemor- rhagic transformation of the infarction. Additional The patient or family understand the potential risks and benefits from vasopressor-related complications may include cardiac ische- mia or arrhythmias. The intervention also may require admis-sion to an intensive care unit and close monitoring. Further tion trials has failed to show a benefit, newer clinical trials testing of drug-induced hypertension is in progress.
testing heparin and other anticoagulants continue.
At present, drug-induced hypertension cannot be recom- No data are available to support changing the recommenda- mended for the treatment of most patients with ischemic tions about the use of anticoagulants in the urgent treatment stroke (grade A, new recommendation).
of patients with acute ischemic stroke.
Surgical and Endovascular Procedures
Antiplatelet Aggregating Agents
Gay et al53 successfully performed carotid endarterectomy Since the publication of the 2003 guidelines, Roden-Jullig et in 21 patients with acute ischemic symptoms. In another al50 have reported the results of a placebo-controlled trial of study of 67 patients, emergency carotid endarterectomy aspirin (325 mg/day) for the treatment of patients with stroke.
achieved recanalization in all but 5 cases.54 The patients The trial enrolled 441 patients (220 took aspirin) within 48 who were selected for surgery had normal preoperative hours of the onset of stroke. Patients were treated for 5 days; flow in the middle cerebral artery. The aim was to avoid no significant reduction in the rate of neurological worsening performing surgery on the internal carotid artery if an was noted. No differences in outcomes were noted at 3 ipsilateral embolic occlusion of the middle cerebral artery months. This study was underpowered to detect the mild had already occurred. Another study found that the pres- beneficial effects of aspirin identified in earlier megatrials. A ence of a diffusion/perfusion mismatch could be used to small study found that the combination of aspirin and a help select patients for surgery.55 low-molecular-weight heparin did not improve outcomes Endovascular and adjunctive mechanical thrombolytic methods include lasers, intraarterial suction devices, Other rapidly acting antiplatelet agents are being evaluated snares, angioplasty, and clot-retrieval devices.56,57 In some for their usefulness in treating patients with stroke. These cases, these devices have been used in conjunction with agents are being administered as a monotherapy or in com- pharmacological thrombolysis.58 In addition, therapeutic bination with thrombolysis.33–36 In a placebo-controlled ultrasonography has been used to help break fibrin mono- study, abciximab was administered within 6 hours of the mers, dissolve thrombi, and improve recanalization.59,60 onset of stroke. The results have been presented in abstract Although these preliminary reports suggest that mechani- April 2005
cal thrombolysis has great potential for the treatment of nesium and patients given placebo when the medication was patients with acute ischemic stroke, these procedures have administered within 12 hours of the onset of stroke; however, not been tested sufficiently to make any recommendation only 3% of the patients were enrolled within 3 hours of the onset about their use.
of symptoms. Another trial of magnesium is under way62; in thistrial, the medication is initiated while the patient is being transported to the hospital.
At present, none of the methods of mechanical thrombolysis Citicoline is another putative neuroprotective agent that has been adequately tested to draw conclusions about effi- has been studied extensively. Although no significant cacy. These interventions cannot be recommended outside the benefit was associated with use of citicoline based on the setting of clinical trials (grade A, no change from 2003).
primary, predetermined end points of any of the stroketrials, Davalos et al performed a meta-analysis of individ-ual patient data.63 The analysis tested the hypothesis of whether 6 weeks of treatment with oral citicoline would The last full guideline statement reviewed the results of several improve outcomes at 3 months. Data from patients receiv- clinical trials that tested putative neuroprotective agents. No ing various doses of citicoline or placebo who were agent had demonstrated clinical benefit. Since the publication of enrolled in 4 clinical trials were analyzed. Only patients the guidelines, the results of the IMAGES (Intravenous Magne- with compatible neuroimaging results, a moderate-to- sium Efficacy in Stroke) study have been reported.61 No overall severe neurological deficit (NIH Stroke Scale score ⱖ8), difference in outcomes was noted between patients given mag- and a prestroke modified Rankin Scale score of 0 or 1 were Approach to Elevated Blood Pressure in Acute Ischemic Stroke
Blood Pressure Level, mm Hg A. Not eligible for thrombolytic therapy Systolic ⱕ220 OR diastolic ⱕ120 Observe unless other end-organ involvement (eg, aortic dissection, acute myocardialinfarction, pulmonary edema, hypertensive encephalopathy) Treat other symptoms of stroke (eg, headache, pain, agitation, nausea, vomiting) Treat other acute complications of stroke, including hypoxia, increased intracranial pressure,seizures, or hypoglycemia Systolic ⱕ220 OR diastolic 121–140 Labetalol 10–20 mg IV for 1–2 min May repeat or double every 10 min (max dose 300 mg) Nicardipine 5 mg/h IV infusion as initial dose; titrate to desired effect by increasing 2.5 mg/hevery 5 min to max of 15 mg/h Aim for a 10%–15% reduction in blood pressure Nitroprusside 0.5 ␮g·kg⫺1·min⫺1 IV infusion as initial dose with continuous blood pressuremonitoring Aim for a 10%–15% reduction in blood pressure B. Eligible for thrombolytic therapy Systolic ⬎185 OR diastolic ⬎110 Labetalol 10–20 mg IV for 1–2 min May repeat 1 time or nitropaste 1–2 in During/after treatment 1. Monitor blood pressure Check blood pressure every 15 min for 2 h, then every 30 min for 6 h, and finally every hourfor 16 h 2. Diastolic ⬎140 Sodium nitroprusside 0.5 ␮g·kg⫺1·min⫺1 IV infusion as initial dose and titrate to desired bloodpressure 3. Systolic ⬎230 OR diastolic 121–140 Labetalol 10 mg IV for 1–2 min May repeat or double labetalol every 10 min to maximum dose of 300 mg, or give initiallabetalol dose, then start labetalol drip at 2–8 mg/min Nicarpidine 5 mg/h IV infusion as initial dose and titrate to desired effect by increasing 2.5mg/h every 5 min to maximum of 15 mg/h; if blood pressure is not controlled by labetalol,consider sodium nitroprusside 4. Systolic 180–230 OR diastolic 105–120 Labetalol 10 mg IV for 1–2 min May repeat or double labetalol every 10–20 min to maximum dose of 300 mg or give initiallabetalol dose, then start labetalol drip at 2–8 mg/min Adams et al
Guidelines for the Early Management of Patients With Ischemic Stroke
included. Recovery was assessed on the basis of a global increased risk of infections including pneumonia, gastroin- estimate of effect on the modified Rankin Scale, NIH testinal bleeding, and pressure sores. Data about the effec- Stroke Scale, and the Barthel Index. Recovery at 3 months tiveness of specific therapies aimed at improving nutrition are was found in 25.2% of citicoline-treated patients versus not yet available. Still, these data provide a strong rationale 20.2% of placebo-treated patients (P⫽0.0034). The data for assessment of the patient's nutritional status at the time of for this exploratory, post hoc analysis were obtained from admission. In addition, measures should be implemented to a highly selected group of patients. Of particular concern maintain or improve the nutritional status of all patients with is that none of the individual clinical trials, which were the recent stroke.
source of the data, was able to find a benefit fromtreatment with citicoline. Thus, additional research is needed to substantiate these results.
Assessment of the patient's baseline nutritional status and institutionof measures to correct any major nutritional problems are recom- mended (grade C, new recommendation).
At present, no agent with putative neuroprotective effects canbe recommended for the treatment of patients with acute ischemic stroke (grade A, no change from 2003).
Small preliminary clinical studies suggest that hypothermiamay be feasible and beneficial for treatment of acute Nutrition and Hydration
stroke.65–68 Two important articles in the New England In a randomized trial, the FOOD (Feed Or Ordinary Diet) Journal of Medicine showed significant benefits for hypo- Trial Collaboration is testing the utility of several feeding thermia in cardiac arrest survivors.69,70 Hypothermia for acute strategies including oral supplementation, early versus de- stroke is a promising area for development, but data are layed nasogastric tube feeding, and nasogastric versus per- insufficient to recommend it.
cutaneous endoscopic gastrostomy feeding. A preliminaryreport based on 3012 patients indicates that poor baseline nutritional status is associated with worse outcomes at 6 Table 6 of the 2003 Guidelines has been updated with the months.64 Although weakened, this relationship persists after table on page 920. The 2003 Guidelines online now show this adjustment for other factors including the patient's age, update, and the table is being printed here for reference.
National Institute of Boehringer Ingelheim; Neurological Disorders and Bristol-Myers Squibb Stroke; Boehringer Ingelheim; Centocor; Eli Lilly; Sanofi-Synthelabo; NMT Medical; Astra-Zeneca; Merck; National Heart, Lung, and Blood Boehringer Ingelheim; Boehringer Ingelheim; Siemens ACUSON; Advanced Institute-National Institutes of Bristol-Myers Squibb; Wyeth Bristol-Myers Squibb; Testing Laboratory; Sanofi-Synthelabo; Wyeth Boehringer Ingelheim; Laboratories; Department of Bristol-Myers Squibb National Institutes of Health Boehringer Ingelheim Grants: National Institutes of Health, Department of Veterans Affairs, Centers for Disease EVEREST; CuraGen Corp; Prevention/University of North Johnson & Johnson; Merck Carolina-Chapel Hill; clinical Research Laboratories; trials site: Boehringer Pfizer/Parke-Davis; AGA Ingelheim, AGA Medical Corp This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all members of the writing group are required to complete and submit.
prestroke functional level, living conditions, and severity ofstroke. A poor nutritional status was associated with an April 2005
20. Hsia AW, Sachdev HS, Tomlinson J, Hamilton SA, Tong DC. Efficacy of IV tissue plasminogen activator in acute stroke: does stroke subtype really matter? 1. Barber PA, Demchuk AM, Zhang J, Buchan AM. Validity and reliability of a quantitative computed tomography score in predicting outcome of . 2003;61:71–75.
hyperacute stroke before thrombolytic therapy. ASPECTS Study Group.
21. Furlan A. Intra-arterial thrombolysis for acute stroke. Cleve Clin J Med. 2004; Alberta Stroke Programme Early CT Score. Lancet. 2000;355:1670 –1674.
2. Coutts SB, Demchuck AM, Barber PA, Hu WY, Simon JE, Buchan AM, Hill 22. Lisboa R, Jovanovic B, Alberts MJ. Analysis of the safety and efficacy of MD; VISION Study Group. Interobserver variation of ASPECTS in real time.
intra-arterial thrombolytic therapy in ischemic stroke. Stroke. 2002;33: 3. Crisostomo RA, Garcia MM, Tong DC. Detection of diffusion-weighted MRI 23. Linfante I, Llinas RH, Selim M, Chaves C, Kumar S, Parker RA, Caplan LR, abnormalities in patients with transient ischemic attack: correlation with clinical Schlaug G. Clinical and vascular outcome in internal carotid artery versus middle cerebral artery occlusions after intravenous tissue plasminogen activator. Stroke.
4. Latchaw RE, Yonas H, Hunter GJ, Yuh WT, Ueda T, Sorensen AG, Sunshine JL, Biller J, Wechsler L, Higashida R, Hademenos G; Council on Cardiovascular 24. Eckert B, Kucinski T, Neumaier-Probst E, Fiehler J, Röther J, Zeumer H. Local Radiology of the American Heart Association. Guidelines and recommendations intra-arterial fibrinolysis in acute hemispheric stroke: effect of occlusion type and for perfusion imaging in cerebral ischemia: a scientific statement for healthcare fibrinolytic agent on recanalization success and neurological outcome. Cere- professionals by the writing group on perfusion imaging, from the Council on brovasc Dis. 2003;15:258–263.
Cardiovascular Radiology of the American Heart Association. Stroke. 2003;34: 25. Ogasawara K, Ogawa A, Yoshimoto T. Cerebrovascular reactivity to acetazol- amide and outcome in patients with symptomatic internal carotid or middle 5. Kidwell CS, Chalea JA, Saver JL, Davis SM, Warach S. Hemorrhage cerebral artery occlusion: a xenon-133 single-photon emission computed early MRI evaluation (HEME) study: preliminary results of a multi- tomography study. Stroke. 2002;33:1857–1862.
center trial of neuroimaging in patients with acute stroke symptoms 26. Arnold M, Schroth G, Nedeltchev K, Loher T, Remonda L, Stepper F, Stur- within 6 hours of onset. Hemorrhage early MRI evaluation (HEME) zenegger M, Mattle HP. Intra-arterial thrombolysis in 100 patients with acute study. Stroke. 2003;34:239. Abstract.
stroke due to middle cerebral artery occlusion. Stroke. 2002;33:1828–1833.
6. Chalea JA, Latour LL, Jeggeries N, Warach S. Hemorrhage and early MRI 27. Higashida RT, Furlan AJ, Roberts H, Tomsick T, Connors B, Barr J, Dillon W, evaluation from the emergency room (HEME-ER): a prospective, single center Warach S, Broderick J, Tilley B, Sacks D; Technology Assessment Committee of comparison of MRI to CT for the emergency diagnosis of intracerebral hemor- the American Society of Interventional and Therapeutic Neuroradiology; Tech- rhage in patients with suspected cerebrovascular disease. Stroke. 2003;34: nology Assessment Committee of the Society of Interventional Radiology. Trial design and reporting standards for intra-arterial cerebral thrombolysis for acute 7. Kidwell CS, Saver JL, Villablanca JP, Duckwiler G, Fredieu A, Gough K, Leary ischemic stroke. Stroke. 2003;34:e109–e127.
MC, Starkman S, Gobin YP, Jahan R, Vespa P, Liebeskind DS, Alger JR, 28. Hill MD, Barber PA, Demchuk AM, Newcommon NJ, Cole-Haskayne A, Vinuela F. Magnetic resonance imaging detection of microbleeds before Ryckborst K, Sopher L, Button A, Hu W, Hudon ME, Morrish W, Frayne R, thrombolysis: an emerging application. Stroke. 2002;33:95–98.
Sevick RJ, Buchan AM. Acute intravenous–intra-arterial revascularization 8. Fiebach JB, Schellinger PD, Gass A, Kucinski T, Siebler M, Villringer A, Olkers therapy for severe ischemic stroke. Stroke. 2002;33:279–282.
P, Hirsch JG, Heiland S, Wilde P, Jansen O, Rother J, Hacke W, Sartor K; 29. Qureshi AI. Endovascular treatment of cerebrovascular diseases and intracranial Kompetenznetzwerk Schlaganfall B5. Stroke magnetic resonance imaging is accurate in hyperacute intracerebral hemorrhage: a multicenter study on the 30. Suarez JI, Zaidat OO, Sunshine JL, Tarr R, Selman WR, Landis DM.
validity of stroke imaging. Stroke. 2004;35:502–506.
Endovascular administration after intravenous infusion of thrombolytic 9. Greer DM, Koroshetz WJ, Cullen S, Gonzalez RG, Lev MH. Magnetic resonance agents for the treatment of patients with acute ischemic strokes. Neuro- imaging improves detection of intracerebral hemorrhage over computed tomography after intra-arterial thrombolysis. Stroke. 2004;35:491–495.
31. Zaidat OO, Suarez JI, Santillan C, Sunshine JL, Tarr RW, Paras VH, Selman 10. Schrader J, Luders S, Kulschewski A, Berger J, Zidek W, Treib J, Einhaupl K, WR, Landis DM. Response to intra-arterial and combined intravenous and intra- Diener HC, Dominiak P; Acute Candesartan Cilexetil Therapy in Stroke Sur- arterial thrombolytic therapy in patients with distal internal carotid artery vivors Study Group. The ACCESS Study: evaluation of Acute Candesartan Cilexetil Therapy in Stroke Survivors. Stroke. 2003;34:1699–1703.
32. Alexandrov AV, Grotta JC. Arterial reocclusion in stroke patients treated with 11. Wardlaw JM, Zoppo G, Yamaguchi T, Berge E. Thrombolysis for acute intravenous tissue plasminogen activator. Neurology. 2002;59:862–867.
ischaemic stroke. Cochrane Database Syst Rev. 2003;CD000213.
33. Morris DC, Silver B, Mitsias P, Lewandowski C, Patel S, Daley S, Zhang ZG, Lu 12. Hacke W, Donnan G, Fieschi C, Kaste M, von Kummer R, Broderick JP, Brott M. Treatment of acute stroke with recombinant tissue plasminogen activator and T, Frankel M, Grotta JC, Haley EC Jr, Kwiatkowski T, Levine SR, Lewandowski abciximab. Acad Emerg Med. 2003;10:1396–1399.
C, Lu M, Lyden P, Marler JR, Patel S, Tilley BC, Albers G, Bluhmki E, Wilhelm 34. Staub S, Junghans U, Jovanovic V, Wittsack HJ, Seitz RJ, Siebler M. Systematic M, Hamilton S; ATLANTIS Trials Investigators; ECASS Trials Investigators; thrombolysis with recombinant tissue plasminogen activator and tirofiban in acute NINDS rt-PA Study Group Investigators. Association of outcome with early middle cerebral artery occlusion. Stroke. 2004;35:705–709.
stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA 35. Lee DH, Jo KD, Kim HG, Choi SJ, Jung SM, Ryu DS, Park MS. Local stroke trials. Lancet. 2004;363:768–774.
intra-arterial urokinase thrombolysis of acute ischemic stroke with or without 13. Graham GD. Tissue plasminogen activator for acute ischemic stroke in clinical intravenous abciximab: a pilot study. J Vasc Interv Radiol. 2002;13:769–774.
practice: a meta-analysis of safety data. Stroke. 2003;34:2847–2850.
36. Kwon OK, Lee KJ, Han MH, Oh CW, Han DH, Koh YC. Intraarterially 14. Katzan IL, Hammer MD, Furlan AJ, Hixson ED, Nadzam DM; Cleveland Clinic administered abciximab as an adjuvant thrombolytic therapy: report of three Health System Stroke Quality Improvement Team. Quality improvement and cases. Am J Neuroradiol. 2002;23:447–451.
tissue-type plasminogen activator for acute ischemic stroke: a Cleveland update.
37. Katzan IL, Graber TM, Furlan AJ, Sundararajan S, Sila CA, Houser G, Landis DM. Cuyahoga County Operation Stroke speed of emergency department eval- 15. Schmulling S, Rudolf J, Strotmann-Tack T, Grond M, Schneweis S, Sobesky J, uation and compliance with National Institutes of Neurological disorders and Thiel A, Heiss WD. Acetylsalicylic acid pretreatment, concomitant heparin stroke time targets. Stroke. 2003;34:994–998.
therapy and the risk of early intracranial hemorrhage following systemic 38. Wojner AW, Morgenstern L, Alexandrov AV, Rodriguez D, Persse D, Grotta JC.
thrombolysis for acute ischemic stroke. Cerebrovasc Dis. 2003;16:183–190.
Paramedic and emergency department care of stroke: baseline data from a 16. Hill MD, Lye T, Moss H, Barber PA, Demchuk AM, Newcommon NJ, Green citywide performance improvement study. Am J Crit Care. 2003;12:411–417.
TL, Kenney C, Cole-Haskayne A, Buchan AM. Hemi-orolingual angioedema 39. Nedeltchev K, Arnold M, Brekenfeld C, Isenegger J, Remonda L, Schroth G, and ACE inhibition after alteplase treatment of stroke. Neurology. 2003;60: Mattle HP. Pre- and in-hospital delays from stroke onset to intra-arterial 17. Rudolf J, Grond M, Prince WS, Schmulling S, Heiss WD. Evidence of ana- 40. Silliman SL, Quinn B, Huggett V, Merino JG. Use of a field-to-stroke center phylaxy after alteplase infusion. Stroke. 1999;30:1142–1143.
helicopter transport program to extend thrombolytic therapy to rural residents.
18. Pancioli A, Brott T, Donaldson V, Miller R. Asymmetric angioneurotic edema associated with thrombolysis for acute stroke. Ann Emerg Med. 1997;30: 41. LaMonte MP, Bahouth MN, Hu P, Pathan MY, Yarbrough KL, Gunawardane R, Crarey P, Page W. Telemedicine for acute stroke: triumphs and pitfalls. Stroke.
19. Rudolf J, Grond M, Schmulling S, Neveling M, Heiss W. Orolingual angion- eurotic edema following therapy of acute ischemic stroke with alteplase. Neu- 42. Nowak-Göttl U, Straeter R, Sebire G, Kirkham F. Antithrombotic drug treatment of pediatric patients with ischemic stroke. Paediatr Drugs. 2003;5:167–175.
Adams et al
Guidelines for the Early Management of Patients With Ischemic Stroke
43. Adams HP Jr. Emergent use of anticoagulation for treatment of patients with 58. Qureshi AI, Siddiqui AM, Suri MF, Kim SH, Ali Z, Yahia AM, Lopes DK, ischemic stroke. Stroke. 2002;33:856–861.
Boulos AS, Ringer AJ, Saad M, Guterman LR, Hopkins LN. Aggressive 44. Albers GW, Amarenco P, Easton JD, Sacco RL, Teal P. Antithrombotic and mechanical clot disruption and low-dose intra-arterial third-generation thrombolytic therapy for ischemic stroke. Chest. 2001;119:300S–320S.
thrombolytic agent for ischemic stroke: a prospective study. Neurosurgery. 2002; 45. Coull BM, Williams LS, Goldstein LB, Meschia JF, Heitzman D, Chaturvedi S, Johnston KC, Starkman S, Morgenstern LB, Wilterdink JL, Levine SR, Saver JL; 59. Daffertshofer M, Hennerici M. Ultrasound in the treatment of ischaemic stroke.
American Academy of Neurology; American Stroke Association. Anticoagulants Lancet Neurol. 2003;2:283–290.
and antiplatelet agents in acute ischemic stroke: report of the Joint Stroke 60. Behrens S, Spengos K, Daffertshofer M, Schroeck H, Dempfle CE, Hennerici M.
Guideline Development Committee of the American Academy of Neurology and Transcranial ultrasound-improved thrombolysis: diagnostic vs. therapeutic the American Stroke Association (a division of the American Heart Association).
ultrasound. Ultrasound Med Biol. 2001;27:1683–1689.
61. Muir KW, Lees KR, Ford I, Davis S; Intravenous Magnesium Efficacy in 46. Sherman DG. Antithrombotic and hypofibrinogenetic therapy in acute ischemic Stroke (IMAGES) Study Investigators. Magnesium for acute stroke (Intrave- stroke: what is the next step? Cerebrovasc Dis. 2004;17:138–143.
nous Magnesium Efficacy in Stroke trial): randomised controlled trial.
47. Al-Sadat A, Sunbulli M, Chaturvedi S. Use of intravenous heparin by North Lancet. 2004;363:439 – 445.
62. Saver JL, Kidwell CS, Eckstein M, Starkman S; FAST-MAG Pilot Trial Inves- American neurologists: do the data matter? Stroke. 2002;33:1574–1577.
tigators. Prehospital neuroprotective therapy for acute stroke: results of the Field 48. LaMonte MP, Nash ML, Wang DZ, Woolfenden AR, Schultz J, Hursting MJ, Administration of Stroke Therapy-Magnesium (FAST-MAG) pilot trial. Stroke.
Brown PM; ARGIS-1 Investigators. Argatroban anticoagulation in patients with acute ischemic stroke (ARGIS-1): a randomized, placebo-controlled safety study.
63. Davalos A, Castillo J, Alvarez-Sabín J, Secades JJ, Mercadal J, Lopez S, Cobo E, Warach S, Sherman D, Clark WM, Lozano R. Oral citicoline in acute ischemic 49. Burak CR, Bowen MD, Barron TF. The use of enoxaparin in children with acute, stroke: an individual patient data pooling analysis of clinical trials. Stroke. 2002; nonhemorrhagic ischemic stroke. Pediatr Neurol. 2003;29:295–298.
50. Roden-Jullig A, Britton M, Malmkvist K, Leijd B. Aspirin in the prevention of 64. FOOD Trial Collaboration. Poor nutritional status on admission predicts poor progressing stroke: a randomized controlled study. J Intern Med. 2003;254: outcome after stroke: observational data from the FOOD trial. Stroke. 2003;34: 51. Sarma GR, Roy AK. Nadroparin plus aspirin versus aspirin alone in the treatment 65. Hammer MD, Krieger DW. Acute ischemic stroke: is there a role for hypo- of acute ischemic stroke. Neurol India. 2003;51:208–210.
thermia? Cleve Clin J Med. 2002;69:770, 773–775, 776–777.
52. Hillis AE, Ulatowski JA, Barker PB, Torbey M, Ziai W, Beauchamp NJ, Oh S, 66. Hammer MD, Krieger DW. Hypothermia for acute ischemic stroke: not just Wityk RJ. A pilot randomized trial of induced blood pressure elevation: effects on another neuroprotectant. Neurologist. 2003;9:280–289.
function and focal perfusion in acute and subacute stroke. Cerebrovasc Dis.
67. Kasner SE, Wein T, Piriyawat P, Villar-Cordova CE, Chalela JA, Krieger DW, Morgenstern LB, Kimmel SE, Grotta JC. Acetaminophen for altering body 53. Gay JL, Curtil A, Buffiere S, Favre JP, Barral X. Urgent carotid artery repair: temperature in acute stroke: a randomized clinical trial. Stroke. 2002;33:130–134.
retrospective study of 21 cases. Ann Vasc Surg. 2002;16:401–406.
68. Krieger DW, De Georgia MA, Abou-Chebl A, Andrefsky JC, Sila CA, Katzan 54. Huber R, Muller BT, Seitz RJ, Siebler M, Modder U, Sandmann W. Carotid IL, Mayberg MR, Furlan AJ. Cooling for acute ischemic brain damage (cool aid): surgery in acute symptomatic patients. Eur J Vasc Endovasc Surg. 2003;25: an open pilot study of induced hypothermia in acute ischemic stroke. Stroke.
55. Krishnamurthy S, Tong D, McNamara KP, Steinberg GK, Cockroft KM. Early 69. Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, Smith carotid endarterectomy after ischemic stroke improves diffusion/perfusion K. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced mismatch resonance imaging: report of two cases. Neurosurgery. 2003;52: hypothermia. N Engl J Med. 2002;346:557–563.
70. Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to 56. Leary MC, Saver JL, Gobin YP, Jahan R, Duckwiler GR, Vinuela F, Kidwell CS, improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346: Frazee J, Starkman S. Beyond tissue plasminogen activator: mechanical inter- vention in acute stroke. Ann Emerg Med. 2003;41:838–846.
57. Lutsep HL, Clark WM, Nesbit GM, Kuether TA, Barnwell SL. Intraarterial KEY WORDS: AHA/ASA Scientific Statements 䡲 stroke 䡲 thrombolytic suction thrombectomy in acute stroke. Am J Neuroradiol. 2002;23:783–786.
therapy 䡲 anticoagulation 䡲 evaluation



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Published online August 25, 2004 Nucleic Acids Research, 2004, Vol. 32, No. 15 RNA expression microarrays (REMs), ahigh-throughput method to measure differencesin gene expression in diverse biological samples Charles E. Rogler*, Tatyana Tchaikovskaya, Raquel Norel, Aldo Massimi1,Christopher Plescia2, Eugeny Rubashevsky, Paul Siebert3 and Leslie E. Rogler Department of Medicine and Marion Bessin Liver Research Center, 1Department of Molecular Genetics, Albert EinsteinCollege of Medicine, Bronx, NY, USA, 2Department of Neurosciences, Mt Sinai College of Medicine, New York, NY,USA and 3BD Biosciences-Clontech, Palo Alto, CA, USA