- Email: [email protected]
Evaluation and Management of Transient Ischemic Attacks
Clin Geriatr Med 23 (2007) 401–412
Evaluation and Management of Transient Ischemic Attacks Marian P. LaMonte, MD, MSNa,b,* a
Department of Neurology and Emergency Medicine, University of Maryland School of Medicine, University of Maryland Medical Center, Room N4W46, 22 South Greene Street, Baltimore, MD 21201, USA b The Maryland Stroke and Brain Attack Center, University of Maryland Medical Center, Baltimore, MD, USA
The risk of a disabling stroke after transient ischemic attack (TIA) is suggested to be highest within the first 48 hours after the TIA event [1,2]. Nearly half of recurrent stroke events ensue within the first 7 days [1–3]. In a United Kingdom study analyzing population-based and clinical trial ischemic stroke studies, 43% of the patients who suffered a stroke and who had a prodrome TIA experienced the TIA event within 7 days of the stroke [3]. A recent population-based study found a risk of stroke after TIA of 15% at 3 months and 4% within 2 days of the index TIA [2]. This finding suggests that a patient who has a TIA should be managed emergently [4]. TIA patients’ access to health care remains variable and depends on many factors. Common patient factors include lack of awareness of the nature of symptoms, confusion with other common coexisting medical problems, denial of illness, and embarrassment. Other common factors include insurer rules and cost concerns. The brief nature of TIAs (in minutes) and possible compromise of cognitive function during TIA produce a situation in which symptoms can be under- or not appreciated (the ‘‘silent’’ TIA). When patients do recognize symptoms, they may access care variably through their primary health provider, an emergency department, or other health provider. Options for effective secondary stroke prevention have expanded with the publication of important data on the efficacy of medical and surgical management of cerebrovascular disease [5,6]. Recently issued guidelines for TIA
* University of Maryland Medical Center, Department of Neurology, Room N4W46, 22 South Greene Street, Baltimore, MD 21201. E-mail address: [email protected] 0749-0690/07/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.cger.2007.01.012 geriatric.theclinics.com
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and stroke examine risk factor management and therapeutics, but the guidelines do not specify the setting (inpatient versus outpatient) or timing, nor do these guidelines identify the optimal health care provider for assessment and management of patients who have TIA [5]. To address these issues, The University of Maryland Medical Center developed and initiated a community-service model for rapid assessment and treatment of the patient who has a TIA that is based in the emergency department (ED) of its tertiary stroke-referral medical center. Similar to programs that have been implemented for patients experiencing chest pain, the Rapid Assessment and Treatment of Transient Ischemic Attack Etiology (RATE) program is an interdisciplinary service that provides evaluation of TIA etiology and enables secondary stroke-prevention interventions to be initiated within 24 hours of the patient’s arrival. In conjunction with the service, a targeted TIA educational strategy was developed for both the community and for health providers to make them aware of the emergency nature of TIA and the availability of the RATE program. RATE program aims are (1) to determine symptom etiology and (2) to initiate treatments for TIA and stroke risk factor management within 24 hours of entry. The aims are monitored continuously through the Medical Center’s quality improvement process. Although this systematic approach is not possible or practical for all geriatric practices, it is presented here as an example of the pragmatic enactment of current guidelines for TIA evaluation and management. A discussion of modifications that can be made for an outpatient setting evaluation and a review of the literature follow.
The rapid assessment and treatment of transient ischemic attack etiology program Patient care setting In the RATE program, patient care is provided in the ED Rapid Diagnostic Unit (RDU) of the University of Maryland Medical Center’s ED. The RDU is a four-bed, short-stay monitored inpatient unit based in the ED. The primary goal is to accept patients from the ED who require extended evaluations that are not completely suited or appropriate for a typical ED visit. This evaluation may include specialty testing that is not routinely available to the ED at all hours as well as extended observation periods for patients who are too ill to discharge safely but who do not require a prolonged hospital stay. The RDU is staffed by board-certified internists and toxicologists, typically with dual training in emergency medicine. Typical patients include patients who have chest pain and suspicion of coronary artery disease, cellulitis, mild-to-moderate decompensated congestive heart failure, chronic obstructive pulmonary disease, dehydration, asthma exacerbations, hyperglycemia, and TIA. Other patients are evaluated and admitted on a case-by-case basis.
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Patient description RATE patients are 18 years or older, are diagnosed with TIA by an emergency physician, and enter the ED between 8:00 AM Monday and 12:00 PM Friday. These are the RDU hours during which 24-hour turn-around of patient testing can be assured. When patients present outside these hours, they are admitted to the hospital. Patients are not evaluated by RATE if they present with focal cerebral ischemic symptoms of more than 24 hours’ duration or have focal cerebral neurologic deficit determined to be caused by trauma, tumor, intracerebral hemorrhage, or postsurgical or interventional procedures. Patients who are already hospitalized with symptoms of TIA are not evaluated by RATE. Ischemic infarction is defined as a neurologic dysfunction caused by ischemia and having consistent brain imaging data, even if neurologic examination has normalized. For etiology of TIA and stroke, RATE uses the classic categories of large artery atherosclerotic infarction (intracranial/extracranial); embolism from a cardiac embolism source; small vessel disease; or other determined cause such as dissection, hypercoagulable state, or sickle disease; and infarcts of undetermined etiology [5]. Protocol Upon ED physician diagnosis of TIA, the RATE diagnostic pathway is initiated. The RATE pathway triggers an emergent neurology consultation and a computerized panel of diagnostic tests and nursing orders (Box 1). Emergency medicine and neurology staff determine vascular risk factors by history and physical examination and verify these findings by contacting family or primary care providers. A predetermined set of laboratory tests elucidates serum and urinary markers for coexisting medical diagnoses and vascular risk factors. CT scans are performed immediately to rule out hemorrhage, cerebral infarct, or other space-occupying lesions. Once other nonischemic causes are excluded, antiplatelet therapy is initiated. Brain MRI/magnetic resonance angiography (MRA) scans are performed to aid in determining ischemic etiology. Patients who have carotid duplex or MRA indicating carotid stenosis of more than 50% are referred immediately for surgical consultation. Chest radiographs are taken to look for aortic and cardiac pathology, and 12-lead ECGs are obtained for evidence of concurrent cardiac ischemia and, specifically, atrial fibrillation. Patients have continuous cardiac telemetry monitoring to observe for intermittent atrial fibrillation. Intravenous or subcutaneous anticoagulation and warfarin are initiated for patients found to have atrial fibrillation who are appropriate candidates for warfarin therapy using American College of Chest Physicians/American Heart Association (ACCP/AHA) guidelines [7]. To evaluate cardiac function and rule out cardioembolic causes, patients undergo transthoracic echocardiography with saline contrast study. If the patient’s ejection fraction is less than 35%, anticoagulation is initiated if appropriate according to ACCP/AHA guidelines [7]. If the patient has atrial
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Box 1. RATE diagnostic pathway Laboratory studies Comprehensive metabolic panel Complete blood cell count with differential Prothrombin time, partial thromboplastin time, international normalized ratio Sedimentation rate Urine toxicology Finger stick and serum glucose Fasting lipid panel Thyroid-stimulating hormone Other laboratory tests as indicated Antinuclear antibodies Rapid plasma reagin Fluorescent treponemal antibody Protein C and S Antithrombin III Factor V Leiden mutation Homocysteine Rheumatoid factor Vitamin B12 Antiphospholipid antibodies Diagnostic studies Brain CT scan 12-lead ECG and continuous cardiac monitoring Chest radiograph Brain MRI/MRA Carotid duplex studies Transcranial Doppler studies (optional) Transthoracic echocardiogram with saline contrast Other Antiplatelet/anticoagulation in emergency department Appointment with primary care physician Educational session with nurse practitioner/emergency department nurse Neurology follow up appointment
fibrillation or another cardioembolic source suggesting the need for warfarin therapy, but has contraindications, antiplatelet therapy is initiated if possible. Antithrombotic therapy may be temporarily discontinued for patients who have a concurrent contraindication such as gastrointestinal bleeding.
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These patients and their primary care givers are given instructions concerning the safe resumption of antithrombotic therapy. The program provides emergent laboratory turn-around time, and RATE patients have priority for diagnostic studies and results. All physician orders are bundled into a standardized computerized care set that provides orders for all studies and serial clinical examinations; therefore diagnostic and therapeutic decisions can be determined as rapidly as possible. Once diagnostic procedures are completed, the neurologist finalizes the TIA etiology, risk-factor profile, and recommended secondary prevention strategies (Box 2). If the neurologic examination is normal and diagnostics and elucidated stroke risk factors exclude the need for further hospitalization, the patient is discharged. Before discharge, patient education includes (1) information about stroke risk factors; (2) information about reducing stroke risk factors; (3) instructions on when to contact the emergency medical system; (4) follow-up appointments with primary care and neurology; and (5) medication education. A follow-up appointment in the neurology clinic is scheduled before the patient leaves the ED. The ED also provides the patient’s primary care physician with a copy of the patient’s evaluation (Fig. 1).
Discussion TIA is a medical emergency, and evaluation and management should be performed as promptly as possible. A reorganization of TIA evaluation and treatment into a rapid protocol can be implemented effectively in an ED setting akin to chest pain observation units. The advantages of a short-stay program for patients experiencing TIA include (1) expedited consultations and diagnostics, as available to hospitalized patients; (2) identification and treatment of patients who actually have stroke rather than TIA; (3) identification and treatment of ‘‘stroke-mimicking’’ diagnoses such as migraine with aura, intracerebral hemorrhage, intracranial tumor, seizure, and hypoglycemia; and (4) identification of stroke risk factors and rapid implementation of specific interventions in the most venerable period for disabling stroke (ie, the first 2–7 days). Stroke diagnosis among patients presenting with transient ischemic attacks Twenty-six percent of RATE patients who have confirmed cerebrovascular symptoms have MRI imaging evidence showing cerebral infarction despite normal clinical examination and CT without evidence of infarction. Other groups that have studied MRI imaging characteristics of patients experiencing TIA have reported similar findings. A Stanford group found that 21% of patients who had TIA and who were imaged with MRI within 3 days of symptoms had lesions detected on diffusion-weighted imaging, and
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Box 2. Checklist for TIA and stroke risk factor management for secondary prevention Maryland Stroke and Brain Attack Center Stroke Risk Factor Management a Hypertension: Wait 24 to 36 hours after stroke, then assess (long-term target: systolic blood pressure <120 mm Hg; diastolic blood pressure <80 mm Hg). Medical therapy: If needed, begin with thiazide diuretic and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. If secondary agent is needed, consider using a b-blocker if the patient has concurrent heart disease or a calcium-channel blocker if the patient is African American (see Joint National Committee on Prevention, evaluation and treatment of high blood pressure guidelines). Patient education: Teach the patient about importance of 20 minutes exercise daily and diet. Cholesterol: Initiation of statin therapy with atorvastatin 80 mg has been shown to reduce recurrent stroke risk. Target low-density lipoprotein cholesterol <100 mg/dL and recommend <70 mg/dL [8,9]. Medical therapy: Initiate medical therapy with statins (check baseline liver function tests before starting). Patient education: Teach patient therapeutic lifestyle changes: diet (eliminate transfats), weight loss, increased physical activity. Smoking: Smoking and second-hand smoke increase risk of ischemic stroke by >50% and of subarachnoid hemorrhage by >100%. Medical therapy: Counseling, cessation, nicotine patch/gum, lozenges and prescription medication. Patient education: Emphasize the need for patient and family to stop smoking completely and to avoid second-hand smoke. Diabetes: Diabetics have a 1.5- to 2.5-fold greater risk for ischemic stroke. Medical therapy: Initiate oral hypoglycemic treatment and recommend schedule of glucose checks for the patient. Hemoglobin A1c should be <7. Consider angiotensin-converting enzyme inhibitor or angiotensin receptor blocker as antihypertensive, and statin agent. Patient education: Consult endocrine service for diabetic teaching before discharge; make follow-up appointment with Diabetes Center. Antithrombotic therapies: These therapies and practices will be lifelong because stroke or TIA increases stroke risk 10 times.
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Medical therapy: Antiplatelets: asprin/dipyridamole 25/200 mg twice daily, aspirin 50–325 mg daily, or clopidogrel 75 mg latest daily. Anticoagulation: Use 2006 American College of Chest Physicians guidelines for patients who have atrial fibrillation. Target international normalized ratio for patients taking warfarin is 2.5. Patient education: Counsel patients about the need to continue these medicines for life. Reinforce the warning signs for stroke and the need to call 911 should they occur. Emphasize that the patient always should discuss the discontinuation of these medicines with the patient’s health care provider. Obesity and nutrition counseling for all patients: Desirable body mass index: 18.5–24.9 kg/m2. Medical therapy: Obtain nutrition/dietary consultation if necessary. Patient education: Teach patient to eliminate transfats, reduce total fat and salt intake, increase fruit/vegetable consumption. Discuss benefits of both aerobic and flexibility and strengthening exercise. Sleep apnea: May increase stroke risk by twofold. Identify risk factors and symptoms and consider recommendation for sleep study. Infections: May increase stroke risk by twofold. Identify underlying infections, especially fungal infections and gum disease. Initiate inpatient treatment for fungal infections or include advisory to begin outpatient treatment in discharge summary. Alcohol: Explicitly advise patients about abstinence or safe drinking (less than three alcohol equivalents per day for men or two alcohol equivalents per day for women). The dose of alcohol in a typical 12-ounce can of beer is approximately equal to the dose of alcohol in a 4-ounce serving of wine or in an ounce of whiskey. Cautionary medications: Sympathomimetic drugs (ie, cough, cold, and some allergy medicines), triptans, hormone replacement therapy, and birth control pills: Advise patient to avoid any drugs that may cause blood vessel constriction or increase the risk of blood clotting. Recommend that patient discuss any over-the-counter medications with the patient’s health care provider and pharmacist before use. a This list is a guide and is not intended as the only source for stroke risk factor management strategies. Follow the most current national guidelines when considering therapies for risk factors.
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a group from the University of California at Los Angeles found that 48% of these patients had such characteristics within 3 days of symptoms [10,11]. Is it possible to predict which patients are at high risk of early stroke following TIA? Groups in Oxfordshire and California have developed models for TIA characteristics that may predict a higher risk of ischemic stroke following TIA within 7 and 90 days, respectively [12,13]. Predictive TIA characteristics found by these groups included age of 60 years or greater, diabetes, systolic blood pressure greater than 140 mm Hg, speech disturbance, and weakness. Among these studies, symptom duration was highly variable as a predictor: the Oxfordshire group found a duration of more than 60 minutes to be a significant predictor, whereas the California group found a duration of more than 10 minutes to indicate an increased risk. The California group has presented a validation study for their model (age O60 years, diabetes, spell duration O10 minutes, and weakness with the spell) [13]. The Oxfordshire model is cumbersome, six features must be scored on a dichotomous scale, and a recent study found the model score to have only minor correlation with clinical outcome (P for trend ¼ .11) [14]. Symptom duration Most TIAs last less than 1 hour, with a median duration of 14 minutes with carotid distribution ischemia and 8 minutes with vertebrobasilar ischemia [15]. The authors total RATE patient population had a mean symptom duration of 58 65 minutes, which was not significantly different from the subgroup of RATE patients whose final diagnosis and imaging data revealed cerebral infarction (56 45 minutes). A group in the United Kingdom analyzed population-based and clinical trial studies that included data on TIA preceding ischemic stroke [3]. No study found a difference in the duration of TIA symptoms that preceded a stroke and those that did not. These findings do not support a shorter duration of symptoms as indicating a lesser risk for stroke, therefore, a short duration TIA is not less worrisome for immenent infarction, and requires the same aggressive workup. Alternative strategies ED-based TIA evaluation is neither possible nor practical for all patients. Modification to provide an efficient outpatient evaluation is based on (1) providing accurate diagnosis and treatment and (2) implementing specific therapies for stroke prevention as rapidly as possible. What are the essential diagnostics for these goals? Foremost is an accurate history that suggests a brief period of the abrupt onset of a focal neurologic deficit. A complete discernment of common stroke risk factors by both history and physical examination provides data on possible mechanisms of TIA such as atherothrombosis or cardioembolism. Neurologist consultation
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Primary Care Provider Discharge Letter Date: _______________ Dear Primary Care Provider______________________________ Ms/Mr _____________was discharged from The University of Maryland Medical Center RATE (Rapid Assessment of Transient Ischemic Attack Etiology) on ____________ with the diagnosis of ______________. Your patient was medically and neurologically observed and had diagnostic and therapeutic management under the care of Dr. __________________ and Dr./NP _____________________. (ED Physician) (Neurology Consultant) Concomitant Diagnoses are: □ Hypertension □ Diabetes Mellitus □ Tobacco Abuse □ Carotid Stenosis (< 50 ) □ Chronic CHF □ Coronary Artery Disease
□ Hypercholesterolemia □ Atrial fibrillation □ Seizure □ Symptomatic Carotid Stenosis (> 50 ) □ Others: _____________ _____________________
Your patient was discharged on the following medication(s) for secondary stroke prevention: □ Asprin/Dipyridamole 1 capsule every 12 hours □ Aspirin _______ mg daily □ Clopidogrel 75 mg daily □ Warfarin ________mg_______ □ Other ____________________
While on the RATE Service the following tests/consults were performed: Results Pending Normal Abnormal □ Comprehensive metabolic panel □ □ □ □ □ □ □ CBC with differential □ □ □ □ PT, PTT, INR □ □ □ □ Sedimentation rate □ □ □ □ Urine and blood toxicology □ Lipid panel (not fasting) □ □ □ □ RPR □ □ □ □ □ □ □ Head CT □ □ □ □ 12 lead ECG □ □ □ □ Chest xray □ MRI/MRA □ □ □ □ □ □ □ Carotid Duplex □ □ □ □ Transcranial duplex □ □ □ □ Transthoracic echocardiogram with saline contrast □ Other Consultation(s): Service: Recommend: _____________________ ___________________________ _____________________ ___________________________ Your patient did/did not (circle one) provide a release of information to allow medical records to be sent to your office. Ms/Mr. ____________________has been instructed to make a follow-up appointment with your practice. We would be happy to provide follow-up neurological care if you request at 410-328-5660 or 410-328-4323. We look forward to collaborating with you in the future. If you have any questions please call 410-328-6484 and ask for Dr./NP________________________.
Sincerely, _____________________________MD/CRNP signature
___________________________MD/CRNP print
Fig. 1. Primary care provider discharge summary.
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can be helpful to elucidate stroke-mimicking diagnoses that may require a different evaluation and management pathway, to confirm the diagnosis of cerebral ischemia, and to guide stroke prevention management. Brain imaging with a noncontrast CT scan can be performed rapidly and inexpensively; relatively few patients are unable to tolerate the study or have a contraindication [16]. In the diagnosis of TIA, CT is not expected to reveal a lesion that would localize to the patient’s neurologic symptoms; it is performed to look for other intracranial diagnoses. Once intracranial hemorrhage and other non-cerebrovascular central nervous system pathology is comfortably excluded, therapy with a antiplatelet agent should be initiated while diagnostics are underway for risk factors that suggest other specific therapeutic measures. Each of the antiplatelet agents approved by the Food and Drug Administration has been shown to lower the risk of recurrent ischemic event, and the choice of agent may be influenced by side-effect profile and cost. With the exception of the combined drug aspirin, 25 mg, and dipyridamole, 200 mg, taken as one tablet twice daily aspirin 50–325 mg daily, or clopridogrel 75 mg daily are effective agents. Combining aspirin (50–325 mg/d) with clopidogrel (75 mg/d) has not been shown to reduce risk of stroke further, and it increases the risk of bleeding [17,18]. Current TIA guidelines recommend more specific therapeutic options for patients who experience TIA and atrial fibrillation and/or symptomatic carotid stenosis of greater than 50%; thus, further investigation for these conditions is warranted [5,19]. Clinical examination and a 12-lead ECG can determine atrial fibrillation, and anticoagulant needs can be assessed using the current guidelines [7]. Clinically ascertaining the presence of a carotid bruit has not been found highly sensitive or specific for carotid stenosis. Imaging modalities for carotid stenosis include carotid duplex, MRA, and CT angiography. Carotid duplex is readily available on an outpatient basis, is highly tolerable for patients, and provides data for surgical intervention of symptomatic carotid stenosis. Identifying carotid stenosis emergently is of importance, because analysis of surgical trials showed that the benefit of carotid endarterectomy was greatest when performed within the first 2 weeks after an index ischemic event [20]. Serum laboratory tests (eg, serum glucose and hemoglobin A1C levels and a total lipid panel) can reveal non-cerebrovascular etiology such as hypoglycemia, or hyperlipidemia determine the level of control of a known risk factor, or uncover previously unknown risk factors. Occasionally, laboratory tests reveal underlying medical disorders resulting in cerebral ischemia such as severe anemia, thrombotic thrombocytopenic purpura, temporal arteritis, endocarditis, and proliferative disorders such as leukemia. Summary Patients who have symptoms of TIA and who present to the emergency health care system provide an important opportunity to intervene and
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prevent disabling stroke [21]. An emergent evaluation allows the rapid assessment of an individual patient’s risk factors, the control of which is an important step in the prevention of stroke [22]. With a standardized protocol, the specific ischemic mechanism can be identified without unnecessary delay to guide decision making regarding the choice of stroke-prevention strategies. In summary, it is feasible to implement a protocol for the rapid evaluation of patients who have symptoms of TIA. With such a protocol, patients at high risk for developing a subsequent stroke can receive timely therapy for secondary stroke prevention during the time they are most vulnerable to disabling events.
References [1] Johnston CS, Gress D, Browne W, et al. Short-term prognosis after emergency department diagnosis of TIA. JAMA 2000;284:2901–6. [2] Kleindorfer D, Panagos P, Pancioli A, et al. Incidence and short-term prognosis of transient ischemic attack in a population-based study. Stroke 2005;36:720–4. [3] Rothwell P, Warlow C. Timing of TIAs preceding stroke, time window for prevention is short. Neurology 2005;64:817–20. [4] Johnston CS. Transient ischemic attacks are emergencies. Stroke 2005;36:724. [5] Sacco RL, Adams R, Albers G, et al. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: The American Academy of Neurology affirms the value of this guideline. Stroke 2006;37:577–617. [6] Johnston DCC, Hill MD. The patient with transient cerebral ischemia: a golden opportunity for stroke prevention. CMAJ 2004;170:1134–7. [7] Fuster V, Ryde´n LE, Cannom DS, et al. A Report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society Circulation 2006;114:700–52. [8] Amarenco P, Bougasslavsky J, Callahan A 3rd, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006;355(6):549–59. [9] Hennekens C, Hollar D, Eidelman RS, et al. Update for primary care providers: recent statin trials and revised National Cholesterol Education Program III guidelines. MedGenMed 2006;8(1):54. [10] Crisostomo RA, Garcia MM, Tong DC. Detection of diffusion-weighted MRI abnormalities in patients with transient ischemic attack: correlation with clinical characteristics. Stroke 2003;34(4):932–7. [11] Kidwell CS, Alger JR, Di Salle F, et al. Diffusion MRI in patients with transient ischemic attacks. Stroke 1999;30:1174–80. [12] Rothwell PM, Giles MF, Flossmann E, et al. A simple score (ABCD) to identify individuals at high early risk of stroke after transient ischaemic attack. Lancet 2005;366(9479):29–36. [13] Johnston SC, Sidney S. Validation of a four-point prediction rule to stratify short term stroke risk after TIA [abstract]. Stroke 2005;36:430. [14] Cucchiara BL, Messe SR, Taylor RA, et al. Is the ABCD score useful for risk stratification of patients with acute transient ischemic attack? Stroke 2006;37(7):1710–4.
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[15] Albers G, Hart R, Lutsep H, et al. Supplement to the guidelines for the management of transient ischemic attacks. Stroke 1999;30:2502–11. [16] Culebras A, Kase CS, Masdeu JC, et al. Practice guidelines for the use of imaging in transient ischemic attacks and acute stroke. Stroke 1997;28:1480–97. [17] Diener HC, Bogousslavsky J, Brass LM, et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischemic stroke or transient ischemic attack in high-risk patients (MATCH): randomized, double-blind, placebo-controlled trial. Lancet 2004;364(9431): 331–7. [18] Bhatt DL, Topol EJ. Clopidogrel added to aspirin versus aspirin alone in secondary prevention and high-risk primary prevention: rationale and design of the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial. Am Heart J 2004;148(2):263–8. [19] Brott TG, Brown RD Jr, Meyer FB, et al. Carotid revascularization for prevention of stroke: carotid endarterectomy and carotid artery stenting. Mayo Clin Proc 2004;79:1197–208. [20] Rothwell PM, Eliasziw M, Gutnikov SA, et al. Endarterectomy for symptomatic carotid stenosis in relation to clinical subgroups and timing of surgery. Lancet 2004;363:915–24. [21] Ovbiagele B. The emergency department: first line of defense in preventing secondary stroke. Acad Emerg Med 2006;13:215–22. [22] Wolf PA, Clagett P, Easton JD, et al. Preventing ischemic stroke in patients with prior stroke and transient ischemic attack. Stroke 1999;30:1991–4.
Evaluation and Management of Transient Ischemic Attacks Marian P. LaMonte, MD, MSNa,b,* a
Department of Neurology and Emergency Medicine, University of Maryland School of Medicine, University of Maryland Medical Center, Room N4W46, 22 South Greene Street, Baltimore, MD 21201, USA b The Maryland Stroke and Brain Attack Center, University of Maryland Medical Center, Baltimore, MD, USA
The risk of a disabling stroke after transient ischemic attack (TIA) is suggested to be highest within the first 48 hours after the TIA event [1,2]. Nearly half of recurrent stroke events ensue within the first 7 days [1–3]. In a United Kingdom study analyzing population-based and clinical trial ischemic stroke studies, 43% of the patients who suffered a stroke and who had a prodrome TIA experienced the TIA event within 7 days of the stroke [3]. A recent population-based study found a risk of stroke after TIA of 15% at 3 months and 4% within 2 days of the index TIA [2]. This finding suggests that a patient who has a TIA should be managed emergently [4]. TIA patients’ access to health care remains variable and depends on many factors. Common patient factors include lack of awareness of the nature of symptoms, confusion with other common coexisting medical problems, denial of illness, and embarrassment. Other common factors include insurer rules and cost concerns. The brief nature of TIAs (in minutes) and possible compromise of cognitive function during TIA produce a situation in which symptoms can be under- or not appreciated (the ‘‘silent’’ TIA). When patients do recognize symptoms, they may access care variably through their primary health provider, an emergency department, or other health provider. Options for effective secondary stroke prevention have expanded with the publication of important data on the efficacy of medical and surgical management of cerebrovascular disease [5,6]. Recently issued guidelines for TIA
* University of Maryland Medical Center, Department of Neurology, Room N4W46, 22 South Greene Street, Baltimore, MD 21201. E-mail address: [email protected] 0749-0690/07/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.cger.2007.01.012 geriatric.theclinics.com
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and stroke examine risk factor management and therapeutics, but the guidelines do not specify the setting (inpatient versus outpatient) or timing, nor do these guidelines identify the optimal health care provider for assessment and management of patients who have TIA [5]. To address these issues, The University of Maryland Medical Center developed and initiated a community-service model for rapid assessment and treatment of the patient who has a TIA that is based in the emergency department (ED) of its tertiary stroke-referral medical center. Similar to programs that have been implemented for patients experiencing chest pain, the Rapid Assessment and Treatment of Transient Ischemic Attack Etiology (RATE) program is an interdisciplinary service that provides evaluation of TIA etiology and enables secondary stroke-prevention interventions to be initiated within 24 hours of the patient’s arrival. In conjunction with the service, a targeted TIA educational strategy was developed for both the community and for health providers to make them aware of the emergency nature of TIA and the availability of the RATE program. RATE program aims are (1) to determine symptom etiology and (2) to initiate treatments for TIA and stroke risk factor management within 24 hours of entry. The aims are monitored continuously through the Medical Center’s quality improvement process. Although this systematic approach is not possible or practical for all geriatric practices, it is presented here as an example of the pragmatic enactment of current guidelines for TIA evaluation and management. A discussion of modifications that can be made for an outpatient setting evaluation and a review of the literature follow.
The rapid assessment and treatment of transient ischemic attack etiology program Patient care setting In the RATE program, patient care is provided in the ED Rapid Diagnostic Unit (RDU) of the University of Maryland Medical Center’s ED. The RDU is a four-bed, short-stay monitored inpatient unit based in the ED. The primary goal is to accept patients from the ED who require extended evaluations that are not completely suited or appropriate for a typical ED visit. This evaluation may include specialty testing that is not routinely available to the ED at all hours as well as extended observation periods for patients who are too ill to discharge safely but who do not require a prolonged hospital stay. The RDU is staffed by board-certified internists and toxicologists, typically with dual training in emergency medicine. Typical patients include patients who have chest pain and suspicion of coronary artery disease, cellulitis, mild-to-moderate decompensated congestive heart failure, chronic obstructive pulmonary disease, dehydration, asthma exacerbations, hyperglycemia, and TIA. Other patients are evaluated and admitted on a case-by-case basis.
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Patient description RATE patients are 18 years or older, are diagnosed with TIA by an emergency physician, and enter the ED between 8:00 AM Monday and 12:00 PM Friday. These are the RDU hours during which 24-hour turn-around of patient testing can be assured. When patients present outside these hours, they are admitted to the hospital. Patients are not evaluated by RATE if they present with focal cerebral ischemic symptoms of more than 24 hours’ duration or have focal cerebral neurologic deficit determined to be caused by trauma, tumor, intracerebral hemorrhage, or postsurgical or interventional procedures. Patients who are already hospitalized with symptoms of TIA are not evaluated by RATE. Ischemic infarction is defined as a neurologic dysfunction caused by ischemia and having consistent brain imaging data, even if neurologic examination has normalized. For etiology of TIA and stroke, RATE uses the classic categories of large artery atherosclerotic infarction (intracranial/extracranial); embolism from a cardiac embolism source; small vessel disease; or other determined cause such as dissection, hypercoagulable state, or sickle disease; and infarcts of undetermined etiology [5]. Protocol Upon ED physician diagnosis of TIA, the RATE diagnostic pathway is initiated. The RATE pathway triggers an emergent neurology consultation and a computerized panel of diagnostic tests and nursing orders (Box 1). Emergency medicine and neurology staff determine vascular risk factors by history and physical examination and verify these findings by contacting family or primary care providers. A predetermined set of laboratory tests elucidates serum and urinary markers for coexisting medical diagnoses and vascular risk factors. CT scans are performed immediately to rule out hemorrhage, cerebral infarct, or other space-occupying lesions. Once other nonischemic causes are excluded, antiplatelet therapy is initiated. Brain MRI/magnetic resonance angiography (MRA) scans are performed to aid in determining ischemic etiology. Patients who have carotid duplex or MRA indicating carotid stenosis of more than 50% are referred immediately for surgical consultation. Chest radiographs are taken to look for aortic and cardiac pathology, and 12-lead ECGs are obtained for evidence of concurrent cardiac ischemia and, specifically, atrial fibrillation. Patients have continuous cardiac telemetry monitoring to observe for intermittent atrial fibrillation. Intravenous or subcutaneous anticoagulation and warfarin are initiated for patients found to have atrial fibrillation who are appropriate candidates for warfarin therapy using American College of Chest Physicians/American Heart Association (ACCP/AHA) guidelines [7]. To evaluate cardiac function and rule out cardioembolic causes, patients undergo transthoracic echocardiography with saline contrast study. If the patient’s ejection fraction is less than 35%, anticoagulation is initiated if appropriate according to ACCP/AHA guidelines [7]. If the patient has atrial
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Box 1. RATE diagnostic pathway Laboratory studies Comprehensive metabolic panel Complete blood cell count with differential Prothrombin time, partial thromboplastin time, international normalized ratio Sedimentation rate Urine toxicology Finger stick and serum glucose Fasting lipid panel Thyroid-stimulating hormone Other laboratory tests as indicated Antinuclear antibodies Rapid plasma reagin Fluorescent treponemal antibody Protein C and S Antithrombin III Factor V Leiden mutation Homocysteine Rheumatoid factor Vitamin B12 Antiphospholipid antibodies Diagnostic studies Brain CT scan 12-lead ECG and continuous cardiac monitoring Chest radiograph Brain MRI/MRA Carotid duplex studies Transcranial Doppler studies (optional) Transthoracic echocardiogram with saline contrast Other Antiplatelet/anticoagulation in emergency department Appointment with primary care physician Educational session with nurse practitioner/emergency department nurse Neurology follow up appointment
fibrillation or another cardioembolic source suggesting the need for warfarin therapy, but has contraindications, antiplatelet therapy is initiated if possible. Antithrombotic therapy may be temporarily discontinued for patients who have a concurrent contraindication such as gastrointestinal bleeding.
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These patients and their primary care givers are given instructions concerning the safe resumption of antithrombotic therapy. The program provides emergent laboratory turn-around time, and RATE patients have priority for diagnostic studies and results. All physician orders are bundled into a standardized computerized care set that provides orders for all studies and serial clinical examinations; therefore diagnostic and therapeutic decisions can be determined as rapidly as possible. Once diagnostic procedures are completed, the neurologist finalizes the TIA etiology, risk-factor profile, and recommended secondary prevention strategies (Box 2). If the neurologic examination is normal and diagnostics and elucidated stroke risk factors exclude the need for further hospitalization, the patient is discharged. Before discharge, patient education includes (1) information about stroke risk factors; (2) information about reducing stroke risk factors; (3) instructions on when to contact the emergency medical system; (4) follow-up appointments with primary care and neurology; and (5) medication education. A follow-up appointment in the neurology clinic is scheduled before the patient leaves the ED. The ED also provides the patient’s primary care physician with a copy of the patient’s evaluation (Fig. 1).
Discussion TIA is a medical emergency, and evaluation and management should be performed as promptly as possible. A reorganization of TIA evaluation and treatment into a rapid protocol can be implemented effectively in an ED setting akin to chest pain observation units. The advantages of a short-stay program for patients experiencing TIA include (1) expedited consultations and diagnostics, as available to hospitalized patients; (2) identification and treatment of patients who actually have stroke rather than TIA; (3) identification and treatment of ‘‘stroke-mimicking’’ diagnoses such as migraine with aura, intracerebral hemorrhage, intracranial tumor, seizure, and hypoglycemia; and (4) identification of stroke risk factors and rapid implementation of specific interventions in the most venerable period for disabling stroke (ie, the first 2–7 days). Stroke diagnosis among patients presenting with transient ischemic attacks Twenty-six percent of RATE patients who have confirmed cerebrovascular symptoms have MRI imaging evidence showing cerebral infarction despite normal clinical examination and CT without evidence of infarction. Other groups that have studied MRI imaging characteristics of patients experiencing TIA have reported similar findings. A Stanford group found that 21% of patients who had TIA and who were imaged with MRI within 3 days of symptoms had lesions detected on diffusion-weighted imaging, and
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Box 2. Checklist for TIA and stroke risk factor management for secondary prevention Maryland Stroke and Brain Attack Center Stroke Risk Factor Management a Hypertension: Wait 24 to 36 hours after stroke, then assess (long-term target: systolic blood pressure <120 mm Hg; diastolic blood pressure <80 mm Hg). Medical therapy: If needed, begin with thiazide diuretic and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. If secondary agent is needed, consider using a b-blocker if the patient has concurrent heart disease or a calcium-channel blocker if the patient is African American (see Joint National Committee on Prevention, evaluation and treatment of high blood pressure guidelines). Patient education: Teach the patient about importance of 20 minutes exercise daily and diet. Cholesterol: Initiation of statin therapy with atorvastatin 80 mg has been shown to reduce recurrent stroke risk. Target low-density lipoprotein cholesterol <100 mg/dL and recommend <70 mg/dL [8,9]. Medical therapy: Initiate medical therapy with statins (check baseline liver function tests before starting). Patient education: Teach patient therapeutic lifestyle changes: diet (eliminate transfats), weight loss, increased physical activity. Smoking: Smoking and second-hand smoke increase risk of ischemic stroke by >50% and of subarachnoid hemorrhage by >100%. Medical therapy: Counseling, cessation, nicotine patch/gum, lozenges and prescription medication. Patient education: Emphasize the need for patient and family to stop smoking completely and to avoid second-hand smoke. Diabetes: Diabetics have a 1.5- to 2.5-fold greater risk for ischemic stroke. Medical therapy: Initiate oral hypoglycemic treatment and recommend schedule of glucose checks for the patient. Hemoglobin A1c should be <7. Consider angiotensin-converting enzyme inhibitor or angiotensin receptor blocker as antihypertensive, and statin agent. Patient education: Consult endocrine service for diabetic teaching before discharge; make follow-up appointment with Diabetes Center. Antithrombotic therapies: These therapies and practices will be lifelong because stroke or TIA increases stroke risk 10 times.
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Medical therapy: Antiplatelets: asprin/dipyridamole 25/200 mg twice daily, aspirin 50–325 mg daily, or clopidogrel 75 mg latest daily. Anticoagulation: Use 2006 American College of Chest Physicians guidelines for patients who have atrial fibrillation. Target international normalized ratio for patients taking warfarin is 2.5. Patient education: Counsel patients about the need to continue these medicines for life. Reinforce the warning signs for stroke and the need to call 911 should they occur. Emphasize that the patient always should discuss the discontinuation of these medicines with the patient’s health care provider. Obesity and nutrition counseling for all patients: Desirable body mass index: 18.5–24.9 kg/m2. Medical therapy: Obtain nutrition/dietary consultation if necessary. Patient education: Teach patient to eliminate transfats, reduce total fat and salt intake, increase fruit/vegetable consumption. Discuss benefits of both aerobic and flexibility and strengthening exercise. Sleep apnea: May increase stroke risk by twofold. Identify risk factors and symptoms and consider recommendation for sleep study. Infections: May increase stroke risk by twofold. Identify underlying infections, especially fungal infections and gum disease. Initiate inpatient treatment for fungal infections or include advisory to begin outpatient treatment in discharge summary. Alcohol: Explicitly advise patients about abstinence or safe drinking (less than three alcohol equivalents per day for men or two alcohol equivalents per day for women). The dose of alcohol in a typical 12-ounce can of beer is approximately equal to the dose of alcohol in a 4-ounce serving of wine or in an ounce of whiskey. Cautionary medications: Sympathomimetic drugs (ie, cough, cold, and some allergy medicines), triptans, hormone replacement therapy, and birth control pills: Advise patient to avoid any drugs that may cause blood vessel constriction or increase the risk of blood clotting. Recommend that patient discuss any over-the-counter medications with the patient’s health care provider and pharmacist before use. a This list is a guide and is not intended as the only source for stroke risk factor management strategies. Follow the most current national guidelines when considering therapies for risk factors.
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a group from the University of California at Los Angeles found that 48% of these patients had such characteristics within 3 days of symptoms [10,11]. Is it possible to predict which patients are at high risk of early stroke following TIA? Groups in Oxfordshire and California have developed models for TIA characteristics that may predict a higher risk of ischemic stroke following TIA within 7 and 90 days, respectively [12,13]. Predictive TIA characteristics found by these groups included age of 60 years or greater, diabetes, systolic blood pressure greater than 140 mm Hg, speech disturbance, and weakness. Among these studies, symptom duration was highly variable as a predictor: the Oxfordshire group found a duration of more than 60 minutes to be a significant predictor, whereas the California group found a duration of more than 10 minutes to indicate an increased risk. The California group has presented a validation study for their model (age O60 years, diabetes, spell duration O10 minutes, and weakness with the spell) [13]. The Oxfordshire model is cumbersome, six features must be scored on a dichotomous scale, and a recent study found the model score to have only minor correlation with clinical outcome (P for trend ¼ .11) [14]. Symptom duration Most TIAs last less than 1 hour, with a median duration of 14 minutes with carotid distribution ischemia and 8 minutes with vertebrobasilar ischemia [15]. The authors total RATE patient population had a mean symptom duration of 58 65 minutes, which was not significantly different from the subgroup of RATE patients whose final diagnosis and imaging data revealed cerebral infarction (56 45 minutes). A group in the United Kingdom analyzed population-based and clinical trial studies that included data on TIA preceding ischemic stroke [3]. No study found a difference in the duration of TIA symptoms that preceded a stroke and those that did not. These findings do not support a shorter duration of symptoms as indicating a lesser risk for stroke, therefore, a short duration TIA is not less worrisome for immenent infarction, and requires the same aggressive workup. Alternative strategies ED-based TIA evaluation is neither possible nor practical for all patients. Modification to provide an efficient outpatient evaluation is based on (1) providing accurate diagnosis and treatment and (2) implementing specific therapies for stroke prevention as rapidly as possible. What are the essential diagnostics for these goals? Foremost is an accurate history that suggests a brief period of the abrupt onset of a focal neurologic deficit. A complete discernment of common stroke risk factors by both history and physical examination provides data on possible mechanisms of TIA such as atherothrombosis or cardioembolism. Neurologist consultation
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Primary Care Provider Discharge Letter Date: _______________ Dear Primary Care Provider______________________________ Ms/Mr _____________was discharged from The University of Maryland Medical Center RATE (Rapid Assessment of Transient Ischemic Attack Etiology) on ____________ with the diagnosis of ______________. Your patient was medically and neurologically observed and had diagnostic and therapeutic management under the care of Dr. __________________ and Dr./NP _____________________. (ED Physician) (Neurology Consultant) Concomitant Diagnoses are: □ Hypertension □ Diabetes Mellitus □ Tobacco Abuse □ Carotid Stenosis (< 50 ) □ Chronic CHF □ Coronary Artery Disease
□ Hypercholesterolemia □ Atrial fibrillation □ Seizure □ Symptomatic Carotid Stenosis (> 50 ) □ Others: _____________ _____________________
Your patient was discharged on the following medication(s) for secondary stroke prevention: □ Asprin/Dipyridamole 1 capsule every 12 hours □ Aspirin _______ mg daily □ Clopidogrel 75 mg daily □ Warfarin ________mg_______ □ Other ____________________
While on the RATE Service the following tests/consults were performed: Results Pending Normal Abnormal □ Comprehensive metabolic panel □ □ □ □ □ □ □ CBC with differential □ □ □ □ PT, PTT, INR □ □ □ □ Sedimentation rate □ □ □ □ Urine and blood toxicology □ Lipid panel (not fasting) □ □ □ □ RPR □ □ □ □ □ □ □ Head CT □ □ □ □ 12 lead ECG □ □ □ □ Chest xray □ MRI/MRA □ □ □ □ □ □ □ Carotid Duplex □ □ □ □ Transcranial duplex □ □ □ □ Transthoracic echocardiogram with saline contrast □ Other Consultation(s): Service: Recommend: _____________________ ___________________________ _____________________ ___________________________ Your patient did/did not (circle one) provide a release of information to allow medical records to be sent to your office. Ms/Mr. ____________________has been instructed to make a follow-up appointment with your practice. We would be happy to provide follow-up neurological care if you request at 410-328-5660 or 410-328-4323. We look forward to collaborating with you in the future. If you have any questions please call 410-328-6484 and ask for Dr./NP________________________.
Sincerely, _____________________________MD/CRNP signature
___________________________MD/CRNP print
Fig. 1. Primary care provider discharge summary.
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can be helpful to elucidate stroke-mimicking diagnoses that may require a different evaluation and management pathway, to confirm the diagnosis of cerebral ischemia, and to guide stroke prevention management. Brain imaging with a noncontrast CT scan can be performed rapidly and inexpensively; relatively few patients are unable to tolerate the study or have a contraindication [16]. In the diagnosis of TIA, CT is not expected to reveal a lesion that would localize to the patient’s neurologic symptoms; it is performed to look for other intracranial diagnoses. Once intracranial hemorrhage and other non-cerebrovascular central nervous system pathology is comfortably excluded, therapy with a antiplatelet agent should be initiated while diagnostics are underway for risk factors that suggest other specific therapeutic measures. Each of the antiplatelet agents approved by the Food and Drug Administration has been shown to lower the risk of recurrent ischemic event, and the choice of agent may be influenced by side-effect profile and cost. With the exception of the combined drug aspirin, 25 mg, and dipyridamole, 200 mg, taken as one tablet twice daily aspirin 50–325 mg daily, or clopridogrel 75 mg daily are effective agents. Combining aspirin (50–325 mg/d) with clopidogrel (75 mg/d) has not been shown to reduce risk of stroke further, and it increases the risk of bleeding [17,18]. Current TIA guidelines recommend more specific therapeutic options for patients who experience TIA and atrial fibrillation and/or symptomatic carotid stenosis of greater than 50%; thus, further investigation for these conditions is warranted [5,19]. Clinical examination and a 12-lead ECG can determine atrial fibrillation, and anticoagulant needs can be assessed using the current guidelines [7]. Clinically ascertaining the presence of a carotid bruit has not been found highly sensitive or specific for carotid stenosis. Imaging modalities for carotid stenosis include carotid duplex, MRA, and CT angiography. Carotid duplex is readily available on an outpatient basis, is highly tolerable for patients, and provides data for surgical intervention of symptomatic carotid stenosis. Identifying carotid stenosis emergently is of importance, because analysis of surgical trials showed that the benefit of carotid endarterectomy was greatest when performed within the first 2 weeks after an index ischemic event [20]. Serum laboratory tests (eg, serum glucose and hemoglobin A1C levels and a total lipid panel) can reveal non-cerebrovascular etiology such as hypoglycemia, or hyperlipidemia determine the level of control of a known risk factor, or uncover previously unknown risk factors. Occasionally, laboratory tests reveal underlying medical disorders resulting in cerebral ischemia such as severe anemia, thrombotic thrombocytopenic purpura, temporal arteritis, endocarditis, and proliferative disorders such as leukemia. Summary Patients who have symptoms of TIA and who present to the emergency health care system provide an important opportunity to intervene and
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prevent disabling stroke [21]. An emergent evaluation allows the rapid assessment of an individual patient’s risk factors, the control of which is an important step in the prevention of stroke [22]. With a standardized protocol, the specific ischemic mechanism can be identified without unnecessary delay to guide decision making regarding the choice of stroke-prevention strategies. In summary, it is feasible to implement a protocol for the rapid evaluation of patients who have symptoms of TIA. With such a protocol, patients at high risk for developing a subsequent stroke can receive timely therapy for secondary stroke prevention during the time they are most vulnerable to disabling events.
References [1] Johnston CS, Gress D, Browne W, et al. Short-term prognosis after emergency department diagnosis of TIA. JAMA 2000;284:2901–6. [2] Kleindorfer D, Panagos P, Pancioli A, et al. Incidence and short-term prognosis of transient ischemic attack in a population-based study. Stroke 2005;36:720–4. [3] Rothwell P, Warlow C. Timing of TIAs preceding stroke, time window for prevention is short. Neurology 2005;64:817–20. [4] Johnston CS. Transient ischemic attacks are emergencies. Stroke 2005;36:724. [5] Sacco RL, Adams R, Albers G, et al. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: The American Academy of Neurology affirms the value of this guideline. Stroke 2006;37:577–617. [6] Johnston DCC, Hill MD. The patient with transient cerebral ischemia: a golden opportunity for stroke prevention. CMAJ 2004;170:1134–7. [7] Fuster V, Ryde´n LE, Cannom DS, et al. A Report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society Circulation 2006;114:700–52. [8] Amarenco P, Bougasslavsky J, Callahan A 3rd, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006;355(6):549–59. [9] Hennekens C, Hollar D, Eidelman RS, et al. Update for primary care providers: recent statin trials and revised National Cholesterol Education Program III guidelines. MedGenMed 2006;8(1):54. [10] Crisostomo RA, Garcia MM, Tong DC. Detection of diffusion-weighted MRI abnormalities in patients with transient ischemic attack: correlation with clinical characteristics. Stroke 2003;34(4):932–7. [11] Kidwell CS, Alger JR, Di Salle F, et al. Diffusion MRI in patients with transient ischemic attacks. Stroke 1999;30:1174–80. [12] Rothwell PM, Giles MF, Flossmann E, et al. A simple score (ABCD) to identify individuals at high early risk of stroke after transient ischaemic attack. Lancet 2005;366(9479):29–36. [13] Johnston SC, Sidney S. Validation of a four-point prediction rule to stratify short term stroke risk after TIA [abstract]. Stroke 2005;36:430. [14] Cucchiara BL, Messe SR, Taylor RA, et al. Is the ABCD score useful for risk stratification of patients with acute transient ischemic attack? Stroke 2006;37(7):1710–4.
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[15] Albers G, Hart R, Lutsep H, et al. Supplement to the guidelines for the management of transient ischemic attacks. Stroke 1999;30:2502–11. [16] Culebras A, Kase CS, Masdeu JC, et al. Practice guidelines for the use of imaging in transient ischemic attacks and acute stroke. Stroke 1997;28:1480–97. [17] Diener HC, Bogousslavsky J, Brass LM, et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischemic stroke or transient ischemic attack in high-risk patients (MATCH): randomized, double-blind, placebo-controlled trial. Lancet 2004;364(9431): 331–7. [18] Bhatt DL, Topol EJ. Clopidogrel added to aspirin versus aspirin alone in secondary prevention and high-risk primary prevention: rationale and design of the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial. Am Heart J 2004;148(2):263–8. [19] Brott TG, Brown RD Jr, Meyer FB, et al. Carotid revascularization for prevention of stroke: carotid endarterectomy and carotid artery stenting. Mayo Clin Proc 2004;79:1197–208. [20] Rothwell PM, Eliasziw M, Gutnikov SA, et al. Endarterectomy for symptomatic carotid stenosis in relation to clinical subgroups and timing of surgery. Lancet 2004;363:915–24. [21] Ovbiagele B. The emergency department: first line of defense in preventing secondary stroke. Acad Emerg Med 2006;13:215–22. [22] Wolf PA, Clagett P, Easton JD, et al. Preventing ischemic stroke in patients with prior stroke and transient ischemic attack. Stroke 1999;30:1991–4.