7/5/23, 12:11 PM Initial evaluation and management of transient ischemic attack and minor ischemic stroke - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Initial evaluation and management of transient ischemic attack and minor ischemic stroke : Natalia S Rost, MD, MPH, Hugo J Aparicio, MD, MPH : Scott E Kasner, MD, Jonathan A Edlow, MD, FACEP : John F Dashe, MD, PhD All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: May 10, 2022. INTRODUCTION Patients with transient ischemic attack (TIA) or minor (ie, nondisabling) stroke are at increased risk of recurrent stroke and therefore require urgent evaluation and treatment since immediate intervention may substantially reduce the risk of recurrent stroke. This topic will review the diagnostic approach and early management of TIA and minor, nondisabling ischemic stroke. Other aspects of transient cerebral ischemia are discussed separately. (See "Definition, etiology, and clinical manifestations of transient ischemic attack" and "Differential diagnosis of transient ischemic attack and acute stroke".) The management of patients hospitalized with acute stroke is reviewed elsewhere. (See "Initial assessment and management of acute stroke".) DIAGNOSIS AND TRIAGE Clinical diagnosis of TIA and minor stroke The diagnosis of TIA (in the absence of tissue infarction) is clinical and is based upon a determination that the symptoms of the attack are more likely caused by brain ischemia than another cause ( table 1). This determination can be challenging and is usually subjective because the symptoms of TIA are transient, highly variable https://www.uptodate.com/contents/initial-evaluation-and-management-of-transient-ischemic-attack-and-minor-ischemic-stroke/print 1/47 7/5/23, 12:11 PM Initial evaluation and management of transient ischemic attack and minor ischemic stroke - UpToDate ( table 2), and often minor. (See "Definition, etiology, and clinical manifestations of transient ischemic attack", section on 'Diagnosis' and "Differential diagnosis of transient ischemic attack and acute stroke", section on 'Symptoms of TIA' and "Differential diagnosis of transient ischemic attack and acute stroke", section on 'Distinguishing transient attacks'.) How is TIA defined? TIA is now defined as a transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction [1]. The end point, ischemic stroke, is biologic (tissue injury) rather than arbitrary ( 24 hours of symptoms). In keeping with this definition of TIA, ischemic stroke is defined as an infarction of central nervous system tissue. (See "Definition, etiology, and clinical manifestations of transient ischemic attack", section on 'Definition of TIA'.) TIA was originally defined as a sudden onset of a focal neurologic symptom and/or sign lasting less than 24 hours and caused by reversible cerebral ischemia. However, this classic, time-based definition of TIA was inadequate for several reasons. Most notably, there is risk of permanent tissue injury (ie, infarction) even when focal transient neurologic symptoms last less than one hour. About one-half of patients with time-based TIA syndromes (<24 hours in duration) have corresponding appropriate ischemic lesions by brain magnetic resonance imaging (MRI) on diffusion-weighted or perfusion-weighted imaging. (See "Definition, etiology, and clinical manifestations of transient ischemic attack", section on 'Symptom duration and infarction'.) Although the revised tissue-based definition is favored by guidelines, the traditional time-based definition of TIA is still widely used in clinical practice; this time-based definition was created in an era prior to thrombolytic treatment for stroke and availability of MRI and prior to recognition of the hyperacute stroke risk following TIA [2]. 2 How is high-risk TIA defined? A simple but suboptimal assessment called the ABCD score (ie, ABCD squared, for Age, Blood pressure, Clinical features, Duration of symptoms, and Diabetes) was designed to identify patients at high risk of ischemic stroke in the first seven days after TIA ( table 3) [3]. However, its predictive performance is unsatisfactory; subsequent studies have found that the score does not provide an accurate estimate of stroke risk [4], and 2 clinical decisions based on an ABCD score cut-off are subject to significant misclassification 2 error. Importantly, one in five patients with TIA and a low ABCD score (<4) will have treatable vascular pathology, such as a symptomatic internal carotid or intracranial large artery stenosis, or atrial fibrillation [5]. 2 Nevertheless, the ABCD score is being used to select patients for treatment with dual antiplatelet therapy after a time-based TIA. (See 'Immediate antiplatelet treatment' below.) 2 The ABCD score is tallied as follows (calculator 1): https://www.uptodate.com/contents/initial-evaluation-and-management-of-transient-ischemic-attack-and-minor-ischemic-stroke/print 2/47 7/5/23, 12:11 PM Initial evaluation and management of transient ischemic attack and minor ischemic stroke - UpToDate Age ( 60 years = 1 point) Blood pressure elevation when first assessed after TIA (systolic 140 mmHg or diastolic 90 mmHg = 1 point) Clinical features (unilateral weakness = 2 points; isolated speech disturbance = 1 point; other = 0 points) Duration of TIA symptoms ( 60 minutes = 2 points; 10 to 59 minutes = 1 point; <10 minutes = 0 points) Diabetes (present = 1 point) Other factors associated with an increased risk of stroke after a time-based TIA include a relevant large vessel stenosis or DWI lesion on MRI. Stroke risk after TIA is reviewed in greater detail separately. (See "Definition, etiology, and clinical manifestations of transient ischemic attack", section on 'Risk of recurrent stroke'.) How is minor, nondisabling stroke defined? The presence of persistent but minor, nondisabling neurologic deficits is the main factor that distinguishes minor ischemic stroke from a time-based TIA. However, both are associated with an increased risk of recurrent ischemic stroke [6,7]. This increased risk of stroke may be more related to the presence of infarction on diffusion-weighted MRI studies than to the duration of minor neurologic deficit. Minor ischemic stroke has been defined in various ways, most often by a low score on the National Institutes of Health Stroke Scale (NIHSS) [8,9], and there is no unified definition. We prefer to define minor stroke by the absence of a persistent neurologic deficit that is potentially disabling. Any of the following should be considered disabling deficits [10]: Any deficits that lead to a total NIHSS >5 (calculator 2) Complete hemianopia: 2 on the NIHSS question 3 ( table 4) Severe aphasia: 2 on NIHSS question 9 Visual or sensory extinction: 1 on NIHSS question 11 Any weakness limiting sustained effort against gravity: 2 on NIHSS question 5 or 6 Inability to walk Any remaining deficit considered potentially disabling by the patient, family, or the treating practitioner Patients who present within the appropriate time window after ischemic symptom onset with a persistent neurologic deficit that is potentially disabling, despite improvement of any degree, should be treated with intravenous thrombolysis in the absence of other contraindications ( table 5) and screened for treatment with mechanical thrombectomy ( algorithm 1). In practical terms, one would never "wait" or delay treatment to see if the symptoms resolve in https://www.uptodate.com/contents/initial-evaluation-and-management-of-transient-ischemic-attack-and-minor-ischemic-stroke/print 3/47 7/5/23, 12:11 PM Initial evaluation and management of transient ischemic attack and minor ischemic stroke - UpToDate patients who present with a persistent neurologic deficit. (See "Approach to reperfusion therapy for acute ischemic stroke" and "Intravenous thrombolytic therapy for acute ischemic stroke: Therapeutic use" and "Mechanical thrombectomy for acute ischemic stroke".) Differential diagnosis Several neurologic disorders give rise to transient focal neurologic symptoms, and these should be considered before establishing a diagnosis of TIA. In addition to TIAs, the most important and frequent causes of discrete self-limited attacks include: Seizure Migraine aura Syncope Less frequent causes include: Peripheral vestibulopathy that causes transient episodic dizziness Pressure- or position-related peripheral nerve or nerve root compression that causes transient paresthesia and numbness Metabolic perturbations such as hypoglycemia and hepatic, renal, and pulmonary encephalopathies that can produce temporary aberrations in behavior and movement Transient global amnesia Cerebral amyloid angiopathy The differential diagnosis of TIA and stroke is discussed in greater detail elsewhere. (See "Differential diagnosis of transient ischemic attack and acute stroke".) Importance of early evaluation and treatment For patients who present with TIA or minor ischemic stroke, we recommend implementation of appropriate diagnostic evaluation and stroke prevention treatment without delay, preferably within one day of the ischemic event. TIA is a neurologic emergency because patients with a time-based TIA (ie, symptoms lasting less than 24 hours) or minor, nondisabling ischemic stroke are at increased risk of recurrent and potentially disabling ischemic stroke, especially in the days following the index event. Accumulating evidence suggests that immediate intervention after a TIA or minor, nondisabling ischemic stroke can reduce the risk of recurrent stroke compared with delayed intervention. The prospective EXPRESS study evaluated the impact of expediting outpatient treatment for TIA or minor ischemic stroke [11]. In order to compare traditional with expedited treatment, the study was conducted in two phases. In phase one, 323 patients were seen in a traditional clinic setting where evaluation required a scheduled appointment and treatment recommendations were made to referring physicians. In phase two, 297 patients were seen in an urgent walk-in stroke clinic without having to arrange an appointment, evaluated with readily available https://www.uptodate.com/contents/initial-evaluation-and-management-of-transient-ischemic-attack-and-minor-ischemic-stroke/print 4/47 7/5/23, 12:11 PM Initial evaluation and management of transient ischemic attack and minor ischemic stroke - UpToDate diagnostic studies (including brain MRI, carotid duplex ultrasound, electrocardiography, and baseline blood tests); treatment was implemented immediately by clinic practitioners. In both phases, treatment of confirmed TIA or stroke was individualized according to patient characteristics, but generally included antiplatelet or anticoagulant therapy, statin therapy, antihypertensive medication, and carotid endarterectomy as required. In EXPRESS, the median delay to assessment in the outpatient clinic was significantly reduced from phase 1 to phase 2 (3 days versus <1 day), as was the median delay to first prescription of treatment (20 days versus 1 day) [11]. The risk of recurrent stroke at 90 days was significantly lower for patients seen in phase 2 than for those seen in phase 1 (2.1 versus 10.3 percent; adjusted hazard ratio 0.20, 95% CI 0.08-0.49), and the lower stroke risk was sustained at 10 years in a follow-up study [12]. Although EXPRESS was not a randomized trial, the study was nested in an ongoing population-based study of stroke and TIA, thus minimizing the potential problems of incomplete ascertainment and selection bias that complicate observational studies. The observational SOS-TIA study analyzed the rapid assessment of 1085 patients with suspected TIA in a hospital-based clinic with 24-hour access [13]. Patients were evaluated within four hours of admission, and those with a final diagnosis of confirmed or possible TIA (n = 845) received immediate treatment with a stroke prevention program that included antiplatelet or anticoagulant treatment and/or carotid revascularization as appropriate. At 90 days, the 2 observed stroke rate was much lower than an expected stroke rate predicted by the ABCD scores (1.24 versus 5.96 percent). The results of this study should be interpreted with caution 2 because of methodologic limitations, including the use of ABCD scores to predict stroke risk, rather than determination of stroke risk in a control population [14]. (See "Definition, etiology, and clinical manifestations of transient ischemic attack", section on 'Stroke risk stratification'.) Hospital or outpatient evaluation? Whether hospitalization is required for TIA evaluation is not clear, but urgent assessment and management is essential regardless of inpatient or outpatient status [1,15-19]. The key guiding principle is that the incidence of a recurrent stroke is highest in the 48 hours following the TIA [20-22], and therefore the rapidity with which the evaluation is performed and treatments initiated is more important than the physical location of where the evaluation takes place [23,24]. Outpatient evaluation can now occur in specialty-run TIA clinics [11,13,25] and in emergency department-based observation units [26,27]; in both settings, the evaluation begins immediately following a TIA diagnosis. Both of these processes of care have led to marked reduction in stroke outcome. Possible advantages of hospitalization include facilitated early use of thrombolytic therapy, mechanical thrombectomy, and other medical management if symptoms recur, expedited TIA evaluation, and expedited institution of secondary prevention [15]. https://www.uptodate.com/contents/initial-evaluation-and-management-of-transient-ischemic-attack-and-minor-ischemic-stroke/print 5/47 7/5/23, 12:11 PM Initial evaluation and management of transient ischemic attack and minor ischemic stroke - UpToDate We suggest hospitalization for patients with a first TIA within the past 72 hours if any of the following conditions are present: High risk of early stroke after TIA or minor stroke as suggested by: The presence of a known cardiac, arterial, or systemic etiology of brain ischemia that is amenable to treatment The presence of acute infarction on diffusion-weighted magnetic resonance imaging (MRI) (see "Definition, etiology, and clinical manifestations of transient ischemic attack", section on 'Factors that affect stroke risk') Certain other clinical and imaging features ( table 6) Uncertainty that the diagnostic workup can be completed within 24 to 48 hours as an outpatient Concurrent serious acute medical issues Patients who need urgent evaluation and are not hospitalized should have rapid access to the following studies (see 'Urgent investigations' below): Brain imaging with head computed tomography (CT) and/or MRI Vascular imaging studies such as CT angiography (CTA), magnetic resonance angiography (MRA), and/or ultrasound Electrocardiogram (ECG) All patients with a suspected TIA within the past two weeks who are not hospitalized should undergo investigations within 24 to 48 hours to determine the mechanism of ischemia and subsequent preventive therapy. Even patients with atypical TIA symptoms (eg, isolated vertigo, ataxia, bilateral decreased vision, or numbness in one body segment) may be at increased risk for early stroke [28]. Patients who are not admitted should be informed that they need to go to an Emergency Department immediately if symptoms recur. IMMEDIATE ANTIPLATELET TREATMENT For most patients with TIA and minor ischemic stroke who do not have a known cardioembolic source at presentation, we start antiplatelet therapy immediately while evaluating the ischemic mechanism ( algorithm 2 and algorithm 3 and table 1). Exceptions are patients who are on oral anticoagulation or have a clear new indication for anticoagulation. https://www.uptodate.com/contents/initial-evaluation-and-management-of-transient-ischemic-attack-and-minor-ischemic-stroke/print 6/47 7/5/23, 12:11 PM Initial evaluation and management of transient ischemic attack and minor ischemic stroke - UpToDate Dual antiplatelet therapy We start dual antiplatelet therapy (DAPT) using aspirin (160 to 325 mg loading dose, followed by 50 to 100 mg daily) plus clopidogrel (300 to 600 mg loading dose, followed by 75 mg daily) for the first 21 days for patients with high-risk TIA, 2 defined as an ABCD score of 4 (calculator 1), and for patients with minor ischemic stroke, defined by a National Institutes of Health Stroke Scale (NIHSS) score 5 (calculator 2). DAPT using aspirin (300 to 325 mg loading dose, followed by 75 to 100 mg daily) plus ticagrelor (180 mg loading dose followed by 90 mg twice daily) is a reasonable alternative for patients not amenable to therapy with clopidogrel. The rationale and evidence for short-term DAPT in this setting is reviewed in detail separately. (See "Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack", section on 'Efficacy of DAPT'.) Aspirin monotherapy We start aspirin (162 to 325 mg/daily) alone for low-risk TIA, 2 defined by an ABCD score <4 (calculator 1). The approach to antithrombotic treatment of acute stroke and TIA is reviewed in detail separately. (See "Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack".) URGENT INVESTIGATIONS Goals of evaluation Patients who have a suspected TIA or minor stroke require urgent evaluation ( algorithm 4) due to the high stroke risk associated with TIA as defined by time- based criteria [1]; immediate intervention may prevent a significant number of strokes. (See "Definition, etiology, and clinical manifestations of transient ischemic attack", section on 'Risk of recurrent stroke'.) Urgent evaluation is necessary for confirming the diagnosis of TIA or ischemic stroke, excluding stroke mimics, and determining the ischemic mechanism, which has important implications for directing targeted treatment for secondary stroke prevention. The urgent evaluation proceeds in tandem with immediate implementation of antiplatelet therapy. (See 'Immediate antiplatelet treatment' above.) The initial evaluation of suspected TIA and minor, nondisabling ischemic stroke includes brain imaging, vascular imaging, cardiac evaluation, and basic laboratory studies that are suggested by the history and physical examination. Laboratory testing is helpful in ruling out metabolic and hematologic causes of neurologic symptoms, including hypoglycemia, hyponatremia, and thrombocytosis. https://www.uptodate.com/contents/initial-evaluation-and-management-of-transient-ischemic-attack-and-minor-ischemic-stroke/print 7/47 7/5/23, 12:11 PM Initial evaluation and management of transient ischemic attack and minor ischemic stroke - UpToDate Timing We recommend that appropriate diagnostic evaluation and stroke prevention treatment be implemented without delay, preferably within one day of the ischemic event, for patients who present with TIA or minor, nondisabling ischemic stroke. Brain imaging Early brain imaging with MRI or CT is indicated for all patients with suspected TIA or minor, nondisabling stroke, particularly for those with symptoms suggestive of hemispheric TIA [1,15]. Brain MRI with diffusion-weighted imaging has a greater sensitivity than CT for detecting small infarcts in patients with TIA; thus, CT is a suboptimal alternative. The 2009 American Heart Association/American Stroke Association (AHA/ASA) guidelines for evaluation of TIA recommend neuroimaging within 24 hours of symptom onset and further recommend MRI with diffusion-weighted imaging (DWI) as a preferred modality [1]. Head CT is recommended if MRI cannot be performed. The presence of a brain infarct on MRI or CT scan located in an area suggested by the anatomy of the TIA or stroke identifies an ischemic etiology of symptoms. Many patients whose clinical history and neurologic examination is suggestive of TIA have infarcts in brain areas appropriate to the neurologic symptoms. (See "Definition, etiology, and clinical manifestations of transient ischemic attack", section on 'Symptom duration and infarction'.) Advantages of DWI Infarction is more likely to be identified acutely on MRI than on CT. DWI and the apparent diffusion coefficient (ADC) map that is derived from DWI can discriminate tissue injury very early after the onset of ischemic symptoms. In most but not all cases of TIA and minor (nondisabling) stroke, early DWI and ADC can confirm whether only ischemia has occurred or if there has also been an element of infarction, thereby differentiating stroke from TIA within the first hours after symptom onset. (See "Neuroimaging of acute stroke", section on 'Parenchymal changes on DWI'.) DWI is advantageous for evaluating patients who have transient symptoms because it is highly sensitive for detecting infarction, thereby confirming an ischemic cause. A systematic review found that DWI detects corresponding appropriate ischemic lesions in 16 to 67 percent of patients with classically defined (ie, time-based) TIA [29]. Also, the combination of DWI with MRI and magnetic resonance angiography (MRA) often provides clues to the underlying pathophysiology. DWI also has an advantage in differentiating acute infarction from chronic lesions. One study estimated that the amount of error potentially imposed by the use of conventional MRI in identifying the clinically responsible infarct in patients with time-based TIA could be as high as 50 percent when compared with DWI [30]. This is in large part because infarctions associated with time-based TIA are often very small. A volumetric study of time- https://www.uptodate.com/contents/initial-evaluation-and-management-of-transient-ischemic-attack-and-minor-ischemic-stroke/print 8/47 7/5/23, 12:11 PM Initial evaluation and management of transient ischemic attack and minor ischemic stroke - UpToDate based TIA-related infarcts showed that 96 percent of all infarcts were smaller than 1 mL [31]. The smallest single lesion that was associated with a time-based TIA was 0.17 mL in volume. The mean infarct volume was 0.66 1.20 mL. The timing of DWI scan is important. In some cases, lesions identified by early DWI may reverse back to normal with rapid reconstitution of blood flow to the ischemic brain tissue [32]. (See "Definition, etiology, and clinical manifestations of transient ischemic attack", section on 'Symptom duration and infarction'.) Infarcts missed by DWI In a minority of cases, early DWI may fail to identify an ischemic mechanism. DWI may occasionally miss small infarctions, especially in the brain stem, often in patients presenting with a lacunar TIA [33-35]. DWI-negative strokes occur five times more often in posterior circulation events [35]. In these cases, an acute thin-section brainstem DWI (coronal, sagittal, or combination) may reveal a small brainstem lesion, or a follow-up MRI or CT may confirm an infarct [36,37]. In some patients, the reduction in blood flow causing ischemic symptoms may not be severe enough to cause an abnormal signal on DWI [38]. In such cases, perfusion-weighted MRI can provide additional information for determining the presence of tissue ischemia [39-42]. Other diseases that mimic TIAs may be identified by neuroimaging techniques, although pathological biopsy examination is occasionally needed (eg, temporal artery biopsy or examination of the cerebrospinal fluid). In rare cases, brain biopsy is indicated. (See "Differential diagnosis of transient ischemic attack and acute stroke".) Vascular imaging The single most important issue to resolve in the initial evaluation of TIA and ischemic stroke is whether or not there is an obstructive lesion in a larger artery supplying the affected territory. Noninvasive options for evaluation of large vessel occlusive disease include MRA, CTA, carotid duplex ultrasonography (CDUS), and transcranial Doppler ultrasonography (TCD). The choice among these depends upon local availability and expertise as well as individual patient characteristics and preferences [1]. (See "Neuroimaging of acute stroke".) The 2009 AHA/ASA guidelines recommend routine noninvasive imaging of the cervicocephalic vessels as part of the evaluation of patients with suspected TIA [1]. The guidelines note that it is reasonable to obtain noninvasive testing of the intracranial vasculature if knowledge of an intracranial stenosis or occlusion will alter management. https://www.uptodate.com/contents/initial-evaluation-and-management-of-transient-ischemic-attack-and-minor-ischemic-stroke/print 9/47 7/5/23, 12:11 PM Initial evaluation and management of transient ischemic attack and minor ischemic stroke - UpToDate A focused Doppler and neuroimaging test (eg, MRA or CTA) can be used to establish an arterial source of the embolism or low flow. These tests can exclude an arterial source in cases where the symptoms are due to proximal embolism from the heart, aorta, or an unknown source, and in cases where the symptoms are due to small vessel disease (see "Evaluation of carotid artery stenosis"). The following are important aspects regarding such testing: Color Doppler ultrasonography and transcranial Doppler studies require considerable technical skill to perform and an experienced interpreter. They should be used only if there is adequate confidence that the testing and interpretation is reliable. Conventional cerebral angiography is associated with a small risk of stroke and should be performed by experienced physicians. It should only be considered when the diagnosis is uncertain by noninvasive methods, and when proof of the diagnosis is essential for proper stroke preventive therapy. As an example, if one of the stroke-producing arterial lesions noted above is suspected but not confirmed by conventional noninvasive Doppler, MRI, or CT methods, then angiography can be considered. The distinction between artery-to-artery and other (mainly cardiac) sources of embolism can be difficult. Suspicion of the former typically arises once vascular pathology in a large vessel has been identified (eg, with noninvasive testing). Repetitive spells within a single vascular territory are also suggestive of an artery-to-artery source, as is a normal echocardiogram. Infrequently, patients can have multiple sources of embolism (eg, tandem carotid stenosis or concomitant arterial stenosis and atrial fibrillation). Cardiac evaluation A possible cardiac source should be considered in patients with TIA or ischemic stroke caused by embolism. At minimum, such patients should have a standard 12-lead electrocardiogram as soon as possible after symptom onset [1]. Cardiac monitoring Cardiac monitoring is an essential part of evaluation to exclude atrial fibrillation in the setting of embolic TIA or stroke. Cardiac rhythm monitoring with inpatient or observation unit telemetry or Holter monitor is useful for patients without a clear etiology after initial brain imaging and electrocardiography [1]. For patients with a cryptogenic TIA and no evidence of atrial fibrillation on ECG and 24-hour cardiac monitoring, we suggest ambulatory cardiac monitoring for several weeks [43]. (See "Overview of the evaluation of stroke", section on 'Monitoring for subclinical atrial fibrillation'.) Echocardiography Echocardiography is reasonable when no cause for TIA or ischemic stroke has been identified by other aspects of the work-up [1]. Transthoracic echocardiogram (TTE) is the preferred initial test for the majority of patients with a https://www.uptodate.com/contents/initial-evaluation-and-management-of-transient-ischemic-attack-and-minor-ischemic-stroke/print 10/47 7/5/23, 12:11 PM Initial evaluation and management of transient ischemic attack and minor ischemic stroke - UpToDate suspected cardiac or aortic source of emboli, including (see "Echocardiography in detection of cardiac and aortic sources of systemic embolism", section on 'Choosing between TTE and TEE'): Patients 45 years with a cerebrovascular event Patients with a high suspicion of left ventricular thrombus Patients in whom transesophageal echocardiogram (TEE) is contraindicated (eg, esophageal stricture, unstable hemodynamic status) or who refuse TEE TEE is the preferred initial test to localize the source of embolism in the following circumstances: Patients <45 years without known cardiovascular disease (ie, absence of myocardial infarction or valvular disease history) Patients with a high pretest probability of a cardiac embolic source ( table 7) in whom a negative TTE would be likely to be falsely negative Patients with atrial fibrillation and suspected left atrial or left atrial appendage thrombus, especially in the absence of therapeutic anticoagulation, but only if the TEE would impact management Patients with a mechanical heart valve Patients with suspected aortic pathology The use of echocardiography for the detection of cardiac sources of embolism is discussed in greater detail separately. (See "Echocardiography in detection of cardiac and aortic sources of systemic embolism".) Blood cultures, an erythrocyte sedimentation rate, or antinuclear antibody testing are indicated if bacterial or nonbacterial endocarditis is suspected. (See "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis" and "Prosthetic valve endocarditis: Epidemiology, clinical manifestations, and diagnosis" and "Overview of management of infective endocarditis in adults" and "Nonbacterial thrombotic endocarditis" and "Infective endocarditis in children".) Blood tests In most patients with suspected TIA, the following blood tests should be obtained as indicated [1,15,44]: Complete blood count (CBC) Prothrombin time and partial thromboplastin time Serum electrolytes and creatinine Fasting blood glucose, hemoglobin A1c, and lipids https://www.uptodate.com/contents/initial-evaluation-and-management-of-transient-ischemic-attack-and-minor-ischemic-stroke/print 11/47 7/5/23, 12:11 PM Initial evaluation and management of transient ischemic attack and minor ischemic stroke - UpToDate Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) when there is suspicion for an inflammatory stroke mechanism, particularly in older patients Suspicion for blood disorders as potential sources of cerebral ischemia should be raised in the following settings [44]: Cryptogenic stroke or TIA Age 45 years or younger History of clotting dysfunction Multiple venous and arterial occlusions Suspected or confirmed cancer Family history of thrombotic events In these settings, additional blood and coagulation studies should be considered. This topic is discussed elsewhere. (See "Overview of the evaluation of stroke", section on 'Blood tests'.) TARGETED TREATMENT FOR SECONDARY PREVENTION The preferred approach to the secondary prevention of TIA and ischemic stroke is to determine the pathophysiology of the event and treat accordingly ( table 1). This is reviewed here briefly and discussed in detail elsewhere. (See "Overview of secondary prevention for specific causes of ischemic stroke and transient ischemic attack".) Intensive medical management Most patients with TIA or ischemic stroke should receive antithrombotic therapy ( algorithm 5 and algorithm 6) and be treated with all available risk reduction strategies ( table 1). Effective strategies include treatment of hypertension, low density lipoprotein-cholesterol (LDL-C) lowering with high-intensity statin therapy, and lifestyle modification, including smoking cessation, exercise, low-salt and Mediterranean diet, weight control, and no or limited alcohol consumption. These interventions are discussed in greater detail separately. (See "Overview of secondary prevention of ischemic stroke".) Large artery disease Options for the secondary prevention of TIA or ischemic stroke caused by large artery disease include revascularization (mainly for symptomatic cervical internal carotid artery stenosis) and intensive medical therapy (ie, antiplatelet, antihypertensive, and LDL-C lowering therapy) for multifactorial risk reduction. (See "Overview of secondary prevention for specific causes of ischemic stroke and transient ischemic attack", section on 'Large artery disease'.) https://www.uptodate.com/contents/initial-evaluation-and-management-of-transient-ischemic-attack-and-minor-ischemic-stroke/print 12/47 7/5/23, 12:11 PM Initial evaluation and management of transient ischemic attack and minor ischemic stroke - UpToDate Selected patients with recently symptomatic cervical internal carotid artery stenosis of 50 to 99 percent who have a life expectancy of at least five years are generally treated with revascularization via carotid endarterectomy or carotid artery stenting. A pooled analysis of the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and European Carotid Surgery Trial (ECST) found that early carotid endarterectomy (within two weeks of a nondisabling stroke or TIA) significantly improved outcome compared with later surgery [45]. Thus, early identification of symptomatic carotid disease is critical. (See "Management of symptomatic carotid atherosclerotic disease", section on 'Timing of revascularization'.) Patients with TIA or ischemic stroke having carotid endarterectomy are usually treated with aspirin monotherapy at a dose of 81 to 325 mg/day started before surgery, so clopidogrel should be stopped at the discretion of the surgeon if it was started as part of dual antiplatelet therapy (DAPT) prior to determination of carotid stenosis as the stroke mechanism. Patients having carotid artery stenting are treated with dual antiplatelet therapy prior to and continuing for 30 days after stenting. (See "Management of symptomatic carotid atherosclerotic disease" and "Carotid endarterectomy", section on 'Antiplatelet therapy' and "Overview of carotid artery stenting", section on 'Dual antiplatelet therapy'.) Symptomatic intracranial large artery atherosclerosis is associated with a high risk of recurrent stroke, but randomized controlled trials have found that endovascular treatment with stenting leads to harm. Recommended treatment includes short-term (eg, 90 days) use of DAPT with 2 aspirin and clopidogrel, regardless of ABCD score, followed by long-term single-agent antiplatelet therapy, and intensive risk factor management. (See "Intracranial large artery atherosclerosis: Treatment and prognosis".) Small vessel disease For patients with TIA or stroke caused by small vessel disease, medical management (see 'Intensive medical management' above) (ie, antiplatelet, antihypertensive, glucose control, and LDL-C lowering therapy) is the mainstay for secondary stroke prevention. 2 Patients with low-risk TIA (ABCD score <4) attributed to small vessel disease should continue on 2 long-term single-agent antiplatelet therapy, while patients with high-risk TIA (ABCD score 4) or minor ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] 5) should continue DAPT for 21 days, followed by long-term single-agent antiplatelet therapy. (See "Overview of secondary prevention for specific causes of ischemic stroke and transient ischemic attack", section on 'Small artery disease' and "Long-term antithrombotic therapy for the secondary prevention of ischemic stroke".) Atrial fibrillation For most patients with atrial fibrillation and a recent ischemic stroke or TIA, we recommend oral anticoagulation with warfarin or a direct oral anticoagulant (DOAC); once https://www.uptodate.com/contents/initial-evaluation-and-management-of-transient-ischemic-attack-and-minor-ischemic-stroke/print 13/47 7/5/23, 12:11 PM Initial evaluation and management of transient ischemic attack and minor ischemic stroke - UpToDate anticoagulation is started, antiplatelet treatment should be stopped. (See "Atrial fibrillation in adults: Use of oral anticoagulants".) DAPT may offer an alternative to therapy with aspirin alone in high-risk patients with atrial fibrillation who cannot be treated with warfarin or a DOAC due to a strong patient preference, following careful consideration of the advantages of oral anticoagulation. However, DAPT is thought to have similar bleeding risk as oral anticoagulation. Although high-quality evidence is lacking, patients with an unacceptably high long-term bleeding risk may be treated with left atrial appendage occlusion if short-term anticoagulation around the time of the procedure can be tolerated. These issues are discussed in separately. (See "Atrial fibrillation in adults: Use of oral anticoagulants" and "Atrial fibrillation: Left atrial appendage occlusion".) Cryptogenic stroke Most patients with a cryptogenic TIA or ischemic stroke should be treated with antiplatelet therapy as described above (see 'Immediate antiplatelet treatment' above) and intensive risk factor management with blood pressure control, LDL-C lowering 2 therapy, and lifestyle modification. Patients with cryptogenic low-risk TIA (ABCD score <4) should continue on long-term single-agent antiplatelet therapy, while patients with cryptogenic 2 high-risk TIA (ABCD score 4) or minor ischemic stroke (NIHSS 5) should continue DAPT for 21 days, followed by long-term single-agent antiplatelet therapy. However, the optimal antithrombotic therapy of patients with cryptogenic stroke who have patent foramen ovale, atrial septal aneurysm, atheromatous aortic disease, or coagulation disorders is uncertain. (See "Cryptogenic stroke and embolic stroke of undetermined source (ESUS)", section on 'Secondary prevention'.) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Stroke in adults".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading https://www.uptodate.com/contents/initial-evaluation-and-management-of-transient-ischemic-attack-and-minor-ischemic-stroke/print 14/47 7/5/23, 12:11 PM Initial evaluation and management of transient ischemic attack and minor ischemic stroke - UpToDate level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Stroke (The Basics)" and "Patient education: Transient