7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Overview of the evaluation of stroke : Louis R Caplan, MD : Scott E Kasner, MD : 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: Mar 23, 2023. INTRODUCTION The symptoms of brain ischemia may be transient, lasting seconds to minutes, or may persist for longer periods of time. Symptoms and signs remain indefinitely if the brain becomes irreversibly damaged and infarction occurs. Unfortunately, neurologic symptoms do not accurately reflect the presence or absence of infarction, and the tempo of the symptoms does not indicate the cause of the ischemia [1,2]. This is a critical issue because treatment depends upon accurately identifying the cause of symptoms. An overview of the evaluation of patients who present with neurologic symptoms that may be consistent with stroke is discussed here. This evaluation includes the following: Understanding the classification of stroke An initial quick evaluation to stabilize vital signs, determine if intracranial hemorrhage is present, and, in patients with ischemic stroke, decide if reperfusion therapy is warranted (see "Initial assessment and management of acute stroke") Forming a hypothesis of the stroke etiology based upon the history, physical examination, and initial brain imaging study (usually a noncontrast head CT scan) Confirming the precise pathophysiologic process with more directed diagnostic testing The approach to patients with transient brain ischemia is reviewed separately. (See "Initial evaluation and management of transient ischemic attack and minor ischemic stroke".) https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 1/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate CLASSIFICATION Cerebrovascular disease is caused by one of several pathophysiologic processes ( table 1) involving the blood vessels of the brain: Intrinsic vessel abnormality The process may be intrinsic to the vessel, as in atherosclerosis, lipohyalinosis, inflammation, amyloid deposition, arterial dissection, developmental malformation, aneurysmal dilation, or venous thrombosis. Embolism The process may originate remotely, as occurs when an embolus from the heart or extracranial circulation lodges in an intracranial vessel. Inadequate blood flow The process may result from inadequate cerebral blood flow due to decreased perfusion pressure or increased blood viscosity. Vessel rupture The process may result from rupture of a vessel in the subarachnoid space or intracerebral tissue. The first three processes can lead to transient brain ischemia (transient ischemic attack [TIA]) or permanent brain infarction (ischemic stroke), while the fourth results in either subarachnoid hemorrhage or an intracerebral hemorrhage (primary hemorrhagic stroke). Approximately 80 percent of strokes are due to ischemic cerebral infarction and 20 percent to brain hemorrhage. Transient brain ischemia TIA is now defined as a transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction. This tissue-based definition of TIA relies on the absence of end-organ injury as assessed by imaging or other techniques. The proposed advantages of the tissue-based definition are that the defined end point is biological (tissue injury) rather than arbitrary (24 hours). (See "Definition, etiology, and clinical manifestations of transient ischemic attack", section on 'Definition of TIA'.) The approach to patients with TIA is reviewed separately. (See "Initial evaluation and management of transient ischemic attack and minor ischemic stroke".) Intracerebral hemorrhage Bleeding in intracerebral hemorrhage (ICH) is usually derived from arterioles or small arteries. The bleeding is directly into the brain, forming a localized hematoma which spreads along white matter pathways. Accumulation of blood occurs over minutes or hours; the hematoma gradually enlarges by adding blood at its periphery like a snowball rolling downhill. The most common causes of ICH are hypertension, trauma, bleeding diatheses, amyloid angiopathy, illicit drug use (mostly amphetamines and cocaine), and vascular malformations. Less frequent causes include bleeding into tumors, aneurysmal rupture, and https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 2/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate vasculitis. Neurologic symptoms usually increase gradually over minutes or a few hours. (See "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis" and "Clinical diagnosis of stroke subtypes".) Subarachnoid hemorrhage Rupture of arterial aneurysms is the major cause of subarachnoid hemorrhage (SAH). Aneurysm rupture releases blood directly into the cerebrospinal fluid (CSF) under arterial pressure. The blood spreads quickly within the CSF, rapidly increasing intracranial pressure. Death or deep coma ensues if the bleeding continues. The bleeding usually lasts only a few seconds but rebleeding is common. With causes of SAH other than aneurysm rupture (eg, vascular malformations, bleeding diatheses, trauma, amyloid angiopathy, and illicit drug use), the bleeding is less abrupt and may continue over a longer period of time. Symptoms of SAH begin abruptly, occurring at night in 30 percent of cases. The primary symptom is a sudden, severe headache (97 percent of cases) classically described as the "worst headache of my life." The headache is lateralized in 30 percent of patients, predominantly to the side of the aneurysm. The onset of the headache may or may not be associated with a brief loss of consciousness, seizure, nausea, vomiting, focal neurologic deficit, or stiff neck ( figure 1) [3]. There are usually no important focal neurologic signs at presentation unless bleeding occurs into the brain and CSF at the same time (meningocerebral hemorrhage). (See "Aneurysmal subarachnoid hemorrhage: Clinical manifestations and diagnosis".) Ischemia There are three main subtypes of brain ischemia: Thrombosis Embolism Systemic hypoperfusion Thrombotic stroke Thrombotic strokes are those in which the pathologic process giving rise to thrombus formation in an artery produces a stroke either by reduced blood flow distally (low flow) or by an embolic fragment that breaks off and travels to a more distant vessel (artery-to- artery embolism). All thrombotic strokes can be divided into either large or small vessel disease ( table 2). Large vessel disease includes both the extracranial and intracranial arterial system; atherothrombosis is by far the most common pathologic process. (See "Intracranial large artery atherosclerosis: Epidemiology, clinical manifestations, and diagnosis".) Small vessel disease refers specifically to penetrating arteries that arise from the distal vertebral artery, the basilar artery, the middle cerebral artery stem, and the arteries of the https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 3/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate circle of Willis. These arteries thrombose due to atheroma formation at their origin or in the parent large artery, or due to lipohyalinosis (a lipid hyaline build-up distally secondary to hypertension). Penetrating artery (small vessel) disease can result in small deep infarcts usually referred to as lacunes. (See "Lacunar infarcts".) Embolic stroke Embolism refers to particles of debris originating elsewhere that block arterial access to a particular brain region. Since the process is not local (as with thrombosis), local therapy only temporarily solves the problem; further events may occur if the source of embolism is not identified and treated. Embolic strokes are divided into four categories ( table 2). (See "Stroke: Etiology, classification, and epidemiology".) Those with a known source that is cardiac Those with a possible cardiac or aortic source based upon transthoracic and/or transesophageal echocardiographic findings Those with an arterial source Those with a truly unknown source in which these tests are negative or inconclusive Systemic hypoperfusion Systemic hypoperfusion is a more general circulatory problem, manifesting itself in the brain and perhaps other organs. Reduced perfusion can be due to cardiac pump failure caused by cardiac arrest or arrhythmia, or to reduced cardiac output related to acute myocardial ischemia, pulmonary embolism, pericardial effusion, or bleeding. Hypoxemia may further reduce the amount of oxygen carried to the brain. (See "Clinical diagnosis of stroke subtypes".) INITIAL GENERAL ASSESSMENT Sudden loss of focal brain function is the core feature of the onset of ischemic stroke. However, patients with conditions other than brain ischemia can present in a similar fashion ( table 3). In addition, patients who have an ischemic stroke may present with other serious medical conditions. Thus, the initial evaluation requires a rapid but broad assessment. The goals in this initial phase include: Ensuring medical stability Quickly reversing any conditions that are contributing to the patient's problem Moving toward uncovering the pathophysiologic basis of the patient's neurologic symptoms https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 4/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate Diagnosing an intracerebral or subarachnoid hemorrhage as soon as possible can be lifesaving and prevent or minimize permanent neurologic damage. The history may provide clues to these diagnoses, but early triage of the patient to CT scan or MRI is critical. However, it is important to assess and optimize vital physiologic function before sending the patient for an imaging study. (See "Initial assessment and management of acute stroke".) Vital signs Parameters of particular concern in patients with stroke include blood pressure, breathing, and temperature. Blood pressure The mean arterial blood pressure (MAP) is usually elevated in patients with an acute stroke. This may be due to chronic hypertension, which is a major risk factor for ischemic stroke. However, an acute elevation in blood pressure often represents an appropriate response to maintain brain perfusion. The decision to treat requires a balance between the potential danger of severe increases in blood pressure, and a possible decline in neurologic functioning when blood pressure is lowered. (See "Initial assessment and management of acute stroke", section on 'Blood pressure management'.) Breathing Patients with increased intracranial pressure (ICP) due to hemorrhage, vertebrobasilar ischemia, or bihemispheric ischemia can present with a decreased respiratory drive or muscular airway obstruction. Hypoventilation, with a resulting increase in the partial pressure of carbon dioxide, may lead to cerebral vasodilation which further elevates ICP. Intubation may be necessary to restore adequate ventilation and to protect the airway. This is especially important in the presence of vomiting, which occurs commonly with increased ICP, vertebrobasilar ischemia, and intracranial hemorrhage. Fever Fever may occur in patients with an acute stroke and can worsen brain ischemia [4]. Normothermia should be maintained for at least the first several days after an acute stroke. (See "Initial assessment and management of acute stroke", section on 'Fever'.) History and physical examination The history and physical examination should be used to distinguish between other disorders in the differential diagnosis of stroke ( table 3). As examples, seizures, syncope, migraine, and hypoglycemia can mimic acute ischemia. The most difficult cases involve patients with focal signs and altered level of consciousness. It is important to ask the patient or a relative whether the patient takes insulin or oral hypoglycemic agents, has a history of a seizure disorder or drug overdose or abuse, medications on admission, recent trauma, or hysteria (see "Differential diagnosis of transient ischemic attack and acute stroke"). The history is also important in separating ischemia from hemorrhage and distinguishing between subtypes of ischemia and hemorrhage. https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 5/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate Ischemia versus hemorrhage Noncontrast computed tomography (CT) is typically the first diagnostic study in patients with suspected stroke. The main advantages of CT are widespread access and speed of acquisition. CT is highly sensitive for the diagnosis of hemorrhage in the acute setting [5]. Intracerebral hemorrhages are evident almost instantly after onset as focal white hyperdense lesions within the brain parenchyma. (See "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis", section on 'Head CT'.) Intracerebral hemorrhages can also be defined by MRI; the use of susceptibility sequences improves the sensitivity of MRI for early detection of hemorrhage. Gradient-echo images can also show the presence of old hemorrhages since this technique is very sensitive to hemosiderin, which can remain in old hemorrhages indefinitely. (See "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis", section on 'Brain MRI'.) Small subarachnoid hemorrhages can be missed by either CT or MRI. Lumbar puncture may be needed to make the diagnosis in such patients. (See "Aneurysmal subarachnoid hemorrhage: Clinical manifestations and diagnosis", section on 'Lumbar puncture'.) MRI is more sensitive than CT for the early diagnosis of brain infarction, although CT may identify subtle indicators of infarction within six hours of stroke onset in a significant number of patients (see "Neuroimaging of acute stroke", section on 'Assessment of early infarct signs'). Fluid-attenuated inversion recovery (FLAIR) MRI sequences and diffusion-weighted images (DWI- MRI) are especially useful in showing infarcts early after the onset of symptoms. In patients with ischemia who do not yet have brain infarction, both CT and MRI may be normal. (See "Neuroimaging of acute stroke", section on 'Assessment of early infarct signs'.) Is the patient a candidate for reperfusion? Timely restoration of blood flow is the most effective maneuver for salvaging ischemic brain tissue that is not already infarcted. Removal of occlusive intracranial thrombi must be accomplished quickly, since the benefit of reperfusion therapy for ischemic stroke decreases in a continuous fashion over time. An important aspect of the hyperacute phase of stroke assessment is to determine if the patient is eligible for intravenous thrombolysis and/or mechanical thrombectomy: Intravenous thrombolytic therapy with alteplase (recombinant tissue-type plasminogen activator or rt-PA) improves outcomes in patients with acute ischemic stroke who can be treated within 3 to 4.5 hours from stroke onset and meet additional eligibility criteria ( table 4). This issue is discussed in detail separately. (See "Approach to reperfusion therapy for acute ischemic stroke", section on 'Alteplase'.) Intra-arterial mechanical thrombectomy using a second-generation stent retriever device can improve outcomes for well-selected patients with ischemic stroke caused by a large https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 6/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate artery occlusion in the proximal anterior circulation when started up to 24 hours from the time last seen. This therapy is reviewed in detail elsewhere. (See "Mechanical thrombectomy for acute ischemic stroke".) DETERMINING A PRESUMPTIVE DIAGNOSIS OF STROKE SUBTYPE After completing the initial assessment, the goal of the subsequent evaluation is to determine the underlying pathophysiology of the stroke in order to guide therapy ( table 1). This part of the discussion assumes that patients with subarachnoid hemorrhage have already been identified by the initial history and physical examination and noncontrast head CT (with or without lumbar puncture). A review of the clinical features and diagnosis of subarachnoid hemorrhage is found separately. (See "Aneurysmal subarachnoid hemorrhage: Clinical manifestations and diagnosis".) In addition, the presence of intracerebral hemorrhage should already be evident by this phase of the evaluation; the diagnostic evaluation in these patients is reviewed elsewhere. (See 'Evaluation of patients with intracerebral hemorrhage' below.) In practice, then, this second stage of evaluation is focused upon distinguishing between embolic and thrombotic strokes; in patients with the latter, it is worth differentiating between large vessel and small vessel (penetrating artery or lacunar) infarcts since the causes, outcomes, and treatments are different. Some patients will have more than one potential etiology for stroke, although the majority will have only one predominant cause [6]. (See "Stroke: Etiology, classification, and epidemiology" and "Clinical diagnosis of stroke subtypes".) A presumptive diagnosis of the stroke subtype can be made following a thorough history, physical examination, and imaging study such as CT or MRI. However, confirmation of the diagnosis requires more extensive testing. A history of carotid stenosis is a significant risk factor for large artery thrombotic stroke, but these patients need to have other stroke subtypes considered in the differential diagnosis. In the North American Symptomatic Carotid Endarterectomy Trial (NASCET), of patients with 70 to 99 percent stenosis who subsequently had an ischemic stroke, 20 and 45 percent of strokes that occurred in the territory of symptomatic and asymptomatic carotid arteries, respectively, were unrelated to carotid stenosis [7]. History A number of features in the clinical history may be useful in determining the type of stroke: https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 7/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate Clinical course Ecology Previous transient ischemic attack (TIA) Activity at the onset or just before the stroke Associated symptoms Clinical course The most important historical item for differentiating stroke subtypes is the pace and course of the symptoms and signs and their clearing [8]. Each subtype has a characteristic course. Embolic strokes most often occur suddenly ( figure 2). The deficits indicate focal loss of brain function that is usually maximal at onset. Rapid recovery also favors embolism. Thrombosis-related symptoms often fluctuate, varying between normal and abnormal or progressing in a stepwise or stuttering fashion with some periods of improvement ( figure 3). Penetrating artery occlusions usually cause symptoms that develop during a period of hours or at most a few days ( figure 4), compared with large artery-related brain ischemia, which can evolve over a longer period. Intracerebral hemorrhage (ICH) does not improve during the early period; it progresses gradually during minutes or a few hours ( figure 5). Aneurysmal subarachnoid hemorrhage (SAH) develops in an instant. Focal brain dysfunction is less common. Patients often do not give a specific history regarding the course of neurologic symptoms. I may ask if the patient could walk, talk, use the phone, use the hand, etc, as the events developed after the first symptoms occurred [8]. Ecology Ecology refers to known demographic and historical features that provide probabilities of the patient having one or more of the stroke subtypes. Age, sex, and race are important demographic variables generally known to the clinician before taking the history [9]. Most thrombotic and embolic strokes related to atherosclerosis occur in older patients. Individuals under age 40 rarely have severe atherosclerosis unless they also have major risk factors such as diabetes, hypertension, hyperlipidemia, smoking, or a strong family history. By contrast, cardiac-origin embolism is common in young people who are known to have heart disease. https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 8/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate Hypertensive ICH is more common among Black individuals and individuals of Asian descent (eg, Chinese and Japanese) compared with White individuals. Premenopausal women have a lower frequency of atherosclerosis than men of similar age unless they have major stroke risk factors. Even after adjusting for age, the incidence of atherosclerotic stroke is four times higher in men [10]. Black and Asian individuals have a lower incidence of occlusive disease of the extracranial carotid and vertebral arteries than White men. Hypertension is the most common and most important stroke risk factor, including isolated systolic hypertension (see "Overview of secondary prevention of ischemic stroke", section on 'Hypertension'). Epidemiologic studies show that there is a gradually increasing incidence of both coronary disease and stroke as the blood pressure rises above 110/75 mmHg ( figure 6) [11,12]. However, these observations do not prove a causal relationship, since increasing blood pressure could be a marker for other risk factors such as increasing body weight, which is associated with dyslipidemia, glucose intolerance, and the metabolic syndrome. The best evidence for a causal role of increasing blood pressure in cardiovascular complications is an improvement in outcome with antihypertensive therapy. This evidence is reviewed elsewhere. Chronic hypertension is a risk factor for both thrombotic extracranial and intracranial large artery disease and penetrating artery disease. Conversely, the absence of a history of hypertension or of present hypertension reduces the likelihood of penetrating artery disease. Smoking increases the likelihood of extracranial occlusive vascular disease, more than doubling the risk of stroke [13]. The risk of ischemic stroke decreases over time after smoking cessation. In one series of middle-aged women, for example, the excess risk among former smokers largely disappeared two to four years after cessation [13]. (See "Cardiovascular risk of smoking and benefits of smoking cessation".) Several other risk factors for stroke have been identified: Diabetes increases the likelihood of large and small artery occlusive disease. The use of amphetamines increases the likelihood of both ICH and SAH but not brain ischemia. Cocaine-related strokes are often hemorrhagic (ICH and SAH), due to aneurysms and vascular malformations [14]. Cocaine is also associated with brain ischemia, especially involving the posterior circulation intracranial arteries; this is probably due to vasoconstriction. https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 9/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate Heart disease, including cardiac valvular disease, prior myocardial infarction, atrial fibrillation, and endocarditis, increases the probability of a stroke due to embolism. Stroke during the puerperium has an increased likelihood of being related to venous or arterial thrombosis. The presence of a known bleeding disorder or prescription of warfarin or other anticoagulants predisposes to hemorrhage, into either the brain or the cerebrospinal fluid (CSF). The link between stroke and oral contraceptive use has been a controversial issue. Initial studies suggesting this association were performed with oral contraceptives containing higher doses of estrogen; the risk may not be as great with current low dose oral contraceptives. (See "Combined estrogen-progestin contraception: Side effects and health concerns", section on 'Cardiovascular effects'.) The presence of these risk factors increases the odds that a stroke is due to a particular mechanism, but the clinician cannot make a firm diagnosis simply on the basis of probability. As examples: some conditions such as hypertension predispose to more than one subtype (thrombosis, intracranial hemorrhage); the presence of a prior myocardial infarction increases the likelihood of cardiac origin embolism, but also increases the likelihood of carotid and vertebral artery neck occlusive disease (thrombosis); and an older patient with severe atherosclerosis may also harbor an unexpected cerebral aneurysm. Previous transient ischemic attack A history of TIA (especially more than one) in the same territory as the stroke strongly favors the presence of a local vascular lesion (thrombosis). Attacks in more than one vascular territory suggest brain embolism from the heart or aorta. TIAs are not a feature of brain hemorrhage. Patients often will not volunteer a prior history of symptoms consistent with a TIA. Many patients, for example, do not relate prior hand or eye problems to subsequent leg problems. Thus, the physician must ask directly about specific symptoms. "Did your arm, hand, or leg ever transiently go numb?" "Did you ever have difficulty speaking?" "Did you ever lose vision? If so, in which part of your vision? Was it in one eye and, if so, which one?" Activity at the onset or just before the stroke Hemorrhages (ICH and SAH) can be precipitated by sex or other physical activity, while thrombotic strokes are unusual under these circumstances. Trauma before the stroke suggests traumatic dissection or occlusion of arteries or traumatic brain hemorrhage. Sudden coughing and sneezing sometimes precipitates brain https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 10/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate embolism. Similarly, getting up during the night to urinate seems to promote brain embolism (a matutinal embolus). Associated symptoms The presence of certain associated symptoms is suggestive of specific stroke subtypes. Fever raises the suspicion of endocarditis and resulting embolic stroke. Infections activate acute phase blood reactants, thereby predisposing to thrombosis. Headache is typically a feature of hemorrhagic strokes, but some patients have headaches in the prodromal period before thrombotic strokes. Vomiting is common in patients with ICH, SAH, and posterior circulation large artery ischemia ( figure 1). Seizures are most often seen in patients with lobar ICH or brain embolism; they are rare in patients with acute thrombosis [15]. Reduced alertness favors the presence of hemorrhage. Accompanying neurologic signs are suggestive of ICH, while the absence of focal signs suggests SAH. Loss of consciousness is also common in patients with thrombotic and embolic strokes that are large or involve the posterior circulation large arteries. Physical examination Important clues in the general physical examination include the following: Absent pulses (inferior extremity, radial, or carotid) favors a diagnosis of atherosclerosis with thrombosis, although the sudden onset of a cold, blue limb favors embolism. The internal carotid arteries in the neck cannot be reliably palpated but, in some patients, occlusion of the common carotid artery in the neck can be diagnosed by the absence of a carotid pulse. The presence of a neck bruit suggests the presence of occlusive extracranial disease, especially if the bruit is long, focal, and high pitched. Palpating the facial pulses is helpful in diagnosing common carotid and internal carotid artery occlusions and temporal arteritis. The facial pulses on the side of the occlusion are often lost with common carotid artery occlusions. By contrast, some patients with internal carotid artery occlusion will have increased facial pulses on the side of the occlusion because collateral channels develop between the external carotid artery facial branches https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 11/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate and the carotid arteries intracranially. In patients with temporal arteritis, the temporal arteries are often irregular and have sausage-shaped areas of dilatation, may be tender, and are often pulseless. Cardiac findings, especially atrial fibrillation, murmurs, and cardiac enlargement, favor cardiac-origin embolism. (See "Auscultation of cardiac murmurs in adults".) Careful examination of the optic fundus may reveal a cholesterol crystal, white platelet- fibrin, or red clot emboli. Subhyaloid hemorrhages in the eye suggest a suddenly developing brain or subarachnoid hemorrhage. When the carotid artery is occluded, the iris may appear speckled and the ipsilateral pupil can become dilated and poorly reactive. The retina in that circumstance may also show evidence of chronic ischemia (venous stasis retinopathy). Neurologic examination The patient's account of his or her neurologic symptoms and the neurologic signs found on examination tell more about the location of the process in the brain than the particular stroke subtype. The blood supply to various parts of the brain and associated neurologic findings are shown in the figures ( figure 7A-G). Nevertheless, some constellations of symptoms and signs occasionally suggest a specific process ( table 5). Weakness of the face, arm, and leg on one side of the body unaccompanied by sensory, visual, or cognitive abnormalities (pure motor stroke) favors the presence of a thrombotic stroke involving penetrating arteries or a small ICH. Large focal neurologic deficits that begin abruptly or progress quickly are characteristic of embolism or ICH. Abnormalities of language suggest anterior circulation disease, as does the presence of motor and sensory signs on the same side of the body ( figure 8). Vertigo, staggering, diplopia, deafness, crossed symptoms (one side of the face and other side of the body), bilateral motor and/or sensory signs, and hemianopia or bilateral visual field loss suggest involvement of the posterior circulation. (See "Posterior circulation cerebrovascular syndromes".) The sudden onset of impaired consciousness in the absence of focal neurologic signs is characteristic of SAH. https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 12/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate Imaging studies Brain imaging and a comprehensive neurovascular evaluation should be obtained for most patients suspected of having acute ischemic stroke or transient ischemic attack. Neurovascular imaging is important to determine the potential sources of embolism or low flow in ischemic stroke and to detect possible aneurysms or vessel malformations in hemorrhagic stroke. (See "Neuroimaging of acute stroke".) The location and size of a brain infarct on CT or MRI may further aid in distinguishing between stroke subtypes. Small subcortical (deep) infarcts are most commonly located in the basal ganglia, internal capsule, thalamus, and pons. They are potentially within the blood supply of a single penetrating artery. The most common cause of a small deep infarct is lacunar infarction due to degenerative changes in the penetrating arteries. Rostral brainstem (midbrain and thalamus), occipital lobe, and cerebellar infarcts are most commonly caused by brain embolism. (See "Posterior circulation cerebrovascular syndromes".) On the other hand, large subcortical infarcts, infarcts that are limited to the cerebral cortex, and infarcts that are both cortical and subcortical are commonly caused by thrombosis or embolism. CONFIRMING THE DIAGNOSIS The previous assessment should allow the formation of a presumptive diagnosis of the underlying stroke pathophysiology. The next phase of the evaluation is to confirm this hypothesis with diagnostic tests. Embolic stroke Embolism is especially likely in the following circumstances: The onset is sudden and the neurologic deficit is maximal from the beginning The infarct and deficit are large There is a known cardiac or large artery lesion present The infarct is or becomes hemorrhagic on CT or MRI There are multiple cortical or cortical/subcortical infarcts in different vascular territories Clinical findings improve quickly (so-called "spectacular shrinking deficit") [16] In addition, embolic stroke is common in patients who have had a posterior circulation stroke; in a registry of 361 patients who had vertebrobasilar strokes or transient ischemic attacks (TIAs) and were admitted to a university hospital, 41 percent had an embolic event [17]. https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 13/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate A possible cardiac source should be considered in all patients with suspected embolic stroke, particularly in patients under age 45, whether or not they have clinical evidence of heart disease. This issue is discussed below. (See 'Cardiac evaluation' below.) Vascular studies The extracranial and intracranial arteries are also common sources of brain embolism and should be studied. (See "Stroke: Etiology, classification, and epidemiology".) If the infarct and brain symptoms are within the anterior circulation (carotid artery supply), then the extracranial and intracranial carotid arteries, and the middle and anterior cerebral artery branches should be the focus of the examinations. When the infarct is within the posterior circulation (vertebrobasilar system), the extracranial and intracranial vertebral arteries, the basilar artery, and the posterior cerebral arteries should be the focus of the vascular investigations. The anterior circulation can be studied using duplex ultrasound of the neck and transcranial Doppler (TCD) of the intracranial arteries [18,19]. B-mode images of the carotid artery also demonstrate the degree of stenosis and irregularities or ulcerations within plaques. Alternatively, CT angiography (CTA) or MR angiography (MRA) of the neck and head arteries may be sufficient. Conventional angiography is performed when the screening tests do not fully define the lesion and more characterization is warranted, and when surgery or interventional treatment through an arterial catheter (angioplasty or intra-arterial thrombolysis) may be indicated. Within the posterior circulation, duplex and color-flow Doppler investigation of the origins of the vertebral arteries [20] and ultrasound of the subclavian arteries (especially when the radial pulse or blood pressure on one side is lower than the other) can detect lesions of the proximal portion of the vertebral arteries. Atherosclerosis most often affects this proximal region. The ultrasonographer can then insonate over the rest of the vertebral artery in the neck using a continuous-wave Doppler to detect the direction of flow within the artery (craniad as would be normal, or reversed or to-and-fro flow suggesting proximal obstruction). CTA and MRA of the neck vertebral arteries are also helpful, but these tests may not adequately show the origins of the vertebral arteries [21]. The clinician must be certain that the films are adequate to see the complete extracranial and intracranial vertebrobasilar system. An important advance in the detection of brain embolism is monitoring by TCD [22]. Emboli that pass under ultrasound probes make a high-pitched chirp and are recorded as high-intensity transient signals (HITS). The location and pattern of these emboli can help define the presence https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 14/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate of embolism and give clues as to the source. TCD monitoring can also help to assess the effectiveness of treatment. Artery-to-artery versus cardiac sources of embolism The distinction between artery-to- artery and non-artery-to-artery 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. However, caution must be used in interpreting the results of a transthoracic echocardiogram. As previously mentioned, this study can exclude a cardiomyopathy and most atrial and mitral valve pathology, but may miss other potential embolic sources such as clot in the atrial appendage, a patent foramen ovale, mitral valve lesions, and aortic atherosclerosis. Transesophageal echocardiography (TEE) is better for identifying these lesions. However, transthoracic echocardiography (TTE) is generally superior to TEE for identifying left ventricular apical thrombus. (See 'Echocardiography' below.) Small vessel (lacunar) stroke Most patients with lacunar infarcts have risk factors for penetrating artery disease (eg, hypertension, diabetes mellitus, or polycythemia). The clinical findings typically conform to one of the well-recognized lacunar syndromes: pure motor hemiparesis, pure sensory stroke, dysarthria-clumsy hand, or ataxic hemiparesis. (See "Lacunar infarcts".) Further testing is of low yield in patients suspected of having a lacunar infarction who have the typical risk factors, clinical neurologic findings, and characteristic brain imaging (eg, small subcortical infarct). On the other hand, some patients seen within the first few hours after symptom onset with clinical findings suggestive of lacunar infarction are found to have large artery disease; this has been particularly true for patients of Asian descent. (See "Intracranial large artery atherosclerosis: Epidemiology, clinical manifestations, and diagnosis", section on 'Racial and ethnic differences'.) Vascular imaging (CTA or MRA) can be performed at the same time as brain imaging (CT or MRI) to exclude occlusion of the parent feeding artery, a condition that can mimic a lacunar infarct. (See "Lacunar infarcts", section on 'Evaluation and diagnosis'.) It is particularly important to perform intracranial vascular imaging in Black patients and patients of Asian descent, since intracranial large artery occlusive disease is common in these patients. An alternative diagnostic test to exclude intracranial occlusive disease is TCD, a technique that measures the blood flow velocities in the large intracranial arteries using an ultrasound probe placed over the orbit, temporal bone, and foramen magnum [18]. (See "Neuroimaging of acute stroke", section on 'Ultrasound methods'.) https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 15/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate Large vessel atherothrombotic stroke Large vessel atherothrombotic strokes are often preceded by TIAs, and the onset may or may not be abrupt. The course of neurologic symptoms and signs fluctuates or is progressive in development. Infarcts that are large and subcortical are usually caused by occlusion of intracranial arteries.