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. Patients with suspected large vessel atherothrombotic strokes need to have both intracranial and extracranial vascular testing. Extracranial vascular testing can be performed with MRA, CTA, or duplex carotid ultrasound. All are reliable and specific for detecting important severe occlusive lesions in the extracranial carotid arteries. Ultrasound devices such as color-flow Doppler imaging and power Doppler improve the resolution and quantification of carotid artery lesions. (See "Evaluation of carotid artery stenosis".) One approach to patients with suspected carotid artery stenosis is to first perform carotid duplex ultrasound. Patients with stenoses less than 50 percent are followed with serial examinations, usually on an annual basis to determine if there is progression. Transcranial Doppler and either MRA or CTA should be performed if the carotid stenosis is greater than 50 percent on the duplex ultrasound. Both MRA and CTA accurately define abnormalities within the carotid and vertebral arteries in the neck and their intracranial branches. MRI can be performed at the same time as MRA; the presence or absence of a brain infarct can help determine treatment. (See "Evaluation of carotid artery stenosis".) Head CT and CTA are acceptable alternatives to MRI and MRA and may be more available than MR in some centers. Head CT and CTA should be done if MRI and MRA are contraindicated or impractical. Conventional angiography is rarely performed; indications include patients who cannot tolerate an MRA or CTA, patients with discrepant CTA/MRA and ultrasound findings, and patients with suspected nonatherosclerotic disease (eg, dissection, fibromuscular dysplasia). Patients with carotid artery stenosis who have had nondisabling strokes may be candidates for carotid endarterectomy or carotid artery stenting. (See "Management of symptomatic carotid atherosclerotic disease".) CARDIAC EVALUATION A cardiac evaluation is important in most patients with brain ischemia [23]. Not only are cardiac and aortic origin emboli common, but many patients with cerebrovascular occlusive disease have concurrent coronary heart disease that can lead to significant morbidity and mortality [24- https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 16/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate 27]. The basic evaluation includes a thorough history focusing on the presence of cardiac ischemia and arrhythmias, a careful cardiac examination, and an electrocardiogram. Monitoring for subclinical atrial fibrillation All patients with ischemic stroke should have cardiac monitoring for at least the first 24 hours after stroke onset to look for subclinical atrial fibrillation (AF) [28]. In addition, we suggest ambulatory cardiac monitoring for several weeks (eg, 30 days) for patients with a cryptogenic ischemic stroke or transient ischemic attack (TIA). These patients are characterized by brain ischemia not attributable to a definite source of cardioembolism, large artery atherosclerosis, or small artery disease despite extensive vascular and cardiac evaluation, including no evidence of AF on standard 12-lead electrocardiogram (ECG) and 24-hour cardiac monitoring (see "Cryptogenic stroke and embolic stroke of undetermined source (ESUS)"). Prolonged cardiac event monitoring increase the detection of subclinical AF in patients with TIA or acute ischemic stroke who present with sinus rhythm [29-34]. By contrast, subclinical AF, if transient, infrequent, and largely asymptomatic, may be undetected on standard cardiac monitoring such as continuous telemetry and 24- or 48-hour Holter monitors. This issue is illustrated by the following observations among trials of patients without an identified mechanism for stroke or TIA: In The CRYSTAL AF trial, 441 patients with cryptogenic stroke and no evidence of AF during at least 24 hours of ECG monitoring were randomly assigned to prolonged ambulatory cardiac monitoring with a subcutaneous insertable cardiac monitor (also sometimes referred to as implantable cardiac monitor or implantable loop recorder) recorder or to a control group with conventional follow-up [29]. At six months, AF detection was significantly higher in the monitored group (8.9 percent, versus 1.4 percent in the control group, hazard ratio [HR] 6.4, 95% CI 1.9-21.7). In the EMBRACE trial, 572 patients who had a cryptogenic stroke or TIA (with no AF after 24-hour cardiac monitoring) in the previous six months were randomly assigned to additional ambulatory monitoring with a 30-day external loop recorder (intervention group) or a 24-hour Holter monitor (control group) [30]. At study end, the rate of AF detection was significantly greater in the intervention group (16.1 percent, versus 3.2 percent in the control group, 95% CI 8.0-17.6). The PER DIEM trial randomly assigned 300 patients within six months of ischemic stroke and no known AF (66 percent had a cryptogenic stroke) in a 1:1 ratio to monitoring with either an insertable cardiac monitor (placed for one year) or an external loop recorder (worn for four weeks) [33]. At 12 months, detection of new AF lasting more than two https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 17/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate minutes was observed in a greater number of patients in the insertable cardiac monitor group compared with the external loop recorder group (15.3 versus 4.7 percent, absolute difference 10.7 percent, 95% CI 4.0-17.3 percent). Long-term cardiac monitoring can detect subclinical AF even among patients with a known mechanism for ischemic stroke. The STROKE-AF trial randomly assigned 492 patients with ischemic stroke attributed to large vessel or small vessel disease in a 1:1 ratio to monitoring with an insertable cardiac monitor or to site-specific usual care (external cardiac monitoring with ECG, Holter, telemetry, or event recorders) [34]. At 12 months, detection of AF lasting more than 30 seconds was higher in the insertable cardiac monitor group compared with the usual care group (12.1 versus 1.8 percent, absolute difference approximately 10.3 percent, HR 7.4, 95% CI 2.6- 21.3). These results parallel other data showing that prolonged cardiac event monitoring increases the detection of subclinical AF [31,35-39]. Such monitoring may then reduce the risk of recurrent ischemic stroke by prompting the appropriate use of long-term anticoagulation [40]. However, rigorous evidence is lacking that anticoagulation of subclinical AF improves outcomes for patients initially diagnosed with cryptogenic stroke [41]. The approach to treatment of subclinical AF detected on monitoring is reviewed separately. (See "Cryptogenic stroke and embolic stroke of undetermined source (ESUS)", section on 'Occult or subclinical atrial fibrillation on monitoring'.) In addition, the minimum duration of time (in minutes) of the episodes of AF that increases the risk of thrombus formation in the atria and thereby increases the risk of cardioembolic stroke has not been firmly established. (See "Stroke in patients with atrial fibrillation", section on 'Long- term anticoagulation'.) The optimal cardiac monitoring method (ie, continuous telemetry, ambulatory electrocardiography, serial electrocardiography, transtelephonic ECG monitoring, or insertable cardiac monitor) is uncertain. (See "Ambulatory ECG monitoring".) Other potential indicators that may predict which patients have or are likely to develop atrial fibrillation include determination of the left atrial appendage ejection fraction by transesophageal echocardiography [42] and demonstration of an atrial fibrillation phenotype on left atrial appendage pulse wave Doppler even when the surface ECG shows normal sinus rhythm [43]. In addition, measurements of B-type (brain) natriuretic protein (BNP) and the N- terminal fragment of BNP indicate that these values are elevated in patients with atrial fibrillation who have cardiogenic embolism, even in those with normal ventricular function, when compared with patients who have noncardiogenic stroke (see "Blood biomarkers for https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 18/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate stroke", section on 'Cardioembolic stroke'). These measurements in patients with normal cardiac ventricular function might identify those who have intermittent atrial fibrillation or are prone to develop it. Further research is needed to confirm whether these indicators are clinically useful. Atrial cardiopathy characterized by a large left atrium and abnormal function and morphology of the left atrium and left atrial appendage can predispose to thrombus formation even without atrial fibrillation. (See "Cryptogenic stroke and embolic stroke of undetermined source (ESUS)", section on 'Atrial cardiopathies'.) Echocardiography All patients with suspected embolic stroke should have an echocardiogram. The choice between transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) as the initial imaging test to identify a source of embolism should be individualized on a case-by-case basis. (See "Echocardiography in detection of cardiac and aortic sources of systemic embolism".) TTE is the preferred initial test for the majority of patients with a suspected cardiac or aortic source of emboli, including: Patients 45 years with a neurologic event and no identified disease on neurovascular imaging studies Patients with a high suspicion of left ventricular thrombus Patients in whom 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 in whom a negative TTE would be likely to be falsely negative Patients with atrial fibrillation (a situation where left atrial or left atrial appendage thrombus is a likely cause of ischemic stroke), but only if the TEE would impact management Patients with a mechanical or bioprosthetic heart valve; although the long-term risk of thrombus is higher with mechanical valve than with bioprosthetic valve, both can develop thrombus Patients with suspected aortic pathology Transesophageal versus transthoracic echo While TTE and TEE have advantages and disadvantages, both are effective diagnostic tests with a role in the evaluation of suspected https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 19/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate cardioaortic source of embolism. In most patients, TEE yields higher quality images and has a greater sensitivity and specificity than TTE, but a few conditions (eg, left ventricular thrombus) are better seen on TTE. However, TEE is an uncomfortable invasive procedure that may not be tolerated by very ill patients. Because it is less invasive and readily available in most institutions, TTE is often reasonable as the initial test of choice. A TEE is often performed to examine the atria, atrial septal region, and the aorta if the TTE and preliminary cardiac and vascular imaging tests do not clarify the cause of brain ischemia [44,45]. (See "Initial evaluation and management of transient ischemic attack and minor ischemic stroke".) A TEE is the best test to exclude significant ascending aortic atheromatous disease. It is also the best test to look for evidence of patent foramen ovale (PFO), atrial septal aneurysm, or atrial septal defect, conditions that can cause otherwise cryptogenic stroke. (See "Thromboembolism from aortic plaque" and "Embolism from atherosclerotic plaque: Atheroembolism (cholesterol crystal embolism)" and "Atrial septal abnormalities (PFO, ASD, and ASA) and risk of cerebral emboli in adults".) TEE is also the best way to identify clot in the left atrial appendage. These emboli are 3 mm or less in diameter and are usually beyond the resolution of the transthoracic echocardiographic ultrasound probe. By contrast, left ventricular thrombi in patients with heart failure or a previous myocardial infarction are best seen with TTE since the true left ventricular apex is not well seen on TEE. (See "Echocardiography in detection of cardiac and aortic sources of systemic embolism".) BLOOD TESTS A number of blood tests may be indicated in select patients with brain ischemia or hemorrhage, including [28,46]: Blood glucose Complete blood count, including hemoglobin, hematocrit, white blood cell count, and platelet count Prothrombin time, international normalized ratio (INR), and activated partial thromboplastin time Thrombin time and/or ecarin clotting time if patient is known or suspected to be taking a direct thrombin inhibitor or a direct factor Xa inhibitor Blood lipids, including total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol, and triglycerides https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 20/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate D-dimer and fibrinogen levels may be helpful in detecting patients whose brain ischemia can be related to cancer or inflammatory disease. (See "Blood biomarkers for stroke".) Hypercoagulable studies While hypercoagulable states are sometimes found in patients who have had an ischemic stroke, widespread testing for these disorders is limited by a number of factors including a relatively low prevalence of thrombophilias and alteration of the sensitivity and specificity of the tests involved in the setting of an acute ischemic event and in patients taking heparin or warfarin [47]. Furthermore, it remains unclear if the inherited thrombophilias directly predispose to stroke as they do to venous thrombosis. A case-control study found that one in seven patients with a first ever acute ischemic stroke tested positive for one of the inherited thrombophilias, but that the relationship was likely to be coincidental rather than causal in almost all cases [48]. In a systematic review, the prevalence of inherited deficiencies of protein C, protein S, antithrombin III, or plasminogen was low in unselected patients with ischemic stroke [49]. The pretest probabilities of other coagulation defects in these patients were as follows: Lupus anticoagulant 3 percent (8 percent in patients 50 years) Anticardiolipin antibodies 17 percent (21 percent in patients 50 years) Activated protein C resistance/factor V Leiden mutation 7 percent (11 percent in patients 50 years) Prothrombin mutation 5 percent (6 percent in patients 50 years) The posttest probabilities of these abnormalities increased with increasing pretest probability and features of the patients' history and clinical presentation suggestive of coagulopathy (eg, cerebral or venous thrombosis without precipitating factors). In the absence of definitive data, it is my practice to obtain testing for hypercoagulable conditions in patients who have: A personal or family history of systemic thromboses No clear etiology for ischemic stroke or transient ischemic attack (TIA), despite cardiac and vascular imaging, especially when involving young patients Clinical findings that suggest systemic lupus erythematosus or the antiphospholipid antibody syndrome Antiphospholipid antibodies The role of antiphospholipid antibodies (aPL) in the pathogenesis of ischemic stroke remains unclear. Transient elevations of aPL or lupus anticoagulants can be seen in the setting of acute stroke. Thus, elevated levels may simply be a https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 21/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate sequel to stroke and not related to its cause. On the other hand, aPL may be associated with thrombosis or a cardiac valve abnormality that is the cause of stroke. The evidence is conflicting as to how to interpret positive aPL assays among the full complement of ischemic stroke patients, as illustrated by the following reports [50,51]: A large, prospective, cohort study (APASS) of 1770 patients with ischemic stroke found that the presence of aPL, either LA or aCL, did not predict increased risk for subsequent vascular ischemic events, including ischemic stroke; did not confer increased risk for subgroups of patients younger than 55 years or those with cryptogenic stroke; and did not predict a differential response to aspirin or warfarin therapy [50]. A small subgroup (120) positive for both LA and ACL had a tendency toward higher risk of vascular occlusive events at two years than those without aPL (31.7 versus 24 percent). (See "Clinical manifestations of antiphospholipid syndrome", section on 'Neurologic involvement'.) In patients with systemic lupus erythematosus, one study found that the levels of both aCL binding to beta 2 glycoprotein I, and anti-phosphatidylserine antibodies binding to prothrombin were significantly higher in patients with a history of cerebral infarction compared with those who had no history of cerebral infarction [52]. Furthermore, lupus patients who were positive for both of these antibodies had a 77 percent prevalence of cerebral infarction (odds ratio 30.0, 95% CI 11-86). The presence of either antibody alone was not associated with a significantly increased stroke risk. In 2712 women and 2262 men in the Framingham Heart Study cohort who were free of stroke or TIA at the time of their baseline examination and were followed for 11 years, elevated serum concentrations of ACL independently and significantly predicted the risk of first ischemic stroke or TIA in women but not men [51]. In the absence of definitive data, we recommend obtaining antiphospholipid antibody testing in patients who have: A history of lupus or symptoms compatible with lupus Features that suggest the antiphospholipid syndrome such as miscarriages, venous thrombosis, or migraine headaches Cryptogenic stroke or TIA at a young age Others Plasma fibrinogen levels are risk factors for coronary heart disease and stroke [53,54]. However, the routine use of fibrinogen as a cardiovascular risk marker is limited by measurement variability. (See "Blood biomarkers for stroke" and "Overview of possible risk factors for cardiovascular disease".) https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 22/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate Other studies may include hemoglobin electrophoresis in patients suspected of having a hemoglobinopathy, and an erythrocyte sedimentation rate, tests for Lyme disease, syphilis, and HIV infection in selected patients. EVALUATION OF PATIENTS WITH INTRACEREBRAL HEMORRHAGE CT scans usually define the size and location of intracerebral hemorrhage (ICH) and the presence of intraventricular blood [55]. Mass effect caused by the intracerebral mass, shift of midline structures, herniation of brain contents from one compartment to another, and the presence of hydrocephalus are also easily seen on CT. MRI with echo-planar T2*-weighted (susceptibility) images can also show hemorrhages soon after the onset of symptoms. Microbleeds (tiny older hemorrhages) are shown using this technique and can be clues to the presence of cerebral amyloid angiopathy. It is not necessary to perform both CT and MRI to exclude hemorrhage if echo-planar MRI scanning is available. A detailed description of the MRI characteristics of hyperacute ICH is found separately. (See "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis", section on 'Brain MRI'.) Vascular malformations and brain tumor are better visualized on MRI. Echo-planar MRI can also show old hemorrhages not visible on CT scans. The location and appearance of the lesion as well as the history of the patient (eg, race, blood pressure, presence of known bleeding disorder, use of drugs) help determine the choice of additional diagnostic studies. Hypertensive ICH No further diagnostic tests are necessary in the severely hypertensive patient with a well circumscribed and homogeneous hematoma that is located in a typical location for hypertensive ICH (eg, putamen/internal capsule, caudate nucleus, thalamus, pons, or cerebellum); the clinician can be confident that the patient has a hypertensive hemorrhage in this circumstance (see "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis"). Similarly, a traumatic etiology can be diagnosed with confidence in the patient who has had recent trauma and lesions in the appropriate location and with the appearance of contusion and traumatic hemorrhages (eg, anterior and/or orbital frontal lobes and anterior-medial temporal lobes). Bleeding disorder Evaluation for a bleeding disorder (platelet count, prothrombin time, international normalized ratio (INR), activated partial thromboplastin time for all patients, and thrombin time and/or ecarin clotting time if the patient is known or suspected to be taking a direct thrombin inhibitor or a direct factor Xa inhibitor) should be performed in every patient with an intracranial hemorrhage, especially if the cause is not immediately https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 23/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate clear. A bleeding tendency can cause or contribute to bleeding initiated by other etiologies. (See "Approach to the adult with a suspected bleeding disorder".) Iatrogenic prescription of anticoagulants is the most common bleeding disorder contributing to brain hemorrhages. Oral anticoagulant-related intracerebral hemorrhage is often lobar [56]. Compared with spontaneous intracerebral hemorrhages, anticoagulant- related hemorrhages are larger and associated with greater hematoma expansion and mortality [56,57]. (See "Risks and prevention of bleeding with oral anticoagulants".) Lobar or atypical hemorrhage Amyloid angiopathy, bleeding into a tumor, and vascular malformations are likely etiologies of hemorrhages that are lobar or atypical in appearance. Cerebral amyloid angiopathy Hemorrhages related to amyloid angiopathy are usually lobar and have a predilection to cluster in posterior brain regions, including the parietal and occipital lobes. The hemorrhages are usually multiple. T2* weighted (susceptibility) MRI images may show the presence of old small hemorrhages ("microbleeds"). Patients with amyloid angiopathy are typically over the age of 60 years. (See "Cerebral amyloid angiopathy".) Vascular malformation or brain tumor Other bleeding lesions should be excluded in patients under the age of 60 if the blood pressure is not sufficiently elevated to make a firm diagnosis of hypertensive lobar hemorrhage. A repeat MRI after the blood has been reabsorbed (four to eight weeks) may show residual vascular malformations or a brain tumor. Vascular imaging using CT angiography (CTA) or MR angiography (MRA) of the intracranial circulation is useful as a screening test for vascular malformations and aneurysms. Contrast angiography by arterial catheterization may be necessary in patients with a CTA or MRA suggestive of vascular malformation. (See "Vascular malformations of the central nervous system" and "Brain arteriovenous malformations".) Cocaine use Patients with intracerebral hemorrhage after cocaine use (but not amphetamines) have a relatively high incidence of underlying aneurysms and vascular malformations. They require vascular imaging tests (eg, CTA, MRA, and/or conventional angiography). SOCIETY GUIDELINE LINKS https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 24/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate 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 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: Hemorrhagic stroke (The Basics)" and "Patient education: Stroke (The Basics)") Beyond the Basics topics (see "Patient education: Stroke symptoms and diagnosis (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS Classification Cerebrovascular disease is caused by one of several pathophysiologic processes ( table 1 and table 2) involving the blood vessels of the brain. (See 'Classification' above.) Initial evaluation Sudden loss of focal brain function is the core feature of the onset of ischemic stroke. However, patients with conditions other than stroke can present in a similar fashion ( table 3). The initial evaluation requires a rapid but broad assessment to stabilize vital signs, determine if intracranial hemorrhage is present, and decide if reperfusion therapy with intravenous thrombolysis ( table 4) or mechanical thrombectomy is warranted for patients with ischemic stroke. (See 'Initial general assessment' above and 'Is the patient a candidate for reperfusion?' above.) https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 25/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate Determining the type of stroke After completing the initial assessment, the goal of the subsequent evaluation is to determine the underlying pathophysiology of the stroke based upon the history, physical examination, and initial neuroimaging findings ( table 1). Certain constellations of symptoms and signs can suggest a specific ischemic process ( table 5). (See 'Determining a presumptive diagnosis of stroke subtype' above.) Confirming the diagnosis Confirming the precise pathophysiologic process is aided by more directed diagnostic testing, including cardiac studies and neurovascular imaging. (See 'Confirming the diagnosis' above.) Cardiac monitoring Cardiac monitoring for at least the first 24 hours after the onset of ischemic stroke is useful to look for arrhythmias. For patients with a cryptogenic ischemic stroke or transient ischemic attack (TIA) and no evidence of atrial fibrillation on electrocardiogram (ECG) and 24-hour cardiac monitoring, we suggest ambulatory cardiac monitoring for several weeks. All patients with suspected embolic stroke should have an echocardiogram. (See 'Cardiac evaluation' above and 'Echocardiography' above.) Blood tests A number of blood tests are indicated in patients with brain ischemia, including a complete blood count, platelet count, prothrombin time and partial thromboplastin time, and serum lipids. However, indications to test for hypercoagulable disorders are limited. Furthermore, it remains unclear if the inherited thrombophilias directly predispose to arterial stroke as they do to venous thrombosis. (See 'Blood tests' above.) Evaluation for a bleeding disorder in patients with hemorrhagic stroke In this setting, all patients require platelet count, prothrombin time, activated partial thromboplastin time, and thrombin time and/or ecarin clotting time if the patient is known or suspected to be taking a direct thrombin inhibitor or a direct factor Xa inhibitor. (See 'Evaluation of patients with intracerebral hemorrhage' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Caplan LR. Terms describing brain ischemia by tempo are no longer useful: a polemic (with apologies to Shakespeare). Surg Neurol 1993; 40:91. 2. Caplan LR. TIAs: we need to return to the question, 'What is wrong with Mr. Jones?'. Neurology 1988; 38:791. https://www.uptodate.com/contents/overview-of-the-evaluation-of-stroke/print 26/53 7/5/23, 12:17 PM Overview of the evaluation of stroke - UpToDate 3. Gorelick PB, Hier DB, Caplan LR, Langenberg P. Headache in acute cerebrovascular disease. Neurology 1986; 36:1445. 4. 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