Cerebral infarction and transient ischemic attacks

Efficient evaluation is essential to beneficial intervention

Kelly D. Flemming, MD; Robert D. Brown Jr, MD

VOL 107 / NO 6 / MAY 15, 2000 / POSTGRADUATE MEDICINE

CME learning objectives

• To identify the most useful steps in evaluation of cerebral infarction and transient ischemic attacks (TIAs)
• To learn to localize ischemic events to the appropriate circulation (anterior versus posterior) and topography (subcortical versus cortical)
• To recognize signs of cardiac, large-vessel, small-vessel, and hematologic causes of cerebral infarction and TIAs

This is the second of four articles on stroke

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Preview: The goals of diagnostic evaluation in patients with cerebral infarction or transient ischemic attacks include (1) distinguishing these attacks from other causes of transient neurologic deficit, (2) localizing the event for determination of appropriate sequential workup, and (3) defining the potential mechanisms involved, specifically any that require treatment other than antiplatelet therapy. In this article, the authors describe how to accomplish these goals.
Flemming KD, Brown RD. Cerebral infarction and transient ischemic attacks: efficient evaluation is essential to beneficial intervention. Postgrad Med 107(6):55-83

In the past decade, advances in understanding of the basic mechanisms of stroke, diagnostic tools, and therapeutic options have introduced a new era of ischemic stroke management. As new interventions emerge, rapid but precise assessment of patients with cerebral infarction or transient ischemic attacks (TIAs) is paramount to safe and effective use of urgent therapeutic measures. In addition, logical, stepwise evaluation to clarify the mechanism of ischemia is required for appropriate secondary prevention and should be undertaken in all patients presenting with cerebral infarction or TIAs (1-3). (For current approaches to primary and secondary prevention, see the article by Dr Timothy Ingall in this issue.)

A broad framework is useful to guide diagnostic evaluation in these patients. Considering all potential mechanisms of stroke can help in building a differential diagnosis. Proximally to distally, mechanisms may be categorized as cardioembolic, large-vessel (extracranial or intracranial), small-vessel, and coagulation abnormalities (table 1).

Initial evaluation

History taking, physical examination, routine testing, and imaging procedures help localize cerebral infarction or TIA, provide insights regarding mechanism, and narrow differential diagnosis.

History taking
Obtaining a complete history from the patient or witnesses is an essential part of diagnosis and evaluation of stroke. Onset and evolution of neurologic symptoms provide clues to the mechanism of the ischemic event.

Maximal deficit at onset suggests an embolic event, and onset associated with the Valsalva maneuver may indicate a cardioembolic source due to a patent foramen ovale. A stuttering course of progressive deficit over several minutes to hours is more common in small-vessel disease or lacunar infarction.

Evolution of symptoms during an episode may help distinguish TIA from other causes of transient neurologic deficit, such as focal seizures, complicated migraine, migraine equivalents, or metabolic derangement (eg, hypoglycemia, hyperglycemia). Focal seizures and migraine equivalents usually "march" slowly, over the course of 1 to 15 minutes, along affected areas and are commonly associated with positive phenomena (eg, flashing lights, paresthesias). In contrast, symptoms of TIAs occur simultaneously in affected areas and usually include negative phenomena (lack of function, such as weakness, numbness, speech problems).

If the patient has multiple spells, it is important to clarify whether they are stereotyped or nonstereotyped. Stereotyped spells in a single vascular distribution suggest focal arterial stenosis, whereas nonstereotyped spells in multiple vascular territories suggest a proximal source (cardiac, aortic) of embolism.

Obtaining a past medical history that details cerebrovascular risk factors and cardiac status is important, because findings can guide a sequential diagnostic approach. Information should be sought regarding recent head or neck trauma, alcohol and drug use, oral contraceptive use, and migraine history. A family history of stroke or other thrombotic derangement may suggest an inherited stroke syndrome or coagulation disorder.

Physical examination
Physical examination should consist of thorough neurologic and neurovascular assessment, including blood pressure in both arms, pulse rate and regularity, temporal and peripheral pulses, cardiac evaluation, and examination for bruits over the supraclavicular space, neck, and eyes.

Several impairment scales have been developed to define stroke severity, monitor clinical course, and predict prognosis. These scales grade motor function, sensation, speech and language, and level of consciousness and are an easy, useful extension of physical examination. The most commonly used is the National Institutes of Health Stroke Scale (4) (table 2). This scale can help triage potential thrombolytic candidates as well as predict outcome. Use of intravenous tissue plasminogen activator should be avoided in patients with a score of less than 4 (unless there is global aphasia) or greater than 22 (because risk of hemorrhage is increased with such severe cerebral infarction). A score of 16 or more is predictive of severe disability or death (5,6).

Table 2. National Institutes of Health Stroke Scale*
Definition	Score and response**
1a. Level of consciousness	0 Alert 1 Not alert but aroused by stimulation 2 Not alert; requires repeated stimulation 3 Coma
1b. Ask patient month and age	0 Answers both correctly 1 Answers one correctly 2 Answers both incorrectly
1c. Ask patient to open and close eyes or hands	0 Obeys both correctly 1 Obeys one correctly 2 Obeys neither correctly
2. Best gaze (horizontal eye movement)	0 Normal 1 Partial gaze palsy 2 Forced eye deviation
3. Visual field testing	0 Normal visual fields 1 Partial hemianopia 2 Complete hemianopia 3 Cortical blindness
4. Facial paresis	0 Normal 1 Minor paralysis 2 Partial paralysis
5a. Right arm motor function	0 Normal 1 Drift 2 Some effort against gravity 3 No effort against gravity 4 No movement 9 Not testable
5b. Left arm motor function	0 Normal 1 Drift 2 Some effort against gravity 3 No effort against gravity 4 No movement 9 Not testable
6a. Right leg motor function	0 Normal 1 Drift 2 Some effort against gravity 3 No effort against gravity 4 No movement 9 Not testable
6b. Left leg motor function	0 Normal 1 Drift 2 Some effort against gravity 3 No effort against gravity 4 No movement 9 Not testable
7. Limb ataxia	0 None 1 In one limb 2 In two limbs
8. Sensory loss (pinprick test)	0 Normal 1 Mild decrease 2 Moderate to severe decrease
9. Best language	0 No aphasia 1 Mild to moderate aphasia 2 Severe aphasia 3 Mute
10. Dysarthria (read words)	0 Normal 1 Mild to moderate slurring 2 Nearly unintelligible or unable to speak 9 Intubated
11. Extinction and inattention	0 Normal 1 Hemi-inattention to one modality 2 Hemi-inattention to more than one modality
*Expanded version available at: http://www.stroke-site.org/Stroke%20Scales/nihscale.shtml. Accessed April 11, 2000. **A score of 16 or more predicts severe disability or death; a score of 6 or less predicts good recovery.

Laboratory and imaging studies
Emergency evaluation is aimed at determining whether the patient is eligible for acute intervention, including use of intravenous tissue plasminogen activator (table 3). Complete history taking, physical examination, and completion of routine testing are required before any intervention is considered. Initial testing should include a complete blood cell count (including platelets); measurement of electrolyte, glucose, and creatinine levels; prothrombin and partial thromboplastin times; electrocardiography; and chest radiology.

Table 3. Exclusion criteria for use of intravenous tissue plasminogen activator
Finding	Exclusion criteria
Present illness	More than 3 hr from onset of focal anterior or posterior circulation ischemic symptom Seizure(s) at onset of stroke
Past medical and surgical history	History of intracranial hemorrhage or bleeding diathesis Major ischemic stroke within 2 wk Lumbar puncture within 7 days Gastrointestinal or urinary tract hemorrhage within 21 days Major surgery within 14 days
Physical examination	Persistent blood pressure elevation (>185 mm Hg systolic, >110 mm Hg diastolic) despite antihypertensive therapy Rapidly resolving or minor deficit Obtunded or comatose condition
Laboratory study	Pregnancy Elevated activated partial thromboplastin time, use of heparin within 48 hr, international normalized ratio <1.7, or use of oral anticoagulant Platelet count <100,000/mm3 Glucose level <50 or >400 mg/dL
Computed tomography	Evidence of early infarction with focal mass effect, hemispheric swelling, or hemorrhage Intracranial tumor

In addition, noncontrast computed tomography (CT) is essential. CT is the preferred imaging procedure in the emergency department because of acquisition time, cost, and ability to distinguish acute bleeding from ischemia. CT is nearly 100% sensitive in detecting intraparenchymal hemorrhage and is 95% sensitive in detecting subarachnoid hemorrhage. It can aid in localization as well as provide insight regarding mechanism. For example, infarctions in multiple arterial territories suggest a proximal cardiac or aortic source. Subcortical localization may suggest lacunar infarction. CT findings are often normal in patients with acute ischemic symptoms, but infarction may evolve over the course of 6 to 48 hours in patients with persistent deficits.

Acute angiography to evaluate for potential intra-arterial thrombolysis may be considered in patients presenting less than 6 hours after an acute basilar artery occlusion or a suspected thrombus in the large-vessel anterior circulation (7).

Localization of ischemia

Precise localization of ischemia is not necessary, but determining answers to the following two questions is useful in diagnostic evaluation of stroke:

• Is the ischemia in the anterior (ie, carotid, middle cerebral, or anterior cerebral artery) or posterior (ie, vertebrobasilar) circulation? This information is important in determining which circulation to image (table 4).
• Is the ischemic event cortical or subcortical? Cortical events are more likely to be embolic or due to large-vessel abnormalities. The presence of aphasia, cortical sensory loss, and weakness involving the face and arm more than the leg (middle cerebral artery) or the leg more than the arm or face (anterior cerebral artery) suggest a cortical deficit. Face, arm, and leg weakness or numbness that is unilateral and of equal intensity in all locations suggests a subcortical lesion.

Table 4. Clinical symptoms of ischemic stroke in the anterior versus posterior circulation
Anterior circulation Motor dysfunction (contralateral face, contralateral extremities) Clumsiness Weakness Paralysis Slurred speech Loss of vision in ipsilateral eye Homonymous hemianopia Aphasia (dominant hemisphere) Sensory deficit (contralateral face, contralateral extremities) Numbness or loss of sensation Paresthesias	Posterior circulation Motor dysfunction (ipsilateral face, contralateral extremities) Clumsiness Weakness Paralysis Loss of vision in one or both homonymous visual fields Sensory deficit (ipsilateral face, contralateral extremities) Numbness or loss of sensation Paresthesias Typical signs but nondiagnostic in isolation Ataxia (gait or extremities) Vertigo Diplopia Dysphagia Dysarthria

Ideally, at this point in the workup, localization of the event to the anterior or posterior circulation and some insight into potential mechanisms should be possible. If hemorrhage is ruled out and clinical localization is established, further imaging is not essential. However, because of transient symptoms, poor description, or symptoms that may localize to either the anterior or posterior circulation, it may not be possible to localize the event (eg, isolated dysarthria). In addition, initial results on head CT are often negative, because signs of infarction may not be seen for several hours. Performing a second CT scan after symptoms have been present for 24 hours is a relatively inexpensive way to define the topography of infarction.

If small-vessel disease, brain stem events, or transient symptoms are of concern, magnetic resonance imaging (MRI) is superior in defining the ischemic site, especially if the diffusion-weighted imaging technique is used. Diffusion-weighted imaging is a relatively new and evolving MRI technique that detects random diffusion of water. When ischemic injury occurs, intracellular water increases where movement is restricted (cytotoxic edema), and diffusion-weighted imaging detects this change (figure 1: not shown).

Diffusion-weighted imaging has several advantages over conventional MR sequences. It can reveal focal ischemia within 2 to 3 hours of symptom onset. In patients with prior white matter changes or lacunar infarcts, it can distinguish a new lesion, because diffusion-weighted imaging irregularities normalize after about 2 weeks. In addition to showing symptomatic lesions, the technique may reveal silent ischemia in multiple arterial territories, thereby providing possible mechanistic clues (8).

Use of diffusion-weighted imaging along with perfusion-weighted imaging provides information about the penumbra (tissue at risk of ischemia but not yet infarcted). The finding of a larger abnormality on perfusion-weighted imaging than on diffusion-weighted imaging (ischemic tissue) suggests that additional tissue is still at risk because of lack of perfusion. The combination of the two imaging techniques may select patients who may benefit from acute intervention (9). Although at present availability and time constraints limit emergency use of MRI, future advances may alter these restrictions.

Large-vessel occlusive disease

Atherosclerosis of the large intracranial or extracranial arteries may result in ischemic stroke caused by artery-to-artery emboli, occlusion, or hemodynamic insufficiency. Other diseases of the large vessels (eg, dissection, inflammatory and noninflammatory vasculopathies) also may result in stroke. In clarifying stroke mechanism, evaluation of the large arteries is a suitable first step unless a known hematologic, cardiac, or small-artery disorder exists (figure 2: not shown). Cerebral infarction or TIA should be localized to the applicable circulation. Then, appropriate use of ultrasound, magnetic resonance angiography (MRA), computed tomographic angiography (CTA), conventional angiography, and transcranial Doppler ultrasonography can help identify the presence and cause of large-vessel disease.

Anterior circulation--extracranial disease
Carotid disease is responsible for 30% of cerebral infarctions or TIAs in the anterior circulation (10). Carotid endarterectomy is beneficial in preventing stroke in symptomatic patients with 70% or greater carotid artery stenosis (11), and moderate benefit has been shown in selected patients with 50% to 69% stenosis (12). Therefore, evaluation of the carotid arteries is the most logical and cost-effective way to begin in patients presenting with symptoms suggestive of anterior circulation cerebral infarction or TIA. Carotid ultrasound, MRA, CTA, and conventional angiography can be used to evaluate the extracranial carotid artery.

The combination of atrial fibrillation and carotid stenosis occurs in about 12% of elderly patients (13). It is often difficult to determine which factor is causative after an event in a single carotid territory, and management of the two problems differs. Therefore, it is reasonable to examine the carotid arteries in these patients as well.

Carotid ultrasound has an 89% specificity and a 93% sensitivity in determining 60% or greater stenosis and is less expensive than MRA (14). In addition, it can provide information on plaque morphology and ulceration. Ultrasound may be falsely positive for complete occlusion of the carotid artery in 2% of cases, so confirmatory testing with angiography may be necessary.

MRA has the potential to image the intracranial circulation simultaneously with the extracranial carotid circulation. Its sensitivity is similar to that of duplex ultrasound, but its specificity is slightly lower, with overestimation of the degree of stenosis. Unlike duplex ultrasound, conventional MRA has poor capability of discerning ulcers in plaques. However, the combination of MRA and carotid ultrasound has very high sensitivity and specificity for degree of stenosis. Newer MRA technologies are evolving, such as multiple overlapping slab acquisition and MRA with gadolinium bolus (15), which may prove to have higher sensitivity and specificity for stenosis and plaque characterization.

CTA is an evolving technology that correlates well with MRA in determining the degree of extracranial carotid stenosis and is superior to carotid ultrasound in determining complete occlusion (16). Disadvantages of CTA in the extracranial circulation include small risks of radiation and intravenous contrast reaction and limitations from bony artifact and overlapping jugular veins (17).

If carotid ultrasound or MRA reveals significant stenosis, further angiography (conventional or MRA) may be performed before carotid endarterectomy or carotid angioplasty and stenting are undertaken. However, many surgeons proceed on the basis of noninvasive imaging, precluding the need for standard angiography and its associated morbidity and cost.

Anterior circulation--intracranial disease
If screening of extracranial vessels and the heart produces negative findings and the patient is a candidate for anticoagulation, evaluation of the intracranial circulation with transcranial Doppler imaging, MRA, or CTA is warranted. MRA is 70% to 100% sensitive and specific in determining stenosis greater than 60% (18). However, as lumen size decreases, so does the resolution of MRA. Transcranial Doppler ultrasonography is a noninvasive technique for evaluating large intracranial vessels. Narrowing of the arteries results in localized increases in the mean and peak flow velocities. Transcranial Doppler imaging is less sensitive than MRA and may be associated with technical difficulties. However, the combination of MRA and transcranial Doppler imaging of the intracranial circulation is superior to either method alone.

CTA is 78% sensitive in detecting significant intracerebral artery stenosis and close to 100% sensitive in detecting intracerebral artery occlusion (19). It is similar to MRA in estimating the degree of intracranial stenosis. CTA's effectiveness may be limited in the petrous section of the carotid artery and the extracranial vertebral segments because bony structures subtracted from images can result in overestimation of stenosis.

If there is evidence of significant intracranial stenosis as a result of atherosclerosis, anticoagulation therapy may be considered on the basis of findings of the Warfarin-Aspirin Symptomatic Intracranial Disease study (20). However, conclusions of this retrospective study were nondefinitive. A prospective trial is ongoing.

Conventional angiography should be considered when noninvasive studies have unclear or conflicting results or suggest but do not confirm dissection, or when vasculitis or noninflammatory vasculopathy is a consideration. In addition, conventional angiography may be warranted in cryptogenic stroke in a patient under age 45 and to rule out the 2% of false-positives when carotid ultrasound suggests complete occlusion.

Conventional angiography is not without risk. Nonneurologic risks include acute renal failure, hypersensitivity or allergic reaction, and development of infection, hematoma, or pseudoaneurysm at the site of entry. The risk of transient neurologic deficit is about 0.5%, and complications may result from thrombus formation at the catheter tip, endothelial flap caused by the guidewire, and dissection. The risk of persistent neurologic deficit is about 0.1% (16).

Posterior circulation
In patients with an event in the posterior circulation, evaluation may include transcranial Doppler imaging, MRA, CTA, or conventional angiography. As in the anterior circulation, the combination of MRA and transcranial Doppler ultrasonography is superior to either technique alone. However, transcranial Doppler of the posterior circulation is difficult. Because of poor signal-to-noise ratio and inadequate depth of insonation, examination of the entire basilar artery is possible in only 30% of patients. The sensitivity of transcranial Doppler imaging in determining significant stenosis of the vertebrobasilar system is only 74% to 87%, and specificity is 80% (21). Sensitivity drops even further in detection of complete occlusion.

In general, in evaluation of the posterior circulation, MRA should be sufficient provided there are no contraindications to MRI. If contraindications are present, CTA could be considered.

Small-vessel occlusive disease

Lacunar infarctions account for 20% of all cerebral ischemic events. A lacunar stroke is a small (<1.5 cm) subcortical infarct resulting from occlusion of a penetrating end artery. Typical lacunar syndromes include pure motor hemiparesis, pure sensory stroke, ataxic hemiparesis, clumsy hand dysarthria, and sensorimotor stroke (table 5).

Table 5. Lacunar syndromes and sites of origin
Lacunar syndrome	Localization
Pure motor hemiparesis	Posterior internal capsule, corona radiata
Pure sensory stroke	Thalamus
Ataxic hemiparesis	Pons, posterior internal capsule or corona radiata
Clumsy hand dysarthria	Pons
Sensorimotor stroke	Posterior internal capsule and thalamus

Lipohyalinosis of the small arterioles caused by diabetes mellitus or hypertension is the most common underlying mechanism in lacunar infarction. However, on pathologic examination, not all lacunar infarctions have arterial abnormalities, which suggests that other mechanisms (eg, emboli) are possible. For this reason, further noninvasive diagnostic testing that is appropriate to potential localization of the infarct may be warranted. Further evaluation is particularly justified in patients who lack ischemic stroke risk factors, present with an atypical lacunar syndrome, have radiographic evidence of lacunae in an atypical territory, or have a typical lacunar syndrome but nonlacunar infarction on imaging (22).

Cardioembolic events

According to epidemiologic studies, only 20% of all strokes are clearly attributable to a cardioembolic source. However, on thorough evaluation, up to half of patients with cerebral infarction or TIA are found to have a possible cardiac source of embolism.

Cardiac sources of embolism are not all of equal risk for future embolic events (table 6). Major sources have been established to be causative risk factors for TIA and cerebral infarction and have definitive treatment strategies. Minor sources carry a potential risk of embolism and an uncertain risk of recurrent stroke, and frequently, management strategies are unclear. Minor risk sources often coexist with other mechanisms of cerebrovascular disease, so the contribution of the cardiac findings to stroke are often ambiguous (23).

Table 6. Cardioembolic sources of ischemic stroke

Major risk sources Atrial fibrillation Mitral valve stenosis Prosthetic cardiac valve Recent myocardial infarction Left ventricular thrombus Atrial myxoma Infectious endocarditis Nonischemic dilated cardiomyopathy Nonbacterial thrombotic endocarditis Sick sinus syndrome Minor risk sources Mitral valve prolapse Severe mitral annular calcification Patent foramen ovale Atrial septal aneurysm Calcific aortic stenosis Left ventricular regional wall motion abnormalities

Thorough history taking, physical examination, electrocardiography, and chest radiology should provide clues to most major cardiac sources of embolism. Echocardiography is a useful adjunct in selected patients. Its yield is high in patients with a history or examination findings suggestive of cardiac disease and patients with cortical stroke. However, findings may not change management. For example, a patient over age 60 with atrial fibrillation may have abnormalities on echocardiography (eg, spontaneous echocardiographic contrast, atrial septal aneurysm) but should receive anticoagulation therapy regardless of echocardiographic findings. In comparison, the yield of echocardiography is lower in patients without a prior history of cardiac disease but may be more likely to change management decisions.

Transesophageal echocardiography is more sensitive than transthoracic echocardiography in detecting potential sources of cardioembolism (23-25), specifically aortic atheromatous disease, left atrial thrombus, and patent foramen ovale. It is also superior to transthoracic echocardiography in detection of potential cardiac sources in patients without a history of cardiac disease (24). However, as mentioned, findings of minor cardiac risk are often of uncertain significance, and detection may not change management. This has led to questions in cost-effective cardiac workup (24,26). While some authorities do not recommend echocardiography in patients without a history of cardiac disease, others suggest that completing transesophageal echocardiography in every patient with ischemic stroke is a more cost-effective approach (26).

Given these considerations, a standard 12-lead electrocardiogram and a chest film should be obtained in all patients presenting with possible ischemic stroke. If evidence of atrial fibrillation is found, echocardiography is not indicated unless endocarditis is suspected or the patient is having elective cardioversion. In addition, echocardiography is not indicated in patients who are clearly not candidates for anticoagulation therapy and in whom endocarditis is not a consideration.

Transesophageal echocardiography should be done in young patients with cryptogenic stroke or with TIA or cerebral infarction in multiple arterial distributions and in patients with history, physical examination, or routine test findings suggestive of cardiac disease (25). Echocardiography also should be considered in patients with cortical cerebral infarction or TIA when noninvasive arterial studies produce negative results. As new studies determine the best treatments for aortic atheromatous disease, patent foramen ovale, and atrial septal aneurysm, indications for echocardiography may become more clearly delineated.

Ambulatory continuous electrocardiographic (Holter) monitoring or continuous telemetry may be useful in patients with a history of palpitations or paroxysmal atrial fibrillation and in young people with cryptogenic cerebral infarction or TIA. Routine monitoring in unselected patients has not proved useful.

Blood cultures or antinuclear antibody testing should be pursued if bacterial or nonbacterial endocarditis is a clinical consideration.

Hematologic disorders

Hematologic disorders are rare causes of arterial cerebral infarction (27). Large case-control studies in unselected patients with stroke have not been performed. Therefore, information about prevalence, stroke recurrence, and therapy is based on small series of predominantly young patients. Extensive hematologic evaluation in all patients presenting with cerebral infarction or TIA yields little additional information and greatly increases cost.

Thorough history taking, physical examination, and routine laboratory testing select those patients who should undergo further evaluation. History taking should include a detailed review of prior thrombotic events, personal or family history of miscarriages, and family history of coagulopathies or thrombotic events. Concurrent medical problems (eg, liver dysfunction, renal disease, malignant tumor, malnutrition, infection) and certain procedures (eg, hemodialysis, plasmapheresis) may cause acquired coagulopathy and should be investigated.

Physical examination should focus on skin signs of coagulation disorder (eg, purpura, livedo reticularis, lupus manifestations).

Laboratory evaluation that should be performed in all patients at the time of presentation includes complete blood cell count, prothrombin and partial thromboplastin times, a VDRL test, erythrocyte sedimentation rate, routine blood chemistries, and cholesterol and triglyceride levels. The fasting serum homocysteine level should also be obtained in patients with premature atherosclerosis or with cerebral infarction or TIA of unclear cause despite other evaluation. Whereas lipid levels remain stable after acute cerebral infarction, homocysteine levels may drop in the acute phase (28). For this reason, follow-up homocysteine measurements may be necessary if the initial level is low.

Further investigation may be required in patients with unexplained stroke, prior thrombotic episodes, family history of thrombosis, or abnormal findings on routine laboratory testing (29). Laboratory screening for coagulopathy in these selected patients may include hemoglobin electrophoresis and evaluation of antithrombin III, protein C, protein S, anticardiolipin antibody, lupus anticoagulant, factor V Leiden, prothrombin 20210A, and thrombin for dysfibrinogenemia. If levels are initially low, follow-up measurement of protein C, protein S, and antithrombin III may be necessary several months after an acute cerebral infarction, because acquired causes of coagulopathy may normalize, eliminating the need for long-term anticoagulation therapy.

Summary and conclusion

Rapid but precise evaluation of patients presenting with cerebral infarction is essential to determine immediate intervention. Initial assessment should include history taking, physical examination, routine laboratory testing, electrocardiography, chest radiology, and noncontrast head CT. Localizing the event to the appropriate arterial circulation (anterior versus posterior) and determining topography (subcortical versus cortical) guide sequential testing to ascertain the mechanism of cerebral infarction. Diagnostic testing focuses on selectively identifying potential cardiac, large-vessel, small-vessel, or hematologic causes. Although diagnostic tools are evolving, 15% of cerebral infarctions still have an unknown cause or multiple potential sources (30).

References

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Dr Flemming is a cerebrovascular fellow and Dr Brown is associate professor, department of neurology, Mayo Medical School, Rochester, Minnesota. Correspondence: Robert D. Brown Jr, MD, Department of Neurology, Mayo Medical School, 200 First St SW, Rochester, MN 55905.

Symposium Index

• STROKE: Introduction to a four-article symposium by David W. Dodick, MD, FRCPC
• PREVENTING ISCHEMIC STROKE: Current approaches to primary and secondary prevention by Timothy J. Ingall, MBBS, PhD, FRACP
• CEREBRAL INFARCTION AND TRANSIENT ISCHEMIC ATTACKS: Efficient evaluation is essential to beneficial intervention by Kelly D. Flemming, MD, Robert D. Brown Jr, MD
• MANAGEMENT OF ACUTE ISCHEMIC STROKE: What is the role of tPA and antithrombotic agents? by James F. Meschia, MD
• CAROTID ENDARTERECTOMY: Which patients can benefit? by Timothy J. Ingall, MBBS, PhD, FRACP, David W. Dodick, MD, FRCPC, Richard S. Zimmerman, MD

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