eMedicine Specialties > Emergency Medicine > Neurology

Stroke, Ischemic

Author: Joseph U Becker, MD, Fellow, Global Health and International Emergency Medicine, Stanford University
Coauthor(s): Charles R Wira, MD, Assistant Professor, Department of Surgery, Section of Emergency Medicine, Yale School of Medicine; Jeffrey L Arnold, MD, FACEP, Chairman, Department of Emergency Medicine, Santa Clara Valley Medical Center
Contributor Information and Disclosures

Updated: Jun 19, 2009

Introduction

Background

Stroke is characterized by the sudden loss of blood circulation to an area of the brain, resulting in a corresponding loss of neurologic function. Also previously called cerebrovascular accident (CVA) or stroke syndrome, stroke is a nonspecific term encompassing a heterogeneous group of pathophysiologic causes, including thrombosis, embolism, and hemorrhage.

Strokes currently are broadly classified as either hemorrhagic or ischemic. Acute ischemic stroke refers to stroke caused by thrombosis or embolism and accounts for 85% of all strokes.

Emergency physicians (EPs) play a central role in the initial evaluation and management of patients with acute stroke. In 1992, a National Institute of Neurologic Disorders and Stroke (NINDS) t-PA Pilot Trial succeeded at enrolling patients within 90 minutes, which led to the NINDS requirement that investigators from emergency medicine be involved in the larger randomized trial. The NINDS recombinant tissue-type plasminogen activator (rt-PA) stroke study group first reported that the early administration of rt-PA benefited carefully selected patients with acute ischemic stroke.1

The trial had a positive outcome leading to the long-standing goal of t-PA administration within a 3-hour window for a patient deemed likely to benefit from thrombolytic intervention. This window has recently been expanded after recent evidence suggested benefit out to 4.5 hours. The collaboration between emergency physicians and neurologists was visionary and enabled the early enrollment of patients, which was an integral component of the positive results. Encouraged by this breakthrough study and the subsequent approval of t-PA for use in acute ischemic stroke by the US Food and Drug Administration (FDA), many medical professionals now newly consider acute ischemic stroke to be a medical emergency—one that may be amenable to treatment.

Building on the success of the NINDS trial and other studies, the European Cooperative Acute Stroke Study III (ECASS III) examined the use of thrombolytic therapy between 3 and 4.5 hours after the onset of symptoms. Thrombolytic therapy was again found to be efficacious in improving neurologic outcomes, suggesting a wider time window for the administration of thrombolytics.2   Based on this and other data, in May 2009, the American Heart Association and the American Stroke Association guidelines for the administration of rt-PA were revised to expand the treatment window from 3 to 4.5 hours.3 This indication has not yet been FDA approved.
 
Since EPs play a central role in the initial evaluation and treatment of patients with acute ischemic stroke, our understanding of its pathophysiology, clinical presentation, and ED evaluation is essential. The EP also must be completely familiar with the entire therapeutic armamentarium currently available to treat acute ischemic stroke, which includes supportive care, treatment of neurologic complications, antiplatelet therapy, glycemic control, blood pressure control, prevention of hyperthermia, and thrombolytic therapy.

In recent years, significant advances have also been made in stroke prevention, supportive care, and rehabilitation. With emerging evidence that the brief counsel of emergency physicians may impact primary and secondary prevention of disease processes, the emergency medicine specialty is also challenged to be vigilant in utilizing "teachable moments" or "brief negotiated interviews" to impact patient education, awareness, and compliance with established preventative treatments. Overall, when the direct costs (care and treatment) and the indirect costs (lost productivity) of strokes are considered together, the cost to US society is $43.3 billion per year.4

Pathophysiology

On the macroscopic level, ischemic stroke most often is caused by extracranial embolism or intracranial thrombosis, but it may also be caused by decreased cerebral blood flow. On the cellular level, any process that disrupts blood flow to a portion of the brain unleashes an ischemic cascade, leading to the death of neurons and cerebral infarction. Understanding this chain of events is important for understanding current therapeutic approaches.

Embolism

Emboli may arise from the heart, the extracranial arteries or, rarely, the right-sided circulation (paradoxical emboli) with subsequent passage through a patent foramen ovale. The sources of cardiogenic emboli include valvular thrombi (eg, in mitral stenosis, endocarditis, prosthetic valve), mural thrombi (eg, in myocardial infarction [MI], atrial fibrillation [AF], dilated cardiomyopathy, severe congestive heart failure [CHF]), and atrial myxoma. MI is associated with a 2-3% incidence of embolic stroke, of which 85% occur in the first month after MI.5

Thrombosis

Thrombotic stroke can be divided into large vessel, including the carotid artery system, or small vessel comprising the intracerebral arteries, including the branches of the Circle of Willis and the posterior circulation. The most common sites of thrombotic occlusion are cerebral artery branch points, especially in the distribution of the internal carotid artery. Arterial stenosis can cause turbulent blood flow, which can increase risk for thrombus formation, atherosclerosis (ie, ulcerated plaques), and platelet adherence; all cause the formation of blood clots that either embolize or occlude the artery.

Less common causes of thrombosis include polycythemia, sickle cell anemia, protein C deficiency, fibromuscular dysplasia of the cerebral arteries, and prolonged vasoconstriction from migraine headache disorders. Any process that causes dissection of the cerebral arteries also can cause thrombotic stroke (eg, trauma, thoracic aortic dissection, arteritis). Occasionally, hypoperfusion distal to a stenotic or occluded artery or hypoperfusion of a vulnerable watershed region between two cerebral arterial territories can cause ischemic stroke.

Flow disturbances

Stroke symptoms can result from inadequate cerebral blood flow due to decreased blood pressure (and specifically decreased cerebral perfusion pressure) or due to hematologic hyperviscosity due to sickle cell disease or other hematologic illnesses such as multiple myeloma and polycythemia vera. In these instances, cerebral injury may occur in the presence of damage to other organ systems.

Ischemic cascade

Within seconds to minutes of the loss of perfusion to a portion of the brain, an ischemic cascade is unleashed that, if left unchecked, causes a central area of irreversible infarction surrounded by an area of potentially reversible ischemic penumbra.

On the cellular level, the ischemic neuron becomes depolarized as ATP is depleted and membrane ion-transport systems fail. The resulting influx of calcium leads to the release of a number of neurotransmitters, including large quantities of glutamate, which, in turn, activates N -methyl-D-aspartate (NMDA) and other excitatory receptors on other neurons. These neurons then become depolarized, causing further calcium influx, further glutamate release, and local amplification of the initial ischemic insult. This massive calcium influx also activates various degradative enzymes, leading to the destruction of the cell membrane and other essential neuronal structures.6

Free radicals, arachidonic acid, and nitric oxide are generated by this process, which leads to further neuronal damage. Within hours to days after a stroke, specific genes are activated, leading to the formation of cytokines and other factors that, in turn, cause further inflammation and microcirculatory compromise.6 Ultimately, the ischemic penumbra is consumed by these progressive insults, coalescing with the infracted core, often within hours of the onset of the stroke.

The central goal of therapy in acute ischemic stroke is to preserve the area of oligemia in the ischemic penumbra. The area of oligemia can be preserved by limiting the severity of ischemic injury (ie, neuronal protection) or by reducing the duration of ischemia (ie, restoring blood flow to the compromised area).

The ischemic cascade offers many points at which such interventions could be attempted. Multiple strategies and interventions for blocking this cascade are currently under investigation. The timing of the restoration of cerebral blood flow appears to be a critical factor. Time also may prove to be a key factor in neuronal protection. Although still being studied, neuroprotective agents, which block the earliest stages of the ischemic cascade (eg, glutamate receptor antagonists, calcium channel blockers), are expected to be effective only in the proximal phases of presentation.

Frequency

United States

Incidence for first-time stroke is more than 700,000 per year, of which 20% of these patients will die within the first year after stroke. At current trends, this number is projected to jump to 1 million per year by the year 2050.7

International

Global incidence of stroke is unknown.

Mortality/Morbidity

Stroke is the third leading cause of death and the leading cause of disability in the United States.8

  • Cerebrovascular disease was the second leading cause of death worldwide in 1990, killing more than 4.3 million people.9
  • Cerebrovascular disease was also the fifth leading cause of lost productivity, as measured by disability-adjusted life years (DALYs). DALYs include years of productivity lost to either death or varying degrees of disability. In 1990, cerebrovascular disease caused 38.5 million DALYs throughout the world.10

Sex

Men are at higher risk for stroke than women. Additionally, women seem to respond better than men to interventions such as rt-PA.

Age

Although stroke often is considered a disease of elderly persons, one third of strokes occur in persons younger than 65 years.7

Clinical

History

  • Stroke should be considered in any patient presenting with an acute neurologic deficit (focal or global) or altered level of consciousness.
  • No historical feature distinguishes ischemic from hemorrhagic stroke, although nausea, vomiting, headache, and change in level of consciousness are more common in hemorrhagic strokes.
  • Common symptoms of stroke include abrupt onset of hemiparesis, monoparesis, or quadriparesis; monocular or binocular visual loss; visual field deficits; diplopia; dysarthria; ataxia; vertigo; aphasia; or sudden decrease in the level of consciousness.
  • Although such symptoms can occur alone, they are more likely to occur in combination.
  • Establishing the time of onset of these symptoms is of paramount importance when considering patients for possible thrombolytic therapy. An essential question is, "When was the patient last seen normal?" It is advisable for emergency clinicians to rapidly enlist the assistance of family members or relatives to establish time of onset and to identify other pertinent components of the patient's history of presentation. The median time from symptom onset to ED presentation ranges from 4-24 hours in the United States.11
  • Multiple factors contribute to delays in seeking care for symptoms of stroke.
    • Many strokes occur while patients are sleeping (also known as "wake-up" stroke) and are not discovered until the patient wakes.
    • Stroke can leave some patients too incapacitated to call for help.
    • Occasionally, a stroke goes unrecognized by the patient or their caregivers.7,12
  • Stroke mimics commonly confound the clinical diagnosis of stroke. One study reported that 19% of patients diagnosed with acute ischemic stroke by neurologists before cranial CT scanning actually had noncerebrovascular causes for their symptoms. The most frequent stroke mimics include seizure (17%); systemic infection (17%); brain tumor (15%); toxic-metabolic cause, such as hyponatremia (13%); and positional vertigo (6%). Miscellaneous disorders mimicking stroke include syncope, trauma, subdural hematoma, herpes encephalitis, transient global amnesia, dementia, demyelinating disease, myasthenia gravis, parkinsonism, hypertensive encephalopathy, and conversion disorders. A critical masquerading metabolic derangement not to be missed by providers is hypoglycemia.13,14

Physical

  • The goals of the physical examination include detecting extracranial causes of stroke symptoms, distinguishing stroke from stroke mimics, determining and documenting for future comparison the degree of deficit, and localizing the lesion.
  • The physical examination always includes a careful head and neck examination for signs of trauma, infection, and meningeal irritation.
  • A careful search for the cardiovascular causes of stroke requires examination of the ocular fundi (retinopathy, emboli, hemorrhage), heart (irregular rhythm, murmur, gallop), and peripheral vasculature (palpation of carotid, radial, and femoral pulses, auscultation for carotid bruit).
  • Patients with a decreased level of consciousness should be assessed to ensure that they are able to protect their airway.
  • Neurologic examination
    • With the availability of thrombolytic therapy for acute ischemic stroke in selected patients, the EP must be able to perform a brief but accurate neurologic examination on patients with suspected stroke syndromes.
    • The goals of the neurologic examination include (1) confirming the presence of a stroke syndrome (to be defined further by cranial CT scanning), (2) distinguishing stroke from stroke mimics, and (3) establishing a neurologic baseline should the patient's condition improve or deteriorate.
    • Essential components of the neurologic examination include evaluation of mental status and the level of consciousness, cranial nerves, motor function, sensory function, cerebellar function, gait, and deep tendon reflexes.
    • The skull and spine also should be examined, and signs of meningismus should be sought.
    • Central facial weakness from a stroke should be differentiated from the peripheral weakness of Bell palsy. With peripheral lesions (Bell palsy), the patient is unable to lift the eyebrows or wrinkle the forehead.
    • The 4 principal neuroanatomic stroke syndromes are caused by disruption of their respective cerebrovascular distributions. Correlating the patient's neurologic deficits with the expected site of arterial compromise may assist in confirming the diagnosis of stroke and interpreting the subsequent cranial CT scan.
    • Middle cerebral artery (MCA) occlusion commonly produces contralateral hemiparesis, contralateral hypesthesia, ipsilateral hemianopsia, and gaze preference toward the side of the lesion. Agnosia is common, and receptive or expressive aphasia may result if the lesion occurs in the dominant hemisphere. Neglect, inattention, and extinction of double simultaneous stimulation may occur in nondominant hemisphere lesions. Since the MCA supplies the upper extremity motor strip, weakness of the arm and face is usually worse than that of the lower limb.
    • Anterior cerebral artery occlusions primarily affect frontal lobe function and can result in dis-inhibition and speech perseveration, producing primitive reflexes (eg, grasping, sucking reflexes), altered mental status, impaired judgment, contralateral weakness (greater in legs than arms), contralateral cortical sensory deficits gait apraxia, and urinary incontinence.
    • Posterior cerebral artery occlusions affect vision and thought, producing contralateral homonymous hemianopsia, cortical blindness, visual agnosia, altered mental status, and impaired memory.
    • Vertebrobasilar artery occlusions are notoriously difficult to detect because they cause a wide variety of cranial nerve, cerebellar, and brainstem deficits. These include vertigo, nystagmus, diplopia, visual field deficits, dysphagia, dysarthria, facial hypesthesia, syncope, and ataxia. A hallmark of posterior circulation stroke is that there are crossed findings: ipsilateral cranial nerve deficits and contralateral motor deficits. This is contrasted to anterior stroke, which produces only unilateral findings.
    • Lacunar strokes result from occlusion of the small, perforating arteries of the deep subcortical areas of the brain. The infarcts are generally from 2-20 mm in diameter. The most common lacunar syndromes include pure motor, pure sensory, and ataxic hemiparetic strokes. Lacunar infarcts are often associated with partial or full occlusion of the parent feeding artery. Lacunar strokes account for 13-20% of all cerebral infarctions. Lacunar infarcts commonly occur in patients with small vessel disease, such as diabetes and hypertension. By virtue of their small size and well-defined subcortical location, lacunar infarcts do not lead to impairments in cognition, memory, speech, or level of consciousness.
    • Stroke scales
      • The National Institutes of Health Stroke Scale (NIHSS) is a rapid and reproducible tool for quantifying neurologic deficits in stroke patients and is useful for following the patient's early course. It is advisable to use this scale because it provides a means of quantitatively following a patient's course (ie, rapidly improving symptoms, or, escalation of symptoms secondary to either a bleed or cerebral edema).
      • The NIHSS is a 42-point scale with minor strokes usually being considered to have a score less than 5. A NIHSS score greater than 10 correlates with an 80% likelihood of visual flow deficits on angiography. Discretion must be also be used in assessing the magnitude of the clinical deficit; for instance, if a patient's only deficit is being mute, then the NIHSS score will be 3. Additionally, the scale does not measure some deficits associated with posterior circulation strokes (ie, vertigo, ataxia).15

Causes

  • Risk factors
    • Briefly assessing the risk factors for stroke may provide clues as to its cause and reinforce the clinical gestalt that clinicians may have in uncertain situations. Risk factors for ischemic stroke include advanced age (the risk doubles every decade), hypertension, smoking, heart disease (coronary artery disease, left ventricular hypertrophy, chronic atrial fibrillation), and hypercholesterolemia. Hyperhomocysteinemia has also been identified as an independent risk factor for all forms of stroke.16
    • Diseases associated with increased blood viscosity and the use of oral contraceptives place patients at higher risk for ischemic stroke.
    • Previous cerebrovascular disease is a risk factor for ischemic stroke.
  • Transient ischemic attack
    • Transient ischemic attack (TIA) has come to be known as a neurologic deficit that resolves within 24 hours. Roughly 80% resolve within 60 minutes. Tissue-based definitions are being proposed with magnetic resonance imaging.16
    • TIA can result from any of the aforementioned mechanisms of stroke. Data suggest that roughly 10% of patients with TIA suffer stroke within 90 days and half of these patients suffer stroke within 2 days.16,17

More on Stroke, Ischemic

Overview: Stroke, Ischemic
Differential Diagnoses & Workup: Stroke, Ischemic
Treatment & Medication: Stroke, Ischemic
Follow-up: Stroke, Ischemic
References
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References

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Further Reading

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Keywords

ischemic stroke, acute stroke, acute ischemic stroke, CVA, loss of neurologic function, cerebrovascular accident, stroke syndrome, thrombosis, embolism, hemorrhage, hemorrhagic stroke, cerebrovascular disease, neurologic complications, antithrombotic therapy, thrombolytic therapy, recombinant tissue-type plasminogen activator, rt-PA, t-PA, extracranial embolism

intracranial thrombosis, death of neurons, cerebral infarction, paradoxical emboli, cardiogenic emboli, valvular thrombi, mitral stenosis, endocarditis, prosthetic valves, mural thrombi, lipohyalinosis, pure motor strokes, pure sensory strokes, ataxic hemiparetic strokes, thrombotic occlusion, arterial stenosis, atherosclerosis, platelet adherence, polycythemia, sickle cell anemia, protein C deficiency, fibromuscular dysplasia of the cerebral arteries, prolonged vasoconstriction, thoracic aortic dissection, arteritis, acute neurologic deficit, altered level of consciousness, hemiparesis, monoparesis, quadriparesis, monocular visual loss, binocular visual loss

visual field deficits, diplopia, dysarthria, ataxia, vertigo, aphasia, carotid bruits, hypesthesia, hemianopsia, homonymous hemianopsia, agnosia, visual agnosia, receptive aphasia, expressive aphasia, cortical blindness, altered mental status, impaired memory, vertebrobasilar artery occlusions, nystagmus, dysphagia, facial hypesthesia, syncope, loss of pain sensation, loss oftemperaturesensation, smoking, heart disease, coronary artery disease, left ventricular hypertrophy, chronic atrial fibrillation, hypercholesterolemia, transient ischemic attacks, TIAs

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Contributor Information and Disclosures

Author

Joseph U Becker, MD, Fellow, Global Health and International Emergency Medicine, Stanford University
Joseph U Becker, MD is a member of the following medical societies: American College of Emergency Physicians, Emergency Medicine Residents Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Coauthor(s)

Charles R Wira, MD, Assistant Professor, Department of Surgery, Section of Emergency Medicine, Yale School of Medicine
Charles R Wira, MD is a member of the following medical societies: American College of Emergency Physicians, Society for Academic Emergency Medicine, and Society of Critical Care Medicine
Disclosure: Nothing to disclose.

Jeffrey L Arnold, MD, FACEP, Chairman, Department of Emergency Medicine, Santa Clara Valley Medical Center
Jeffrey L Arnold, MD, FACEP is a member of the following medical societies: American Academy of Emergency Medicine and American College of Physicians
Disclosure: Nothing to disclose.

Medical Editor

Richard S Krause, MD, Senior Faculty, Department of Emergency Medicine, State University of New York at Buffalo School of Medicine
Richard S Krause, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

J Stephen Huff, MD, Associate Professor, Emergency Medicine and Neurology, Department of Emergency Medicine, University of Virginia Health Sciences Center
J Stephen Huff, MD is a member of the following medical societies: American Academy of Emergency Medicine, American Academy of Neurology, American College of Emergency Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Rick Kulkarni, MD, Assistant Professor of Surgery, Section of Emergency Medicine, Yale-New Haven Hospital
Rick Kulkarni, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: WebMD Salary Employment

 
 
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