AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Stroke is the clinical term for acute loss of perfusion to vascular territory of the brain, resulting in ischemia and a corresponding loss of neurologic function. Classified as either hemorrhagic or ischemic, strokes typically manifest with the sudden onset of focal neurologic deficits, such as weakness, sensory deficit, or difficulties with language. Ischemic strokes have a heterogeneous group of causes, including thrombosis, embolism, and hypoperfusion, whereas hemorrhagic strokes can be either intraparenchymal or subarachnoid.

Only in recent years have advances allowed for significant improvment in the outcome of this devastating disease. A new era in acute stroke care began in 1995, when the National Institute of Neurologic Disorders and Stroke (NINDS) tissue plasminogen activator (t-PA) Stroke Study Group first presented data indicating that early administration of t-PA benefited a carefully selected patient group with acute ischemic stroke (AIS). Currently, t-PA is the only approved therapy for AIS, and despite proven efficacy, utilization rates of rt-PA remain low.

Pathophysiology

The brain is the most metabolically active organ in the body. While representing only 2% of the body's mass, it requires 15-20% of the total resting cardiac output to provide the necessary glucose and oxygen for its metabolism. Ischemic strokes result from events that limit or stop blood flow, such as embolism, thrombosis in situ, or relative hypoperfusion. As blood flow decreases, neurons cease functioning, and irreversible neuronal ischemia and injury begin at blood flow rates of less than 18 mL/100 mg/min.

Ischemic cascade

The processes involved in stroke injury at the cellular level are referred to as the ischemic cascade. Many factors are thought to result in cell death and dysfunction, and others are being discovered at a rapid rate. Within seconds to minutes of the loss of glucose and oxygen delivery to neurons, the cellular ischemic cascade begins. This is a complex process that begins with cessation of the normal electrophysiologic function of the cells. The resultant neuronal and glial injury produces edema in the ensuing hours to days after stroke, causing further injury to the surrounding tissues.

Ischemic penumbra

An acute vascular occlusion produces heterogeneous regions of ischemia in the dependent vascular territory. The quantity of local blood flow is comprised of any residual flow in the major arterial source and the collateral supply, if any. Regions of the brain without significant flow are referred to collectively as the core, and these cells are presumed to die within minutes of stroke onset. Zones of decreased or marginal perfusion are collectively called the ischemic penumbra. Tissue in the penumbra can remain viable for several hours because of marginal tissue perfusion, and currently studied pharmacologic interventions for preservation of neuronal tissue target this penumbra.

Administration of t-PA to the patient with an acute stroke attempts to establish revascularization so that cells in the penumbra can be rescued before irreversible injury occurs. Restoring blood flow can mitigate the effects of ischemia only if performed quickly. Neuroprotective strategies are intended to preserve the penumbral tissues and extend the time window for revascularization techniques. While none to date have shown broad benefit in clinical trials, several trials are underway.

Mechanisms of stroke

Embolic strokes

Emboli may either be of cardiac or arterial origin. Cardiac sources include atrial fibrillation, recent myocardial infarction, prosthetic valves, native valvular disease, endocarditis, mural thrombi, dilated cardiomyopathy, or patent foramen ovale allowing passage of venous circulation emboli. Arterial sources are atherothrombolic or cholesterol emboli that develop in the arch of the aorta and in the extracranial arteries (ie, carotid and vertebral arteries). Embolic strokes tend to have a sudden onset, and neuroimaging may demonstrate previous infarcts in several vascular territories or calcific emboli.

Thrombotic strokes

Thrombotic strokes include large-vessel strokes and small-vessel or lacunar strokes. They are due to in situ occlusions on atherosclerotic lesions in the carotid, vertebrobasilar, and cerebral arteries, typically proximal to major branches. Thrombogenic factors may include injury to and loss of endothelial cells exposing the subendothelium and platelet activation by the subendothelium, activation of the clotting cascade, inhibition of fibrinolysis, and blood stasis. Thrombotic strokes are generally thought to originate on ruptured atherosclerotic plaques. Intracranial atherosclerosis may be the cause in patients with widespread atherosclerosis. In other patients, especially younger patients, other causes should be considered, including hypercoagulable states (eg, antiphospholipid antibodies, protein C deficiency, protein S deficiency), sickle cell disease, fibromuscular dysplasia, arterial dissections, and vasoconstriction associated with substance abuse.

Lacunar stroke

Lacunar strokes represent 20% of all ischemic strokes. They occur when the penetrating branches of the middle cerebral artery (MCA), the lenticulostriate arteries, or the penetrating branches of the circle of Willis, vertebral artery, or basilar artery become occluded. Causes of lacunar infarcts include microatheroma, lipohyalinosis, fibrinoid necrosis secondary to hypertension or vasculitis, hyaline arteriosclerosis, and amyloid angiopathy. The great majority are related to hypertension.

Watershed infarcts

These infarcts, also known as border zone infarcts, develop from relative hypoperfusion in the most distal arterial territories and can produce bilateral symptoms. Frequently, these occur perioperatively or in situations of prolonged hypotension.

Frequency

United States

Approximately 705,000 strokes occur each year, including both new and recurrent cases. Of these strokes, approximately 625,000 are ischemic strokes. By the year 2025, the annual number of strokes is expected to reach 1 million. Currently, more than 4.4 million people in the United States are stroke survivors.

International

As in the United States, stroke is the third leading cause of death in the industrialized countries of Europe and the leading cause of adult disability. The global incidence of stroke will only increase, since the population older than 65 years will rise from 390 million now to 800 million by 2025, representing 10% of the total population.

Mortality/Morbidity

• Stroke is the third leading cause of death in the United States (60.2 per 100,000), following cardiac and cancer-related deaths. Approximately 29% of patients die within 1 year following a stroke; this percentage rises in patients older than 65 years. Worldwide in 1990, more than 4.3 million people died of cerebrovascular disorders.
• Stroke is the leading cause of disability in the United States; 31% of stroke survivors assistance with daily living, 20% need some type of assistance for walking, and 16% require admission to a long-term care facility. Furthermore, at least one third of stroke survivors have depression as well as many of their care providers.
• The direct costs (ie, treatment) and indirect costs (ie, lost productivity) of stroke in the United States are approximately $43 billion/year.

Race

In the United States, stroke has a higher incidence in the black population than in the white population.

• In black males, the incidence is approximately 93 per 100,000, with a death rate of approximately 51%. In black females, incidence is 79 per 100,000 with a death rate of 39.2%. Young blacks have a 2-5 times greater risk of ischemic stroke than the white population of the same age, and they are 2.5 times more likely to die of stroke. Blacks have an age-adjusted risk of death from stroke that is 1.49 times that of whites.
• White males have a stroke incidence of 62.8 per 100,000, with death being the final outcome in 26.3% of cases, compared with women who have a stroke incidence of 59 per 100,000 and a death rate of 39.2%.
• Hispanics have a lower overall incidence of stroke than whites and blacks but more frequent lacunar strokes and stroke at an earlier age.

Sex

In patients younger than 60 years, the incidence of stroke is greater in males (3:2 ratio).

Age

• Stroke can occur in patients of all ages, including children.
• Risk of stroke increases with age, especially in patients older than 64 years, in whom 75% of all strokes occur.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

• The American Stroke Association advises the public to be aware of the symptoms of stroke that are easily recognized and to call 911 immediately. These symptoms include the following:
• • Sudden numbness or weakness of face, arm, or leg, especially on one side of the body
  • Sudden confusion, difficulty in speaking or understanding
  • Sudden deterioration of vision of one or both eyes
  • Sudden difficulty in walking, dizziness, and loss of balance or coordination
  • Sudden, severe headache with no known cause
• A focused medical history aims to identify risk factors for atherosclerotic and cardiac disease, including hypertension, diabetes mellitus, tobacco use, high cholesterol, and a history of coronary artery disease, coronary artery bypass, or atrial fibrillation. Consider stroke in any patient presenting with acute neurological deficit or any alteration in level of consciousness. Common signs of stroke include the following:
• • Acute hemiparesis or hemiplegia
  • Complete or partial hemianopia, monocular or binocular visual loss, or diplopia
  • Dysarthria or aphasia
  • Ataxia, vertigo, or nystagmus
  • Sudden decrease in consciousness
• In younger patients, elicit a history of recent trauma, coagulopathies, illicit drug use (especially cocaine), migraines, or use of oral contraceptives.
• Family members, bystanders, and especially prehospital personnel can provide invaluable information regarding the time and events surrounding the onset of symptoms or when the patient was last seen normal.
• Establishing time of onset is especially critical when thrombolytic therapy is an option. If the patient awakens with the symptoms, then the time of onset is defined as the time the patient was last seen without symptoms. Family members, coworkers, or bystanders may be required to help establish the exact time of onset, especially in right hemispheric strokes accompanied by neglect or left hemispheric strokes with aphasia.
• If the patient is a candidate for thrombolytic therapy, a thorough review of the inclusion and exclusion criteria must be performed. The exclusion criteria largely focus on identifying risk of hemorrhagic complication associated with thrombolytic use.

Physical

Physical examination is directed toward 5 major areas: (1) assessing the airway, breathing, and circulation (ABCs), (2) defining the severity of the patient's neurologic deficits, (3) identifying potential causes of the stroke (4) identifying potential stroke mimics, and (5) identifying comorbid conditions.

• The physical examination must encompass all the major organ systems, starting with the ABCs and the vital signs. Patients with stroke, especially hemorrhagic, can clinically deteriorate quickly; therefore, constant reassessment is critical. Ischemic strokes, unless large or involving the brainstem, do not tend to cause immediate problems with airway patency, breathing, or circulation compromise. On the other hand, patients with intracerebral or subarachnoid hemorrhage frequently require intervention for both airway protection and ventilation.
• • Vital signs, while nonspecific, can point to impending clinical deterioration and may assist in narrowing the differential diagnosis. Many patients with stroke are hypertensive at baseline, and their blood pressure may become more elevated after stroke. While hypertension at presentation is common, blood pressure decreases spontaneously over time in most patients. Acutely lowering blood pressure has not proven to be beneficial in these stroke patients in the absence of signs and symptoms of associated malignant hypertension, AMI, congestive heart failure (CHF), or aortic dissection.
  • Head, ears, eyes, nose, and throat examination: A careful examination of the head and neck is essential. Contusions, lacerations, and deformities may suggest trauma as the etiology for the patient's symptoms. Auscultation of the neck may elicit a bruit, suggesting carotid disease as the cause of the stroke.
  • Cardiac: Cardiac arrhythmias, such as atrial fibrillation, are found commonly in patients with stroke. Similarly, strokes may occur concurrently with other acute cardiac conditions, such as AMI and acute CHF; thus, auscultation for murmurs and gallops is recommended.
  • Extremities: Carotid or vertebrobasilar dissections, and less commonly, thoracic aortic dissections, may cause ischemic stroke. Unequal pulses or blood pressures in the extremities may reflect the presence of aortic dissections.
• The neurologic examination must be thorough, and yet this is perhaps the weakest area of training for primary care and emergency providers. A directed and focused examination can be performed in minutes and not only provides great insight into the potential cause of the patient's deficits, but also helps determine the intensity of treatment required.
• A useful tool in measuring neurological impairment is the National Institutes of Health Stroke Scale (NIHSS). This scale can be used easily, is reliable and valid, provides insight to the location of vascular lesions, and can be correlated with outcome in patients with ischemic stroke. It focuses on 6 major areas of the neurologic examination: (1) level of consciousness, (2) visual function, (3) motor function, (4) sensation and neglect, (5) cerebellar function, and (6) language. The NIHSS is used most by stroke teams. It enables the consultant to rapidly determine the severity and possible location of the stroke. A patient's score on the NIHSS is strongly associated with outcome, and it can help identify those patients who are likely to respond to thrombolytic therapy and those who are at higher risk to develop hemorrhagic complications of thrombolytic use.

  Table 1. NIH Stroke Scale (For a Printable Version, See Multimedia file 1.)

  	Category	Description	Score
  1a	Level of consciousness (LOC)	Alert Drowsy Stuporous Coma	0 1 2 3
  1b	LOC questions (month, age)	Answers both correctly Answers 1 correctly Incorrect on both	0 1 2
  1c	LOC commands (open-close eyes, grip and release hand)	Obeys both correctly Obeys 1 correctly Incorrect on both	0 1 2
  2	Best gaze (follow finger)	Normal Partial gaze palsy Forced deviation	0 1 2
  3	Best visual (visual fields)	No visual loss Partial hemianopia Complete hemianopia Bilateral hemianopia	0 1 2 3
  4	Facial palsy (show teeth, raise brows, squeeze eyes shut)	Normal Minor Partial Complete	0 1 2 3
  5	Motor arm left* (raise 90°, hold 10 seconds)	No drift Drift Cannot resist gravity No effort against gravity No movement	0 1 2 3 4
  6	Motor arm right* (raise 90°, hold 10 seconds)	No drift Drift Cannot resist gravity No effort against gravity No movement	0 1 2 3 4
  7	Motor leg left* (raise 30°, hold 5 seconds)	No drift Drift Cannot resist gravity No effort against gravity No movement	0 1 2 3 4
  8	Motor leg right* (raise 30°, hold 5 seconds)	No drift Drift Cannot resist gravity No effort against gravity No movement	0 1 2 3 4
  9	Limb ataxia (finger-nose, heel-shin)	Absent Present in 1 limb Present in 2 limbs	0 1 2
  10	Sensory (pinprick to face, arm, leg)	Normal Partial loss Severe loss	0 1 2
  11	Extinction/neglect (double simultaneous testing)	No neglect Partial neglect Complete neglect	0 1 2
  12	Dysarthria (speech clarity to "mama, baseball, huckleberry, tip-top, fifty-fifty")	Normal articulation Mild to moderate dysarthria Near to unintelligible or worse	0 1 2
  13	Best language** (name items, describe pictures)	No aphasia Mild to moderate aphasia Severe aphasia Mute	0 1 2 3
  	Total	—	0- 42

  
  * For limbs with amputation, joint fusion, etc, score 9 and explain.
  ** For intubation or other physical barriers to speech, score 9 and explain. Do not add 9 to the total score.

Causes

Risk factors for ischemic stroke comprise both modifiable and nonmodifiable etiologies. Identification of risk factors in each patient can uncover clues to the cause of the stroke and the most appropriate treatment and secondary prevention plan.

• Nonmodifiable risk factors include age, race, sex, ethnicity, history of migraine headaches, sickle cell disease, fibromuscular dysplasia, and heredity.
• Modifiable risk factors include the following:
• • Hypertension (the most important)
  • Diabetes mellitus
  • Cardiac disease - Atrial fibrillation, valvular disease, mitral stenosis, and structural anomalies allowing right to left shunting, such as a patent foramen ovale and atrial and ventricular enlargement
  • Hypercholesterolemia
  • Transient ischemic attacks (TIAs)
  • Carotid stenosis
  • Hyperhomocystinemia
  • Lifestyle issues - Excessive alcohol intake, tobacco use, illicit drug use, obesity, physical inactivity
• Oral contraceptive use

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Other Problems to be Considered

Intracranial Abscess
Bell Palsy
Botulism
Encephalitis
Hyperglycemia
Hypertensive urgency/emergency
Hypoglycemia
Psychiatric disorders/conversion disorder
Seizure
Spinal injury
Uremia
Ingestions (eg, ethanol)
Intracranial neoplasm

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• Laboratory evaluation of the patient with ischemic stroke should be driven by comorbid illnesses as well as the potential acute stroke.
• • Glucose and electrolyte tests: Hypoglycemia is the most common electrolyte abnormality that produces strokelike symptoms. It is easily corrected, and correction leads to rapid resolution of symptoms. Electrolyte disorders, hyperglycemia, hypoglycemia, and uremia should be considered as the cause of ongoing mental and physical deficits while pursuing the diagnosis of stroke.
  • Complete blood count: CBC provides key information regarding hemoglobin and hematocrit, as well as platelet count, which is important in fibrinolytic candidates. Additionally, sickle cell disease, polycythemia, and thrombocytosis increase the risk for stroke.
  • Prothrombin time (PT) and activated partial thromboplastin time (aPTT) tests: Many patients with acute stroke are on anticoagulants, such as heparin or warfarin. Treatment decisions, such as thrombolytic use, require data on coagulation status. An elevated international normalized ratio (INR) may preclude patients from receiving thrombolytics.
  • Cardiac enzymes: Not infrequently patients with acute stroke also experience acute myocardial ischemia. In addition to ECG findings, increased cardiac enzymes might suggest concomitant cardiac injury.
  • Arterial blood gas (ABG) analysis: Although infrequent in patients with suspected hypoxemia, ABG defines the severity of hypoxemia and may detect acid-base disturbances. If considering thrombolytics, arterial punctures should be avoided unless absolutely necessary.
• Additional laboratory tests are tailored to the individual patient. They may include rapid plasma reagent (RPR), toxicology screen, fasting lipid profile, sedimentation rate, pregnancy test, antinuclear antibody (ANA), rheumatoid factor, and homocysteine. In select patients with possible hypercoagulable states, protein C, protein S, antithrombin III, and Factor V Leiden testing may be required. These blood abnormalities mainly contribute to venous thrombosis but may be relevant in patients with cardiac shunts or cerebral venous thromboses. The anticardiolipin antibody and the lupus inhibitor, both antiphospholipid antibodies, correlate with arterial stroke, as well as with deep venous thrombosis, pulmonary embolism, myocardial infarction, and miscarriage.

Imaging Studies

• CT is, and probably will likely remain for the next decade, the most commonly used form of neuroimaging in the acute evaluation of patients with apparent acute stroke. Noncontrast CT is very sensitive in detecting intracerebral and subarachnoid hemorrhage, as well as subdural hematomas. Treatment algorithms are dichotomous for the presence of intracranial blood, and recanalization strategies for ischemic stroke require the absence of intracranial hemorrhage on CT scan.
• • Although CT is not very sensitive for early ischemia (<6 h), several findings can suggest ischemic changes relatively early in the time course of stroke. Loss of the gray-white matter interface, loss of sulci, and loss of the insular ribbon are subtle signs of early ischemia.
  • Early mass effect and areas of hypodensity suggest irreversible injury and identify patients at higher risk of postfibrinolysis hemorrhage. Significant hypodensity on the baseline scan should prompt a question about the time of onset. Hypodensity in an area greater than one third of the MCA distribution is considered by many a contraindication for thrombolytics.
  • A dense MCA sign suggests a clot in the MCA, potentially producing large hemispheric strokes.
  • CT may demonstrate other causes of the patient's symptoms, including neoplasm, hemorrhagic stroke, epidural and subdural hemorrhage, aneurysm, abscess, arteriovenous malformation, and hydrocephalus.
  • CT angiography may demonstrate the location of vascular occlusion. CT perfusion studies are capable of producing perfusion images and together with CT angiography may become more available and utilized in the acute evaluation of stroke patients.
• MRI with magnetic resonance angiography (MRA) is a major advance in the neuroimaging of stroke. MRI not only provides great structural detail but also can demonstrate impaired metabolism. A major limitation of MRI is its availability and the skills required to interpret the images.
• • Diffusion-weighted MRI (DW-MRI) can detect areas of ischemic brain injury earlier in the evolution of ischemia than standard T1/T2-weighted MRI images or CT scan by detecting changes in water molecule mobility.
  • Perfusion MRI (PW-MRI) uses injected contrast material to demonstrate areas of decreased perfusion. These sequences in combination with DW-MRI yields areas of diffusion-weighted imaging/perfusion-weighted imaging (DW-MRI/PW-MRI) mismatch, theoretically identifying potentially salvageable tissues.
  • MRA: This noninvasive technique demonstrates vascular anatomy and occlusive disease of the head and neck.
• Digital subtraction angiography is considered the definitive method for demonstrating vascular lesions, including occlusions, stenoses, dissections, and aneurysms. Cerebrovascular angiography not only provides useful information on the extracranial and intracranial vasculature, but also allows for intra-arterial therapies, both intra-arterial thrombolytics and investigational catheter devices. Angiography requires special facilities and a skilled operator and it carries a stroke risk of 1%.
• MR spectroscopy is an experimental technique that may have potential for distinguishing areas of salvageable neurons from those that are injured irreversibly.
• Carotid duplex scanning is one of the most useful tests in evaluating patients with stroke. Increasingly, it is being performed earlier in the evaluation, not only to define the cause of the stroke but also to stratify patients for either medical management or carotid intervention if they have carotid stenoses. Patients with symptomatic critical stenoses on carotid duplex scanning may require anticoagulation before intervention is performed.
• Transcranial Doppler ultrasonography (TCD) can assess the location and degree of arterial occlusions in the extracranial carotid and large intracranial vessels, including the middle cerebral and vertebrobasilar arteries. It can also be used to detect restoration of flow after thrombolytic therapy, and the recent Combined Lysis of Thrombus in Brain Ischemia Using Transcranial Ultrasound and Systemic TPA (CLOTBUST) study has suggested that TCD may even facilitate recanalization.
• The use of single-photon emission computed tomography (SPECT) in stroke is still relatively experimental and available only at select institutions; it can theoretically define areas of altered regional blood flow.

Other Tests

• Echocardiography: Transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) are useful tools in evaluating patients with possible cardiogenic sources of their stroke. TEE is more sensitive than TTE and can evaluate the aortic arch and thoracic aorta for plaques or dissections.
• Electrocardiography/ECG: Stroke and cardiovascular disease share many risk factors. ECG may demonstrate cardiac arrhythmias, such as atrial fibrillation, or may indicate acute ischemia. All patients with stroke should have an ECG as part of their initial evaluation.
• Chest radiography should be performed when clinically indicated.

Procedures

• Lumbar puncture (LP): An LP is required to rule out meningitis or subarachnoid hemorrhage when the CT scan is negative but the clinical suspicion remains high.

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical Care

Medical care for AIS occurs on a continuum, beginning in the prehospital setting and ending at home after discharge. Stroke centers and organized protocols for the acute and in-house treatment of stroke patients have been shown to decrease morbidity and mortality associated with stroke.

• Prehospital care personnel are critical elements in the AIS chain of survival. Emergency medical services (EMS) personnel should begin with the ABCs and, once the patient's condition is stable, should perform a more directed assessment and administer supportive treatment.
  
  
  • Prehospital stroke assessment tools, such as the Cincinnati Prehospital Stroke Scale or Los Angeles Prehospital Stroke Scale, identify patients with potential stroke. Providing supplemental oxygen when indicated, establishing intravenous lines, measuring serum glucose, and administering glucose in hypoglycemic patients are elements of prehospital stroke care.
  • Equally important is prehospital triage and notification of a potential stroke patient. This allows for early mobilization of necessary resources, such as a stroke team, radiology, and pharmacy.
  • With the creation and certification of primary stroke centers, regional health care systems should determine the best triage policy for potential stroke patients in their area.
• The goal of acute stroke management in the emergency department is rapid and efficient care. Continuing from the assessment of the ABCs, stroke patient evaluation and, if eligible, fibrinolytic therapy should be administered within 1 hour from presentation as shown below.

  Table 2. NINDS Recommended Stroke Evaluation Time Benchmarks for Potential Thrombolysis Candidate
  

• Time Interval	Time Target
  Door to doctor Access to neurologic expertise Door to CT scan completion Door to CT scan interpretation Door to treatment Admission to monitored bed	10 min 15 min 25 min 45 min 60 min 3 h

• Again, general stroke management is a team effort with the nursing and medical staff working closely together. General stroke care issues are outlined in the table below.

  Table 3. General Management of Patients With Acute Stroke

  Blood glucose	Treat hypoglycemia with D50 Treat hyperglycemia with insulin if serum glucose >200 mg/dL
  Blood pressure	See recommendations for thrombolysis candidates and noncandidates (Table 4)
  Cardiac monitor	Continuous monitoring for ischemic changes or atrial fibrillation
  Intravenous fluids	Avoid D5W and excessive fluid administration IV isotonic sodium chloride solution at 50 mL/h unless otherwise indicated
  Oral intake	NPO initially; aspiration risk is great, avoid oral intake until swallowing assessed
  Oxygen	Supplement if indicated (Sa02 <90%, hypotensive, etc)
  Temperature	Avoid hyperthermia, oral or rectal acetaminophen as needed

• Hypoglycemia and hyperglycemia need to be identified and treated early in the evaluation. Not only can both produce symptoms that mimic ischemic stroke, but both also can aggravate ongoing neuronal ischemia. Administration of glucose in hypoglycemia produces profound and prompt improvement, while insulin should be started for patients with stroke and hyperglycemia. Ongoing studies will help determine the optimal level of glycemic control.
• Hyperthermia is infrequently associated with stroke but can increase morbidity. Administration of acetaminophen, by mouth or per rectum, is indicated in the presence of fever (temperature >100.4°F).
• Supplemental oxygen is recommended when the patient has a documented oxygen requirement. To date, conflicting evidence exists that supernormal oxygenation improves outcome.
• Optimal blood pressure targets remain to be determined. Many patients are hypertensive on arrival. Recent American Stroke Association guidelines have reinforced the need for caution in lowering blood pressures acutely. Table 4 shows current recommendations for both candidates and noncandidates for thrombolytic therapy.
• In the small proportion of patients with stroke who are relatively hypotensive, pharmacologically increasing blood pressure may improve flow through critical stenoses.

  Table 4. Blood Pressure Management in Patients With Stroke*
   

    

  	Blood Pressure	Treatment
  Candidates for fibrinolysis	Pretreatment SBP >185 or DBP >110 mm Hg	Labetalol 10-20 mg IVP 1-2 doses or Enalapril 1.25 mg IVP
  	Posttreatment DBP >140 mm Hg SBP >230 mm Hg or DBP 121-140 mm Hg SBP 180-230 mm Hg or DBP 105-120 mm Hg	Sodium nitroprusside (0.5 mcg/kg/min) Labetalol 10-20 mg IVP and consider labetalol infusion at 1-2 mg/min or nicardipine 5 mg/h IV infusion and titrate Labetalol 10 mg IVP, may repeat and double every 10 min up to maximum dose of 150 mg
  Noncandidates for fibrinolysis	DBP >140 mm Hg SBP >220 or DBP 121-140 mm Hg or MAP >130 mm Hg SBP <220 mm Hg or DBP 105-120 mm Hg or MAP <130 mm Hg	Sodium nitroprusside 0.5 mcg/kg/min; may reduce approximately 10-20% Labetalol 10-20 mg IVP over 1-2 min; may repeat and double every 10 min up to maximum dose of 150 mg or nicardipine 5 mg/h IV infusion and titrate Antihypertensive therapy indicated only if AMI, aortic dissection, severe CHF, or hypertensive encephalopathy present

  *Adopted from 2005 Advanced Cardiac Life Support (ACLS) guidelines and 2003 American Stroke Association Scientific Statement
  Abbreviations: SBP - systolic blood pressure; DBP - diastolic blood pressure; IVP - intravenous push; MAP - mean arterial pressure

• Fibrinolytic therapy: Intravenous t-PA for appropriate patients within 3 hours from symptom onset remains a Class I recommendation by the American Stroke Association. A recent re-analysis of the original NINDS data reaffirmed the original findings. Similarly, a meta-analysis of published t-PA use demonstrated efficacy and safety comparable to that of the original NINDS trial.¹ See Stroke Team Creation and Management.

Surgical Care

Surgical intervention is rarely required urgently in AIS; however, current recommendations suggest that neurosurgical care should be available within 2 hours when needed, eg, to evaluate surgical options in hemorrhagic transformation following t-PA or in the management of life-threatening elevations of ICP (see Head Trauma).

• Increased ICP is a life-threatening event occurring in as many as 20% of all strokes; it is more common in large, hemispheric strokes. Edema and herniation are the most common causes of early death in patients with hemispheric stroke.
• • Patient position, hyperventilation, hyperosmolar therapy, and rarely, barbiturate coma may be used, as in patients with increased ICP secondary to closed head injury.
  • Recent reports of hemicraniectomy to treat life-threatening ICP have suggested that these patients have shorter ICU stays and a lower mortality rate if surgery is performed before clinical deterioration. One randomized clinical trial did not confirm these benefits.²
• Selected patients with either hemorrhagic transformation or intracerebral hemorrhage after thrombolytic therapy may benefit from surgical evacuation of the hematoma.
• If neurosurgical care is not available in house, a transfer policy is encouraged to expedite patient transfer when neurosurgical expertise is needed.

Consultations

Consultations are tailored to individual patient needs.

• In the first hours of acute stroke, an experienced professional sufficiently familiar with stroke or a stroke team should be available within 15 minutes of the patient's arrival in the emergency department.
• Often, physical medicine and rehabilitation (PM&R), occupational therapy, physical therapy, and speech therapy experts are consulted within the first day of hospitalization.
• Consultation of cardiology and vascular surgery or neurosurgery may be warranted based on the results of TTE/TEE, carotid duplex scanning, neuroimaging, and clinical course.
• During hospitalization, additional useful consultations include home health care coordinator, rehabilitation coordinator, social worker, psychiatrist (commonly for depression), and dietitian.

Diet

• Patients with acute stroke are at great risk of aspiration. All patients should remain NPO until a swallowing assessment is performed.
• Because of dysphagia, a temporary feeding tube may be required.
• If the patient remains at a significant aspiration risk for the foreseeable future, a percutaneous endoscopic gastrostomy (PEG) feeding tube may be required.
• A dietitian can help identify a diet that not only addresses the aspiration risk but also ensures adequate caloric intake to help prevent poststroke malnutrition.
• The dietitian also must consider special dietary needs of patients with hypertension, diabetes mellitus, and hyperlipidemia.

Activity

Activity is tailored to the severity of stroke.

• Aspiration precautions, with the head of the bed elevated to 30°, need to be observed.
• Physical therapy will test and suggest level of activity. This should be performed within the first 24 hours of hospitalization.
• Increase activity if tolerated as per the suggestions of the rehabilitation coordinator, with the goal of mobilizing the patient as early as possible. At discharge, encourage patients to increase activity as tolerated.

MEDICATION

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

While only one drug, t-PA, has demonstrated efficacy and effectiveness in treating AIS and is approved by the US Food and Drug Administration (FDA), other medications are equally important. National consensus panels have included antihypertensives, anticonvulsants, and osmotic agents in their recommendations. Additional agents may be required for comorbid illnesses in many patients with stroke.

Drug Category: Antihypertensives

Optimal blood pressure management in acute stroke remains subject to some debate. Treatment parameters largely depend on whether the patient is a candidate for thrombolytic therapy. While the target blood pressures may differ, the therapeutic agents are largely the same.

Drug Category: Antiplatelet agents

Besides thrombolytics, aspirin is the only other therapeutic agent shown to improve outcome in acute stroke. This class of medications is well known to decrease the risk of stroke recurrence.

Drug Category: Anticonvulsant agents

While seizures associated with stroke are relatively uncommon, recurrent seizures may be life threatening. Generally, agents used for treating recurrent convulsive seizures are also used in patients with seizures after stroke. Benzodiazepines, typically diazepam and lorazepam, are the first-line drugs for ongoing seizures.

Drug Category: Antipyretic agents

Hyperthermia in acute stroke is potentially harmful and should be treated. Agents with potential bleeding risk should be avoided if possible.

Drug Category: Fibrinolytic agents

Tissue plasminogen activator is a fibrinolytic protein that is produced normally by the endothelial lining of blood vessels. It is an enzyme (serine protease) that converts plasminogen to plasmin in the presence of fibrin but produces limited conversion of plasminogen in the absence of fibrin. When introduced into the systemic circulation at pharmacologic concentration, it binds to fibrin in the thrombus and converts the entrapped plasminogen to plasmin. This initiates local fibrinolysis with limited systemic proteolysis.

While several new fibrinolytic agents have been introduced for AMI, only alteplase has received FDA approval in treating AIS.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Further Inpatient Care

• Inpatient care is tailored to the severity of the acute stroke and comorbid illnesses. Recent studies support the admission to a dedicated stroke unit with specially trained staff to reduce morbidity and mortality rates.³
• The goals of early supportive care after admission (adapted from the American Stroke Associations guidelines) include the following:
• • Observe changes in the patient's condition that might prompt different medical or surgical interventions. Notably, 25% of patients worsen in the first 24-48 hours after admission.
  • Facilitate medical or surgical measures aimed at improving outcome after stroke. This includes evaluation for carotid stenoses and cardioembolic sources.
  • Institute measures to prevent subacute complications. Foley catheters increase the risk for urinary tract infection and should be used only when absolutely necessary. Sequential compression stockings, subcutaneous heparin, and low-molecular-weight heparin decrease the risk of deep vein thrombosis.
  • Initiate therapies to prevent recurrent stroke.
  • Begin efforts to restore neurologic function through rehabilitation or other techniques. This includes occupational, physical, and speech therapy.
• Acute hospitalization is an opportune time to begin smoking cessation.
• Further inpatient care is directed toward other potential comorbid conditions and risk factor reduction. This includes managing hypertension, diabetes mellitus, hypercholesterolemia, and cardiac arrhythmias or diseases.
• Depression is prevalent in stroke survivors and caregivers. It should be addressed with survivors and their families during hospitalization.

Further Outpatient Care

• Poststroke outpatient care largely focuses on rehabilitation and prevention of recurrent stroke. Rehabilitation planning begins within the first day of the acute stroke.
• The American Stroke Association guidelines for rehabilitation focus on 6 major areas, as follows:
• • Preventing, recognizing, and managing comorbid conditions and medical complications
  • Training for maximum independence
  • Facilitating maximum psychosocial coping and adaptation by patient and family
  • Preventing secondary disability by promoting community reintegration, including resumption of home, family, recreational, and vocational activities
  • Enhancing quality of life in view of residual disability
  • Preventing recurrent stroke and other vascular conditions

In/Out Patient Meds

• Patients discharged from the hospital after ischemic stroke should be considered for antiplatelet medications unless contraindicated. Current choices include the following:
• • Aspirin, taken daily in low-to-medium doses (50-325 mg), is an effective and inexpensive first-choice agent for reducing recurrent stroke risk.
  • Newer antiplatelet agents, such as clopidogrel (Plavix) and aspirin/dipyridamole combinations (Aggrenox) are also effective in reducing recurrent stroke rate but may cause adverse effects that must be monitored.
• Initiating long-term anticoagulation (eg, warfarin) reduces the risk of recurrent stroke in patients at risk for cardioembolic stroke.
• • In patients with atrial fibrillation, the recommended target INR is in the range of 2-3. In patients with mechanical prosthetic valves, target INR is in the range of 2-3.5, depending on the type of valve.
  • Patients with rheumatic valvular heart disease, cardiomyopathy, arrhythmias, heart failure, or arterial dissection should be considered for long-term anticoagulation. Patients without one of these indications for anticoagulation do not appear to benefit from warfarin therapy, judging by results of the Warfarin Aspirin Recurrent Stroke Study (WARSS).
• Additional outpatient medications should be tailored to the patient's comorbid conditions and to risk factors identified during hospitalization.
• Use of HMG-coreductase inhibitors has been proven to be beneficial in reducing the rates of stroke in patients with coronary artery disease and elevated or high-normal levels of low-density lipoprotein (LDL) cholesterol.
• Medications to address hypertension, hyperlipidemia, and diabetes mellitus should be reviewed with the patient prior to discharge.

Transfer

• EMS triage and transfer of patients with stroke is an important issue in stroke care. The recommendation for the establishment of stroke centers, as well as JCAHO certification, has helped define for consideration the elements of both primary and comprehensive stroke centers. The reader is referred to the eMedicine article by Helmi Lutsep, MD, Stroke Team Creation and Management.
• EMS agencies in many states and regions are being instructed to selectively triage patients with potential stroke to centers that have demonstrated capabilities to evaluate and treat these patients in a timely fashion.
• As part of each hospital's stroke protocol and pathway, criteria for patient transfer to other medical facilities must be established before the actual need. If available, patients with acute stroke should be admitted to stroke units.
• • Hospitals without neuroimaging capabilities should stabilize and immediately transfer patients with potential stroke to centers with CT scan availability.
  • Hospitals without intensive care units or access to timely neurosurgical expertise should transfer patients who are candidates for thrombolytics or who have received thrombolytics to institutions that can provide those services.
  • Patients with large hemispheric strokes who may be at significant risk for edema and increased ICP and who may require neurosurgical expertise should be transferred before clinical deterioration occurs.

Deterrence/Prevention

• The acute hospitalization is focused not only on treating the acute stroke but also on identifying risk factors for recurrent stroke and beginning to modify these risk factors if possible.

Complications

• Complications following a stroke can be divided into those occurring acutely, typically within 72 hours, and those occurring later.
• • Acute complications include cerebral edema, increased ICP and possible herniation, hemorrhagic transformation, aspiration pneumonia, and seizures.
  • Postfibrinolytic complications center around bleeding. Of greatest concern is intracerebral hemorrhage, typically occurring within the first 12 hours after treatment. Other potential sites of bleeding include GI tract, genitourinary tract (associated with Foley catheters), and skin, typically at sites of intravenous lines.
  • Subacute complications include pneumonia, deep venous thrombosis and pulmonary emboli, urinary tract infections, decubitus ulcers, contractures, spasticity, joint problems such as the shoulder-hand syndrome, and malnutrition.
  • A significant number of stroke survivors also experience depression. Identification and treatment of depression is extremely important in maximizing quality of life, not only for stroke survivors, but also for their families and care providers.

Prognosis

• The prognosis after AIS varies greatly, depending upon the premorbid condition, stroke severity, age, and poststroke complications.
• Mortality rate: In the Framingham and Rochester stroke studies, the overall mortality rate at 30 days after stroke was 28%. The mortality rate at 30 days after ischemic stroke was 19%. The 1-year survival rate for patients with ischemic stroke in the Framingham study was 77%.
• Morbidity: In stroke survivors from the Framingham Heart Study, 31% needed help caring for themselves, 20% needed help when walking, and 71% had impaired vocational capacity in long-term follow-up.

Patient Education

• Education is paramount in the fight to prevent and treat stroke. Education must include all elements of the stroke chain of survival. While medical education is often difficult and requires constant reinforcement, it has potential for minimizing the stroke burden.
• Public education must involve all age groups. Incorporating stroke into basic life support (BLS) and cardiopulmonary resuscitation (CPR) curricula is just one way to reach a younger audience. Avenues to reach an audience with a higher stroke risk include using local churches, employers, and senior organizations to promote stroke awareness.
• Prehospital care providers are essential to timely stroke care. Course curriculum for prehospital care providers is beginning to include more information on stroke than ever before. Through certification and ACLS instruction, as well as continuing medical education classes, prehospital care providers can remain current on stroke and promote stroke awareness in their own communities.
• Physician and nursing staff involved in the care of patients who have had a stroke, both in the emergency department and in the hospital, should participate in scheduled stroke education. This will help them maintain the skills required to treat stroke patients effectively and to remain current on medical advances for all stroke types.
• For excellent patient education resources, visit eMedicine's Stroke Center. Also, see eMedicine's patient education articles Stroke and Transient Ischemic Attack (Mini-stroke).

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• In patients with TIAs, failure to recognize the potential for further stroke and perform a timely assessment for stroke risk factors exposes the patient to undue risk of stroke and clinicians to potential litigation. TIAs confer a 10% risk of stroke within 30 days. Recent studies suggest that of the strokes occurring after a TIA, half occurred within 48 hours of the TIA.
• Failure to thoroughly document the evaluation and treatment plan of the patient with acute stroke is behind a significant proportion of medical malpractice cases involving stroke. Carefully consider thrombolytic therapy in all patients presenting within 3 hours of symptom onset, and reasons for treating (risk/benefit analysis) or not treating the patient must be documented clearly.

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  NIH Stroke Scale. Image courtesy of National Institute for Health.
	View Full Size Image
Media type:  Image

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

1. Hacke W, Donnan G, Fieschi C, et al. Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet. Mar 6 2004;363(9411):768-74. [Medline].
2. Sterzi R, Candelise L, Gattinoni M, Bersano A, Micieli G. Stroke-unit care for patients with acute stroke. Lancet. Apr 14 2007;369(9569):1255. [Medline].
3. Vahedi K, Hofmeijer J, Juettler E, Vicaut E, George B, Algra A. Early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomised controlled trials. Lancet Neurol. Mar 2007;6(3):215-22. [Medline].
4. Adams H, Adams R, Del Zoppo G, et al. Guidelines for the early management of patients with ischemic stroke: 2005 guidelines update a scientific statement from the Stroke Council of the American Heart Association/American Stroke Association. Stroke. Apr 2005;36(4):916-23. [Medline].
5. Adams HP Jr, Brott TG, Furlan AJ, et al. Guidelines for thrombolytic therapy for acute stroke: a supplement to the guidelines for the management of patients with acute ischemic stroke. A statement for healthcare professionals from a Special Writing Group of the Stroke Council, American Heart As. Circulation. Sep 1 1996;94(5):1167-74. [Medline].
6. Adams HP Jr, Davis PH, Leira EC, et al. Baseline NIH Stroke Scale score strongly predicts outcome after stroke: A report of the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Neurology. 1999;53:126-131. [Medline].
7. Adams HP, Adams RJ, Brott T, et al. Guidelines for the early management of patients with ischemic stroke: A scientific statement from the Stroke Council of the American Stroke Association. Stroke. Apr 2003;34(4):1056-83. [Medline].
8. Albers GW, Bates VE, Clark WM, et al. Intravenous tissue-type plasminogen activator for treatment of acute stroke: the Standard Treatment with Alteplase to Reverse Stroke (STARS) study. JAMA. Mar 1 2000;283(9):1145-50. [Medline].
9. Alberts MJ, Hademenos G, Latchaw RE, et al. Recommendations for the establishment of primary stroke centers. Brain Attack Coalition. JAMA. Jun 21 2000;283(23):3102-9. [Medline].
10. American Heart Association. Textbook of Advanced Cardiac Life Support. American Heart Association;1997.
11. Brott TG, Clark WM, Fagan SC. Stroke: The first hours. Guidelines for Acute Treatment. National Stroke Association;2000.
12. CAST Collaborative Group. CAST: randomised placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. CAST (Chinese Acute Stroke Trial) Collaborative Group. Lancet. Jun 7 1997;349(9066):1641-9. [Medline].
13. Chen ZM, Sandercock P, Pan HC, et al. Indications for early aspirin use in acute ischemic stroke : A combined analysis of 40 000 randomized patients from the chinese acute stroke trial and the international stroke trial. On behalf of the CAST and IST collaborative groups. Stroke. Jun 2000;31(6):1240-9. [Medline].
14. Hacke W, Kaste M, Fieschi C, et al. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. Lancet. Oct 17 1998;352(9136):1245-51. [Medline].
15. Ingall TJ, O'Fallon WM, Asplund K, et al. Findings from the reanalysis of the NINDS tissue plasminogen activator for acute ischemic stroke treatment trial. Stroke. Oct 2004;35(10):2418-24. [Medline].
16. Katzan IL, Furlan AJ, Lloyd LE, et al. Use of tissue-type plasminogen activator for acute ischemic stroke: the Cleveland area experience. JAMA. Mar 1 2000;283(9):1151-8. [Medline].
17. Kothari R, Jauch E, Broderick J, et al. Acute stroke: delays to presentation and emergency department evaluation. Ann Emerg Med. Jan 1999;33(1):3-8. [Medline].
18. Kothari RU, Pancioli A, Liu T, et al. Cincinnati Prehospital Stroke Scale: reproducibility and validity. Ann Emerg Med. Apr 1999;33(4):373-8. [Medline].
19. Lattimore SU, Chalela J, Davis L, et al. Impact of establishing a primary stroke center at a community hospital on the use of thrombolytic therapy: the NINDS Suburban Hospital Stroke Center experience. Stroke. Jun 2003;34(6):e55-7. [Medline].
20. Lewandowski CA, Frankel M, Tomsick TA, et al. Combined intravenous and intra-arterial r-TPA versus intra-arterial therapy of acute ischemic stroke: Emergency Management of Stroke (EMS) Bridging Trial. Stroke. Dec 1999;30(12):2598-605. [Medline].
21. Lyden P, Brott T, Tilley B, et al. Improved reliability of the NIH Stroke Scale using video training. NINDS TPA Stroke Study Group. Stroke. 1994;25(11):2220-2226. [Medline].
22. Marler JR, Jones PW, Emr M, eds. Proceedings of a National Symposium on Rapid Identification and Treatment of Acute Stroke. Bethesda MD: The National Institute of Neurological Disorders and Stroke, National Institutes of Health; August 1997.
23. NINDS rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med. Dec 14 1995;333(24):1581-7. [Medline].
24. Schneider AT, Kissela B, Woo D, et al. Ischemic stroke subtypes: a population-based study of incidence rates among blacks and whites. Stroke. Jul 2004;35(7):1552-6. [Medline].
25. Schwamm LH, Panciol