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Stroke, Ischemic
Last Updated: March 24, 2005

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AUTHOR INFORMATION

Section 1 of

Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Author: Jeffrey L Arnold, MD, FACEP, Medical Director, Office of Emergency Preparedness, Assista
Professor of Emergency Medicine, Section of Emergency Medicine, Yale New Haven Hospital

Editor(s): Richard S Krause, MD, Program Director, Clinical Assistant Professor, Department of Eme
Medicine, State University of New York at Buffalo; Francisco Talavera, PharmD, PhD, Senior Pharm
eMedicine; J Stephen Huff, MD, Associate Professor of Emergency Medicine and Neurology, Depar
Emergency Medicine, University of Virginia Health System; John Halamka, MD, Chief Information O
CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine
Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Charles V
MD, MA, FACEP, Associate Professor of Emergency Medicine, University of Pennsylvania School of
Chairman, Department of Emergency Medicine, Pennsylvania Hospital
Disclosure

INTRODUCTION

Section 2 of 10

Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Background: Stroke is characterized by the sudden loss of circulation to an area of the brain, resultin
corresponding loss of neurologic function. Also called cerebrovascular accident or stroke syndrome, s
nonspecific term encompassing a heterogeneous group of pathophysiologic causes, including thromb
and hemorrhage.

Strokes currently are classified as either hemorrhagic or ischemic. Acute ischemic stroke refers to str
thrombosis or embolism and accounts for 80% of all strokes.

In the past, almost nothing could be done to help patients with acute stroke. Only in the past 25 years
advances been made in stroke prevention, supportive care, and rehabilitation. Still, little treatment exi
ischemic stroke until 1995, when the National Institute of Neurologic Disorders and Stroke (NINDS) re
tissue-type plasminogen activator (rt-PA) stroke study group first reported that the early administration
benefited some carefully selected patients with acute ischemic stroke. Encouraged by this breakthrou
the subsequent approval of t-PA for use in acute ischemic stroke by the US Food and Drug Administra
medical professionals now consider acute ischemic stroke to be a medical emergency which, when d
treated early, can have few, if any, permanent sequelae.

Since emergency physicians play a central role in the initial evaluation and treatment of patients with
stroke, their understanding of its pathophysiology, clinical presentation, and ED evaluation is essentia
emergency physician also must be completely familiar with the entire therapeutic armamentarium cur
to treat acute ischemic stroke, which includes supportive care, treatment of neurologic complications,
therapy, and thrombolytic therapy. Finally, the emergency physician must exercise good judgment in a
treatment options to selected patients.

When the direct costs (care and treatment) and the indirect costs (lost productivity) of strokes are con
together, strokes cost US society $43.3 billion per year.

Pathophysiology: On the macroscopic level, ischemic strokes most often are caused by extracrania
intracranial thrombosis. On the cellular level, any process that disrupts blood flow to a portion of the b
an ischemic cascade, leading to the death of neurons and cerebral infarction. Understanding this cha
important for understanding current therapeutic approaches.
Embolism

Emboli may arise from the heart, the extracranial arteries or, rarely, the right-sided circulation (parado
The sources of cardiogenic emboli include valvular thrombi (eg, in mitral stenosis, endocarditis, prosth
mural thrombi (eg, in myocardial infarction [MI], atrial fibrillation, dilated cardiomyopathy); and atrial m
associated with a 2-3% incidence of embolic stroke, of which 85% occur in the first month after MI.

Lacunar infarcts account for 13-20% of all cerebral infarctions and usually involve the small terminal v
the subcortical cerebrum and brainstem. Lacunar infarcts commonly occur in patients with small vess
as diabetes and hypertension. Small emboli or an in situ process called lipohyalinosis is thought to ca

infarcts. The most common lacunar syndromes include pure motor, pure sensory, and ataxic hemipar
virtue of their small size and well-defined subcortical location, lacunar infarcts do not lead to impairme
memory, speech, or level of consciousness.
Thrombosis

The most common sites of thrombotic occlusion are cerebral artery branch points, especially in the di
internal carotid artery. Arterial stenosis (ie, turbulent blood flow), atherosclerosis (ie, ulcerated plaque
adherence cause the formation of blood clots that either embolize or occlude the artery. Less commo
thrombosis include polycythemia, sickle cell anemia, protein C deficiency, fibromuscular dysplasia of
arteries, and prolonged vasoconstriction from migraine headache disorders. Any process that causes
cerebral arteries also can cause thrombotic stroke (eg, trauma, thoracic aortic dissection, arteritis). O
hypoperfusion distal to a stenotic or occluded artery or hypoperfusion of a vulnerable watershed regio
cerebral arterial territories can cause ischemic stroke.
Ischemic cascade

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

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

Free radicals, arachidonic acid, and nitric oxide are generated by this process, leading to further neur
Within hours to days after a stroke, specific genes are activated, leading to the formation of cytokines
factors that in turn cause further inflammation and microcirculatory compromise. Ultimately, the ischem
consumed by these progressive insults, coalescing with the infarcted core, often within hours of the o
stroke.

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

The ischemic cascade offers many points at which such interventions could be attempted. Multiple str
blocking this cascade are currently under investigation. The timing of restoring cerebral blood flow ap
critical factor, since initial animal and human imaging studies suggest that reperfusion must occur with
the ischemic penumbra to be saved. Time also may prove to be a key factor in neuronal protection. A
being studied, neuroprotective agents, which block the earliest stages of the ischemic cascade (eg, c

blockers, glutamate receptor antagonists), are expected to be effective only within the earliest window
Frequency:

In the US: Incidence for first-time strokes is more than 400,000 per year. At current trends, this
projected to jump to one million per year by the year 2050.

Internationally: Global incidence of stroke is unknown.

Mortality/Morbidity: Stroke is the third leading cause of death and the leading cause of disability in t

Cerebrovascular disease was the second leading cause of death worldwide in 1990, killing ove
people.

Cerebrovascular disease was also the fifth leading cause of lost productivity, as measured by d
adjusted life years (DALYs). DALYs include years of productivity lost to either death or varying
disability. In 1990, cerebrovascular disease caused 38.5 million DALYs throughout the world.

Sex: Men are at higher risk than women for stroke.

Age: Although stroke often is considered a disease of the elderly, 25% of strokes occur in persons yo
years.

CLINICAL

Section 3 of 10

Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

History:

Stroke should be considered in any patient presenting with an acute neurologic deficit (focal or
altered level of consciousness.

No historical feature distinguishes ischemic from hemorrhagic stroke, although nausea, vomitin
and change in level of consciousness are more common in hemorrhagic strokes.

Common symptoms of stroke include abrupt onset of hemiparesis, monoparesis, or quadripare

or binocular visual loss; visual field deficits; diplopia; dysarthria; ataxia; vertigo; aphasia; or sud
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 considerin
possible thrombolytic therapy. The median time from symptom onset to ED presentation range
hours in the US.

Multiple factors contribute to delays in seeking care for symptoms of stroke.

Many strokes occur while patients are sleeping and are not discovered until the patient

o
o

Strokes leave some patients too incapacitated to call for help.

Occasionally, strokes go unrecognized by patients or their caregivers.

Stroke mimics commonly confound the clinical diagnosis of stroke. One study reported that 19
diagnosed with acute ischemic stroke by neurologists before cranial CT scanning actually had
noncerebrovascular causes for their symptoms. The most frequent stroke mimics include seizu
systemic infections (17%); brain tumors (15%); toxic-metabolic causes, such as hyponatremia
positional vertigo (6%). Miscellaneous disorders mimicking stroke include syncope, trauma, su
hematoma, herpes encephalitis, transient global amnesia, dementia, demyelinating disease, m
gravis, parkinsonism, hypertensive encephalopathy, and conversion disorders.

Physical:

The goals of the physical examination include detecting extracranial causes of stroke symptom
distinguishing stroke from stroke mimics.

The physical examination always includes a careful head and neck examination for signs of tra
and meningeal irritation.

A careful search for the cardiovascular causes of stroke requires examination of the ocular fun
emboli, hemorrhage), heart (irregularities, murmurs, gallops), and peripheral vasculature (palp
radial, and femoral pulses, auscultation for carotid bruits).

Patients with a decreased level of consciousness should be assessed to ensure that they are a
their airway.

Neurologic examination
o

With the availability of thrombolytic therapy for acute ischemic stroke in selected patient
emergency physician must be able to perform a brief but accurate neurologic examinati
with suspected stroke syndromes.

The goals of the neurologic examination include (1) confirming the presence of a stroke
defined further by cranial CT scanning), (2) distinguishing stroke from stroke mimics, an

establishing a neurologic baseline should the patient's condition improve or deteriorate.

Essential components of the neurologic exam include evaluation of mental status and th
consciousness, cranial nerves, motor function, sensory function, cerebellar function, ga
tendon reflexes.

The skull and spine also should be examined, and signs of meningismus should be sou

Central facial weakness from a stroke should be differentiated from the peripheral weak
palsy. With peripheral lesions (Bell palsy), the patient is unable to lift the eyebrows or wr
forehead.

Clinical correlation
o

The 4 major neuroanatomic stroke syndromes are caused by disruption of their respect
cerebrovascular distributions. Correlating the patient's neurologic deficits with the expec
arterial compromise may assist the emergency physician in confirming the diagnosis of
interpreting the subsequent cranial CT scan.

Anterior cerebral artery occlusions primarily affect frontal lobe function, producing altere
impaired judgment, contralateral lower extremity weakness and hypesthesia, and gait a

Middle cerebral artery (MCA) occlusions commonly produce contralateral hemiparesis,

hypesthesia, ipsilateral hemianopsia (blindness in one half of the visual field), and gaze
toward the side of the lesion. Agnosia is common, and receptive or expressive aphasia
lesion occurs in the dominant hemisphere. Since the MCA supplies the upper extremity
weakness of the arm and face is usually worse than that of the lower limb.

Posterior cerebral artery occlusions affect vision and thought, producing homonymous h
cortical blindness, visual agnosia, altered mental status, and impaired memory.

Vertebrobasilar artery occlusions are notoriously difficult to detect because they cause a
cranial nerve, cerebellar, and brainstem deficits. These include vertigo, nystagmus, diplo
deficits, dysphagia, dysarthria, facial hypesthesia, syncope, and ataxia. Loss of pain and
sensation occurs on the ipsilateral face and contralateral body. In contrast, anterior strok
findings on one side of the body only.

Stroke scales: The National Institutes of Health Stroke Scale (NIHSS) is a rapid and reproducib
quantifying neurologic deficits in stroke patients and is useful for following the patient's early co
is available online at National Institutes of Health Stroke Scale.

Causes:

Briefly assessing the risk factors for stroke may provide clues as to its cause and reinforce the

the emergency physician may have in uncertain situations. Risk factors for ischemic stroke inc
age (the risk doubles every decade), hypertension, smoking, heart disease (coronary artery dis
ventricular hypertrophy, chronic atrial fibrillation), and hypercholesterolemia.

Diseases associated with increased blood viscosity and the use of oral contraceptives place pa
risk for ischemic stroke.

Previous cerebrovascular disease is a risk factor for ischemic stroke.

Transient ischemic attacks (TIAs) precede nearly 30% of ischemic strokes. If left untreated, on
lead to ischemic stroke: 20% within the first month, and 50% within the first year.
DIFFERENTIALS

Section 4 of 10

Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Guillain-Barr Syndrome
Hyperosmolar Hyperglycemic Nonketotic Coma
Status Epilepticus

WORKUP
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Lab Studies:

CBC, basic chemistry panel, coagulation studies, and cardiac biomarkers should be obtained i
o

CBC serves as a baseline study and may reveal a cause for the stroke (eg, polycythem
provide evidence of concurrent illness (eg, anemia).

Chemistry panel serves as a baseline study and may reveal a stroke mimic (eg, hypogly
illness (eg, diabetes, renal insufficiency).

Coagulation studies may reveal a coagulopathy and are useful when thrombolytics or a

Some authors recommend cardiac biomarkers because of the association of cerebral va

Toxicology screens may be useful in selected patients.

Imaging Studies:

Head CT scan
o

Emergent noncontrast head CT scanning is mandatory for rapidly distinguishing ischem

anatomic distribution of stroke.

Head CT scan is a fundamental branch point in the evaluation of stroke, since patients w
thrombolytic therapy, while patients with hemorrhagic stroke are taken down a complete

CT scans also may rule out other life-threatening processes, such as hematomas, neop

The changes in CT scan over the time course of acute cerebral infarction must be unde
stroke symptoms within 6 hours initially will have normal findings on CT scan. After 6-12
to produce a regional hypodensity on CT scan. A large hypodense area present on CT s
prompt careful requestioning regarding the time of stroke symptom onset.

Other radiologic clues to acute ischemic infarction include the insular ribbon sign, the hy
sulcal asymmetry, and loss of gray-white matter differentiation.

Unfortunately, as many as 5% of patients with subarachnoid hemorrhages also have no

subarachnoid hemorrhage is suspected. CT scans also may fail to demonstrate some p

Noninvasive arterial studies

o

Carotid duplex scanning is reserved for patients with acute ischemic stroke in whom car

Transcranial Doppler ultrasound is useful for evaluating more proximal vascular anatom
vertebrobasilar artery.

Results of these studies may guide the decision to initiate anticoagulation or to perform

Echocardiography
o

Echocardiography is reserved for patients with acute ischemic stroke in whom cardioge

Transesophageal echocardiography is useful for detecting thoracic aortic dissection, an

diagnosis of acute MI.

Since early anticoagulation of patients with cardioembolic stroke is controversial, emerg

change in the patient's ED management.

Magnetic resonance imaging

o

MRI is useful for patients with acute ischemic stroke involving cerebellar or lacunar path

Disadvantages include its high cost, lack of ready availability at most centers, and insen

Other Tests:

Electrocardiogram: ECG should be obtained on all patients with acute stroke, since as many a
fibrillation or acute MI.

Continuous cardiac monitoring has been recommended by some for all patients, since 4% of p
course of their illness, and 3% have concurrent MI.

Procedures:

Angiography
o

Angiography is useful for patients with acute ischemic stroke in whom characterization o
medical or surgical management, such as patients with subtle occlusive diseases (eg, fi

Angiography continues to play an important role in the preoperative evaluation of carotid

TREATMENT
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Prehospital Care: Recognition that a stroke may have occurred and rapid transport to the appropriat
Stroke should be a priority dispatch with prompt EMS response.
Emergency Department Care:

Airway and breathing: Patients presenting with Glasgow Coma Scale scores less than or equa
inadequate airway protection reflexes require emergent airway control via rapid sequence intu
o

When increased intracranial pressure is suspected, rapid sequence induction might idea
fentanyl (3 mcg/kg IV), and a subparalytic dose of a nondepolarizing neuromuscular blo
before paralysis with succinylcholine (2 mg/kg IV) and oral endotracheal intubation.

The goal of mechanical ventilation is hyperventilation, which decreases intracranial pres

recommended endpoint of hyperventilation is an arterial pCO 2 of 30-35 mm Hg. Supplem
oximetry.

Circulation: Patients require intravenous access and cardiac monitoring in the ED. Since overh
lead to underperfusion of the ischemic penumbra, care must be taken to appropriately individu
Normoglycemic patients should not be given excessive glucose-containing intravenous fluids,

Blood pressure control: Since lowering the systemic blood pressure also may cause underperf

hypertension (systolic BP >220 mm Hg, diastolic BP >120 mm Hg, or mean arterial BP >140 m
stroke transformation, cardiac ischemia, aortic dissection, or renal damage should be treated.
successive measurements at 15-minute intervals.
o

The ideal agent for blood pressure control is titratable, with rapid onset and offset and li
agent is ideal. Acceptable agents for lowering systemic blood pressure in acute ischemi

Use of sublingual nifedipine to lower blood pressure in the ED is discouraged since extr

Fever control: Antipyretics are indicated for febrile stroke patients, since hyperthermia accelera
evidence suggests that mild brain hypothermia is neuroprotective. No randomized, controlled c
ischemic stroke have been performed.

Cerebral edema control: Cerebral edema occurs in up to 15% of patients with ischemic stroke,
of stroke. Hyperventilation and mannitol are used routinely to decrease intracranial pressure q
use of corticosteroids to decrease cerebral edema in acute ischemic stroke.

Seizure control: Seizures occur in 5-7% of patients within the first 24 hours after stroke. Althou
subsequent seizures with standard antiepileptic therapy is recommended.

MEDICATION
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

The therapeutic approach to patients with cerebrovascular disease involves multiple phases, includin
disease in general, (2) supportive and medical management during the acute phase of stroke, (3) me
process, and (4) appropriate rehabilitative and physical therapy programs during the poststroke perio

Neuroprotectants have not yet been shown to benefit patients with acute stroke. Nevertheless, substa
indication. Since the ischemic cascade is a dynamic process, the efficacy of interventions to protect th
dependent.

Theoretically, calcium channel blockers (eg, nimodipine) should have the narrowest window of therap
earliest events in the ischemic cascade. A recent study suggests that lubeluzole (an inhibitor of glutam
stroke if given within 6 h. Aptiganel (noncompetitive inhibitor of the NMDA receptor) also appears prom

Neuroprotectants affecting later events in the ischemic cascade include free-radical scavengers (tirila
(citicoline). Monoclonal antibodies against leukocyte adhesion molecules also are being evaluated as
system yet exists for the many neuroprotectants being investigated, since many agents appear to hav

Anticoagulants are considered potential treatments. However, although heparin prevents recurrent ca
cerebrovascular thrombosis, no definitive evidence exists to show that initiating anticoagulation reduc
evidence suggests that heparin may benefit some patients with progressive stroke, especially in the v
area of the brain that are associated with an arterial or cardiac mechanism.

Anticoagulation is not without risk. Overall, intracranial hemorrhage occurs in 1-4% of patients who re
Accordingly, uncontrolled hypertension, intracranial hemorrhage, and uncontrolled bleeding at anothe
anticoagulation should be avoided in patients at risk for hemorrhagic transformation, eg, patients who
combined hemiparesis and hemisensory deficits, or strokes showing early hypodense areas on crania
be at risk for hemorrhagic transformation. Although some evidence indicates that early heparinization
cardioembolic stroke should not be given anticoagulants until at least 48 hours after symptom onset b
for large cardioembolic strokes).

Although the role of heparin in conjunction with thrombolytic agents for acute ischemic stroke has not
prospective trials evaluating t-PA for acute ischemic stroke excluded patients who were receiving anti
caused by t-PA.

Immobilized stroke patients who are not receiving anticoagulants, such as IV heparin or an oral antico
unfractionated or low-molecular-weight heparin, which reduces the risk of deep vein thrombosis. The
acute ischemic stroke has not yet been studied adequately.

Several new oral anticoagulant medications, including ximelagatran, are in the final stages of clinical
thromboembolic stroke. Once approved for use, the potential of such drugs in the arena of stroke trea

Drug Category: Antiplatelet agents -- Although antiplatelet agents have been shown useful for pre

the treatment of acute ischemic stroke has not been demonstrated. The International Stroke Trial rand
treatment with aspirin 325 mg, subcutaneous heparin in 2 different dose regimens, aspirin with hepar
reduced the risk of early stroke recurrence. Ticlopidine, another antiplatelet agent, also prevents ische
neutropenia, as well as elevated cholesterol levels in some patients.

Drug Name

Aspirin (Bayer, Anacin, Bufferin) -- Blocks prostaglandin

prostaglandin synthesis and prevents formation of platel
hypothalamic heat-regulating center to reduce fever.

Adult Dose

1.3 g/d PO divided bid/qid

Pediatric Dose

10-15 mg/kg/dose PO q4-6h; not to exceed 60-80 mg/kg

Contraindications

Documented hypersensitivity; liver damage; hypoprothro

disorders; asthma
Because of association with Reye syndrome, do not use

Interactions

Antacids and urinary alkalinizers may decrease effects;

anticoagulants may cause additive hypoprothrombinemi
antagonize uricosuric effects of probenecid and increase

>2 g/d may potentiate glucose-lowering effect of sulfony

Pregnancy

D - Unsafe in pregnancy

Precautions

May cause transient decrease in renal function and aggr

severe anemia or coagulation defects, or in patients taki

Drug Name

Ticlopidine (Ticlid) -- Second-line antiplatelet therapy for

whom aspirin not effective.

Adult Dose

250 mg PO bid

Pediatric Dose

Not established

Contraindications

Documented hypersensitivity; severe neutropenia or thro

disorders

Interactions

Corticosteroids and antacids decrease effects; theophyll

toxicity

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Discontinue if absolute neutrophil count decreases to <1

<80,000/mm3

Drug Category: Recombinant tissue-plasminogen activators -- Thrombolytics restore cerebral

improvement or resolution of neurologic deficits. Unfortunately, thrombolytics also cause intracranial h

While both streptokinase and rt-PA have been shown to benefit patients with acute MI, only alteplase
ischemic stroke. At this time, only 2 large randomized, double-blinded, placebo-controlled studies, the
Acute Stroke Study (ECASS), have evaluated the efficacy of alteplase in patients with acute ischemic
disability outcomes.

In 1995, the NINDS t-PA stroke study group reported that recombinant t-PA reduced disability in patie
ECASS reported that t-PA conferred equivocal benefit and led to increased mortality in patients with a
these studies rated both as having excellent overall validity. Since these 2 studies have had such pro
stroke, both are described in detail here.
NINDS enrolled 624 patients in 39 centers during the period 1991-1994, with inclusion and exclusion
the participating centers were eligible for the study.

To be enrolled, patients must have had onset of stroke symptoms within 3 h of presentation; only pati
were eligible. Excluded patients were those who had rapidly improving or minor symptoms; significan
aggressive therapy); symptoms suggestive of subarachnoid hemorrhage; previous history of intracran
mo); or recent major surgery (within 14 d). Also excluded were patients who had received heparin or
prothrombin time (PT) or activated partial thromboplastin time (aPTT); or were thrombocytopenic (pla
mg/dL), or hyperglycemic (glucose >400 mg/dL).

Patients in the t-PA group were given 0.9 mg/kg of t-PA to 90 mg total over 1 hour (10% of the total w
an ICU, and antiplatelet and anticoagulation therapies were withheld for the first 24 h after treatment.

NINDS reported a statistically significant increase in full recovery in patients given t-PA (39% vs 26%
scales used to measure disability in the NINDS study, the modified Rankin Scale is probably the mos
outcome. Patients were considered to be completely recovered from stroke if, 90 days after treatmen
(either no residual deficits or deficits without disability).

NINDS found a 6.4% rate of symptomatic intracranial hemorrhage in the t-PA group. Moreover, appro
intracranial bleeding died. NINDS also failed to document a statistically significant decrease in mortal

Subsequent number needed to treat (NNT) analysis of the NINDS stroke trial revealed that 1 of 8 pati
days, while 1 of 17 suffered symptomatic intracranial hemorrhage within the first 36 hours; 1 of 40 of t

ECASS enrolled 620 patients in 75 hospitals in 14 European countries during the period 1992-1994. E
of stroke symptom onset and had no hemorrhage by cranial CT scan. Excluded patients had severe h
impaired level of consciousness or forced head or eye deviation) or improving symptoms, had recent
signs of early infarct on cranial CT scan, such as hypodensity or sulcal effacement in more than 33%
given 1.1 mg/kg of t-PA to 100 mg total over 1 hour (10% of the total dose was given over the first 1-2
hours after treatment.

Although ECASS, like the NINDS study, found an equivocally significant increase in full recovery by m
group (36% vs 29%), it also documented a statistically significant increase in mortality rate at 90 days
data revealed that 1 in 14 patients given t-PA had full neurologic recovery.

Proponents of t-PA have argued that the results of ECASS and NINDS cannot be compared directly b
vs 0.9 mg/kg), t-PA was given during a longer window of time after symptom onset (6 vs 3 h), and pat
participating centers (Europe vs US).

Streptokinase has not been shown to benefit patients with acute ischemic stroke, but it has been sho
death. Of 3 major randomized controlled trials, all were terminated prematurely because streptokinas

The failure of streptokinase as a thrombolytic agent for acute ischemic stroke has been attributed to i
specifically activates plasminogen already bound to a thrombus, streptokinase activates unbound circ

Drug Name

Alteplase (Activase) -- Tissue plasminogen activator (t-P

ischemic stroke, and pulmonary embolism. Safety and e
heparin or aspirin during first 24 h after symptom onset h

Adult Dose

0.9 mg/kg IV over 60 min; not to exceed 90 mg; 10% of

1 min; administer only within 3 h of onset of stroke symp

Pediatric Dose
Contraindications

Not established

Documented hypersensitivity; concurrent aspirin or antic

hemorrhage on pretreatment evaluation; seizure at onse
suspected subarachnoid hemorrhage; active internal ble
or trauma; intracranial neoplasm; arteriovenous malform

uncontrolled hypertension
Interactions

Drugs that alter platelet function (aspirin, dipyridamole, a

to, during, or after alteplase therapy; may give heparin w
of rethrombosis; either heparin or alteplase may cause b

Pregnancy

D - Unsafe in pregnancy

Precautions

Monitor for bleeding, especially at arterial puncture sites

antagonists; control and monitor BP frequently during an
managing acute ischemic stroke); do not use >0.9 mg/kg
mg/kg may cause ICH

FOLLOW-UP
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Further Inpatient Care:

Referral to a physician with special interest in stroke is ideal. Stroke care units exist and are sa
personnel. Comorbid medical problems need to be addressed. Serial monitoring and intervent
eventual stroke rehabilitation are the ideals.

Patient Education:

For excellent patient education resources, visit eMedicine's Stroke Center and Dementia Cent
Stroke, Transient Ischemic Attack (Mini-stroke), and Stroke-Related Dementia.
MISCELLANEOUS

Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Medical/Legal Pitfalls:

Informed consent
o

If a treatment option is available, patients or their proxies should be allowed to decide w

Since t-PA can harm some patients, patients must understand clearly its risks and bene
administered.

Fortunately, the NNT analysis of the NINDS study provides a simple quantitative way th

Although in the NINDS study, emergency physicians alone administered t-PA to patients
instituted policies requiring neurologists to administer t-PA to shift any medicolegal risk s

Special Concerns:

With the advent of t-PA for use in selected patients with acute ischemic stroke, many medical p
symptom duration less than 3 hours to be a medical emergency.
o Advocates of thrombolysis have called for public education to help patients and their fam
attack and for medical professionals to relinquish their skepticism about the treatment fo
respond rapidly to patients with stroke symptoms. Accordingly, substantial efforts are no
survival, which facilitates bringing stroke patients as rapidly as possible to the ED for ca
Association and the National Stroke Association have established clinical guidelines cal
to acute stroke.
o Critics have likened this approach to therapeutic boosterism, pointing out that only rarel
analysis of the NINDS t-PA Stroke Trial revealed that only one patient per hospital was e
except for t-PA in selected patients, no other emergency treatment modality has been sh
changing the public and medical professional perceptions of stroke as a medical emerg
with acute ischemic stroke for t-PA within the 3-hour window from the onset of symptom
in acute ischemic stroke diagnosis and treatment should be based on demonstrated imp
effectiveness.

Diagnostic recommendations

Regardless of how few stroke patients ultimately benefit from t-PA, emergency physicia
possible acute ischemic stroke.

The clinical diagnosis of stroke must be as accurate as possible, and special care must

Hospital protocols must be in place to ensure that patients with undifferentiated stroke h
cranial CT scanning and definitive image interpretation, ideally within 2 hours of their sy

The radiologic diagnosis of stroke also must be as accurate as possible. At this time, the
ischemic stroke (because of decreased image quality) and the exclusion of intracranial
administering t-PA is limited.

Immediate diagnostic urgency dissipates once any contraindication to t-PA is found.

Therapeutic recommendations
o
o

The value of early aspirin or heparin in acute ischemic stroke is unknown.

If administered exactly as in the NINDS Stroke Trial, t-PA may benefit some patients.

o
o

If the administration of t-PA is considered, scrupulous care must be given to follow the in
Currently, no neuroprotectant can be recommended for the treatment of acute ischemic

BIBLIOGRAPHY
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Adams HP Jr, Brott TG, Crowell RM, et al: Guidelines for the management of patients with acu
professionals from a special writing group of the Stroke Council, American Heart Association. S
Albers GW: Medical treatment for acute ischemic stroke. Am J Med 1996; 3-9.
Barsan WG, Kothari R: Stroke. Emergency Medicine Concepts and Practices. Vol 3. 1998: 218
Grotta J, Bratina P: Subjective experiences of 24 patients dramatically recovering from stroke.
Gustafsson D, Elg M: The pharmacodynamics and pharmacokinetics of the oral direct thrombin
melagatran: a mini-review. Thromb Res 2003 Jul 15; 109 Suppl 1: S9-15[Medline].
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NOTE:

Medicine is a constantly changing science and not all therapies are clearly established. New research changes drug and treatment therapies daily. The authors, e
that is up-to-date and accurate and is generally accepted within medical standards at the time of publication. However, as medical science is constantly changing
party involved with the publication of this article do not warrant the information in this article is accurate or complete, nor are they responsible for omissions or erro
information in this article from other sources prior to use. In particular, all drug doses, indications, and contraindications should be confirmed in the package insert
Stroke, Ischemic excerpt

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