100 
Transient Ischemic Attack
and Acute Ischemic Stroke
Holly K. Ledyard
KEY POINTS
• Transient ischemic attack (TIA) is a high-risk warning
sign for stroke within 90 days, with the highest risk
occurring in the first 2 days.
• Patients with TIA can be accurately risk-stratified for
recurrent stroke.
• Large artery atherosclerosis, cardioembolism, and small
vessel disease are the leading causes of TIA and acute
ischemic stroke.
• Magnetic resonance imaging is valuable in
differentiating TIA from acute ischemic stroke.
• The goal of management of patients with TIA is to
prevent recurrent stroke with antiplatelet,
anticoagulation, or surgical therapy.
• The best outcomes for strokes treated with
thrombolytic therapy are found with early delivery of
recombinant tissue plasminogen activator (rt-PA) within
established guidelines.
• Recent evidence supports extending the time window
for treatment of ischemic stroke with rt-PA to 4.5 hours
for specific patient populations.
• Stroke units and stroke teams provide comprehensive
stroke care that improves patient outcomes.
PERSPECTIVE
Transient ischemic events and acute ischemic strokes are
separate points on a continuum of cerebral vascular disease
and share a relationship similar to that of unstable angina and
acute myocardial ischemia.1 The most common causes are
large artery atherosclerosis, cardioembolism, or small vessel
(lacunae) disease. Patients with transient ischemic attacks
(TIAs) have a significant short-term risk for recurrent stroke,
myocardial infarction, and death. Although TIA is typically a
reversible process, ischemic stroke is a pathologic process that
permanently injures the brain. Ischemic stroke is defined as a
permanent cerebral injury secondary to prolonged disruption
of cerebral blood flow (typically <10 mL/100 g brain/min).2
Acknowledgment and thanks to Scott Jolley and Todd L. Allen for contribu-
tions from the first edition.
870
EPIDEMIOLOGY
The yearly incidence of TIA in the United States has been
estimated to be approximately 200,000 to 500,000 but may be
higher because of the high frequency of underreporting of
these events by medical professionals.3-6 The annual incidence
of TIA may be less and the annual incidence of stroke may
be higher if the tissue-based definition were applied to all
patients evaluated for TIA.4 It has been estimated that the
overall incidence rate of TIA is 1.1 per 1000 U.S. population.7
This incidence increases with age from 0.1 per 1000 for
patients younger than 50 years to 11.7 per 1000 for patients
older than 80 years.3 The incidence of TIA also varies with
race and gender: it is significantly greater in blacks and men
than in whites and women. The greatest incidence of TIA
occurred in black men older than 85 years, who had an inci-
dence of 16 events per 1000.3
TIAs account for 0.3% of all emergency department (ED)
visits, and it is estimated that 8.7% to 30% of patients will
have a TIA before stroke.8,9 Only 28% of TIA patients arrive
via ambulance, and 36% of patients arrive during daylight
hours. Emergency physicians (EPs) obtain computed tomog-
raphy (CT) scans on 56% to 70% of all TIA patients and
magnetic resonance imaging (MRI) scans on 7% of TIA
patients. Nearly half of all patients with TIA are admitted to
the hospital, although there is geographic variability in this
practice; another 20% of patients are referred for follow-up.
Finally, patients seen in the ED with TIA receive preventive
aspirin therapy in 18% of cases, other antiplatelet therapy in
7%, and no preventive therapy in an estimated 42%.7
Clearly defined risk factors for stroke and adverse events
following a TIA are now well described in the literature, and
several groups of investigators have independently developed
short-term risk stratification methods applicable to TIA
patients in the ED.10-13 These investigators reported a 10% rate
of stroke in the 90 days following the TIA, with 50% of these
strokes occurring in the immediate 48 hours after the TIA.
Recently, the ABCD2 score, which combines elements
from existing risk stratification systems, was devised to create
a robust prediction standard for determining high-risk popula-
tions that will benefit from emergency investigation and
therapy to prevent short-term adverse events (Table 100.1).12
Patients with the following characteristics were at high risk
for having a stroke in the next 2 to 90 days: age older than 60
years, blood pressure higher than 140 mm Hg systolic or
90 mm Hg diastolic, clinical features such as unilateral
 CHAPTER 100 Transient Ischemic Attack and Acute Ischemic Stroke

weakness or speech disturbance, longer duration of symptoms

of TIA, and diabetes. Table 100.1  Two-Day Risk for Stroke Stratified
According to the ABCD2 Score
Ischemic stroke accounts for 80% to 88% of the total
strokes occurring annually.14 Each year approximately 795,000
people experience a new or recurrent stroke. It is an important RISK FACTOR NUMBER OF POINTS
cause of death in the United States and ranks third behind Age > 60 yr 1
heart disease and cancer.15
Approximately 8% to 12% of all patients suffering an isch- Initial blood pressure > 1
emic stroke die within 30 days of the initial stroke. Ischemic 140/90 mm Hg
stroke disproportionately affects the elderly, with a mean age
Symptoms of focal motor 2
at onset of 70.5 years. Ischemic stroke affects black and His- weakness
panic populations more frequently than white populations.
The age-adjusted incidence of first ischemic stroke per Symptoms of speech 1
100,000 population is 88 in whites, 149 in Hispanics, and 191 impairment without
weakness
in blacks.16 Ischemic stroke is an enormous economic burden,
with an average 30-day cost of $20,346 for a severe stroke Duration > 60 min 2
and mean lifetime cost of $140,048.15,17 The United States
spends approximately $73.7 billion yearly on the direct and Duration 10-59 min 1
indirect cost of stroke care.15
Diabetes mellitus 1

ABCD2 SCORE 2-DAY RISK FOR STROKE

FACTS AND FORMULAS
8.7% to 30% of stroke patients suffer a TIA before the
stroke.
10% of TIA patients have a stroke in the next 90 days, 25%
to 50% of whom will have their stroke within the first 2
days.
33% of TIA patients with symptoms lasting less than 1 hour
will have an infarct shown on diffusion-weighted mag-
netic resonance imaging.
50% of TIA patients never report symptoms to a
physician.
19.2% of patients with untreated symptomatic carotid ste-
nosis of greater than 70% will have a stroke in the next
90 days.
For each minute that reperfusion is delayed, 1.9 million
neurons die.
TIA, Transient ischemic attack.
PATHOPHYSIOLOGY
An ischemic injury involving the central nervous system
disrupts normal cerebral blood flow to the brain (40 to
60 mL/100 g brain/min). The extent of injury is based on
three principles: the duration of disrupted flow, the flow rate,
and collateral circulation. Loss of consciousness occurs within
10 seconds and cell death within minutes of disrupted cerebral
circulation.
Cerebral tissues with blood flow between 12 and
20 mL/100 g brain/min are termed the ischemic penumbra.
These cells are at risk for permanent injury but have the ability
to recover if flow is reestablished. When cerebral blood flow
falls below 10 mL/100 g brain/min, electrical activity ceases
and cell death occurs. Many areas of the brain may be pro-
tected by collateral circulation between the anterior and
0-1 0%
2-3 1.3%
4-5 4.1%
6-7 8.1%
Adapted from Johnston SC, Rothwell PM, Nguyen-Huynh MN, et al.
Validation and refinement of scores to predict very early stroke risk
after transient ischaemic attack. Lancet 2007;369:283-92.
posterior circulation through vessels that make up the circle
of Willis.
Classification of TIAs is important because the pathophysi-
ology and risk for recurrent stroke differ among the subtypes.
The five mechanisms described are large artery atherosclero-
sis, cardioembolism, small vessel disease, other rare deter-
mined cause, and undetermined cause.9,18
Large artery atherosclerosis is defined as greater than 50%
narrowing of vessel caliber. It accounts for 15% of all isch-
emic strokes and is the most common cause of low-flow TIA.
Symptoms are the result of thrombus formation in a ruptured
atherosclerotic plaque. The most commonly affected vascular
territories are the origin of the internal carotid and intracranial
portion of the internal carotid (siphon), the middle cerebral
artery stem, and the junction of the vertebral and basilar arter-
ies. It is found more commonly in men and has a greater
incidence in African and Hispanic populations. Patients with
large artery atherosclerosis have a higher recurrence rate than
do patients with other stroke subtypes: 4%, 12.6%, and 19.2%
at 7, 30, and 90 days, respectively.19 These patients have tran-
sient or stuttering symptoms in the same vascular territory.
Symptoms and disability may be less severe than those in
patients with cardioembolic stroke.14
Cardioembolic disease represents 20% to 25% of ischemic
cerebrovascular events. The most common sources are abnor-
mal cardiac rhythm, abnormal left ventricular wall motion,
and aortic and mitral valve disease.20 The clinical features are

871
SECTION IX NERVOUS SYSTEM DISORDERS
abrupt in onset, with nonprogressive symptoms that may
occur in multiple vascular territories. Cardioemboli affect the
anterior circulation in 70% of patients. These patients tend to
have more severe symptoms and higher mortality rates; dis-
ability is more severe in survivors.14 Patients with embolic
TIA have a lower recurrence rate of 2.5%, 4.6%, 11.9% at 7,
30, and 90 days, respectively.19
Lacunar strokes represent 20% of all ischemic strokes and
are caused by small vessel disease—obstruction of the small
vessels that penetrate the brain parenchyma at right angles to
major parent arteries and supply the basal ganglia, internal
capsule, thalamus, and pons.21,22 The vessels most commonly
involved are small branches of the middle cerebral and basilar
arteries.21 The most common causes of small vessel disease
are microatheroma and lipohyalinosis, which are increased in
the setting of older age, hypertension, diabetes, and smoking.
Small embolic events rarely cause ischemia in these vessels.21,22
Patients with lacunar TIA and stroke commonly have
hypertension and diabetes. Black populations are affected
more than white populations, and there does not seem to be a
gender preference in patients with lacunar infarcts. These
patients have a favorable prognosis with low, short-term recur-
rence rates of 0%, 2%, and 3.4% at 7, 30, and 90 days,
respectively.19,21,22
Rare causes of stroke account for approximately 2% to 3%
of annual cases. Common causes are nonatherosclerotic vas-
culopathies (acute arterial dissection, vasculitis, polyarteritis,
giant cell arteritis, infectious arteritis), hypercoagulable con-
ditions (deficiencies in proteins C and S and antithrombin III,
antiphospholipid antibody syndrome/systemic lupus erythe-
matosus, pregnancy, postmenopausal hormone replacement),
hematologic disorders (sickle cell disease, polycythemia,
myeloproliferative disorders), and other causes of emboli
(patent foramen ovale, endocarditis, air).23
Cryptogenic stroke is the designation used for stroke
without a well-defined etiology despite extensive evaluation.
It accounts for 30% to 40% of all strokes in some stroke
databases. Patients with cryptogenic stroke have a better
1-year prognosis than do those with other subtypes; the 2-year
risk for recurrence is 14% to 20%.14
Systemic hypoperfusion is an uncommon cause of cerebral
ischemia that represents a global decrease in cerebral blood
flow. Causes include cardiac arrest and reduced cardiac output
as a result of cardiac ischemia, pericardial effusion, arrhyth-
mias, pulmonary emboli, hemorrhage, and medications.
Symptoms consist of diffuse brain dysfunction in the setting
of unstable vital signs.14,23
PRESENTING SIGNS AND SYMPTOMS
Patients who have suffered a TIA often have no physical find-
ings but a variety of historical clinical symptoms. Several
studies have demonstrated that interobserver disagreement is
high when making the diagnosis of TIA.24,25
A few basic principles can guide accurate diagnosis of TIA.
The symptoms are sudden in onset and vascular in nature.
TIAs are commonly brief, lasting less than 1 to 2 hours with
many lasting less than 10 to 15 minutes. Symptoms are associ-
ated with loss of function such as hemiparesis, hemiparesthe-
sia, dysarthria, aphasia, monocular vision loss, diplopia, and
gait and balance disturbances. Symptoms such as shaking,
872
scotomata, and marching of symptoms to other body parts are
more consistent with migraine or seizure.26
Approximately 80% of ischemic strokes occur in the dis-
tribution of the anterior circulation and give rise to deficits in
behavior, sensation, movement, and speech, as well as some
elements of visual awareness. The minority of strokes occur
in the distribution of the posterior circulation. Common pos-
terior circulation symptoms are limb weakness, gait and limb
ataxia, oculomotor palsy, and oropharyngeal dysfunction. In
addition, patients often exhibit nausea and vomiting because
of brainstem involvement, as well as vertigo and balance
disorders related to cerebellar and brainstem injury.
OPTHALMIC ARTERY
Transient monocular blindness, known as amaurosis fugax, is
caused by transient occlusion of the ophthalmic artery. It is
commonly associated with internal carotid artery stenosis and
carries a better prognosis than does carotid disease associated
with hemispheric TIA.27
MIDDLE CEREBRAL ARTERY
Patients with middle cerebral artery occlusion typically
exhibit sensory loss hemiplegia, contralateral sensory loss,
and contralateral homonymous hemianopia. Patients with
dominant hemispheric lesions have aphasia; those with non-
dominant hemispheric lesions demonstrate contralateral
hemisensory neglect. Subtle findings include gaze preference
toward the side of the lesion and contralateral gaze
weakness.
ANTERIOR CEREBRAL ARTERY
Occlusion of branches of the anterior cerebellar artery is more
common than stem lesions and is associated with well-
recognized clinical findings: contralateral motor weakness
and sensory deficit in the lower extremity. Other symptoms
include urinary incontinence because of contralateral weak-
ness of the pelvic floor muscles, memory loss or apathy sec-
ondary to occlusion of the orbital or frontopolar branch,
dysarthria secondary to compromise of the medial striate
artery, and ideomotor apraxia (inability to perform skilled
movements) as a result of occlusion of the pericallosal branch.
SMALL VESSEL DISEASE (LACUNAE)
Patients with lacunar ischemia are commonly hypertensive,
diabetic, or both, and they do not have associated cortical
dysfunction (speech, calculation, and spatial orientation defi-
cits). Lacunar infarcts result from ischemic events involving
small penetrating branches of the middle cerebral, anterior
cerebral, posterior cerebral, and basilar and anterior choroidal
arteries. These lesions affect the basal ganglia, internal
capsule, thalamus, putamen, and internal capsule. Five major
lacunar syndromes are recognized: pure motor hemiparesis,
ataxic hemiparesis, pure sensory syndrome, mixed sensorimo-
tor syndrome, and dysarthria–clumsy hand syndrome.
Pure motor hemiparesis is the most common lacunar syn-
drome and occurs in 50% of patients with lacunar strokes.
Patients have stuttering symptoms that develop over hours, as
well as contralateral facial and arm weakness, but do not have
sensory or higher cortical dysfunction. The injury involves the
corona radiata or internal capsule.22
Ataxic hemiparesis syndrome is characterized by weakness
and dysmetria (inability to fix the range of movement) on the
 CHAPTER 100 Transient Ischemic Attack and Acute Ischemic Stroke
same side. The lower extremity is more often affected and the
face is least affected. The injury involves the internal capsule,
basis pontis, or corona radiata.22
Patients with pure sensory syndrome have contralateral
sensory loss in the face, arm, and leg. Symptoms include
sensory ataxia, a movement disorder secondary to sensory
impairment; a wide-stance gait with gaze directed to the feet;
and a walking pattern characterized by a stamping action that
maximizes any remaining proprioception. The injury involves
the ventral posterior nucleus of the thalamus.22
In mixed sensorimotor syndrome, patients have hemipare-
sis or hemiplegia associated with sensory loss on the same
side. This syndrome is distinguished from the other syn-
dromes by the lack of associated cortical symptoms. The
posterolateral thalamus and the posterior limb of the internal
capsule are the sites of injury.22
Dysarthria–clumsy hand syndrome is the least common of
the lacunar syndromes and affects 6% of patients with lacunar
stroke. Patients are typically dysarthric secondary to paresis
of the lip, tongue, and jaw musculature and report clumsiness
of hand movement. The injury involves fibers descending
through the genu of the internal capsule.22
VERTIBROBASILAR ARTERIES
Twenty percent of ischemic events affect brain tissue supplied
by the posterior circulation. Patients with posterior circulation
ischemia rarely have a single initial sign or symptom. Typical
symptoms are dizziness, vertigo, headache, vomiting, double
vision, loss of vision, transient interruption of consciousness,
numbness, weakness, and ataxia. These patients often have
crossed signs that include ipsilateral cranial nerve deficits
associated with contralateral motor deficits. The most common
signs include contralateral limb weakness, gait and limb
ataxia, oculomotor palsy, and oropharyngeal dysfunction.
POSTERIOR CEREBRAL ARTERY
Occlusion of the posterior cerebral artery and its branches
leads to a variety of defects in the cerebral cortex, midbrain,
thalamus, subthalamic nuclei, and corpus callosum. Stem
lesions in the posterior cerebral artery cause isolated contra-
lateral homonymous hemianopia. Midbrain lesions result in
crossed symptoms with ipsilateral third nerve palsy accompa-
nied by contralateral motor hemiplegia. Thalamic branch
lesions cause contralateral sensory loss accompanied by
hemianopia. Injury to the subthalamic nuclei results in ballism
of the contralateral arm. Finally, corpus callosum injury
results in an inability to transfer written information from
right to left, as well as alexia (inability to read written
material).23
CEREBELLAR INFARCT
The most common cause of an ischemic injury involving the
cerebellum is an embolic infarct in the upper part of the
cerebellum. Symptoms include dizziness, vertigo, vomiting,
blurred vision, and difficulty walking. Patients may report that
they veer to a specific side or are unable to sit upright without
assistance. Cerebellar infarcts are distinguished from infarcts
in other anatomic locations by the lack of hemiparesis or
hemisensory deficits.23,28 Hypotonia may be present in the arm
on the affected side. This sign is best elicited by having
patients hold their arms straight out at 90 degrees from the
trunk, quickly lower them, and then abruptly stop the lowering
motion. The affected side is detected because the hypotonic
arm will overshoot the rapid descent.
LATERAL MEDULLARY SYNDROME
(WALLENBERG SYNDROME)
Occlusion or narrowing of the intracranial vertebral artery
causes signs and symptoms related to ischemic injury to the
lateral medullary tegmentum. Symptoms include ipsilateral
facial sensory loss, ataxia, and nystagmus. Patients may also
have Horner syndrome, hoarseness, difficulty swallowing, and
contralateral hemisensory loss of pain and temperature sense.
DIFFERENTIAL DIAGNOSIS AND MEDICAL
DECISION MAKING
Evaluation of patients with suspected ischemic injury is sum-
marized in Box 100.1. The results of these fundamental tests
combined with risk stratification can guide the EP in deter-
mining whether cerebral injury has occurred, as well as the
cause of the ischemia.
Patients with TIA and ischemic stroke require rapid and
accurate diagnosis to determine the cause and location of the
event and the extent of damage. This knowledge allows the
EP to estimate the risks and benefits associated with therapies
that will reestablish cerebral blood flow and preserve viable
brain tissue.
Rapid diagnosis of acute ischemic stroke begins with public
education about recognition of the major warning signs of
stroke. Prehospital personnel also play a crucial role in early
diagnosis and rapid transport of stroke patients to treatment
facilities. Tools such as the Cincinnati Prehospital Stroke
Scale and the Los Angeles Prehospital Stroke Screen (LAPSS)
are used to evaluate facial droop, arm weakness, and speech
abnormalities in patients with suspected stroke. In addition,
the LAPSS screens for mimics of stroke such as hypoglyce-
mia, hyperglycemia, and seizure and has high sensitivity
(93%) and specificity (97%) for the diagnosis of acute
stroke.29,30
EPs caring for patients with acute ischemic stroke are often
under enormous time constraints. A systematic method is
necessary to distinguish patients with stroke from those with
conditions that mimic stroke.31 In addition, the EP must
combine historical and physical data with the results of
BOX 100.1  Diagnostic Evaluation for Transient
Ischemic Attack and Stroke
History
Physical examination—blood pressure; cardiac, vascular,
and neurologic evaluation; National Institutes of Health
Stroke Scale score
Laboratory tests—chemistry, coagulation, complete blood
count, fasting lipid panel
Electrocardiogram
Cerebral imaging—computed tomography and magnetic
resonance imaging if available
Vascular and cardiac imaging
873
SECTION IX NERVOUS SYSTEM DISORDERS
neurologic imaging to exclude hemorrhage and determine the
extent of injury. These elements, coupled with basic labora-
tory tests and an electrocardiogram (ECG), as recommended
by the American Heart Association (AHA), are the foundation
for accurate diagnosis of an acute ischemic stroke.
The history is the cornerstone of accurate stroke diagnosis.
Historical evidence that has been identified as being predictive
of a patient having a stroke includes persistent focal neuro-
logic deficits, acute onset during the previous week, and no
history of head trauma.31 Clinical symptoms such as arm and
leg weakness and speech impairment are more reliable indica-
tors than subjective isolated sensory symptoms are. The single
most important piece of historical information is the time of
onset of the symptoms. This is considered to be the last time
that the patient was at the previous baseline or symptom-free
state. For patients unable to provide this information or awaken
with stroke symptoms, onset is defined as time when the
patient was last seen to be normal.32 Other key historical
factors include contraindications to thrombolytic therapy,
medications being taken by the patient, heart disease, previous
stroke, TIA, seizures, vomiting, or headache occurring at the
beginning of the patient’s acute symptoms.
EPs must use a reproducible standardized physical exami-
nation to assess the severity of injury in stroke patients. Three
key physical findings—facial paresis, arm drift, and abnormal
speech—are highly predictive of an acute stroke. The National
Institutes of Health Stroke Scale (NIHSS) (see the Documen-
tation box) is a valid, standardized tool that records clinical
findings and provides information that is helpful in determin-
ing the prognosis and therapeutic options. This 42-point scale
evaluates level of consciousness, cranial nerves, motor func-
tion, ataxia, sensation, speech, and neglect. It can be used for
serial examinations and is a predictor of patient outcome and
risk associated with therapy, which can be useful when dis-
cussing treatment options with specialists, patients, and family
members.
DOCUMENTATION
Time of onset of symptoms or the last time that patient was
seen to be normal
Initial National Institutes of Health Stroke Scale (NIHSS)
score
Resolution of symptoms and NIHSS score of 0 for patients
with a transient ischemic attack (TIA)
Single or multiple events
History of stroke risk factors
Current medications, including antiplatelet drugs and
anticoagulants
Results of cerebral imaging
ABCD2 score for patients with TIA
Suspected cause and initiation of preventive or thrombolytic
therapy
Specialist consultation and early (within 48 hours) follow-up
for low-risk patients with TIA discharged from the emer-
gency department
Specialist consultation and admission to a stroke unit for
patients with stroke
874
Patients with an NIHSS score lower than 6 have a predicted
excellent outcome at 6 months, and 81% are discharged home.
Nearly half the patients with an NIHSS score higher than 15
will require transfer to a nursing facility. Patients with an
NIHSS score higher than 20 have a 17% risk for intracerebral
hemorrhage when treated with recombinant tissue plasmino-
gen activator (rt-PA). Finally, each additional point on the
NIHSS decreases the likelihood of an excellent outcome by
17%.33-35
Although the history and physical examination are impor-
tant elements in making an accurate diagnosis of patients with
acute neurovascular events, neuroimaging is the key diagnos-
tic tool. The goals of modern neuroimaging evaluation are to
(1) obtain evidence of a vascular origin of the symptoms; (2)
exclude an alternative nonischemic origin; (3) ascertain the
underlying vascular mechanism of the event, which helps
guide therapy; (4) identify prognostic outcome categories; and
(5) improve selection of patients to be treated with reperfusion
therapies by identifying those with regions of salvageable
brain tissue, low risk for hemorrhagic transformation, or
occlusion of large arteries that might be amenable to
therapy.1,32 Currently, EPs have a multitude of imaging options
that are based on availability of the imaging modality and
local expertise in interpretation of the images.
Non–contrast-enhanced CT remains the standard imaging
technique for evaluating patients with acute stroke. It can be
performed in the majority of hospitals, images are acquired
rapidly, and it is sensitive in detecting acute hemorrhage. For
patients with TIA, CT has been shown to provide an alterna-
tive diagnosis in 1% of all cases, and a new infarct has been
found within 48 hours in 4% of patients with TIA. Of these
patients, 38% eventually experienced a new ischemic stroke
in the next 90 days.26 CT findings not associated with an
increased short-term risk for stroke include old infarction,
periventricular white matter disease, cerebral atrophy, and
vascular calcification.36 Unfortunately, CT scans are fre-
quently negative in the first hours after an ischemic stroke, are
limited in defining posterior fossa structures and discriminat-
ing between infarct and viable at-risk tissue (penumbra), and
provide no information on the presence or location of vascular
pathology.32
Subtle clues found on CT scanning are cortical hypoden-
sity, hyperdense middle cerebral artery, middle cerebral artery
dot sign, sulcal effacement, hypoattenuation of the insular
ribbon, and obscuration of the lentiform nucleus. The Alberta
Stroke Program Early CT Score (ASPECTS) organized these
early subtle clues into a semiquantitative 10-point grading
system for early ischemic changes in the middle cerebral
artery territory found on CT scans. Patients with an ASPECTS
higher than 7 were found to have a much higher incidence of
parenchymal hematoma after receiving rt-PA therapy.37
Perfusion CT is an advanced neuroimaging technique that
uses intravenous (IV) contrast material to provide semiquan-
titative information on cerebral blood flow and cerebral blood
volume. Other useful calculations include the mean transit
time of the contrast agent from the arterial to the venous
circulation and time to peak, which measures the time between
the first arrival of contrast agent in the artery and the peak
of the bolus within the brain tissue.38 Studies suggest that a
CT battery that includes non–contrast-enhanced CT, CT angi-
ography, and CT perfusion can be performed quickly in
patients with acute stroke and can provide comprehensive
 CHAPTER 100 Transient Ischemic Attack and Acute Ischemic Stroke
information.1,39 Benefits include more rapid identification of
the location of ischemia and the presence of viable tissue.
Disadvantages include the need for IV contrast material and
normal renal function, which limits imaging of the posterior
fossa, and lack of local expertise in interpretation of the
images.
MRI with diffusion-weighted imaging (DWI) is very accu-
rate in early detection of hyperacute stroke and determination
of the stroke subtype.40 It is more sensitive than standard CT
in identifying both new and preexisting ischemic lesions in
patients with TIA.1 Multimodal MRI provides physiologic
data and distinction between cytotoxic edema (diffusion-
weighted MRI), reduced cerebral blood flow (perfusion MRI),
and increased water content, which is a marker of permanent
brain injury (T2 imaging). On average, 42% of TIA patients
will have abnormalities on diffusion-weighted MRI, and in up
to one third of cases the results of diffusion-weighted MRI
change the clinically suspected vascular location and cause of
the TIA.41 Clinical predictors of positive findings on diffusion-
weighted MRI include a duration of symptoms longer than 1
hour, motor deficits, and aphasia, as well as large vessel occlu-
sion on magnetic resonance angiography (MRA).1,24 Addition-
ally, patients with TIA who exhibit abnormalities on DWI
have a higher risk for recurrent ischemic events than do those
without such abnormalities.42 DWI positivity also correlates
with the ABCD2 score for predicting stroke risk.43
MRI coupled with perfusion-weighted imaging and MRA
increases diagnostic certainty and allows detection of isch-
emic injury, determination of tissue viability, and localization
of vascular clot, stenosis, and dissection. MRI provides better
imaging of the brainstem and posterior fossa than CT does.
Furthermore, MRI is as accurate as CT in detecting acute
hemorrhagic transformation and is more accurate in distin-
guishing acute from chronic hemorrhage.44 Limitations
include cost, availability, incompatibility with implantable
devices, and requirement for patient tolerance and stability.
However, if available, MRI is a first-line imaging modality for
patients whose neurologic symptoms are transient.
Diagnostic testing is completed with laboratory and ancil-
lary tests. Laboratory tests recommended by the AHA include
a complete blood count with platelets, prothrombin time,
partial thromboplastin time, international normalized ratio
(INR), chemistry panel including renal function and glucose,
and cardiac enzymes. Other laboratory tests to consider in
selected patients include liver function tests, pregnancy
testing, arterial blood gas analysis (if hypoxia is suspected),
drug toxicology, and urinalysis. An ECG should be obtained
to look for atrial fibrillation, acute myocardial infarction, or
other disturbances in rhythm. Ancillary testing includes a
chest radiograph if pulmonary pathology, aspiration, or
congestive heart failure is suspected.1 Echocardiography and
carotid Doppler ultrasonography also play limited roles in the
diagnostic evaluation and are generally part of a complete
inpatient work-up.32
TREATMENT
The goal of management of patients with TIA is the introduc-
tion of therapy that will prevent stroke and thus avoid perma-
nent disability and untimely death. Three types of medical
therapy to achieve this goal are available: antiplatelet therapy,
anticoagulation therapy, and surgical or endovascular therapy.
In addition, patients should be instructed about measures that
modify risk factors for stroke.
ED management of patients with acute ischemic stroke
requires a team approach that is organized, time sensitive, and
goal directed. The goal of ED care is to ensure medical stabil-
ity, identify the cause of the ischemic event, determine the
extent of injury, and create a therapeutic plan that reestab-
lishes cerebral function and prevents or limits further injury.45
Four time goals for therapy have been established (see the
Priority Actions box).
  PRIORITY ACTIONS
10 Minutes from Time of Arrival
Secure the ABCs, obtain vital signs, and check a fingerstick
blood glucose level.
Establish an IV line, administer O2, and place the patient on
a cardiac monitor.
Calculate the NIHSS score.
Consult the stroke team or neurology.
Send the patient for a CT scan.
25 Minutes from Time of Arrival
CT scan is completed.
Establish an accurate time of onset with the patient, family,
or EMS personnel.
Review the history with the stroke team or neurologist.
45 Minutes from Time of Arrival
CT scan is reviewed and interpreted.
Review contraindications to thrombolysis (see Box 100.5).
Repeat the neurologic examination to assess for worsening
clinical status.
Treat hypertension (SBP > 185 mm Hg, DBP > 110 mm Hg),
hyperglycemia (glucose > 120 mg/dL), and fever (tem-
perature > 38° C).
60 Minutes from Time of Arrival
Establish a plan of care.
Review the risks and benefits of the plan of care with the
patient and family.
Initiate thrombolytic therapy for patients who are
candidates.
Screen for aspiration in patients who are not candidates for
thrombolysis and administer aspirin orally or rectally.
Admit for further monitoring and therapy.
ABCs, Airway, breathing, and circulation; CT, computed tomography;
DBP, diastolic blood pressure; EMS, emergency medical service; IV,
intravenous; NIHSS, National Institutes of Health Stroke Scale; SBP,
systolic blood pressure.
ANTIPLATELET THERAPY
The use of antiplatelet agents rather than oral anticoagulation
is the treatment of choice for the prevention of stroke in
patients with TIA secondary to atherothrombotic disease (Box
100.2).46,47 Aspirin is the most widely used and the most eco-
nomical drug available for prevention of stroke. Currently,
875
SECTION IX NERVOUS SYSTEM DISORDERS
BOX 100.2  Antiplatelet Recommendations
Acceptable options for initial therapy are aspirin monother-
apy, 50 to 325 mg/day; the combination of aspirin, 25 mg,
and extended-release dipyridamole, 200 mg twice daily;
and clopidogrel monotherapy, 75 mg.
The addition of aspirin to clopidogrel increases the risk for
hemorrhage and is not recommended for routine second-
ary prevention after a transient ischemic attack.
Clopidogrel is a reasonable option for patients allergic to
aspirin.
For patients who have an ischemic stroke while taking aspirin,
no evidence has indicated that increasing the dose of
aspirin provides additional benefit; the addition of alterna-
tive antiplatelet agents in this scenario has not been
studied.
From Furie KL, Kasner SE, Adams RJ, et al. Guidelines for the prevention
of stroke in patients with stroke or transient ischemic attack: a guideline
for healthcare professionals from the American Heart Association/
American Stroke Association. Stroke 2011;42:227-76.
clopidogrel, ticlopidine, and combined dipyridamole-aspirin
(DPA) are antiplatelet agents that are effective alternatives to
aspirin. Unfortunately, despite being the standard of care in
the AHA guidelines, these agents are often underused, with
only 18% of TIA patients encountered in the ED receiving
aspirin, 7% receiving other antiplatelet agents, and 42%
receiving no treatment.7
Aspirin is a mainstay of antiplatelet therapy for prevention
of atherothrombotic stroke in TIA patients. It achieves this
benefit though irreversible block of the enzyme cyclooxygen-
ase, which in turn prevents the metabolism of arachidonic acid
to the potent vasoconstrictor and platelet aggregator throm-
boxane A2. The effective dose of aspirin is 50 to 325 mg. It is
associated with an overall reduction of 15% to 18% in the
combined end points of stroke, myocardial infarction, and
death.47 It is well tolerated and inexpensive; however, gastro-
intestinal bleeding is a documented major side effect.
Clopidogrel (75 mg daily) and ticlopidine (250 mg twice
daily) are adenosine diphosphate receptor antagonists that
prevent platelet aggregation. Clopidogrel has the advantages
of once-daily dosing, less neutropenia, and fewer gastrointes-
tinal side effects. It must be noted that clopidogrel has been
reported to induce thrombotic thrombocytopenic purpura in a
very small percentage of patients.48 In addition, clopidogrel
has not been compared with placebo for secondary stroke
prevention.46
Large, multicenter randomized controlled trials have com-
pared clopidogrel with aspirin49 and combined clopidogrel-
aspirin with clopidogrel alone in the prevention of stroke,
myocardial infarction, and death.50 Subgroup analysis failed
to find a statistically significant reduction in ischemic stroke
in favor of clopidogrel or the combined drugs. In addition, no
increase in reduction of the risk for stroke was achieved by
giving aspirin to symptomatic patients currently taking clopi-
dogrel; in fact, major bleeding increased with the combination
of the two drugs.51 Clopidogrel remains a viable option for
patients who are aspirin sensitive, and it has been shown to
876
be beneficial in patients who have concomitant cerebral vas-
cular and coronary disease or recent stent placement.
Dipyridamole is a cyclic nucleotide phosphodiesterase
inhibitor that inhibits platelet aggregation by increasing levels
of cyclic adenosine monophosphate. Extended-release dipyri-
damole in combination with aspirin has been shown to reduce
the risk for stroke by 37% when compared with placebo and
to reduce risk by 23% when compared with aspirin alone.36
Studies comparing extended-release DPA and clopidogrel
have demonstrated that they are not different in their effi-
cacy.52 Common side effects include headache and gastroin-
testinal disturbances.
ANTICOAGULATION
Atrial fibrillation (AF) is responsible for 50% of all cardio-
genic embolic events. Patients with a TIA or ischemic stroke
and paroxysmal or sustained AF should receive warfarin as
the therapy of choice for the prevention of stroke.46,53 These
patients have a target INR of 2.5 (range, 2.0 to 3.0). Risk
factors for stroke in patients with AF include congestive heart
failure, hypertension, age older than 75 years, diabetes, and
previous stroke or TIA.54 For these high-risk patients who
require temporary interruption of oral anticoagulation, bridg-
ing therapy with low-molecular-weight heparin administered
subcutaneously is reasonable.46
Other cardiac risk factors include left ventricular thrombus
in the setting of acute myocardial infarction, native valvular
heart disease, and prosthetic heart valves. Warfarin is a rea-
sonable option for all these conditions with slight variations.
With a left ventricular thrombus, oral anticoagulation with a
target INR of 2.5 (range, 2.0 to 3.0) should be continued for
at least 3 months. In the setting of rheumatic mitral valve
disease, oral anticoagulation with a similar target is also rea-
sonable. Because of the increased risk for stroke in patients
with mechanical prosthetic heart valves, the target range for
anticoagulation is increased and the target INR should be 3.0
(range, 2.5 to 3.5). Patients with bioprosthetic valves can be
maintained at an INR of 2.5 (range, 2.0 to 3.0). In general, to
avoid additional bleeding risk, antiplatelet agents should not
be routinely added to warfarin unless a patient with a pros-
thetic heart valve has an ischemic stroke or systemic embo-
lism despite adequate therapy with oral anticoagulants and
is not at high risk for bleeding.46 Warfarin has not been
shown to be superior to aspirin in the prevention of noncar-
dioembolic forms of stroke.55
SURGICAL MANAGMENT
Carotid endarterectomy (CEA) performed in patients with
symptomatic severe carotid stenosis greater than 70% to 99%
results in a long-term benefit in preventing strokes.56-58 Patients
with symptomatic stenosis of 50% to 69% may also benefit
from CEA, depending on age, sex, and comorbid conditions,
if their perioperative risk for morbidity and mortality is esti-
mated to be less than 6%.46 Finally, CEA is not beneficial or
is harmful in symptomatic patients with stenosis of less
than 50% (Box 100.3).59-61 When performed within 2 weeks,
surgery is reasonable in patients with no contraindications to
early revascularization.46
Recently, carotid angioplasty plus stenting (CAS) has been
deemed a possible alternative to surgical carotid therapy and
has been shown to have outcomes comparable with those
achieved with CEA.62-64 The AHA now recommends CAS as
 CHAPTER 100 Transient Ischemic Attack and Acute Ischemic Stroke
BOX 100.3  Carotid Endarterectomy
(CEA)/Carotid Angioplasty and Stenting
(CAS) Recommendations*
CEA is recommended for symptomatic stenosis of 70% to
99%.
CEA may be recommended for symptomatic stenosis of 50%
to 69%, depending on patient-specific factors such as
age, sex, and comorbid conditions.
CEA is best performed within 2 weeks of symptomatic
events.
No benefit is achieved with performance of CEA for stenosis
of less than 50%.
CAS is an alternative to CEA in patients at low to average
risk for complications when the luminal diameter of the
internal carotid artery is found to be reduced more than
70% by noninvasive imaging or more than 50% by cath-
eter angiography.
CAS may be considered in patients with greater than 70%
stenosis if the stenosis is difficult to access surgically or
if they are deemed to be poor surgical candidates.
From Furie KL, Kasner SE, Adams RJ, et al. Guidelines for the prevention
of stroke in patients with stroke or transient ischemic attack: a guideline
for healthcare professionals from the American Heart Association/
American Stroke Association. Stroke 2011;42:227-76.
*Assumes that the perioperative or periprocedural risk for stroke or death
is less than 6% for surgeon, interventionalist, or center.
an alternative to CEA for symptomatic patients at average or
low risk for complications associated with endovascular inter-
vention when the diameter of the lumen of the internal carotid
artery is found to be reduced by more than 70% by noninva-
sive imaging or by more than 50% by catheter angiography,
and CAS can be used in patients with greater than 70% ste-
nosis if they are deemed to be poor surgical candidates.46
RISK FACTOR REDUCTION
Several factors portend an increased risk for stroke in patients
who have experienced a TIA. Modifiable risk factors include
hypertension, diabetes, hyperlipidemia, cigarette smoking,
and heavy alcohol consumption. The AHA recommends that
blood pressure be reduced in all patients with TIA beyond the
first 24 hours of symptoms, with an average reduction of
approximately 10/5 mm Hg and an ultimate goal of less than
120/80 mm Hg. Reduction of blood pressure can be attained
through lifestyle modification and antihypertensive therapy.46
In diabetic patients, diet, exercise, oral hypoglycemic drugs,
and insulin are recommended to gain glycemic control.
Elevations in total cholesterol or low-density lipoprotein
cholesterol (LDL-C) and low levels of high-density lipopro-
tein cholesterol (HDL-C) are modest risk factors for stroke.
A metaanalysis of statin trials showed that the larger the
reduction in LDL-C, the greater the reduction in risk for
stroke.65 Therefore, the AHA recommends statin therapy with
intensive lipid-lowering effects in patients with TIA who have
evidence of atherosclerosis and an LDL-C level higher than
100 mg/dL. It is reasonable to target a reduction of at least
50% or levels of less than 70 mg/dL. For patients with TIA
and low HDL-C, treatment with niacin or gemfibrozil can be
considered.46
Additional lifestyle risk factor reduction includes providing
TIA patients with smoking cessation counseling and advising
patients to avoid environmental (passive) tobacco smoke.
Patients who are heavy drinkers should eliminate or reduce
their consumption of alcohol to no more than two drinks per
day for men and one drink per day for women who are not
pregnant.46
THROMBOLYSIS
The only treatment of acute ischemic stroke approved by the
Food and Drug Administration (FDA) is IV rt-PA therapy,
which has traditionally been recommended for carefully
selected patients older than 18 years who are seen within 3
hours of the onset of an acute ischemic stroke.There have been
some recent updates to recommendations for the use of IV
rt-PA outside the traditional 3-hour time window, as well as
the use of intraarterial thrombolysis for patients initially seen
between 3 and 6 hours after the onset of symptoms.32,66
Adjuncts to intraarterial thrombolysis include angioplasty,
stenting, and clot retrieval devices. Other therapies include
prevention of hypoxemia and dehydration, administration of
antiplatelet and anticoagulation agents, normalization of
glucose, and temperature control.32
The era of emergency intravenous thrombolysis for acute
ischemic stroke began in 1995 with the National Institute of
Neurological Disorders and Stroke (NINDS) rt-PA trial.67 This
study was a single randomized controlled trial that compared
patients with ischemic stroke treated with IV rt-PA versus
placebo (given at 0 to 90, 90 to 180, and 0 to 180 minutes).
Despite no difference in the NIHSS score at 24 hours, the
main outcome of the trial was a 30% decrease in disability at
3 months in patients treated with IV rt-PA versus 20% in those
treated with placebo. This benefit was similar 1 year after
stroke.68 Adverse events included a 10-fold increase in the rate
of intracerebral hemorrhage 36 hours after treatment with
rt-PA (6% versus 0.6%); however, the death rate in the two
treatment groups was similar at 3 months (17% versus 20%)
and at 1 year (24% versus 28%).67
Concern over data that support the use of thrombolytics for
acute ischemic stroke and external validity in community
hospitals has been raised by some EPs.69 Some community
hospital groups have reported high rates of intracranial hem-
orrhage and fewer favorable outcomes. In these studies the
risk for hemorrhage is proportional to the degree to which the
NINDS protocol is not followed.70-72 Critics also observed that
the relative predominance of mild strokes (NIHSS score < 5)
with a probably good outcome in the rt-PA group may explain
the entire benefit reported in patients treated between 91 and
180 minutes. Neither reanalysis of the data by the NINDS
study group nor a separate analysis by an independent group
could demonstrate that the effect of the imbalance in severity
influenced the overall result that rt-PA therapy positively influ-
enced outcome.73,74 Several recent studies also demonstrated
improved neurologic outcomes and similar hemorrhage rates
as the original NINDS data.75-79
The effectiveness of thrombolysis is determined by several
variables. Time until treatment is extremely important: 75%
of patients in one pooled analysis who were treated within 60
minutes of the onset of stroke in the initial pooled analysis
877
SECTION IX NERVOUS SYSTEM DISORDERS
had the best chance of achieving complete or partial reopen-
ing of the occluded artery.78 Patients with mild to moderate
strokes (NIHSS score < 20) and patients younger than 75
years had the greatest potential for a favorable response to
treatment.80 Predictors of a poor postthrombolysis prognosis
include older patient age, higher stroke severity (NIHSS score
> 22), systemic hypertension or hypotension, hyperglycemia,
and fever.
Despite its effectiveness in improving neurologic outcomes,
the majority of patients with ischemic stroke are not treated
with rt-PA, largely because they arrive after the 3-hour window
for treatment. One potential solution would be to designate a
longer time window for treatment. A pooled analysis of previ-
ous large trials suggested that the upper limit of the treatment
window may be as late as 5 to 6 hours.78 The ECASS-3 trial
enrolled patients to either rt-PA or placebo by using the
current guideline protocols of between 3 and 4.5 hours after
the onset of symptoms. It excluded patients older than 80
years, those taking oral anticoagulants, those with a history
of both previous stroke and diabetes, and patients with a
baseline NIHSS score higher than 25. The rate of symptom-
atic intracranial hemorrhage (as defined by NINDS criteria)
was 7.9% for the treatment group and 3.5% for the placebo
group, neurologic improvement was significantly higher in the
rt-PA group than in the placebo group, and mortality in the
two treatment groups did not differ significantly.66 These find-
ings are consistent with the results in this time window from
pooled analyses of previous trials.78 Subsequently, the AHA
made recommendations regarding expansion of the time
window for the treatment of ischemic stroke with IV rt-PA
(Box 100.4).81
Centers that care for stroke patients must develop guide-
lines for the appropriate selection of patients and develop
BOX 100.4  Recommendations of the American
Heart Association Regarding Extension
of the Time Window for Administration
of Recombinant Tissue Plasminogen Activator
in Patients with Ischemic Stroke
Recombinant tissue plasminogen activator should be admin-
istered to eligible patients who can be treated in the 3- to
4.5-hour period after the onset of stroke.
Exclusion criteria for the extended treatment window include:
• Patients older than 80 years
• Baseline National Institutes of Health Stroke Scale
score higher than 25
• Patients with a history of both stroke and diabetes
• All patients receiving oral anticoagulants regardless of
their international normalized ratio
Delays in evaluation and initiation of therapy should be
avoided because of the opportunity for greater neurologic
improvement with earlier treatment.
From del Zoppo GJ, Saver JL, Jauch EC, et al. Expansion of the time
window for treatment of acute ischemic stroke with intravenous tissue
plasminogen activator: a science advisory from the American Heart
Association/American Stroke Association. Stroke 2009;40:2945-8.
878
systems to rapidly deliver thrombolysis therapy to these
patients. Candidates for IV thrombolysis must have a clearly
defined time of symptom onset of less than 270 minutes, must
be older than 18 years, and must have no contraindications
to thrombolytic therapy (Box 100.5).32 The dosing regimen
is 0.9 mg/kg (maximum of 90 mg) of rt-PA, with 10%
(maximum of 9 mg) given as a bolus over a 1- to 2-minute
period, followed by the remaining dose (maximum of 81 mg)
infused by pump over a 1-hour period. Any indwelling cath-
eters should be placed before the administration of thrombo-
lytics. The patient should be admitted to an intensive care or
stroke unit for frequent neurologic examination and blood
pressure checks, with the goal of maintaining blood pressure
lower than 180/105 mm Hg. If severe headache, acute hyper-
tension, nausea, or vomiting develops, the infusion should be
discontinued and an emergency non–contrast-enhanced head
CT scan should be obtained. The institution must have a pro-
tocol for the management of thrombolytic-induced intracere-
bral hemorrhage. The patient should not receive aspirin or
heparin during the first 24 hours after thrombolytic therapy.
A follow-up non–contrast-enhanced head CT scan should be
done at 24 hours and before starting anticoagulant or anti-
platelet therapy.32
ENDOVASCULAR PROCEDURES
Procedures such as intraarterial thrombolysis with or without
mechanical embolectomy, angioplasty, and carotid stenting
are considered experimental therapies that may benefit
BOX 100.5  Contraindications to Administration
of Recombinant Tissue Plasminogen Activator
Head trauma or stroke in the previous 3 months
Myocardial infarction in the previous 3 months
Gastrointestinal or urinary tract hemorrhage in the previous
3 weeks
Major surgery in the past 2 weeks
Arterial puncture at a noncompressible site in the previous
7 days
History of previous intracranial hemorrhage
Systolic blood pressure higher than 185 mm Hg, diastolic
blood pressure higher than 110 mm Hg
Evidence of active bleeding or acute trauma (fracture) on
examination
Oral anticoagulation with an international normalized ratio
higher than 1.7
Receiving heparin in the previous 48 hours with an abnormal
activated partial thromboplastin time
Platelet count lower than 100,000/mm3
Blood glucose level lower than 50 mg/dL
Seizure with postictal residual neurologic impairments
Computed tomography scan demonstrating multilobar
infarction (hypodensity in more than a third of the cerebral
hemisphere)
Adapted from Adams HA, del Zoppo G, Alberts MJ, et al. Guidelines for
the early management of adults with ischemic stroke. Stroke 2007;
38:1655-711.
 CHAPTER 100 Transient Ischemic Attack and Acute Ischemic Stroke
specific patient groups who are seen outside the 3-hour
window or have contraindications to IV thrombolysis, such as
recent surgery.82 Benefits of this therapy include a lower dose
of thrombolytic, direct visualization of the occluded vessel,
and higher recanalization rates. The FDA has approved use of
the MERCI (Mechanical Embolus Removal in Cerebral
Embolism) devise. Treatment requires the patient to be at an
experienced stroke center with immediate access to cerebral
angiography and qualified interventionalists.32
ADJUVANT THERAPIES
Blood Pressure Management
Management of blood pressure in an acute stroke patient is
controversial. In an ED study of patients with acute ischemic
stroke, systolic blood pressure outside the range of 155 to
220 mm Hg and diastolic blood pressure outside the range of
71 to 105 mm Hg were associated with increased 90-day mor-
tality. These findings demonstrate the harmful effects of both
hypertension and hypotension and indicate that there is an
optimal range of blood pressure required to perfuse at-risk
tissue in these patients.83
Current American Stroke Association and European Stroke
Initiative guidelines recommend withholding antihypertensive
therapy in patients with acute ischemic stroke unless they are
thrombolysis candidates or show evidence of end-organ dys-
function (acute myocardial infarction, aortic dissection, pul-
monary edema, and renal failure). Short-acting IV medications
with reliable dose response and safety profiles should be used.
Medications that meet these requirements include labetalol,
nicardipine, and esmolol.32,84 Despite concern that lowering
blood pressure in the acute stroke setting might be harmful,
pilot data from the CHHIPS trial demonstrated that labetalol
and lisinopril are effective antihypertensive drugs for patients
with acute stroke and do not increase serious adverse events.
Early lowering of blood pressure also resulted in a reduction
in mortality. However, in view of the small sample size, care
must be taken when these results are interpreted, and further
evaluation in larger trials is needed.85 Conversely, small clini-
cal studies suggest that drug-induced hypertension could be
used in the management of some patients with acute ischemic
stroke to improve cerebral blood flow, but data from large
clinical trials are lacking. The AHA recommends using this
method only in exceptional cases or within the setting of clini-
cal trials.32
Glucose Management
Hyperglycemia (glucose > 185 mg/dL) and hypoglycemia
(glucose < 60 mg/dL) are associated with worsening of clini-
cal and tissue outcome in patients with acute ischemic stroke.
Hyperglycemia can accelerate the course of ischemic injury,
actively convert penumbra to infarcted tissue, and increase the
risk for hemorrhagic events and poor outcome in patients
receiving rt-PA therapy.86,87 Glycemic control with rapidly
acting insulin should be instituted to maintain blood glucose
between the suggested levels of 140 to 185 mg/dL while
taking care to avoid hypoglycemia.32
Temperature Management
Hyperpyrexia (temperature > 38.0° C) is associated with
increased morbidity and mortality. The pathologic effects
stem from increased neurotransmitter and free radical produc-
tion and adverse effects on the blood-brain barrier, which
seem to be most pronounced at the border zone or penumbra
of the infarct and lead to loss of potentially viable tissue.
Therefore, the source of the fever should be actively sought
and treated with acetaminophen.88
Anticoagulation
Currently, early administration of heparin is not recommended
for any type of acute ischemic stroke because of the increased
risk for secondary hemorrhagic conversion; furthermore,
clinical trial data have shown no reduction in stroke recur-
rence or improvement in patient outcome.89-93 Additionally,
initiation of anticoagulant therapy within 24 hours of treat-
ment with IV rt-PA is not recommended.32
Antiplatelet Therapy
The goals of antiplatelet therapy in patients with stroke are a
reduction in stroke recurrence and stroke-related morbidity
and mortality. Aspirin (50 to 325 mg/day) therapy resulted in
a significant reduction in death and disability when given
within 48 hours of ischemic stroke.89,94 It reduced the risk for
early recurrent stroke in all stroke subtypes. Therefore,
patients who are not aspirin sensitive or at risk for aspiration
and are not being administered t-PA should receive aspirin
within 48 hours of ischemic stroke.
Other oral antiplatelet agents, including clopidogrel, ticlop-
idine, and combination drugs such as DPA, have not been
proved to be safer or more cost-effective than aspirin alone.
Clopidogrel is recommended for aspirin-sensitive patients
who require emergency antiplatelet therapy in the ED. The use
of IV antiplatelet agents such as glycoprotein IIb/IIIa inhibi-
tors is still investigational and is not recommended for use
outside the setting of clinical trials.32
FOLLOW-UP, NEXT STEPS IN CARE,  
AND PATIENT EDUCATION
The areas that should be emphasized when making decisions
regarding admission or discharge are the completeness of the
evaluation, the source of the event, and resolution of the
symptoms. These issues, coupled with proper risk stratifica-
tion and cerebral vascular imaging, represent a logical
approach to achieving safe and proper disposition of the
patient.
A thorough diagnostic evaluation that determines the cause
of the TIA plays a crucial role in the decision to hospitalize
or discharge patients from the ED. Patients who are at high
risk for recurrent events and are unable to undergo appropriate
cerebral and vascular imaging should be hospitalized to expe-
dite the evaluation and allow observation for recurrent events
in the period of vulnerability (hours or days) after the event.8
Diagnostic benefits of hospital admission include rapid evalu-
ation, monitoring for acute neurologic deterioration, and
cardiac telemetry monitoring. Therapeutic benefits include the
ability to deliver thrombolytic therapy, rapid institution of
antiplatelet and anticoagulation therapy, and early consider-
ation for carotid surgery.95
The AHA has recently recommended hospital admission
for patients initially seen with TIA within 72 hours of the
event and when any of the following criteria are present: (1)
ABCD2 score higher than 3, (2) ABCD2 score of 0 to 2 and
879
SECTION IX NERVOUS SYSTEM DISORDERS
uncertainty that diagnostic work-up can be completed within
2 days as an outpatient, and (3) ABCD2 score of 0 to 2 and
other evidence indicating that the patient’s event was caused
by focal ischemia.1
Patients deemed to be at low risk after a complete evalua-
tion and those who have a clear cause and are receiving
preventive therapy can be discharged after appropriate con-
sultation with a neurologist, cardiologist, or vascular surgeon.
It should be emphasized to all patients that a TIA is a high-risk
event and that the risk for stroke is highest in the next 2 to 90
days (see the Patient Teaching Tips box). All patients dis-
charged from the ED should be scheduled for follow-up
during the next 2 days, which is the most critical period for
recurrent events. Preventive therapy, especially antiplatelet
therapy, should be initiated before discharge.1
PATIENT TEACHING TIPS
A transient ischemic attack is a serious warning sign for
stroke, myocardial infarction, and death in the next 2 to
90 days.
Patients should understand the warning signs of stroke and
be instructed to return to the emergency department if
symptoms recur.
Patients with significant carotid disease should be evaluated
promptly for surgery within the next 2 weeks and should
be treated with antiplatelet agents.
Patients who are discharged should have early outpatient
follow-up and evaluation in the following 2 to 7 days.
Patients should control modifiable risk factors and adhere patients who may be candidates for thrombolytic therapy.
to antiplatelet, anticoagulation, and antihypertensive
therapy.
Unlike TIA, all patients with acute ischemic stroke require
admission to the hospital to be observed for changes in their
condition, facilitate medical or surgical procedures, receive
preventive therapy, and recover neurologic function with reha-
bilitative services. Optimal disposition is dependent on local
hospital expertise, severity of the stroke, and intensity of
therapy. Following early therapy initiated at a community hos-
pital, patients may be transferred to a stroke center for more
comprehensive care, which is often coordinated by stroke
teams in hospitals throughout the United States. Patients
undergoing thrombolysis should have access to the intensive
care unit, neurology and neurosurgery consultation, and blood
bank services.
Admission to a stroke unit has been validated in clinical
trials as being statistically significant in decreasing disability
and mortality while increasing the probability that the patient
will return home and resume daily living activities.96 These
effects are independent of age, sex, and severity of stroke and
are reproducible in a community setting.
Intensive monitoring in a stroke unit allows early detection
and treatment of fever, hypoxemia, hyperglycemia, and cardiac
rhythm disturbances and permits early mobilization coupled
880
with physical and occupation therapy. Stroke units have been
found to be effective for patients with large artery–associated
stroke and more costly but equally efficacious as medical
ward care for patients with small vessel–associated stroke.97
Hospitals without stroke units should have comprehensive
protocols and quality assurance programs that actively manage
the variables shown to affect outcome and ensure optimal care
for all patients.
Patients who require intensive care unit admission are those
with severe stroke and the potential for decompensation.
High-risk populations include patients treated with IV or
intraarterial thrombolysis or catheter-based therapies, patients
with an NIHSS score higher than 17, and patients with large
strokes in the cerebellar or middle cerebral artery distribution
who are at risk for the development of cerebral edema.
TIPS AND TRICKS
Use diffusion-weighted magnetic resonance imaging to dif-
ferentiate a true transient ischemic attack from ischemic
stroke.
Use risk stratification criteria to determine the need for
hospitalization.
Patients with motor and speech deficits and prolonged
symptoms are more likely to have positive findings on
diffusion-weighted imaging.
An antiplatelet agent should be prescribed for patients with
transient ischemic attacks to minimize the risk for stroke.
A stroke team or neurologist should be consulted early for
Patients with acute stroke should be admitted to a stroke
unit for further care.
SUGGESTED READINGS
Adams HA, del Zoppo G, Alberts MJ, et al. Guidelines for the early management of
adults with ischemic stroke. Stroke 2007;38:1655-711.
del Zoppo GJ, Saver JL, Jauch EC, et al. Expansion of the time window for treatment
of acute ischemic stroke with intravenous tissue plasminogen activator: a science
advisory from the American Heart Association/American Stroke Association. Stroke
2009;40;2945-8.
Easton JD, Saver JL, Albers GW, et al. Definition and evaluation of transient ischemic
attack: a scientific statement for healthcare professionals from the American Heart
Association/American Stroke Association Stroke Council; Council on
Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and
Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council
on Peripheral Vascular Disease. Stroke 2009;40:2276-93.
Furie KL, Kasner SE, Adams RJ, et al. Guidelines for the prevention of stroke in
patients with stroke or transient ischemic attack: a guideline for healthcare
professionals from the American Heart Association/American Stroke Association.
Stroke 2011;42:227-76.
REFERENCES
References can be found on Expert Consult @
www.expertconsult.com.
 CHAPTER 100 Transient Ischemic Attack and Acute Ischemic Stroke
REFERENCES
1. Easton JD, Saver JL, Albers GW, et al. Definition and evaluation of transient
ischemic attack: a scientific statement for healthcare professionals from the
American Heart Association/American Stroke Association Stroke Council;
Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular
Radiology and Intervention; Council on Cardiovascular Nursing; and the
Interdisciplinary Council on Peripheral Vascular Disease. Stroke
2009;40:2276-93.
2. Kucinski T, Koch C, Zeumer H. CT in acute stroke. Lincolnshire, Ill: Remedica;
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